FitSugar

All You Can Eat - Recession Buster or Fat Maker?

FitSugar — Thu, 29 Oct 2009 03:00:15 -0700

Taybarns restaurant is introducing a new dining concept to the English - all you can eat. It's nothing we haven't seen in the United States. We have all-you-can-eat baked potato and pizza bars, endless breadsticks and salad, and the kind of buffets that would make Elvis weep if he was still kickin' it in Vegas.

The Taybarns message is clear: "Enjoy as much as you like, as many times as you like. All for one fixed price!" That fixed price gives you a 111-foot counter filled with pizza, Chinese food, carving stations, fry stations, desserts, and more. The English are going crazy for the buffet-style chain, and while neighboring restaurants continue to close, Taybarns is on the up.

During tough economic times, giving people the most bang for their buck seems like a smart business model, but at what cost? As reported by the BBC, not everyone likes Taybarns. They think the chain encourages unhealthy eating habits and will cause England's collective waistline to expand.

It's a common argument, and one that's been batting around in the US for some time. Is it the fault of (insert any fast food giant here), or does the responsibility fall on the individual? Does walking into Taybarns rob a human of their free will, and why isn't healthy food more accessible to the masses?

Healthy Eating Tip: Hit the Buffet

FitSugar — Wed, 23 Jul 2008 10:00:00 -0700

The buffet can be your friend or foe. It all depends on how you look at it. You can either load up your plate with piles of high fat, high calorie foods with little nutritional value or you can take advantage of the variety and opt to cover your plate with the abundance of healthy foods usually available on any given buffet.

When you have the option to choose, you can spend time to really make the healthier decisions than if you had to order a set meal. Also you're able to determine your own portion size, rather than be tempted with a gigantic meal. You can often choose all kinds of lean proteins as well as veggies and fruits. Just be sure to steer clear of foods that are fried, glistening with butter, and loaded with sugar. When in doubt, ask a server how a food item is prepared.

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How to Deal With the Buffet at a Wedding Reception

FitSugar — Fri, 06 Jun 2008 12:00:00 -0700

It is June and wedding season in is in full bloom. Weddings are fun-filled events, but beware of the buffet. It is all too easy to pile the calories onto one little plate. Here are a few suggestions on how to survive with the buffet table.

Survey the Table: Don't start at the beginning of the table and take one of everything the buffet has to offer. Give the table a once over and pick out the healthiest options. Put those options on your plate.
Easy on the Drinks: Alcoholic drinks are surprisingly high in calories. Plus they diminish your willpower, making it harder for you to make wise decisions.
Drink Plenty of Water: By all means toast with a glass of bubbly, but stick to water for the rest of the evening. It is refreshing, zero calories, and might just make you feel more full.
Walk the Line Once: Don't go back for seconds. Just don't. You want to save room for cake, right?
Avoid Hors d'oeuvre: Starters tend to be high in calories. It seems like food eaten off a napkin doesn't really count; but it does. Go for the crudités – feel no need to limit your consumption of these raw veggies. For dipping sauce, on the other hand, keep a light tough.
Stop When You're Full: Sometimes we all need to be reminded for the obvious. When you are full, stop eating. That is the best way to not over indulge. Just think how light you will feel on the dance floor.

How do you deal with the buffet table at any event? Share your advice in the comments section below.

Don't forget top check out all the wedding fun on IDoSugar.

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Holiday Fit Tip: Buffet Strategies

FitSugar — Wed, 19 Dec 2007 02:30:00 -0800

This time of year, holiday parties are a plenty and with them come plenty of tempting foods and drinks. It is best to walk into a party with a game plan and here are some strategies to help.

Never go to a party hungry. Meeting a buffet table with an empty stomach usually spells diet disaster. Have an apple and a handful of nuts before going out, this way you will not be starving when you start to party.
Alternate your alcoholic beverages with sparkling water. This way you avoid not only calories, but a hangover as well. Champagne and wine have significantly fewer calories than egg nog and hot buttered rum.
Fill your buffet plate with veggies. This way you will fill up on healthy foods. Look for veggies that are simply prepared and not smothered in butter or cheese.

I have a few more tips based on experience. To learn from my mistakes just read more.

When filling your plate take a bite sized portion of dishes that look tasty, but not overly indulgent. This way you will feel like you are treating yourself, without going overboard.
Don’t hang out by the food table. This one seems pretty obvious, but is always worth repeating. Doesn't everything come down to location? You will be less likely to mindlessly snack if you are not near all the food.
Sit down to eat. Even if it is a "stand and talk" party, find a chair and take time to taste and enjoy the party food. This will give you the psychological perspective of having eaten a meal, and help you keep yourself in check.

Soure

10 Eating Tips For Avoiding the Freshman 15

FitSugar — Thu, 27 Aug 2009 05:50:12 -0700

The dorm dining hall can be dangerous - like a giant, all-you-can-eat buffet available all day, every day. It's no wonder most of us gain some weight when going off to college, though the infamous "freshman 15" is really more like 10 pounds.

Whether you're eating in a dining hall or cooking for yourself in your first apartment, a few simple strategies can help you avoid that first-year college weight gain. Here are my tips for eating healthy at the university level.

Don't skip meals, especially breakfast. Starting with a filling breakfast helps steady your metabolism throughout the day. Here are five ideas for quick but healthy starts.
Drink lots of water. At the dining hall, during lectures, throughout cram sessions, whenever! Skip the soda and carry a water bottle that you can refill throughout the day to prevent constipation and bloating.
Include at least three food groups in every meal. When choosing from the endless dining hall bounty, make an effort to get plenty of fresh fruits and veggies, lean protein, and calcium - not just pizza and chicken fingers.

For the rest of my top 10 healthy eating tips, read more.

Control your portions. Just because you can fill your plate every time doesn't mean you should. Familiarize yourself with what proper portions look like and stick to them.
Treat yourself once a day. From sundae bars to fresh baked cookies, desserts abound at the dining hall. Go ahead and indulge, but limit yourself to one treat a day. If you have a cookie after lunch, skip the ice cream after dinner.
Avoid a fourth meal. In my dorm-room days, there were always late-night pizzas being delivered or roommates making mac and cheese at midnight. It's OK to fortify yourself with the occasional snack while studying, but make sure it's actually a snack, not the equivalent of a second dinner or dessert.
Stock healthy snacks. For those late-night study sessions when you do get hungry, keep your dorm room full of healthy snacks, like nuts, pretzels, fruit, popcorn, and nutrition bars.
Pick your liquor carefully. Freshman aren't supposed to drink! But chances are, you will anyway. Remember: alcoholic beverages are full of empty calories, and sugary cocktails are the worst for both calories and hangovers.
Shop smart. If you live in an apartment, learn to shop for one person by choosing healthy foods that won't go bad before you can finish them: frozen vegetables and fruit, yogurt, low-fat string cheese, and healthy frozen meals are all great options.
Exercise! OK, this isn't really a healthy eating tip, but it's an essential part of keeping the pounds off in college. Walk or bike to class, frequent the school gym, or join an intramural team and get moving!

What are your tips for incoming freshmen looking to avoid the traditional weight gain?

Staying Fit While on A Cruise

FitSugar — Fri, 10 Aug 2007 10:15:00 -0700

Unless it's a fitness cruise, most cruises are notorious for being horrible for your health. This could be due to the ever present buffets or the laziness that being on a giant ship evokes.

Regardless of your reasons for gaining a few extra pounds while cruising, if you're planning a cruise this year, be sure to use these tips on staying fit on a cruise:

Eat 5-6 meals: Get out of your 3-meal rut. It's healthier to eat 5-7 small meals per day than 3 large traditional meals. Take advantage of the all-day food access by having more, but smaller, meals.
Grab a snack: If going on a day excursion off the ship remember to grab something healthy like a banana or an apple at the breakfast buffet so you can conveniently snack on it later.
Sushi is the same price as French fries: Many landlubbers eat junk food because it's cheap and easy. On a cruise, the food and its preparation are included in the price. Hence, healthy choices are as accessible as the 99¢ menu back home. Room service is often free as well.
Buffet tips & tricks: Buffets: Many people think "buffet" is a French term for "fat." This can be the case if you aren't careful. Start with the healthiest items you enjoy first. Odds are you may fill-up before you can get to the "danger" items. Danger items include: hamburgers, eggs benedict, pizza, creamy pastas, waffles with whipped cream, anything fried, sweets. Power foods include: oatmeal, almonds, salmon, turkey, sashimi, whole wheat bread, eggs/egg whites, edamame, peanut butter, fruit, low fat yogurt.
Drink plenty of water: While the food is included, sodas are not. Sodas can be expensive onboard the ship- often $2 per can. Sodas are full of empty calories; this is an ideal time to kick your 4 can-per-day Coke habit by drinking lots of water.

There are five more tips, so read more

Avoid fatty "side dishes": Don't fill up on the mashed potato or macaroni & cheese side items that come with an entrée. You are better off appeasing your appetite with two main entrees (e.g., chicken, fish) than filling up on these empty calorie side dishes. Remember the food is all-inclusive so there is no additional cost.
Sign-up for a class: Most ships come equipped with state of the art gyms. Many offer specialty classes (generally an additional fee of $10). Sign-up for a paid specialty class - if you have a paid commitment you will most likely stick to it. Take the opportunity to try something new like Power Yoga. If you can balance on a ship you can balance anywhere.
Get off the ship: When in port try and spend most of your time off the ship. Simply walking and exploring will help burn calories. Also, if you're doing an athletic event like snorkeling or hiking simply add 10 minutes at the end of it where you do a little sprint swimming or jogging.
Take the stairs: Skip the small and claustrophobic elevator rides and get some exercise by taking the stairs. At a minimum, avoid the elevators at peak times - generally around meals and when first arriving at port.
Jet Lag: Often you will be traveling to a location that has a different time zone. The first few days will take awhile for you to acclimate. Take advantage of your body waking up early by hitting the gym. Most cruise gyms are open 24 hours. Since it will be dark out, it's one of the few activities available at this time so you won't be missing out on anything.

Source

Acute lymphocytic leukemia

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Acute Lymphocytic Leukemia (ALL)

There are four major types of leukemia. ALL is the most common type of leukemia diagnosed in children, and the least common type diagnosed in adults. About 5,200 people are diagnosed with ALL each year. Children account for two-thirds of these cases. In general, children with ALL have a better prognosis than adults. Most children with ALL can be cured of this cancer.

Symptoms and Diagnosis

Symptoms of ALL include fatigue, pale skin, recurrent infections, bone pain, bruising, and small red spots under the skin. Doctors use various tests, including blood counts and bone marrow biopsies, to diagnose ALL.

Treatment

ALL is treated with chemotherapy and, sometimes, radiation. Children receive different types of chemotherapy regimens than adults. Patients with advanced cancer that has not responded to these treatments may need a stem cell transplant.

Infection Prevention

Both chemotherapy and transplantation increase the risk for infection. Patients must take serious precautions to avoid exposure to germs. Ways to prevent infection include:

Practice good hygiene including regular handwashing and dental care (brushing, flossing)
Avoid crowds, especially during cold and flu season
Eat only well-cooked foods (no raw fruits or vegetables)
Boil tap water before drinking it
Do not keep fresh flowers or plants in your house as they may carry mold

Introduction

The word leukemia literally means "white blood" and is used to describe a variety of cancers that begin in the blood-forming cells of the bone marrow.

White blood cells (leukocytes) evolve from immature cells referred to as blasts. Malignancy in these blasts is the source of leukemias, which generally progresses as follows:

Normally, blasts constitute 5% or less of healthy bone marrow. In leukemia, however, these blasts remain abnormally immature and multiply continuously, eventually constituting between 30 - 100% of the bone marrow.
Eventually these malignant blast cells fill up the bone marrow and prevent production of healthy red cells, platelets, and mature white cells (leukocytes).

They spill out of the marrow into the bloodstream and lymph system and can travel to the brain and spinal cord (the central nervous system). As the number of normal cells decline, dangerous symptoms develop, which, if untreated, become lethal.

Leukemias are divided into two major types:

Acute (which progresses quickly with many immature white cells)
Chronic (which progresses more slowly and has more mature white cells)

Some blasts are called lymphoblasts (which become mature cells called lymphocytes) and others are called myeloblasts (which mature to myeloid cells). Acute leukemias are in turn subdivided into two classifications according to whether the malignant blasts are lymphocytes or myeloid:

Acute lymphocytic leukemia (ALL), which is the subject of this report
Acute myeloid leukemia (AML), which is not covered in this report

Acute lymphocytic leukemia (ALL) is also known as acute lymphoid leukemia or acute lymphoblastic leukemia. The majority of childhood leukemias are of the ALL type. Malignancies in this disease can arise either in T-cell or B-cell lymphocytes.

T cell ALL is diagnosed in 15% of children and adults with ALL.
About 85% of ALL cases are of the B-cell lymphocyte lineage (often referred to as "early" or "pre" B-cell lineage).

Blood Cell Lines

In adults, blood cells are produced by the bone marrow, the spongy material filling the body's bones. The bone marrow produces two blood cell groups, myeloid and lymphoid.

Myeloid Cell Line. The myeloid cell line includes the following:

Immature cells called erythrocytes that later develop into red blood cells
Blood clotting cells (platelets)
Some white blood cells, including macrophages (which act as scavengers for foreign particles), eosinophils (which trigger allergies and also defend against parasites), and neutrophils (the main defenders against bacterial infections)

Lymphoid Cell Line. The lymphoid cell line includes the lymphocytes, which are the body's primary infection fighters. Among other vital functions, certain lymphocytes are responsible for producing antibodies, factors that can target and attack specific foreign substances (antigens).

Lymphocytes develop in the thymus gland or bone marrow and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).

Lymphocytes and the Lymph System

Understanding how acute lymphocytic leukemia (ALL) arises requires knowledge of lymphocytic development and function:

B cells develop and mature in their final form (known as differentiation) in the bone marrow.
T cells also start out in the bone marrow but differentiate and mature in the thymus gland, located beneath the breastbone. This small gland is active mostly in the fetal stage through the first 10 years of life, after which it atrophies (shrinks).
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Once they leave the capillaries, some lymphocytes migrate into the surrounding tissues. Some of these lymphocytes (along with fluid, proteins, and other substances) then enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes and lead to larger lymphatic ducts and branches. They drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, which are oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or are added to the contents of the node.

Symptoms

The symptoms of ALL may be difficult to recognize. ALL usually begins abruptly and intensely, but in some cases symptoms may develop slowly. They may be present one day, and absent the next, particularly in children. Symptoms develop when:

There are not enough healthy mature white blood cells (leukocytes) to mount a defense against infection.
There are not enough healthy platelets to prevent bleeding.
The depleted oxygen-bearing red blood cells can't provide enough oxygen to organs.

Symptoms include:

Fatigue
Paleness -- patients may have poor coloring from anemia caused by insufficient red blood cells
Recurrent minor infections
Fevers
Bone pain
Bruising -- may result from only slight injury
Poor healing of minor cuts
Uncontrolled bleeding -- bleeding events increase as the bone marrow fails to produce enough platelets to make a normal blood clot, a condition called thrombocytopenia.
Small, red spots on the skin (petechiae)
Vision changes (rare)

Causes

Between 1973 - 1990, the number of acute lymphocytic leukemia cases in children under age 15 rose by 27%. The causes of the disease are not known, but experts believe that ALL develops from a combination of genetic, biologic, and environmental factors.

Advances in genetic technologies have allowed identification of a number of mutations associated with ALL. Missing or defective genes that suppress tumors are responsible for some of these cases. Identifying specific genetic allows doctors to determine how aggressive a specific case is and eventually could provide targets for developing highly specific treatments.

Translocations. Up to 65% of leukemias contain genetic rearrangements, called translocations, in which some of the genetic material (genes) on a chromosome may be altered, or shuffled, between a pair of chromosomes.

The most common genetic injury in ALL is t(12;21), which means a translocation with a genetic shift occurred between chromosome 12 and 21. This translocation is also referred to as TEL-AML1 fusion. It occurs in about 20% of patients with ALL. Researchers believe that this translocation may occur during fetal development in some patients.
About 20% of adults and about 5% of children with ALL have a genetic abnormality called the Philadelphia (Ph) chromosome [t(9;22)].
Another important chromosome translocation is t(4;11) involving the MLL gene, also called HRX or ALL-1.

Ikaros. A defective gene known as Ikaros, which regulates lymphocyte development, may play a major role in childhood ALL.

MTHFR. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism. Children with certain variations in the gene for MTHRF have a reduced risk of developing ALL. Variations in the MTHRF gene may also influence response to antifolate chemotherapy.

Risk Factors

ALL in Children. ALL is the most common type of cancer diagnosed in children. ALL accounts for about 75% of cases of childhood leukemia. Each year, about 2,400 American children and adolescents are diagnosed with ALL. ALL can strike children of all ages, but is most likely to occur when children are 2 - 3 years of age.

ALL in Adults. ALL is the least common type of leukemia among adults. About 1 in 3 cases of ALL occur in adults.

Caucasian and Hispanic children have a much higher risk for ALL than African-American children.

Certain inherited disorders can increase the risk for leukemia. For example, children with Down syndrome have a 20-times greater risk of developing ALL than the general population. Other rare genetic disorders associated with increased risk include Bloom syndrome, Fanconi's anemia, ataxia-telangiectasia, neurofibromatosis, Shwachman syndrome, IgA deficiency, and congenital X-linked agammaglobulinemia.

Previous cancer treatment with high doses of radiation or chemotherapy can increase the risk for developing ALL. Prenatal exposure to x-rays also appears to increase risk in children. Lower levels of radiation (living near power lines, video screen emissions, small appliances, cell phones) are unlikely to pose any cancer risk.

Diagnosis

Laboratory tests provide the basis for diagnosing ALL.

Flow cytometry uses light to count blood cells in a stream of fluid. It is an important tool used to diagnose leukemia, determine its progress, and tell if any disease remains after treatment. It can also determine the components and structural features of individual cells. Flow cytometry can process thousands of cells in seconds.

A complete blood cell count (CBC) is the first step in diagnosing ALL. However, blood tests do not always detect leukemia. About 10% of patients with ALL have a normal blood cell count. A CBC may show various findings, including:

Presence of circulatory leukemic blast cells (may miss the cells on occasion)
Presence and severity of anemia
Count of a variety of blood cell types (a high white blood cell count indicates a more severe disease)

Click the icon to see an illustrated series detailing a complete blood cell count test.

If blood test results are abnormal or the doctor suspects leukemia despite normal cell counts, a bone marrow aspiration and biopsy are the next steps. These are very common and safe procedures. However, because this test can produce considerable anxiety, particularly in children, parents may want to ask the doctor if sedation is appropriate for their child.

A local anesthetic is given.
A needle is inserted into the bone, usually the rear hipbone. There may be brief pressure or pain. A small amount of marrow is withdrawn. Marrow looks like blood.
A larger needle is then inserted into the same place and pushed down to the bone. The health professional will wiggle the needle from side to side to loosen a larger specimen for the biopsy. The patient will feel some pressure.
The sample is then taken to the lab to be analyzed. All the results are completed within a couple of days.

Click the icon to see an image of bone marrow removal.

Normal bone marrow contains 5% or less of blast cells (the immature cells that ordinarily develop into healthy blood cells). In leukemia, abnormal blasts constitute between 30 - 100% of the marrow.

If bone marrow examination confirms ALL, a spinal tap may be performed, which uses a needle inserted into the spinal canal. The patient feels some pressure and usually must lie flat for about an hour afterward to prevent severe headache. This can be difficult, particularly for children, so parents should plan reading or other quiet activities that will divert the child during that time. Parents should also be certain that the professional administering this test is highly experienced.

Click the icon to see an image of a spinal tap.

A sample of cerebrospinal fluid with leukemia cells is a sign that the disease has spread to the central nervous system. In most cases of childhood ALL, leukemia cells are not found in the cerebrospinal fluid.

Once a diagnosis of leukemia has been made, further tests are performed to check:

Whether the cells are myeloid or lymphocytic
Stage of maturity of the ALL B cell
Specific markers, or immunologic features, on the surface of the cancer cell
The genetic makeup of the cells ( cytogenetics)
The physical characteristics of the cells ( morphology)

First, the doctors must determine the cell of origin. In other words, they want to determine if the cell is myeloid or lymphocytic. One method is to measure an enzyme called terminal deoxynucleotidyl transferase (TdT).

About 95% of all ALL types (except the subtype B cell) have elevated TdT.
Only about 20% of cases of acute myeloid leukemia (AML) express TdT, however, so its use in determining the cell line is limited.

The stage of maturity of the leukemic B cell helps determine prognosis. There are three stages:

Early precursor-B. About 80% of patients with ALL have the early precursor-B subtype, which is the least mature. It also offers the best prognosis.
Precursor-B. This is the intermediate stage.
B cell. This is the mature cell and ALL in this stage is identical to Burkitt's non-Hodgkin's lymphoma. It is therefore treated differently from other ALL cases.

A series of tests are used to determine the immunologic pattern of the leukemia cell (how it can be expected to interact with the immune system).

On the surface of malignant ALL cells are markers for certain antigens (molecules that set off a targeted attack by the immune system using antibodies). Such antigens are proving to be very helpful in predicting outcome.

An antigen is a substance that can provoke an immune response. Typically, antigens are substances not usually found in the body.

Important antigens associated with ALL include:

CD10, more frequently referred to as cALLa (common ALL antigen). This antigen occurs in about half of all ALL cases and in about 80% of ALL B-precursor patients. It is associated with a good prognosis.
CD95 (associated with a good prognosis)
CR19
DR

The surfaces of T-cell ALL cancer cells express several antigens as well. For example, the presence of one of these, CD2, suggests a favorable prognosis.

Genetic tests are useful for a number of important criteria:

Diagnosing a specific ALL subtype
Designing appropriate treatment
Deciding prognosis
Monitoring patients throughout treatment and beyond

Cytogenetics is a technique that researchers use to determine specific genetic abnormalities, which are found in nearly 65% of all leukemias. Detecting these genetic defects is helpful in making a full diagnosis of ALL and in planning the most appropriate therapy. Specific technologies called microarray chips are capable of checking up to 48,000 different genes in a single test, which holds promise for assessing prognosis and developing very targeted therapies in the future. Research on DNA microarray analysis continues to reveal different prognostic subgroups of ALL. As the precision, logistics, and cost effectiveness of DNA microarray assays improve, they may be used more commonly in the clinical setting.

MTHFR Variants. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism. Variations in the MTHRF gene may also influence response to antifolate chemotherapy. A 2004 study showed that patients with one of two specific variations of the MTHFR gene had a lower probability of survival following treatment with methotrexate.

Translocations. Genetic translocations (swapping of genes on chromosomes) may affect outlook. Examples include:

Patients with the t(12;21) genetic translocation (also referred to as TEL-AML1 fusion) have an excellent prognosis.
Patients who carry the defective gene called ETV6 often respond well to chemotherapy.
The t(4;11), sometimes referred to as MLL, is the most common translocation in children under age 1 year. Unfortunately, anyone with t(4;11) has a poor outlook. One study suggested that this genetic variant may actually be a unique leukemia and require treatments that differ from standard ALL.
The Philadelphia translocation t(9;22) also indicates a poor outlook. It represents about 20% of adult cases and about only 5% of childhood cases.
The t(1;19) location occurs in about 5% of ALL childhood cases and requires aggressive treatment.

Ploidy. Ploidy refers to the number of chromosomes. Additional copies (hyperdiploidy) or absence of copies (hypodiploidy) of chromosomes affect prognosis. For example, in children hyperdiploidy is associated with a more favorable outcome and hypodiploidy with a poorer outcome. (Hypodiploidy occurs in only 1% of children with ALL.)

The morphology of a cell includes its physical characteristics, such as shape and structure. To determine the morphology of the leukemia cells, samples of the bone marrow are taken and particular contents of the cells are stained with a dye. They are then examined under a microscope.

Acute lymphocytic leukemia cells are grouped, according to the French-American-British (FAB) classification system, into three ALL morphologic types. (It should be noted that this system is subjective and is now used to complement other diagnostic tests mentioned above):

L1 cells. These are small blasts with scant amounts of cytoplasm (the substance in a cell between its membrane and nucleus). L1 cells usually contain a round nucleus and there is little variation among them. L1 represents the most common ALL morphology and offers the best prognosis. It occurs in about 85% of children and 30% of adults with ALL.
L2 cells. These cells are larger than L1 and have more abundant cytoplasm. They vary significantly among each other and have an irregularly shaped nucleus. L2 morphology conveys a poorer prognosis than L1, although the two cells' types are treated similarly. Subtype L2 is the most common morphologic type in ALL adults; 64% of adults with ALL have this subtype compared with only 15% of children.
L3 cells. These are uncommon. They resemble another malignancy called Burkitt's lymphoma, and their treatments are now the same.

Assays that test for cancerous cells are improving, allowing doctors to detect smaller and smaller amounts of hidden disease. For example, flow cytometry assays can detect 0.01% leukemic cells, and PCR assays can detect 0.001% leukemic cells. A new concept called minimal residual disease (MRD) is becoming an important prognostic factor in ALL. A more precise measure of disease response, MRD may soon replace existing measures such as "complete response" and "partial response" when assessing the effectiveness of ALL treatment. Ongoing studies of MRD in ALL may help identify patients in remission who are at risk of relapse. In addition, early therapeutic intervention based on the presence of MRD may improve outcome and prolong survival.

Using the results of the tests described above, patients are classified into low-, average-, and high-risk groups. This information allows the doctor to diagnosis the type of leukemia and plan the best treatment. Each classification requires unique therapies.

Doctors attempt to make a prognosis and determine an optimal treatment plan by assessing all the cell characteristics plus the white blood cell count. As examples:

Patients who have an L1 or L2 morphology, a white blood cell count of less than 15,000 mm3, a t(12;21) genetic translocation, and a cALLa-positive antigen marker have an excellent outlook.
On the other hand, patients who have an L2 morphology, a white blood cell count greater than 30,000 mm3, and who lack the cALLa marker have a poorer prognosis and require more aggressive treatment

Outlook

Acute lymphocytic leukemia is responsible for about 1,400 deaths a year in the U.S., and it can progress quickly if untreated. However, ALL is one of the most curable cancers and survival rates are now at an all-time high. People who have Philadelphia chromosome-positive ALL tend to have a poorer prognosis, although new treatments are helping many of these patients achieve remission.

Outlook in Children with ALL. More than 95% of children with ALL attain remission.

Certain children are at higher risk for a poor outcome than others:

Infants and children age 10 years and older tend to have a poorer outcome than young children (ages 1 - 9 years).
Some studies indicate a better prognosis for girls than boys. This may be partly due to boys’ risks for testicular cancer.
Survival rates for African-American and Hispanic children are lower than Caucasian and Asian children, but this may be due to poorer access to treatment.

Responding well to early treatment is a good sign regardless of the risk category. Other positive predictors include:

Less than 5% of cells being blasts after 7 - 14 days of treatment
Less than 1,000 blasts per microliter on peripheral smear after 7 days

Outlook in Adults with ALL. Adults tend to have a more severe condition than children, even if they are carrying the same ALL genes. Still, 60 - 80% of adults with ALL can expect to achieve full remission with standard treatments, and 35 - 40% survive beyond 2 years with aggressive treatments. Younger adults with ALL have better long-term survival rates than older adults with the disease.

Treatment

The aim of initial treatment is to get rid of the leukemia cells in the body (achieve complete remission) and have 5% of lower levels of blasts in the bone marrow.

There are typically four treatment stages for the average-risk patient with ALL:

Induction therapy in order to achieve a first remission
Central nervous system prophylaxis (preventive treatment), usually given along with induction therapy
Consolidation, intensive therapy to prevent relapse after remission has been achieved
Maintenance treatment, lower intensity therapy given for several years to prevent relapse after remission

The following are specific treatments used for ALL:

Chemotherapy is the primary treatment for each stage.
Radiation to the brain and spinal cord is also administered in some cases.
A bone marrow transplant is often recommended for relapsed ALL or in cases that cannot be induced into remission (refractory disease). It is also sometimes considered after remission is achieved for certain high-risk ALL types. The timing of bone marrow transplantation can be controversial, particularly after a first remission, although it has produced excellent long-term survival rates in appropriate patients.
New drugs known as biological therapies are also being used.

Drugs Used to Prevent Infections During Treatment. Half of all patients with ALL develop fever in the early stages, especially if patients also have low levels of the white blood cells called neutrophils (a condition called neutropenia).

Blood is made of red blood cells, platelets, and various white blood cells.

Neutropenia, common in ALL, is a significant risk factor for serious infection. Doctors are increasingly concerned about fungal infections, which are becoming more common in these patients, particularly after transplant procedures.

Antibiotics and Antifungal Medications. The use and timing of antibiotics and antifungal medications depend on the particular organisms and severity of the infection. In some cases of neutropenia, patients may need preventive antibiotics.
Granulocyte Colony-Stimulating Factor. Granulocyte colony-stimulating factor (lenograstim, filgrastim) is often given to patients who receive chemotherapy in order to stimulate the growth of infection-fighting white blood cells. This helps prevent neutropenia.

Intravenous Fluids. Patients may also need to receive intravenous fluids and be treated for fluid imbalances, which can cause abnormal levels of sodium, potassium, calcium, and uric acid. Such treatments might include sodium bicarbonate, allopurinol, and aluminum hydroxide or calcium carbonate.

Transfusions. Red blood cell or platelet transfusions may be needed. (Patients who may need allogeneic transplantations should not receive transfusions from potential donors.)

Home Management

A parent should call the doctor if the child has any symptoms that are out of the ordinary, including (but not limited) to:

Any fever of 101°F or higher
Any signs of a flu or cold
Shortness of breath
Severe diarrhea
Blood in the urine or stools
Trouble urinating

Tracking Neutrophils. Parents should track their child's absolute neutrophil count. This measurement for the amount of white blood cells is an important gauge of a child's ability to fight infection.

Counts over 1,000 usually provide sufficient protection so that children can engage in normal activities, including school and other functions where they are exposed to other children.
If the count is between 500 - 1,000, the child should avoid large groups.
If it falls between 200 - 500, the child should stay at home and should see only healthy visitors who have washed their hands vigorously.
Neutrophil counts below 200 indicate that the child is at high risk for infection and should have no visitors.

Maintaining Strict Hygiene. Children with ALL and anyone exposed to them, not only friends and family members but also doctors and nurses, should maintain strict hygiene:

Frequent hand washing with antibacterial soap is particularly essential.
Everyone should wash their hands before and after meals, after being outside, before preparing food, and after going to the bathroom.
When visiting the doctor, a parent should ask about a side entrance or areas where the patient will not be exposed to other sick children.

Vaccinations. Studies now suggest that young survivors of leukemia have an increased risk for measles, mumps, and rubella (MMR), even if they have been previously vaccinated. Children may need reimmunization. Siblings of patients with ALL who require polio vaccinations should be given the killed virus (IPV), not the live polio vaccination (OPV).

Use a soft toothbrush when counts are low to prevent gum bleeding.
Avoid common pain relievers known as nonsteroidal anti-inflammatory drugs (NSAIDs). They increase the risk for bleeding and include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), and ketoprofen (Actron, Orudis KT).

Some of the drugs used for leukemia cause extreme sun sensitivity. Children should wear sunblock and be covered with sun-protective clothing when going outside to avoid sunburn, which can cause skin infection.

Treatment to Achieve Remission

The aim of induction therapy, the first treatment phase, is to reduce the number of leukemia cells to undetectable levels. The general guidelines for induction therapy are as follows:

Patients are given intensive chemotherapy that uses powerful multi-drug regimens. (Infants require special regimens not discussed here.)
For both children and adults, some of these therapies are administered orally, others intravenously.
Hospitalization is usually necessary at some point to help prevent infection and to administer blood products. However, much of this therapy can be given on an outpatient basis.
After the first cycle of induction, bone marrow tests are done to determine if the patient is in remission.
Another bone marrow test is sometimes done about a week later to confirm the first results.
A bone marrow transplant is considered for patients who do not respond at all to induction treatment.

Both children and adults typically start with a 3-drug regimen. Imatinib (Gleevec) or dasatanib (Sprycel) may be added for patients with Philadelphia chromosome-positive ALL.

For children, the standard drugs are:

Vincristine (Oncovin), a vinca alkaloid drug
Prednisone or dexamethasone. These drugs are corticosteroids. Dexamethasone may be more effective than prednisone, but it increases the risk for infections and other serious side effects.
Asparaginase. Generally provided as pegaspargase (Oncaspar) in place of L-asparaginase (Elspar) for treating newly diagnosed ALL in children. With pegaspargase, patients need only 3 injections over a 20-week period instead of the 21 injections required for L-asparaginase.

For adults, the standard drugs are:

Vincristine
Prednisone
Anthracycline drug, such as such as doxorubicin, daunorubicin, or epirubicin. Some adult chemotherapy regimens also add on an asparaginase drug or cyclophosphamide (Cytoxan).

The induction chemotherapy described above does not penetrate the blood-brain barrier sufficiently to destroy leukemic cells in the brain. CNS prophylaxis is critical for preventing disease that has spread to the brain, spine, and testes (called sanctuary disease sites). Although only 3% of children with ALL have evidence of leukemia in the central nervous system (CNS) at the time of diagnosis, leukemia will spread to this region in 50 - 70% of children who don't receive preventive (prophylactic) treatment. The brain is one of the first sites for relapsing leukemia.

For children, CNS prophylaxis uses intrathecal chemotherapy, in which a drug is injected directly into the spinal fluid. Intrathecal chemotherapy is given with methotrexate alone or a combination of methotrexate, cytarabine, and hydrocortisone.

Some high-risk children also receive radiation to the skull (cranial irradiation), radiation to the spine, or both at the same time. This combination can be very toxic and can cause later learning problems. It is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. Later complications can include learning and neurologic problems. Using lower-dose units of radiation, however, may significantly reduce the risk for mental impairment. Cranial radiation is also associated with increased risks for stroke and secondary cancers.

Adult CNS prophylaxis is performed in one of three ways:

Cranial radiation plus intrathecal chemotherapy with methotrexate
High-dose systemic infusion of methotrexate plus intrathecal methotrexate without cranial radiation
Intrathecal methotrexate chemotherapy alone

Survival in acute leukemia depends on complete remission. Although not always clear-cut, remission is indicated by the following:

All signs and symptoms of leukemia disappear.
There are no abnormal cells in the blood, bone marrow, and cerebrospinal fluid.
The percentage of blast cells in the bone marrow is less than 5%.
Blood platelet count returns to normal.

Induction can produce extremely rapid results, and the faster the time to remission the better the outlook:

A complete remission usually occurs within the first 4 weeks. Patients who show low disease levels within 7 - 14 days have an excellent outlook, particularly if they have favorable genetic factors, and may need less-intensive treatments afterward.
Patients with high disease levels at 14 days or who require more than 4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment.

Side effects and complications of any chemotherapeutic regimen and radiation therapy are common, are more severe with higher doses, and increase over the course of treatment. Administering drugs for shorter duration can sometimes reduce toxicities without affecting the drugs' cancer-killing effects.

Common Side Effects. Typical side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs, and most patients who take more powerful drugs. In one study, nearly all patients who took a combination of dexamethasone (a steroid) in combination with ondansetron within 24 hours of chemotherapy experienced either a significant or complete reduction in nausea and vomiting.
Diarrhea
Hair loss
Weight loss
Depression

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used.

Infection from suppression of the immune system or from severe drops in white blood cells is a common and serious side effect. Patients should make all efforts to prevent infection. The patient at high risk for infection may need very potent antibiotics and antifungal medications as well as granulocyte colony-stimulating factors or G-CSF (lenograstim, filgrastim) to stimulate the growth of infection-fighting white blood cells. Patients should make all efforts to minimize exposure to bacteria and viruses. (See “Infection Prevention” in the Transplant section of this report.)

Other serious side effects include:

Liver and kidney damage
Immediate and short-term risks of radiation therapy may include seizures, stroke, and paralysis
Very high levels of uric acid in the blood, which can damage the kidneys
Very high levels of calcium in the blood
Abnormal blood clotting
Allergic reaction
Low blood sugar (hypoglycemia) -- a rare complication in young, thin children who are taking purine analogues such as mercaptopurine and thioguanine
Suppression of adrenal glands in children who take short-term, high-dose corticosteroids such as prednisolone

Long-Term Complications.

Fatigue is very common after chemotherapy and can be significant and long-lasting.
Combinations of intrathecal chemotherapy plus brain radiation in children can cause some serious complications, including seizures and problems in learning and concentration. Methotrexate is particularly toxic. (The effects of intrathecal chemotherapy alone on mental functioning, however, did not seem significant.) Seizures can often be treated successfully with anti-epilepsy medications.
Delayed puberty. The effects of treatment in the brain can affect regions that regulate reproductive hormones, which may affect fertility later on. Chemotherapy, cranial radiation, or both can impair fertility in male and female patients. Cranial radiation can also result in impaired growth.
Bone loss can occur after chemotherapy, particularly with corticosteroids and after bone marrow transplantation. Drugs are available, particularly bisphosphonates, which may help reduce this risk.
Pancreatic beta-cell damage. A 2004 study reported that children who have been off treatment for at least 1 year have a higher risk of impaired insulin response. This suggests that chemotherapy-induced beta cell damage persists after therapy has been stopped.
Heart damage. Some of the treatments increase risk factors for future heart disease, including unhealthy cholesterol levels and high blood pressure. Anthracyclines (doxorubicin, daunorubicin, epirubicin) have been associated with later development of heart failure. Lower doses used for many ALL children may not pose a high risk to the heart. Some anthracyclines (DaunoXome, Myocet, Doxil) now come in tiny protective capsules that may reduce toxic effects. Patients with ALL should be sure to maintain a healthy lifestyle and be regularly monitored for heart risks to help reduce these effects.
Stroke. Survivors of childhood leukemia are at increased risk of later stroke, especially if they received treatment with cranial radiation.
Obesity. Children treated for ALL are at higher risk for obesity, possibly because the treatments trigger an earlier than normal occurrence in childhood weight gain. Corticosteroid drugs used in treatments also increase appetite, which contributes to the problem.
Central nervous system. Radiation and intrathecal MTX therapy may be associated with an increased risk of mood disturbances (such as depression) among adult survivors of childhood ALL. Patients with depression may benefit from psychosocial support. Cranial radiation and drugs used in chemotherapy, especially specific corticosteroids and spinal injection treatments, may also impair mental functioning and cause neurologic problems, such as movement problems.
Infections. Some children may be more vulnerable to infections after completing chemotherapy, although the immune system tends to improve over time. Patients who have had a bone marrow transplantation or lung damage from the treatments may be particularly vulnerable. Studies suggest that young survivors of leukemia have an increased risk for measles, mumps, and rubella (MMR), even if they have been previously vaccinated. Children, then, may need reimmunization.
Secondary Cancers. Studies indicate that survivors of childhood ALL are at increased risk of later developing other types of cancers, including brain and spinal cord tumors, basal cell skin carcinoma, and myeloid (bone marrow) malignancies. Radiation and older types of chemotherapy are mainly responsible for this risk. Newer types of ALL treatment may be less likely to cause secondary cancers.

Treatment During Remission

Consolidation and maintenance therapies follow induction and first remission. The goal of consolidation and maintenance therapies is to prevent a relapse. The specific treatment choices and degree of aggressiveness after induction therapy depend on a number of factors, particularly the risk factors for relapse.

Consolidation therapy is additional treatment that is administered after induction therapy and before maintenance therapy. This is an intense regimen that is designed to prevent the high relapse rates that occur with induction therapy alone. (The benefits of this therapy are clearer in children than in older adults, who may just be given maintenance.)

Consolidation therapy usually continues for about 6 months and uses 1 - 6 courses of chemotherapy, depending on risk factors for relapse.

Examples of consolidation regimens for children at standard risk:

A limited number of courses of intermediate- or high-dose methotrexate, one of the oldest drugs used for leukemia.
An anthracycline drug, such as daunorubicin (Cerubidine), used for reinduction followed by cyclophosphamide (Cytoxan, Neosar) 3 months after remission. These are very powerful drugs, but when used in this way toxicity is limited.
Extended use of an asparaginase drug.

More intense regimens are used for children at high-risk for relapse.

Instead of chemotherapy alone as consolidation therapy, some high-risk patients in first remission who are unlikely to be cured by standard chemotherapy alone may undergo allogeneic stem cell or autologous stem cell bone marrow transplant after the intensive chemotherapy regimens. Many adult patients may fall into this category. Studies on high-risk children have been conflicting about the value of transplants during a first remission.

Allogeneic transplantation is an option when a well-matched donor is available. Although this treatment can be effective in keeping the leukemia away, significant complications -- such as graft versus host disease, blood clots, liver problems, and lung damage -- can occur and may be a cause of death even without a return of cancer.
Autologous stem cell bone marrow transplant (using the patient's own bone marrow cells) seems to be helpful also and may be as effective as allogeneic transplantation.

The last phase of treatment is maintenance, or continuation therapy:

Maintenance therapy typically uses weekly administration of methotrexate (usually in oral form) and daily doses of mercaptopurine. (Mercaptopurine should be given in the evening.)
Treatment continues for 2 - 3 years for most children with ALL (with the exception of those with mature B-cell leukemia). It is not yet clear if prolonged maintenance therapy benefits adults with ALL.
If children were not given CNS prophylaxis before, it may be given now.
Vincristine and a corticosteroid drug (generally dexamethasone) are often added to standard maintenance therapy, although some studies indicate that they do not provide additional benefit.

A maintenance regimen is usually less toxic and easier to tolerate than induction and consolidation. Some studies, however, indicate that overall survival could further be improved with more-aggressive maintenance therapies, including:

Vincristine and a corticosteroid added to the standard maintenance regimen
Longer term low-dose maintenance
Intense regimens similar to induction (called reinduction)

Maintenance is typically ongoing until complete remission has lasted 2 - 3 years.

Investigation is ongoing to determine the best drugs and schedules to use. For example, doctors have debated whether thioguanine is a better choice than mercaptopurine (a 2006 study recommended that mercaptopurine remain the standard thiopurine drug for treating childhood ALL). Researchers are also trying to pinpoint patients who would best benefit from aggressive maintenance treatments.

The following are factors that increase the risk for relapse after initial treatments:

Microscopic evidence of leukemia after 20 weeks of therapy (minimal disease)
Age over 30
A high white blood cell count at the time of diagnosis
Disease that has spread beyond the bone marrow to other organs
Certain genetic abnormalities, such as the presence of the Philadelphia chromosome or MLL gene translocations
Patients with high disease levels after 7 - 14 days of induction therapy
The need for 4 or more weeks of induction chemotherapy in order to achieve a first complete remission

Patients with one or more of these risk factors may be candidates for bone marrow transplantation once they are in first remission.

Treatment After Relapse

Between 50 - 70% of children and 40 - 50% of adults who achieve complete remission after initial therapy but then suffer a relapse may be able to go into a second complete remission.

Treatment for relapse after a first remission may be standard chemotherapy or experimental drugs, or more aggressive treatments such as stem cell transplants.

The decision depends on a number of factors:

Children who relapse 3 or more years after achieving a first complete remission have an excellent chance for a second remission without aggressive treatments.
Those who relapse fewer than 6 months following initial treatment, especially while on chemotherapy, have about a 20% chance of long-term freedom from disease. In such cases, remission is possible following another course of standard chemotherapy but the duration of remission is usually fewer than 6 months.

Treatment decisions also rely on prior treatments and where the relapse has occurred. Relapse can occur in the bone marrow, central nervous system, or sanctuary disease sites (brain, spine, or testicles). The incidence of relapse in sanctuary sites is about 10%.

Candidates for transplantation include:

Patients who relapse following initial remission with standard chemotherapy.
High-risk patients in first remission who are unlikely to be cured by standard chemotherapy alone. Many adult patients may fall into this category. Studies on high-risk children have been conflicting about the value of transplants during a first remission.
Patients who fail to achieve a complete remission during initial chemotherapy.

Transplantation procedures do not appear to offer any additional advantages for patients at low or standard risk.

Many different drugs are used to treat ALL relapses. These drugs include vincristine, asparaginase, anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine (ara-C), and epipodophyllotoxins (etoposide, teniposide). Corticosteroids, such as prednisone or dexamethasone, may also be used.

In 2004, the Food and Drug Administration (FDA) approved clofarabine (Clolar) for treatment of relapsed or refractory ALL in children. This drug was the first new leukemia treatment approved specifically for young patients in more than a decade. In 2005, nelarabine (Arranon) was approved to treat adults and children with relapsed or refractory T-cell acute lymphocytic leukemia (T-ALL). In 2006, the FDA approved imatinib (Gleevec) for treating patients with Philadelphia chromosome-positive ALL that has not responded to or has returned after treatment. Also in 2006, the FDA approved dasatinib (Sprycel) for patients who are not helped by imatinib.

Tyrosine kinase inhibitors. Tyrosine kinase is a growth-stimulating protein. Tyrosine kinase inhibitor drugs block the cell signals that trigger cancer growth. Several tyrosine kinase inhibitors, including imatinib (Gleevec) and dastinib (Sprycel), have recently been approved for treating Philadelphia chromosome-positive ALL. In 2006 clinical trials, Nilotinib (AMN-107) produced excellent results in patients with Philadelphia chromosome positive ALL who are resistant to imatinib.

Monoclonal antibodies (MAbs). Used alone or in combination with chemotherapy, MAbs target specific antigens on ALL blast cells. Although MAbs have been studied primarily in the treatment of B-cell non-Hodgkin's lymphoma, drugs demonstrating benefit in preliminary trials of ALL include anti-CD20 (rituximab) and anti-CD22 (epratuzumab). Alemtuzumab (MabCampath) is also showing promise in treating relapsed or refractory T-ALL. More studies are needed to determine the best MAb regimens in ALL.

In order to administer high-dose chemotherapy for advanced cancer cases, stem cell transplantation procedures may be used. These procedures are based on removal and replacement of stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them from the donor into the patient.

Sources of Cells. Stem cells must first be collected either from:

Bone marrow (bone marrow transplantation)
Blood (peripheral blood stem cell transplantation). Evidence suggests that peripheral blood stem cell transplantation may be the superior approach. Studies report survival rates of 45% in bone marrow transplant patients compared to 65 - 70% in stem cell transplant patients, with benefits being significant in those with more severe disease.
Fetal umbilical cord or placentas. This procedure uses donor cells but has a lower risk for immune system rejection of the cells than with a standard donor transplant. It takes longer to restore blood cells with this process, however, so at this time its use is limited to children and sometimes adults with low weight. (Some studies indicate success for adults with normal weights.)

Donor or Patient Cells. The sources of marrow or blood cells can be taken from the patient or a donor:

If the bone marrow or stem cells are taken from a donor, the transplant is referred to as allogeneic. Allogeneic transplants from genetically matched sibling donors offer the best results in ALL. With new techniques, donor bone marrow from unrelated but immunologically similar donors is proving to work as well as those from matched siblings. This approach is still reserved for patients in second remission or beyond. A 2006 study indicated that allogeneic transplant is also a good treatment option for patients with Philadelphia chromosome-positive ALL who are resistant to imatinib (Gleevec).
If the marrow or blood cells used are the patient's own, the transplant is called autologous. Autologous transplants in patients with ALL are generally not beneficial, since there is some danger that the cells used may contain tumor cells and the cancer can regrow. Treatment advances that reduce this risk, however, may make autologous transplantation feasible in patients without family donors.

The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim) to stimulate stem cell growth.
The donor (or patient in an autologous procedure) then undergoes apheresis. With this process, the blood is withdrawn from one of the patient's veins and passed through a machine that filters out the white cells and platelets, which contain the stem cells. The blood is returned through another vein. The entire procedure takes 3 - 4 hours but needs to be repeated several times.
The stem cells are then frozen.

The patient is given high-dose chemotherapy with or without radiation -- a treatment known as conditioning. The point is to inactivate the immune system and to kill any residual malignant cells. Drugs used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning includes radiation with drugs.
A few days after treatment, the patient is rescued using the stored stem cells, which are administered through a vein. This may take several hours. Patients may experience fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
The patient is kept in a protected environment to minimize infection, and the patient usually needs blood cell replacement and nutritional support.

Two- to 5-year survival rates after transplantation plus chemotherapy range from 40 - 80%. Certain patients with the Philadelphia chromosome, which carries a poor prognosis, may achieve significant success with an allogeneic bone marrow transplant from a closely matched related donor.

Common side effects include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

Blood stem cell transplantation itself is fairly dangerous and has a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now, mortality rates are below 5%. Potentially serious complications include:

Infection resulting from a weakened immune system is the most common side effect. Because the stem cell procedure is done more swiftly, the risk period is shorter than with bone marrow transplantation. The risk for infection is most critical during the first 6 weeks following the transplant, but it takes 6 - 12 months post-transplant for a patient’s immune system to fully recover. Immune systems of patients with graft-versus-host disease can take even longer to function normally

Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

It is very important that patients take precautions to avoid infections. Guidelines for post-transplant infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about hand washing and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. To reduce the risk for GVHD, doctors remove some immune T cells from the donor’s stem cells before the transplant. Researchers are investigating new techniques to refine this process of T cell depletion.

Acute GVHD occurs in 30 - 50% of allogeneic transplants, usually within 25 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). The first sign of acute GVHD is a rash, which typically develops on the palms of hands and soles of feet and can then spread to the rest of the body. Other symptoms may include nausea, vomiting, stomach cramps, diarrhea, loss of appetite and jaundice (yellowing of skin and eyes). To prevent acute GVHD, doctors give patients immune-suppressing drugs such as steroids, methotrexate, cyclosporine, tacrolimus, and monoclonal antibodies.

Chronic GVHD can develop 70 - 400 days after the allogeneic transplant. Initial symptoms include those of acute GVHD. Skin, eyes, and mouth can become dry and irritated, and mouth sores may develop. Chronic GVHD can also sometimes affect the esophagus, gastrointestinal tract and liver. Bacterial infections and chronic low-grade fever are common. Chronic GVHD is treated with similar medicines as acute GVHD.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Other potentially serious complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems, including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (thinning of bones) and hypothyroidism (underactive thyroid)

Resources

www.leukemia-lymphoma.org -- Leukemia and Lymphoma Society
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.bmtnews.org -- Blood and Marrow Transplant Information Network
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.aspho.org -- American Society of Pediatric Hematology/Oncology
www.candlelighters.org -- Candlelighters Childhood Cancer Foundation
www.clf4kids.com -- Childhood Leukemia Foundation

References

Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review. Environ Health Perspect. 2007 Jan;115(1):138-45. Campbell LK, Scaduto M, Sharp W, et al. A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer. 2007 Jul;49(1):65-73.

Hijiya N, Hudson MM, Lensing S, et al. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA. 2007 Mar 21;297(11):1207-15.

Ribera JM, Ortega JJ, Oriol A, et al. Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial. J Clin Oncol. 2007 Jan 1;25(1):16-24.

Waber DP, Turek J, Catania L, et al. Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. J Clin Oncol. 2007 Nov 1;25(31):4914-21.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Non-Hodgkin's lymphoma

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Staging and Treatment Guide...
Chemotherapy
Biologic Therapy (Immunothe...
Radiation
Transplantation
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, which include epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.

In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels have stronger warnings and updated dosing-related safety information.

The FDA advises that for treating anemia associated with chemotherapy, dosing should increase hemoglobin levels to no more than 12 g/dL. Treatment with these drugs should stop as soon as the chemotherapy course is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists. The FDA is currently reviewing additional data concerning the safety of these drugs.

Positron Emission Tomography (PET) Scans and Lymphoma

PET scans are used to help diagnose and stage lymphoma, and they may also be helpful in assessing treatment outcomes for some types of lymphoma. In 2007, an international team of cancer specialists drew up new guidelines for evaluating how well lymphoma responds to treatment in clinical trials. The guidelines now recommend that PET scans be used to help determine if a patient has achieved remission.

Introduction

Lymphomas are malignancies of the lymph system that are generally subdivided into two groups, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Hodgkin's disease accounts for about 15% of all lymphomas. [For more information, see In-Depth Report #83: Hodgkin's disease.]

Non-Hodgkin's lymphomas is a term for malignancies that range from a very slow disease to an extremely aggressive but curable condition. They have certain features in common.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if they are enlarged include the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

Lymphomas, such as non-Hodgkin's lymphomas and Hodgkin's disease, represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, important cells involved in defending the body against infectious organisms. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation, and its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.

Lymphocytes. The lymphatic system is involved in the production and transportation of lymphocytes, white blood cells that are a primary component of the immune system. Among other vital functions, certain lymphocytes are responsible for producing antibodies, factors that can target and attack specific foreign proteins (antigens). To understand the lymphatic system, it is helpful to track part of the life cycle of these lymphocytes:

Lymphocytes develop in the bone marrow or thymus gland and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
T cells also start out in the bone marrow but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it atrophies (shrinks).
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Some lymphocytes, along with fluid, proteins, and other substances, migrate out of the capillaries into the surrounding tissues. A proportion of these lymphocytes and other substances then enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes and lead to larger lymphatic ducts and branches until they drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.

Lymph Nodes. In the lymph node, lymphocytes receive their initial exposure to foreign substances (antigens), such as bacteria or other microorganisms, activating the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are in clusters located throughout the system. Important node clusters are found in the neck, lower arm, armpit, and groin.

Other Structures in the Lymphatic System. The tonsils and adenoids are secondary organs composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.

Click the icon to see an animation about lymph nodes.

Click the icon to see an image of lymph nodes in the head and neck.

Click the icon to see an image of the immune system structures.

Non-Hodgkin's lymphomas occur most often in lymph nodes in the chest, neck, abdomen, tonsils, and the skin. NHLs may also develop in sites other than lymph nodes such as the digestive tract, central nervous system, and around the tonsils.

About 85% of non-Hodgkin's lymphomas (NHLs) arise in B cells; the rest occur in T cells. Activation of a gene called BCL-2 is believed to be partly responsible for many B-cell lymphomas. This defect prevents apoptosis (a natural process whereby cells self-destruct) in the lymphoma cells.

There are more than 20 distinct types of non-Hodgkin's lymphomas. Most first arise in the lymph nodes, but about 20 - 30% of cases are now found outside the nodes, most often in the stomach, small intestine, skin, and brain.

Even experts disagree about the exact groupings. Lymphomas are categorized in a number of ways.

Classification by Cell Type, Appearance, and Genetic Make-up: The REAL System. Different classification systems for lymphoma have been proposed. The system used in this report is called REAL (Revised European-American Lymphoma Classification). It classifies all lymphomas by appearance, cell type, and genetic make-up:

Non-Hodgkin's lymphomas are first grouped as B cell or T cell.
Next, they are categorized by whether the B-cell and T-cell lymphomas were derived from immature (precursor) cells or mature (peripheral) cells.
The peripheral B and T cells are then classified by their appearance, genetic make-up, and specific chemical "markers," which further identify them.

T-cell lymphomas, Hodgkin's disease, and certain leukemias and aggressive lymphomas are covered in the REAL classification but are not discussed in any depth in this report.

Groups by Slow or Fast Growth. Each non-Hodgkin's lymphoma is further defined by its grade, or how aggressive it is:

Indolent (slow-growing), also called low-grade
Aggressive (fast-growing), also called intermediate- or high-grade

According to one report, half of new cases are now intermediate-grade lymphomas. Low-grade makes up 30%, while high-grade makes up 10% of all lymphomas.

Groups by Properties. Lymphomas are also grouped by certain properties:

Size (large versus small)
Shape (round versus irregular)
Whether they are or resemble blood plasma cells
Whether they are follicular (organized in round clusters) or diffuse (spread evenly throughout the lymph node)

Staging. Staging the disease is the next important step in classifying lymphomas. The stage (I - IV) of an NHL is determined by the number of tumors and whether they are still localized or have spread beyond the lymph node. In general, the higher the stage, the poorer the outcome, but other factors are important for a precise prognosis.

Indolent (Slow-Growing) Lymphomas (also Called Low-Grade Lymphomas)

Follicular lymphomas (FLs). Follicular small cleaved cell lymphoma (grade I) and follicular mixed small and large cell lymphoma (grade II). FLs account for 70% of indolent tumors and 20% of all NHLs in industrialized countries. It is very rare in developing countries and in Asia.

Lymphoplasmacytoid/Waldenstrom's macroglobulinemia. Often found in bone marrow, lymph nodes, and spleen. Can cause blood to become viscous and "sticky."

Marginal zone lymphomas (MZL). MZLs often occur as a result of a pre-existing disorder such as hepatitis C, bacterial infection in the stomach (H. pylori ), or an autoimmune disorder (Sjögren syndrome in the salivary glands or Hashimoto's thyroiditis in the thyroid gland). They may be classified as:

Monocytoid B-cell lymphoma, which involves only lymph nodes
Splenic marginal zone lymphoma, which affects the spleen, blood, and bone marrow
Mucosa-associated lymphoid tissue (MALT) lymphoma, which usually involves the gastrointestinal tract, thyroid, lung, breast, or skin

There is some controversy over whether MALT is a variation of MZL or a completely separate type of lymphoma that is more suitably classified as a separate low-grade lymphoma. At this time, it is classified as an MZL.

Aggressive Lymphomas (also Called Intermediate- and High-Grade Lymphomas)

Diffuse large-cell lymphomas (DL). DLs are the most common NHLs, accounting for about 40% of all cases. Subtypes include the following:

Primary mediastinal large B-cell lymphoma
Follicular large cell lymphoma
Anaplastic large cell lymphoma
T-cell lymphomas (not covered in this report)

In about 40% of cases, these DL lymphomas appear in areas outside lymph nodes, including digestive tract, skin, bone, thyroid, and testes.

Burkitt's lymphoma/diffuse, small noncleaved cell lymphoma. This is the most common childhood NHL. In African children, it often involves facial bones and is associated with Epstein-Barr infection.

Mantle cell lymphoma. Mantle cell lymphomas are found in lymph nodes, the spleen, bone marrow, blood, and sometimes the gastrointestinal system (lymphomatous polyposis). This lymphoma is similar to indolent lymphomas at the time of diagnosis, but it is more aggressive.

Lymphoblastic lymphoma. This lymphoma often occurs in young people. It is associated with a large mediastinal mass (occurring in chest cavity between the lungs) and carries a high risk for spreading to bone marrow and central nervous system.

Risk Factors

About 63,000 Americans were diagnosed with non-Hodgkin's lymphomas in 2007, and nearly 19,000 people died of the disease. For the past 25 years, the incidence in NHL has increased continuously. Most of this increase has occured in people over age 65.

Part of the reason for the dramatic rise was AIDS, which increases the risk for high-grade lymphomas. However, even after eliminating changes in diagnosing NHLs and known causes (such as AIDS), the incidence over the past 40 years is 40% higher. The number of cases in which lymphomas first occur outside the lymph nodes has also increased compared to those limited to the nodes. (This observed increase, however, may in large part be due to different methods of diagnosing lymphomas).

The cancer can develop in people at all ages, including children, although it is most common in those ages of 45 - 60. In general, the incidence of NHL is 50% higher in men than in women. This higher rate has been observed in many countries. Nevertheless, recent reports suggest that the rate is leveling off or even declining in men, but is increasing in women, particularly African-American women. Overall, the risk is slightly higher in Caucasians than in African-Americans.

The risks for NHL among men versus women and among African-Americans versus Caucasians may vary by lymphoma subtype. For example, follicular lymphomas were significantly higher in Caucasians than in African-Americans, and there was little gender difference. High-grade lymphomas were the most rapidly increasing type, particularly among men, with follicular lymphomas increasing most rapidly in African-American men.

Other studies have also reported ethnic differences by specific lymphoma subtypes. For example, follicular lymphomas constitute 20% of all NHLs in Western nations but are very uncommon in Asia and in developing countries.

The brother or sister of a person with the disease has more than twice the risk of developing NHL than the general population. Some cases of NHL in such cases are due to inherited disorders of the immune system. Studies suggest, however, that such family clusters are more likely to be due to environmental conditions that trigger the genetic factors.

Because of the rapid rise in NHL, investigators are looking for lifestyle factor that may contribute to this increase. No real association between lymphomas and body weight or shape or amounts of exercise has been found.

A number of reports suggest an influence of diet in the development of non-Hodgkin's involvements. However, for the most part a strong association remains speculative. Some of the possible dietary risk factors include:

A number of studies have observed an association between an increased risk for non-Hodgkin's lymphomas and high consumption of red meat (beef, pork, and lamb).
A higher risk for lymphoma has also been suggested for trans fatty acids (hydrogenated polyunsaturated fats, which are contained in hard margarines and commercial baked goods and fast foods). There appears to be no higher risk with natural polyunsaturated fats (found in most vegetable and fish oils).
Fish may be protective.
Some evidence suggests that milk may also be protective.
One major study observed a reduction in risk with high intake of vegetables. Another found no protection from vegetables, but did with diets rich in fruit.
Vitamin supplements have no effect on NHL.

Despite these kinds of reports, the influence of diet on the development of non-Hodgkin's lymphomas remains speculative.

Alcohol Use. Studies on alcohol have been mixed, with some showing a higher risk, some a lower risk, and some no difference at all.

Smoking. There is no evidence that smoking increases the risk for NHL itself, although it has been linked with high-grade and follicular NHLs in people with lymphomas.

Viruses or other microorganisms also play a role in some lymphomas. A number are being investigated:

Epstein-Barr virus, the cause of mononucleosis, is highly associated with Burkitt's disease and NHLs associated with immunodeficiency diseases. It is also a risk factor for Hodgkin's disease
Adult T-cell leukemia-lymphoma, which appears to be caused by a virus known as HTLV-I, has been found in southwestern Japan, the Caribbean, and the southeastern United States.
People who have stomach inflammation due to Helicobacter pylori or H. heilmannii bacteria are at increased risk for mucosa-associated lymphoid tissue lymphomas (MALT). (The use of antibiotics to get rid of the bacteria may cause remission in some patients who have an early stage form of lymphoma in an early stage.)
Human herpes virus 8 has been associated with NHL.
Borrelia burgdorferi, the bacteria that causes Lyme disease, has been associated with primary B-cell lymphoma.
Heavy antibiotic use during adulthood may increase risk. A 2005 study found that adults who used antibiotics more than 10 times had 1.8 times the risk of developing NHL than nonusers. However, researchers were not certain if antibiotics themselves, or the underlying infections they treated, were responsible for the increased risk.

Click the icon to see an image of Lyme disease.

Studies are reporting a higher prevalence of viral hepatitis C and B in patients with lymphomas, although such viruses do not appear to play a major role in triggering lymphoma.

Patients with diseases or conditions that affect the immune system may be at higher risk for lymphomas:

HIV-positive patients and those with full-blown AIDS are at higher risk for NHL, and the disease is more likely to be widespread in these patients than in those without the immune disease. Most AIDS-related NHLs are high-grade lymphomas. Burkitt's lymphoma is often seen in patients with AIDS. Although these patients have had a very poor prognosis, advances in antiviral therapy for HIV now allow better management of NHL with some success in achieving favorable outcomes. Part of the dramatic increase in NHL incidence over the past decades can be traced to AIDS.
Patients with a history of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, Hashimoto's thyroiditis, Crohn's disease, and Sjögren syndrome, are at an increased risk for certain NHLs, such as marginal zone lymphomas.
People who have organ transplants are at higher risk for NHL, probably due to multiple factors, including the drugs used to suppress the immune system and the transplanted organ itself.
Patients who have had high-dose chemotherapy with stem-cell transplantation are at higher risk.
Other immunodeficiency syndromes that put people at risk for NHL include Chediak-Higashi syndrome, ataxia-telangiectasia, B-cell lymphoproliferative syndrome, Bruton agammaglobulinemia, common variable immunodeficiency, and Wiskott-Aldrich syndrome.

Note on Allergies: There appears to be no association between NHL and allergies, overactive responses of the immune system. Allergies are the most common immune disorder.

Overexposure to a number of industrial and agricultural chemicals has been frequently linked to an increased risk for lymphomas. The data, however, are not consistent.

Organochlorines are chemicals produced when solid waste is burned. These by-product chemicals include dioxin, polychlorinated biphenyls (PCBs), and furans. Many studies have indicated that exposure to these chemicals increases the risk of developing NHL.
A number of studies have found an association between NHL and certain pesticides and herbicides, although more research is needed to confirm any definitive risk.
White spirits, thinners, phenoxy herbicides, wood preservative, aviation gasoline, plastic, and rubber chemicals have been associated with a higher risk for lymphomas. Specifically, in one study, painters and lumberjacks had a higher risk for NHL, while office and house workers had a lower risk.
Some studies have found an association with long duration and early use of permanent dark hair dyes. There is no consistent evidence, however, that hair dye increases the risk for lymphomas.

Symptoms

The most common first sign of lymphomas is painless enlargement of one or more lymph node, usually in the neck, armpits, or groin. Patients should see their doctors if these symptoms do not go away within 2 - 3 weeks.

The most common lumps or swellings in the neck are enlarged lymph nodes. They can be caused by bacterial or viral infections, cancer, and other rare causes.

Lymphomas sometimes cause systemic symptoms -- symptoms that affect the whole body, rather than a specific location. Some systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.

B systemic symptoms include:

Drenching night sweats and weight loss
Fever (may occur sporadically and only at night)

Other systemic symptoms include:

Itching all over the body caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of NHL, this is due to abnormalities in the immune system. Although this is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
In late stages, some patients develop a skin rash.
Tumor masses in the chest can cause coughing or breathlessness.
Lymphomas in the stomach can cause nausea and vomiting.

Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as "swollen glands"). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.

Infections. In the great majority of cases, swollen glands are caused by an infection:

Enlarged lymph nodes in the neck are much more likely to be a sign of strep or other throat infection than NHL.
Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
Travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
Other infections that cause swollen glands include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.

Hodgkin's Disease. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin's disease under some circumstances. [For more information, see In-Depth Report #83: Hodgkin's disease.]


Characteristics	Hodgkin's Disease	Non-Hodgkin's Lymphomas
Age and Prevalence	Average age is 28 with two age peaks, the major one occuring between 15 - 24, anda lesser peak after age 55. It is less common than NHL.	Average age is about 67. It is more common than HD.
Location	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases.	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.
Symptoms	More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis.	Less likely to have systemic symptoms (27%) at the time of diagnosis.
Progression	Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.	More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread.

Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.

Very serious causes of enlarged lymph nodes include disorders of the lymph system, such as Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #83: Hodgkin's disease or Report #86: Acute lymphocytic leukemia.]

Exposure to Medications. Exposure to certain medications such as phenytoin (Dilantin) may cause enlarged nodes. Other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash, which may resemble Hodgkin's disease.

Diagnosis

The doctor will first ask questions about the patient's medical history and perform a physical examination to detect any node enlargements. If these steps point to lymphoma, additional tests will be done to rule out other diseases or to confirm the diagnosis and extent of the lymphoma.

It is sometimes reasonable to wait a little while for the swelling and symptoms to go away before deciding that additional testing is necessary. In some cases, lymph node swelling may be due to a temporary infection. However, some lymphomas cause off and on lymph node swelling. This is particularly true with small cleaved cell lymphoma (the most common NHL). Lymph nodes should be checked periodically for any return of swelling.

The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node sometimes indicates certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma. Soft nodes suggest infection or inflammatory conditions.

Blood tests help rule out infection and other diseases. Such tests include those blood counts and blood chemistries for kidney and liver function, uric acid, calcium, and phosphate levels. In a patient already diagnosed with lymphoma, blood tests that measure the enzyme lactate dehydrogenase are important in determining the prognosis. High levels indicate bulkier tumors. The presence of anemia may indicate specific NHLs, such as diffuse, small lymphocytic lymphoma.

A biopsy is the most important test for diagnosing lymphomas and can be used to tell the difference between non-Hodgkin's and Hodgkin's disease. A biopsy has risks and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually go away on their own if a temporary infection is causing the swelling. (However, some lymphomas may go away and appear to be benign, only to reappear at a later time.)

The Procedure. The doctor removes the node and checks the surrounding areas. The tissue in the node is then examined under a microscope for signs of infection and abnormalities indicating cancer or other conditions.

Results. Even if biopsies do not show any problems, disease may still be present in some cases. The doctor should continue to observe the patient until swelling or other signs of disease are gone. Biopsied tissue samples should be frozen in case special tests are later required. Such tests may include detection of particular antibodies, genetic and immune factors, and certain markers (substances that may indicate disease) located on the surface of the cells. If lymphoma has been diagnosed, the tissue will be examined for its histology, the cellular structures that will determine the lymphoma type.

Bone marrow aspirate and biopsy are routinely performed to determine whether the disease has spread. With bone marrow aspirate, bone marrow cells are sucked out through a special needle. A biopsy may be performed before or after the aspiration. In this procedure, a special needle removes a core of the marrow that is structurally intact.

Click the icon to see an image of bone marrow aspiration.

Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area. It is particularly useful in detecting Hodgkin's disease and enlarged lymph nodes.

Click the icon to see an image of an x-ray machine.

Computer Tomography. Computed tomography (CT) scans are more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, monitor response to treatment, and evaluate when the symptoms occur. A CT scan is also often used in detecting lymphomas in the abdominal and pelvic areas, the brain, and chest area.

Click the icon to see an image of a CT machine.

Magnetic Resonance Imaging (MRI). MRIs may be used to detect the spread of the disease to the brain, spine, chest, pelvis, and abdomen.

Click the icon to see an image of a MRI machine.

Positron Emission Tomography (PET). PET scans can help tell whether or not an enlarged lymph node is benign or cancerous. PET scans are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.

Tests of lymphoma's DNA are in use or are being developed to detect particular genetic abnormalities that help determine outlook and may eventually lead to new treatments. Examples of such abnormal genetic arrangements are those that affect normal cell death, resist chemotherapy, or trigger aggressive cancer growth.

An advanced approach called the microarray technique uses chips that contain up to thousands of DNA sequences that represent specific normal and abnormal genes. Such sequences have been compiled for lymphomas. Eventually, experts may be able to match a patient's DNA to these patterns and identify specific subtypes.

Biologic markers, also called biomarkers, are high levels of substances released by tumors. They indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), and growth factors. Some under investigation include:

CD44. This molecule binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
BCL-6. This cancer gene is implicated in diffuse large B-cell lymphoma. High levels of this gene in these patients indicate a better outlook after treatment.

Outlook

Five-year survival rates for NHL range from 20 - 95%, depending on the lymphoma type, stage, age of the patient, and other variables. Because the outlook varies so widely, making a definite prognosis is very difficult. For example, patients with very slow growing (indolent) lymphomas can live many years. However, they are usually diagnosed at a late stage, after the cancer has spread, thus reducing the survival rate. Aggressive lymphomas are more likely to cause rapid death, but they are also often curable. New drugs that target specific factors in the tumor cells are improving survival rates.

Follicular lymphomas, the most common indolent (slow-growing) NHLs, are potentially curable in early stages I and II. Unfortunately, however, these slow-growing malignancies produce no symptoms until they are in advanced stages. In most cases, these lymphomas are not diagnosed until they have spread to other sites, including the spleen and bone marrow. In such cases, they are difficult to cure. Predicting outcome for indolent follicular lymphomas is more difficult than for aggressive lymphomas. Even if treatment achieves a response, these tumors almost always recur. Even after relapse, however, the tumors can be treated again if they are still very slow-growing.

In general, the average survival rate for follicular lymphoma is 7 - 10 years, depending on other risk factors. New drug treatments, particularly monoclonal antibodies, have significantly improved survival rates. According to a 2005 study, 91% of patients with follicular lymphoma now survive the first 4 years after diagnosis, compared with 69% of patients treated in the past with older types of drugs. The research team found the best 4-year survival rates for patients treated with the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy regimen followed by monoclonal antibody biologic drugs (rituximab or iodine-131 tositumomab).

Factors for Predicting Outlook in Indolent Lymphomas. Six risk factors are proving to be useful for predicting outlook:

Being male
Being older
Having stage III or IV disease
Elevated levels of the enzyme lactate dehydrogenase (LDH)
The presence of B symptoms
Erythrocyte sedimentation rate over 30

Patients with a good chance for a positive outcome (65% chance for survival rates of 10 years or greater) have one or none of these factors. Those with intermediate risk (23%) have two factors, and those likely to have a poor outcome (11%) have three or more factors. MALT lymphomas generally have a good prognosis. Primary gastric lymphomas have a 3-year survival rate of 89%.

High-grade aggressive lymphomas are often symptomatic early on and are potentially curable with aggressive treatments. Diffuse large-cell lymphomas, the most common aggressive non-Hodgkin's lymphomas, while fatal if not treated, are often curable with intensive chemotherapy combinations. If relapse occurs after chemotherapy, it usually does so within 2 years.

Most other aggressive lymphomas respond to aggressive chemotherapy. Mantle cell lymphoma is less responsive to chemotherapy. The average survival time is 3 - 5 years.

Factors for Predicting Outlook in Aggressive Lymphomas: A scoring system called the International Prognostic Index has proved to be fairly accurate for predicting outcome in patients with most aggressive B-cell lymphomas. It uses five risk factors to help predict whether the disease will be aggressive:

Being older than 60 -- this age group tends to have other medical conditions, which contribute to the poorer prognosis
Having a disseminated tumor (stage III or IV)
Disease that has spread to more than one site beyond the lymph nodes
A poor performance status
Having elevated levels of lactate dehydrogenase (LDH)

Having one or none of these risk factors indicates the best outlook. Two factors indicate a low-to-intermediate likelihood of a poor outlook. Three factors predict an intermediate-to-high likelihood of poor outlooks. Finally, four or five factors pose the highest likelihood of poor survival.

Lymphoma can spread to the central nervous system, or it can appear there first. Called primary CNS lymphomas (PCNSL), this condition is a very serious, particularly if it occurs at relapse.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

Risk Factors for CNS Involvement After a Diagnosis of NHL. AIDS-related lymphomas often involve the central nervous system (CNS), including the brain and spinal column. CNS involvement also occurs with aggressive lymphomas, such as Burkitt’s lymphoma.

Risk Factors of Primary CNS Lymphomas. PCNSL used to account for only about 2% of lymphomas, but the incidence is on the rise in all age groups and in both. The reason for the increase is not known.

Medical Problems. The radiation and chemotherapies used in treating NHL can have long-term effects on many organs in the body and can increase the risk for serious illnesses, including heart disease and certain cancers.

Negative Emotional Problems. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Many patients also suffer from fatigue and aches and pains, called somatic symptoms, which have no apparent physical basis. In one study, such symptoms were more highly associated with intensive chemotherapy. Women and people in lower social and economic groups are at higher risk for depression and somatic symptoms -- just as they are in the general population.

Staging and Treatment Guidelines

Treatment for non-Hodgkin's lymphoma is highly specific for each patient and is determined by the tumor classification. It includes the following factors:

Stage
Grade
Histologic type (cellular structure)
Location
Other factors, such as blood levels of lactate dehydrogenase

Treatment for lymphomas has been primarily dependent on chemotherapy (particularly intensive regimens using several drugs) or a combination of chemotherapy and radiation. For advanced or refractory lymphomas and for relapse, patients may undergo bone marrow or stem cell transplantation. New treatments, especially those known as immunotherapies, or biological response modifier (BRM) therapies, are showing promise. Some experts recommend that patients ask their doctors about getting into well-designed clinical trials as early as possible.

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

In assessing the success of a clinical trial, experts often refer to the tumor response. A complete response, for example, means that there is no longer any evidence at all of the disease by examination, blood tests, or x-ray studies. It does not necessarily mean, however, that the disease is cured. It may still recur later on.

In judging the success of a treatment for NHL, the most important criteria are overall survival and the duration of time until the disease progresses or the patient dies.

In Stage I, lymphoma is found in only one lymph node area or in only one area or organ outside the lymph nodes. Either of the following indicates stage II:

Lymphoma is found in two or more lymph node areas on the same side of the diaphragm.
Lymphoma is found in only one area or organ outside the lymph nodes and in the lymph nodes around it. Other lymph node areas on the same side of the diaphragm may also have lymphoma.

Early Stage Indolent (Low-Grade) Lymphoma. Below are the general treatment options:

Radiation therapy. Radiation to local areas can achieve a cure in 40 - 50% of patients.
Chemotherapy. Chemotherapy uses drugs to kill cancer cells.
Watchful waiting. Patients who choose watchful waiting must be aware of signs and conditions indicating the need for treatment. These include B symptoms, endangered organs, massive bulky tumors, or a steady progression that lasts at least 6 months.
Investigative treatments, such as conjugated and unconjugated monoclonal antibodies or radiation plus chemotherapy. In one study, a combination of therapies worked better than radiation alone.

The following are treatment options for some specific low-grade lymphomas:

Mucosa-associated lymphoid tissue (MALT) lymphoma. When disease is in the stomach (gastric MALT) and the patient is infected with H. pylori bacteria, antibiotics can cause regression in a significant number of patients with stage I lymphoma. In certain patients where antibiotics fail, or are not appropriate, radiation alone can achieve significant cure rates. Surgery with or without radiation, or chemotherapy with or without radiation, are possible options. Treatment options for patients with MALT localized in other sites depend on the location of the specific disease and range from radiation to chemotherapy to biologic therapies, such as interferon.
Primary gastric lymphoma (indolent). Radiation is the typical treatment for this lymphoma, which is located only in the stomach, small intestine, or other nearby regions. Surgery is being reconsidered since it seems to offer no advantage.

Click the icon to see an image of the digestive system.

Early Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options include:

Chemotherapy alone
Combinations of chemotherapy (usually CHOP) plus radiation therapy
Radiation alone (rarely)
Chemotherapy alone or with surgery for lymphoma in the gastrointestinal region
Immunotherapies (rituximab, Bexxar) with or without chemotherapy (usually CHOP), or high dose chemotherapy and bone marrow or stem cell transplantation

In stage III, lymphoma is found in lymph node areas on both sides of the diaphragm (for instance, in both the chest and the abdomen). The lymphoma may also have spread to the spleen. In stage IV, lymphoma has spread via the bloodstream to organs outside the lymph system, such as the bone marrow or brain. Lymphoma cells may or may not be in the lymph nodes near these organs.

Advanced Stage Indolent (Low-Grade Lymphomas). Treatment options are controversial because of the low-cure rate and yet slow-growing nature of these lymphomas. Patients without symptoms are often managed by watchful waiting, in which the disease is monitored closely for development of symptoms or bulky tumor masses, particularly if they threaten major organs. At such times, treatment is started. Treatment may include:

Chemotherapy combinations (CHOP, CVP, CMOPP)
Nucleoside analogs (for example, fludarabine) alone or with chemotherapy
Oral alkylating chemotherapy drugs such as cyclophosphamide or chlorambucil with or without steroids
Monoclonal antibodies (MAbs) such as rituximab alone or in combinations with CHOP or nucleoside analogs
Chemotherapy plus interferon
Clinical trials involving intensive chemotherapy and radiation followed by bone marrow or stem cell transplantation

Advanced Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options may include:

Doxorubicin-based combination chemotherapy with or without rituximab
Chemotherapy plus radiation therapy
Immunotherapies with or without chemotherapy
Treatments to prevent disease from spreading to the central nervous system in high-risk patients
Clinical trials for patients at high risk for relapse, involving intensive chemotherapy, high dose chemotherapy, and bone marrow or stem cell transplantation

Indolent-Lymphomas Relapses. Nearly all patients with indolent lymphomas relapse after initial treatment, with length of remission after a first treatment averaging 18 - 50 months. Successful retreatment is often possible, but disease-free periods become increasingly shorter with each subsequent treatment.

Older patients may choose watchful waiting. Other treatment options may include:

Radiation alone or with chemotherapy -- in one study low-dose involved-field radiotherapy was very effective in recurring indolent lymphoma
Chemotherapy
High-dose chemotherapy with autologous stem cell transplant
Clinical trials involving monoclonal antibodies, radioimmunotherapy, nucleoside analogues alone or in combination with other drugs, or stem cell transplantation followed by biologic therapies

Aggressive Lymphomas Relapse. After initial treatment, more than half of patients with aggressive lymphomas are cured, while about 20% progress, and the other 30% relapse after a disease-free period. Among those who relapse, many can still be cured with aggressive treatments.

Treatment options:

Bone marrow or peripheral stem cell transplantation
Bone marrow transplantation with radiation
Clinical trials that involve continuous infusion chemotherapy, biologic therapies (monoclonal antibodies) alone or in combination with transplantation

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Treating Lymphoma Restricted to the Central Nervous System. Treatment options may include:

High-dose methotrexate regimens alone or in combination with radiation
Corticosteroids and radiation
Clinical trials that involve biologic therapies, such as rituximab or interferon alpha administered directly into the spinal fluid (intrathecal administration) for meningitis related to central nervous system lymphoma

Preventing (Prophylactic Treatment) Lymphomas in High-Risk Patients. Treatment to prevent the spread of NHL to the central nervous system may be appropriate in some patients. It is not recommended for patients with low-grade NHL. Preventive treatment may be appropriate for certain patients with high-grade NHL, such as those with lymphoblastic and Burkitt's lymphoma or if they have 4 - 5 of the following risk factors: Elevated levels in the blood of the enzyme acetate dehydrogenase and albumin (a common protein), being older than 60, and having lymph nodes beyond the peritoneum (the lining of the abdomen) and involvement of more than one site outside a lymph node.

Chemotherapy

Chemotherapy plays a role in the treatment of nearly all lymphoma patients and has achieved remarkable results, even in late stages. It uses drugs to kill cancer cells. Such drugs are called cytotoxic drugs. Chemotherapy is referred to as bodywide or systemic therapy because the drugs travel throughout the bloodstream to the entire body.

Studies indicate that chemotherapy as sole treatment is adequate for most children and young adults in early, and perhaps in many advanced, stages. (Radiation has been commonly used for these patients but can be particularly dangerous for children.)

A chemotherapy cycle is usually 21 - 28 days. Patients take the drugs for a few days, then have a period of rest. The drugs may be taken by mouth or given by injection. Chemotherapy is injected into the spinal fluid if the cancer has spread to the brain. This is called intrathecal chemotherapy. Intrathecal chemotherapy is also used as a preventive measure in patients at high risk for central nervous system involvement. Chemotherapy may be administered at a medical center or in a doctor's office. Some patients receiving chemotherapy need to remain in the hospital for several days so the effects of the drug can be monitored. Patients with lymphoblastic lymphoma may need long-term maintenance chemotherapy. Such therapy does not seem to benefit patients with small-noncleaved-cell and large-cell lymphomas.

CHOP. The current standard chemotherapy regimen for NHL is CHOP. CHOP is a combination of cyclophosphamide, doxorubicin hydrochloride (Adriamycin), vincristine (Oncovin), and prednisone. It is proving to be particularly effective for many stages of lymphoma when used in combination with rituximab (Rituxan), a monoclonal antibody. (See Biologic Therapy section.) Some studies of this combination in low-grade lymphomas have reported response rates of 70 - 100%. CHOP alone is still preferred for HIV patients, who tend to have a toxic response to rituximab.

CVP. This stands for cyclophosphamide, vincristine, and prednisone. It may be used with CHOP in certain cases.

Fludarabine and Nucleoside Analogues. Fludarabine (Fludara) is a type of drug called a nucleoside analogue. It is one of the most active drugs for treating low-grade lymphomas and may be effective for other NHLs, including mantle cell lymphomas. Promising regimens containing fludarabine are under investigation. For example, FND (fludarabine, mitoxantrone, and dexamethasone) may be helpful in combination with rituximab for certain patients, including those with indolent NHL. Other nucleoside analogues include gemcitabine and cladribine. Toxicities and infection rates from high dose nucleoside analogues have been high. Fludarabine also has been associated with a risk for leukemia.

Bendamustine. This potent drug has shown to be effective for indolent NHLs and possibly aggressive lymphomas. One study suggested that a single dose of low-dose etoposide, taken by mouth, may be beneficial for elderly patients.

Antibiotics. Antibiotics, such as doxycycline, may cure or put into complete remission about half of mucosa-associated lymphoid tissue (MALT) lymphoma cases. MALT lymphoma is a type of lymphoma that sometimes affects the eyes. It is associated with the bacterium Helicobacter pylori (H. pylori ), which also causes stomach ulcers. Recent studies indicate that antibiotics are a good alternative to chemotherapy or radiation for patients with this type of lymphoma. Patients most likely to respond positively to antibiotics are those with MALT lymphoma in its early stages.

Vorinostat. Vorinostat (Zolinza) was approved in 2006 for treatment of cutaneous T-cell lymphoma (CTCL), a rare form of NHL.

Side effects and complications of any chemotherapeutic regimen are common. They are more severe with higher doses. Side effects may increase over the course of treatment.

Common Side Effects. Common side effects include:

Nausea and vomiting -- Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Hair loss
Weight loss
Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps a few days a month.

Serious Side Effects. Serious chemotherapy side effects can also occur and may vary depending on the specific drugs used. They include:

Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta), can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to treat only anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
Liver and kidney damage
Abnormal blood clotting (thrombocytopenia)
Allergic reaction

Long-Term Complications.

Fatigue and Somatic Symptoms. Chemotherapy has been associated with long-term somatic symptoms, which are general conditions, such as fatigue and aches and pains that have no apparent physical basis. Fatigue is especially common after chemotherapy and can even last for years.
The most serious long-term complications from chemotherapy are secondary cancers, particularly in people over age 40.
Infertility is a risk, particularly with the use of cyclophosphamide.
Some patients get osteoporosis (bone thinning) and damage in bone cells.
Regimens containing certain drugs, particularly doxorubicin or mitoxantrone, increase the risk for future heart failure.

Click the icon to see an image of the uterus and ovaries.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Doctors are particularly concerned about the effects of combinations of chemotherapy with radiation, especially leukemia and heart problems. Interestingly, in one study on patients with intermediate- and high-grade NHL, those on chemotherapy alone had more toxic effects than those on combined modality, most likely because it employed fewer cycles of chemotherapy. Better radiation techniques are also reducing the risks of combined modality treatments.

Biologic Therapy (Immunotherapy)

Biological response modifier therapy, also called immunotherapy, uses the body's own immune system to fight cancer using natural or laboratory-developed factors. These drugs are often combined with other treatments.

Monoclonal antibodies (MAbs) are designed in the laboratory to produce the same effects as natural antibodies and are exciting new weapons in the anti-cancer armament. They bind to specific proteins called antigens and make them vulnerable to attack by other factors in the immune system. Lymphomas carry antigens that provoke strong immune responses and so are believed to be particularly good candidates for MAb therapy.

MAbs are called either unconjugated or conjugated, depending on how they are designed to destroy the cancer cell.

Unconjugated monoclonal antibodies rely on a strong natural immune system. The antibody builds up at the tumor site until it is able to trigger an immune response against the cancer. A possible downside to this form is the potential development of tolerance to the antibody so that it loses its effectiveness. Rituximab is an unconjugated form and the first MAb to be approved for any cancer.
Conjugated monoclonal antibodies are linked to a plant or bacterial toxin or radioisotope. The antibody specifically attacks the antigen on the lymphoma cell, and the toxin or radioactive material from the isotope kills it.

Unconjugated MAbs (Rituximab). Rituximab (Rituxan) was the first monoclonal antibody approved for cancer. This drug targets the CD-20 antigen, which is found on most B-cell lymphomas.

First approved in 1997 for treatment of relapsed or refractory NHL, rituximab has received several expanded indications since that time. As of 2006, rituximab is approved for:

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, NHL
First-line treatment of diffuse large B-cell (DLBC), CD20-positive, NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens
First-line treatment of follicular, CD20-positive, B-cell NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy
Low-grade, CD20-positive, B-cell NHL in patients with stable disease or patients who have been partially or completely helped by first-line treatment with CVP chemotherapy

Rituximab in combination with CHOP (a regimen called R-CHOP, or CHOP-R) is used for first-line treatment for aggressive lymphomas, with studies reporting 3-year event-free survival of 53% compared to 35% with CHOP alone. A 2006 study also indicated that rituximab provides benefits when used as maintenance treatment after CHOP or R-CHOP induction therapy. Rituximab plus CHOP is also showing promise as a first-line treatment for mantle cell lymphoma.

Rituximab is given by infusion. The treatment has mild-to-moderate short-term side effects, including nausea, fever, chills, hives, dizziness, and headache. Uncommon and more serious side effects are severe allergic reactions, very low blood pressure, blood abnormalities, wheezing, infections, and sudden heart events.

Rituximab has also been associated with cases of progressive multifocal leukoencephalopathy (PML), a rare and potentially deadly brain infection. Patients who experience any of the following symptoms should immediately contact their doctors:

Vision problems or unusual eye movements
Confusion
Dizziness or loss of balance
Difficulty talking or walking

Patients who have previously had hepatitis B, or who are at high-risk for this viral infection, should be tested before taking rituximab because the drug has been linked to reactivation of the hepatitis B virus. Patients who are HIV-positive may experience more adverse effects from rituximab than with CHOP.

Conjugated Monoclonal Antibodies with Radioimmunotherapy. Conjugated MAbs with radioimmunotherapy contain tiny amounts of radioactive materials. When the drug is injected, the monoclonal antibody targets an antigen (protein) on the surface of the tumor. The radioisotope is then delivered directly into the tumor where it kills the cancer. Ibritumomab and tositumomab both target the CD-20 antigen. Treatment with these drugs takes about 7 - 9 days to complete, compared to several months for traditional chemotherapy treatments.

Ibritumomab (Zevalin) is approved for patients with relapsed or refractory low-grade, follicular or transformed B-cell NHL. It is also approved for patients with follicular NHL who have not responded to rituximab (Rituxan). Research indicates it may also be safe for patients with advanced NHL who have had stem cell transplantation. Zevalin uses an yttrium-90 (90-Y) radioactive isotope.
Tositumomab and Iodine I-131 (Bexxar) combines the monoclonal antibody tositumomab with the radioisotope I-131. The Bexxar treatment is approved for treatment of relapsed or refractory low-grade, follicular, or transformed B-cell NHL. Overall response rates of 56% have been reported with Bexxar, with up to 30% being complete responses (no evidence of cancer). Recent studies suggest that when Bexxar is used as a first treatment, it may produce long-term complete remission in patients with advanced stage follicular lymphoma. In a 2005 New England Journal of Medicine study, 95% of previously untreated patients with advanced follicular lymphoma responded to Bexxar, and 75% had complete responses. Seventy percent who had complete responses from Bexxar treatment were still disease-free 4 - 7 years later.

In general, these drugs cause fewer side effects than traditional chemotherapy. However, serious complications may include skin infections, severe allergic reactions, and temporary lowering of blood counts.

Other Monoclonal Antibodies. Other MAbs are being developed that target other antigens on lymphomas. For example, epratuzumab targets CD-22 and is showing promise in early studies. Some are being studied in both conjugated and unconjugated forms and also in combination with MAbs that target different antigens.

Interferon alpha (Intron A) is used as an antiviral drug that also has properties that are effective against some common forms of NHL, particularly low-grade, follicular NHL in advanced stages. It is usually combined with chemotherapy regimens such as CHOP that contain an anthracycline drug (usually doxorubicin). The combination is toxic, however, and outcomes vary. Interferon is also being studied for lymphomas in the central nervous system. It may be useful after autologous stem cell transplantation.

Side Effects. Side effects of interferon include flu-like symptoms, severe depression, irritability, weight loss, vomiting, general weakness and loss of strength, and fever. About a third of patients have a severe drop in white blood cells. About 10% of patients cannot tolerate the drug's side effects.

Cytotoxic Deoxyguanosine Analogue Prodrugs. Nelarabine (Arranon) is approved for treating T-cell lymphoblastic lymphoma (T-LBL). T-LBL is a rare form of lymphoma that accounts for less than 2% of all cases of NHL.

Proteasome Inhibitors. In 2006, bortezomib (Velcade) was approved for treatment of mantle cell lymphoma in patients who have received at least one prior therapy.

Cyclin-Dependent Kinase Inhibitors. Flavopiridol, a drug known as a cyclin-dependent kinase inhibitor, is showing some effect in patients with mantle-cell lymphoma. This drug is designed to block enzymes that regulate cell cycles and help block their growth.

Vaccines. Although still experimental, lymphoma vaccines are used to treat -- not prevent -- cancer. They are part of an immunotherapy approach called personalized medicine; each vaccine is individually tailored to the genetic composition of the patient’s tumor. The vaccine is usually given a few months after a patient receives chemotherapy. Several different vaccines, including the BiovaxID and MYVax, are in late-stage clinical trials.

Radiation

Radiation is commonly used to treat indolent lymphomas. The dose administered ranges from 35 - 50 Gy and depends on a number of factors: The type of lymphoma, the age of the patient, whether the intent is to cure or relieve symptoms, how close sensitive organs are to the diseased area, and whether radiation is being combined with chemotherapy.

Radiation is tailored to the individual and usually limited to the diseased areas and possibly nearby regions:

If the lymphoma is confined to tissues above the diaphragm, radiation is delivered to the neck, chest, and under arms (called the mantle-field) and sometimes to lymph nodes in the upper abdomen or spleen or both.
If the lymphoma is below the diaphragm, subtotal nodal radiation may be used, which is directed to other regions, including lymph nodes in the upper abdomen, spleen, and pelvis, in addition to the mantle-field.
Radiation to the brain is called cranial radiation.
Total body irradiation is sometimes performed, although it is not clear whether its high toxicity outweighs any advantages.

Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.

Side effects and complications of radiation generally depend on the target site in the body. They include:

Dental problems
Inflammation in the lungs -- with carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.
Hypothyroidism
Infections
Long-term risk for heart disease
Long-term risk for certain cancers -- of particular concern is a possible increased risk for breast cancer. Studies indicate that young women and adolescent girls are at highest risk, with the incidence increasing significantly 15 years after treatment. The risk is greater in those who had higher radiation doses. Radiation may also increase the risk over time for other cancers, including lymphoma and thyroid, lung, and colon cancers, although the risk is still low. Smoking, of course, increases the risk for lung cancer. Radiation of bone marrow increases the risk for leukemia.
Impaired bone growth -- children and adolescents are at special risk for bone problems caused by radiation. Experts are finding that radiation for many children and young adults in early stages or NHL is no more effective and has more serious long-term effects than chemotherapy. Some believe that radiation should play no role in the treatment of young people, except in special cases, such as lymphomas that require radiation to the brain.
Infertility -- the negative effects on fertility may be worse in women than in men; sperm usually recover within 5 years. To protect the ovaries, a technique called ovarian transposition is sometimes used. Transposition may sometimes be performed through a laparoscope, a thin tube containing tiny instruments and cameras, which is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.

Click the icon to see an image of the lungs.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of the uterus and ovaries.

Transplantation

Stem cell procedures have proven to produce long-term survival and even cures in some patients with intermediate- and high-grade non-Hodgkin's lymphomas.

Stem cell transplantation involves removing and replacing stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them from the donor into the patient.

Sources of Cells. Stem cells must first be collected in one of the following ways:

Directly from blood, called peripheral blood stem cell transplantation
From bone marrow, called bone marrow transplantation
From umbilical cords or placentas -- this procedure uses donor cells, but has a lower risk for immune system rejection of the cells than with a standard donor transplant. It takes longer to restore blood cells with this process, so it is generally used for children and sometimes adults with low weight.

Some evidence suggests that both stem cell and bone marrow procedures produce similar benefits in terms of response rates and duration of remission. However, in one study, stem cell transplantation was associated with better overall survival rates. It also seems to be superior in terms of cost, quality of life, and the need for less supportive care.

Donor or Patient Cells. The marrow or blood stem cells can be taken from the patient (autologous) or from a matched donor (allogeneic):

In an autologous transplant, the marrow or blood cells used for replacement are taken from the patient. There is some danger, however, that these cells may contain tumor cells, and that the cancer can regrow. It is unclear if this approach improves survival compared to standard chemotherapy for newly diagnosed disease. However, it clearly has benefits in the treatment of some forms of relapsed non-Hodgkin's lymphomas. There is also a higher risk for leukemia. (This risk is lower in peripheral stem cells transplants than in bone marrow transplants.)
In an allogeneic transplant, bone marrow or stem cells are taken from a donor. Siblings are the best donors. Relapse rates can be very low with this approach, and cure may be possible in some cases. However, it is highly toxic and donor and recipient must be matched as closely as possible to avoid rejection by the immune system, a serious complication called graft-versus-host disease. Advances in techniques are reducing the toxicities associated with this approach. Older patients who cannot tolerate the preparatory treatment required for a standard allogeneic transplant may be able to receive a non-myeloblative transplant (“mini-transplant), which uses lower doses of chemotherapy and radiation.

The Blood Stem Cell Collection Procedure. With peripheral blood stem cell transplantation:

The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim, pegfilgrastim) to stimulate stem cell growth.
The patient (or donor in an allogeneic procedure) then undergoes apheresis. With this process the blood is withdrawn from one of the patient's veins, then passes through a machine that filters out the white cells and platelets, which contain the stem cells. The blood is returned through another vein. The entire procedure takes 3 - 4 hours but needs to be repeated several times.
The stem cells are treated to remove contaminants and then are frozen to keep them alive until the patient is ready to receive them back.

Blood is the only fluid tissue in the body. Blood transports oxygen and nutrients to body tissues, and returns waste and carbon dioxide. Blood distributes nearly everything that is carried from one area in the body to another place within the body. For instance, blood helps transport hormones from the endocrine organs to their target organs. Blood also helps maintain body temperature. The protective functions of blood include clot formation and the prevention of infection.

Allogeneic transplants are preceded by chemotherapy treatment known as conditioning. The point of this treatment is to inactivate the immune system and to kill any residual malignant cells. It is extremely toxic since it also destroys non-malignant marrow cells. Drugs used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning to reduce toxicity includes total-body radiation plus drugs. Monoclonal antibodies, such as rituximab, are promising drugs, since they have low toxicity and may add benefits for all stages of transplantation.
A few days after treatment, the patient given the stored stem cells, which are administered through a vein. This may take several hours. Patients may have a fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
The patient may be treated with granulocyte colony-stimulating factor after chemotherapy. The goal is to stimulate the growth of infection-fighting white blood cells. Adding thrombopoietin may help enhance stem cell production.
The patient is kept in a protected environment to minimize infection. Patients who have received an allogeneic transplant may need blood cell replacement, nutritional support, and drugs to treat graft-versus host disease. They usually can leave the hospital within 3 - 5 weeks.

Candidates. These procedures are typically used for patients with relapsed aggressive lymphoma who are still sensitive to the effects of chemotherapy. The procedures do not work for patients whose tumors are not responsive to drugs. Some evidence suggests that certain primary (non-relapsed) lymphomas initially unresponsive to a first round of chemotherapy but who respond to a second round may benefit from combination of high-dose chemotherapy and radiation followed by transplantation. Transplantation is also being investigated as first-line therapy for patients with aggressive lymphomas, although at this time evidence does not support its use.

Success Rates. Success rates vary depending on many factors. The following are survival rates reported by a few studies of patients with different lymphomas:

In patients with refractory or relapsed intermediate grade NHL who received autologous transplantation, 5-year survival rates averaged 34%.
In a study of allogeneic bone marrow transplantation, 58% of patients with late-stage low-grade lymphoma had survived after an average of 29 months.
Patients with anaplastic large-cell lymphoma were treated with autologous stem cell transplantation with intensified chemotherapy as first line-therapy. Survival rates were 87% at 5 and more years afterward. (Survival was much lower with other lymphomas.)
Patients with diffuse aggressive NHL who did not achieve a first remission but who are still sensitive to chemotherapy achieved a 5-year survival rate of up to 37% after autologous stem cell transplantation.
In one study, 35% of patients with an initial poor prognosis were still alive 5 years after an allogeneic stem cell transplantation, although mortality probability from the treatment itself was very high (48%).

Common side effects include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.

It is very important that patients take precautions to avoid infections. Guidelines for post-transplant infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about handwashing and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. Mild cases of GVHD can actually be helpful as they can cause graft-versus-lymphoma where the immune system kills remaining lymphoma cells. Still, severe GVHD can pose serious complications.

To reduce the risk for GVHD, doctors remove some immune T-cells from the donor’s stem cells before the transplant. Researchers are investigating new techniques to refine this process of T-cell depletion.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Secondary cancers. There is a small long-term risk for leukemia after transplantation in young people. Use of newer chemotherapeutic drugs, however, may not pose as high a danger as older treatments.

Other potentially serious complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)

Surgery

Surgery is sometimes used to remove as much malignant tissue as possible before administering chemotherapy. This is particularly useful for bulky tumors that occur in the stomach.

Surgery is sometimes performed for primary gastric lymphoma, but its advantages are uncertain. Some studies indicate that chemotherapy alone or with radiation may be sufficient and could spare many patients from surgery.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.leukemia.org -- The Leukemia and Lymphoma Society
www.canceradvocacy.org -- National Coalition for Cancer Survivorship
www.marrow.org -- National Marrow Donor Program
www.asco.org -- American Society of Clinical Oncology
www.lymphoma.org -- Lymphoma Research Foundation
www.plwc.org -- People Living with Cancer
www.oncolink.org -- Cancer information
www.fhcrc.org/science/clinical/ltfu/patient -- Fred Hutchinson Cancer Research Center -- Transplant Infection Guidelines for Patients
www.lymphomainfo.net -- Lymphoma Information Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Boffetta P, de Vocht F. Occupation and the risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2007: 16(3):369-72.

Ferrara JL. Novel strategies for the treatment and diagnosis of graft-versus-host-disease. Best Pract Res Clin Haematol. 2007. 20(1):91-7.

Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma. V.3.2007.

Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood. 2007 Nov 15;110(10):3507-16. Epub 2007 Aug 20.

A.D.A.M. Copyright

adam.com

Hodgkin's disease

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Staging and Treatment Guide...
Treatment Options by Stage...
Radiation Treatments
Chemotherapy
Transplantation
Immunotherapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, including epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.

In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels contain stronger warnings and updated dosing-related safety information.

Preventing Infection after Cancer Treatment

Both chemotherapy and stem cell transplants increase the risk for serious infections. Patients must take precautions to avoid exposure to germs. Ways to prevent infection include:

Practice good hygiene, including regular handwashing and dental care (brushing, flossing)
Avoid crowds, especially during cold and flu season
Eat only well-cooked foods (no raw fruits or vegetables)
Boil tap water before drinking it
Do not keep fresh flowers or plants in your house as they may carry mold

Introduction

Hodgkin's disease is a type of lymphoma. Lymphomas are cancers of the lymphatic system. They are generally subdivided into two groups: Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). NHL is discussed in another report. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people talk about swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

HD is the major tumor in a group known as malignant lymphomas. Most often HD starts in B cell lymphocytes located in lymph nodes in the neck area, although any lymph node may be the site of initial disease.

Click the icon to see an image of the lymph nodes in the head and neck.

The following is a possible description of the process leading to HD:

In early development, B cells normally undergo a series of genetic rearrangements until they create immunoglobulins, proteins that act as antibodies.
Antibodies are produced by the immune system. They contain receptors that match and bind to a wide array of foreign substances (such as viral proteins) called antigens. Antibodies help launch an immune attack against antigens.
B cells normally undergo limited cycles of genetic rearrangement that result in immunoglobulin production. In rare cases, however, the genetic arrangements create a mutation that does produce immunoglobulins. The results are large, abnormal cells referred to as Reed-Sternberg cells.
Without immunoglobulin, Reed-Sternberg cells can be infected by certain viruses (notably the Epstein-Barr virus -- the cause of infectious mononucleosis). Genetic byproducts of these viruses appear to inhibit a natural process of self-destruction (called apoptosis) that would normally kill off these natural cells. Instead, the abnormal B cells grow non-stop, causing most forms of HD.

Click the icon to see an image of an antibody.

Only a very small percentage (about 1%) of cells found in the affected lymph tissues of HD are actually Reed-Sternberg cells. Researchers are unable to completely explain why so few cells can cause such severe symptoms. One explanation is that these cells trigger production of very powerful immune system proteins called cytokines (including those known as interleukin-1, interleukin-6, and tumor necrosis factor). These cytokines produce an inflammatory response that can cause local pain, fever, and other symptoms typical of HD. The dominance of different kinds of cytokines may also explain why HD takes different forms.

Classical Hodgkin's Lymphoma. Based on the variations and numbers of Reed-Sternberg cells, as well as other features, four major subtypes of classical HD have been identified:

Nodular Sclerosis. Nodular sclerosis is the most common subtype, representing almost 60% of HD cases. Younger patients are more likely to have this type. The nodes first affected are often those located in the center of the chest (the mediastinum).
Mixed Cellularity. Mixed cellularity is the next most common HD form, occurring in about 25% of patients, mostly in older patients, children, and those with immune disorders, such as AIDS. It usually indicates a more severe condition.
Lymphocyte Depleted. Lymphocyte-depleted HD occurs in about 4% of patients, nearly always in elderly people. It indicates extensive disease and a poor outlook. It can easily be confused with non-Hodgkin's lymphoma.
Lymphocyte-Rich Classical Hodgkin's Lymphoma. This form is similar to nodular lymphocyte predominant HD, but has more cell characteristics that conform to classical HD.

Nodular Lymphocyte-Predominant Hodgkin's Disease. Nodular lymphocyte-predominant Hodgkin's disease (LPHD) occurs in about 5% of patients. The cells in LPHD known as lymphocytic and histolytic cells are proving to be distinctly different from classic Reed-Sternberg B cells. Patients with lymphocyte predominance are usually young men, who often have no symptoms. LPDH is very slow growing and may be associated with long survival. There is a 3% risk, however, that LPDH will transform to non-Hodgkin's lymphoma. In fact, lymphocyte-predominant HD may eventually be defined as a non-Hodgkin's lymphoma.

Lymphomas represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, which are important cells involved in defending the body against infections. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation. Its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.

Lymphocytes. The lymphatic system helps produce and transport lymphocytes, white blood cells that are a primary component of the immune system. Some lymphocytes produce antibodies that can target and attack specific foreign substances (antigens).

Lymphocytes develop in the bone marrow or thymus gland. They are categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
T cells also start out in the bone marrow, but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it shrinks.
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Some lymphocytes, along with fluid, proteins, and other substances, move out of the capillaries into the surrounding tissues. Some enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes. They lead to larger lymphatic ducts and branches, and drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, which are oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.

Lymph Nodes. In a lymph node, lymphocytes typically receive their initial exposure to foreign substances, such as bacteria. This exposure prompts the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are clustered throughout the body. Important node clusters are found in the neck, lower arm, armpit, and groin.

Other Structures in the Lymphatic System. The tonsils and adenoids are secondary lymphatic organs. They are composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.

Click the icon to see an animation about lymph nodes.

Click the icon to see an image of an antibody.

Click the icon to see an image of the immune system structures.

Risk Factors

Hodgkin’s disease accounts for about 11.5% of all types of lymphomas. According to the American Cancer Society, about 8,200 new cases of Hodgkin's disease (HD) were diagnosed in the United States in 2007 and about 1,000 people died of the disease. Experts believe that the malignant process leading to Hodgkin's disease is triggered by a combination of environmental and genetic factors along with a susceptible immune system. The exact triggers, however, are unknown.

Hodgkin's disease occurs most often in people between the ages of 15 - 40, (especially in the 20s), and in people over age 55. About 10 - 15% of Hodgkin’s disease cases are diagnosed in children and teenagers.

Hodgkin's disease is slightly more common among males than females. Women who get Hodgkin's disease appear to have a slightly lower risk for relapse after treatment than men.

Infectious mononucleosis (“mono”), which is caused by the Epstein-Barr virus (EBV), appears to increase the risk for Hodgkin’s disease. Research suggests that the virus activates some pathway within the lymphocyte cell that leads to cell proliferation. However, only 1 in 1,000 patients with mononucleosis develops Hodgkin's disease. The Epstein-Barr virus itself is present in 90% of the population and, in the great majority of these cases, causes a mild infection or none at all. Very few people who have had mononucleosis go on to develop HD. Other factors must be present to trigger the malignancy.

Hodgkin's disease runs in families in about 5% of cases. Siblings have three times more risk than the general population.

Symptoms

The onset of Hodgkin's disease symptoms is highest during late winter months, with lymph node enlargement usually being the first sign. Lymph nodes may be enlarged in the following regions:

The most common first sign of Hodgkin's disease is painless enlargement of one or more lymph nodes above the diaphragm, most often those in the neck, chest, or armpits.
Enlarged lymph nodes are often detected in the chest cavity between the lungs (the mediastinum), particularly in younger patients.
Only about 15% of cases occur exclusively below the diaphragm.

Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site.

If it spreads below the diaphragm, it usually reaches the spleen first; the disease may then spread to the liver and bone marrow.
If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.

Symptoms in or around the Lymph Nodes. Occasionally, patients may have a cough or chest pain if the disease is located in the middle of the chest, but usually the enlarged nodes produce no symptoms. Sometimes patients experience pain in the diseased lymph nodes after drinking alcohol.

Systemic (B) Symptoms. Between 20 - 40% of patients have systemic symptoms that affect the whole body rather than just the specific location of the disease. Some of systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.

Systemic symptoms include:

Drenching night sweats and weight loss (B symptoms)
Fever -- may occur only at night in episodes that come and go (B symptoms)
Itching all over the body -- caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of Hodgkin's disease, histamine release is due to abnormalities in the immune system. Although itching is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
Rash (late stages)

Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as “swollen glands”). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.

Infections. In the great majority of cases, swollen glands are caused by an infection:

For example, although Hodgkin's often first appears in the neck, enlarged lymph nodes in that location are much more likely to be a sign of strep throat, or other throat infections.
Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
Recent travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
Other infections that cause similar symptoms include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.

Lymph nodes play an important part in the body's defense against infection. Swelling might occur even if an infection is small or not apparent.

Non-Hodgkin's Lymphomas. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin’s disease under some circumstances. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]


Characteristics	Hodgkin's Disease	Non-Hodgkin's Lymphomas
Age and Prevalence	Average age is 27.7 with two age peaks, the major one between 15 - 24 with a lesser peak after age 55. It is less common than NHL.	Average age is about 67. It is more common than HD.
Location	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases.	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.
Symptoms	More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis.	Less likely to have systemic symptoms (27%) at the time of diagnosis.
Progression	Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.	More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread.

Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.

Very serious causes of enlarged lymph nodes include disorders of the lymph system that include Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas or Report #86: Acute lymphocytic leukemia.]

Exposure to Chemicals. Exposure to industrial chemicals or certain medications, such as phenytoin (Dilantin), may cause enlarged nodes. In addition, other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash that may resemble Hodgkin's disease.

Diagnosis

The doctor will take a medical history and perform a physical examination. If these simple procedures point to Hodgkin's disease, a number of additional tests may be needed to either rule out other diseases or confirm HD and determine the extent of the cancer.

The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node is sometimes indicative of certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma (including Hodgkin's). Soft nodes suggest infection or inflammatory conditions.

Blood tests are performed to measure white and red blood cells, blood protein levels, the uric acid level, blood proteins, and the liver's function. Another blood test is the erythrocyte sedimentation rate (ESR), which is sometimes elevated in Hodgkin's disease (although it is not specific for this condition).

Click the icon to see an image of the formed elements of blood.

Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area, where Hodgkin's disease usually starts. It a useful step for detection of enlarged lymph nodes.

Click the icon to see an image of an x-ray machine.

Click the icon to see an image of a CT machine.

Positron Emission Tomography (PET). PET scans combined with CT scans can help doctors clarify the location of the cancer. PET scans can also provide information on whether or not an enlarged lymph node is benign or cancerous and are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.

A biopsy of the suspicious lymph node is the most definitive way to diagnose Hodgkin's disease. A biopsy has risks, and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually regress on their own if a temporary infection is causing the enlargement. However, some lymphomas may regress and appear to be benign, only to reappear at a later time.

The Procedure. During a biopsy, the doctor usually removes the node and checks the surrounding areas. The tissue in the node is then examined for signs of infection and blood cell or other abnormalities. Biopsies of bone marrow may also be performed in patients with existing Hodgkin's disease if the doctor suspects that it may have spread to the marrow.

Biologic markers, called biomarkers for short, are high levels of substances that are released by tumors and indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some under investigation include:

CD44 is a molecule that binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
Interleukin (IL) 10 is another immune factor that may indicate a poor outlook when it occurs in high levels.

Outlook

Hodgkin’s disease is considered one of the most curable forms of cancer, especially if it is diagnosed and treated early. Unlike other cancers, Hodgkin's disease is even potentially curable in late stages. About 85% of patients with Hodgkin’s disease survive at least 5 years after cancer treatment. Five-year survival rates for patients diagnosed with stage I or II Hodgkin’s disease are 90 - 95%. Patients who survive 15 years after treatment are more likely to later die from other causes than Hodgkin’s disease.

Survival rates are poorest for:

Those who relapse within a year of treatment
Patients who do not respond to the first-line therapy and have signs of disease progression

The good news about Hodgkin's disease is that treatment can cure the disease. The bad news is that survivors face a higher than average risk for long-term complications of these treatments, some very serious.

Many patients may experience chronic fatigue that could persist for years. One study indicated that aerobic exercise may significantly improve fatigue; in doing so it could have a positive effect on mood as well.

The most serious complications are secondary cancers and heart disease, which occur over the 2 - 3 decades following treatments. Secondary cancers include non-Hodgkin's lymphoma, leukemia, melanoma, stomach and lung cancers, and breast and uterine cancers. Heart disease complications include coronary artery disease, stroke, heart valve problems, and cardiomyopathy (weakening of the heart muscle). Thyroid disorders are also a potential complication. Combinations of radiation and chemotherapies are especially associated with these problems.

A 2006 study in the New England Journal of Medicine evaluated the long-term health status of adult survivors of various childhood cancers. The study found that, 30 years after treatment, patients with Hodgkin’s disease had among the highest risk of developing serious health problems. Female survivors had a significantly greater risk than male survivors. In particular, women who received chest radiation are at very high risk for developing breast cancer. Still, in a 2000 study, 20 years after treatment, 90% of patients who had survived treatments were still living.

Patients with Hodgkin’s disease should get a written record of the treatments they received as children, and the potential risks of these treatments. These records can help the doctors who later oversee their care monitor for potential health problems. Survivors of Hodgkin’s disease should receive regular screening tests for cancer and heart disease. They may need to get these tests at a younger age than most patients. In particular, patients who were treated with chest radiation should get blood tests every 5 years to measure their cholesterol levels. Female patients who received chest radiation should get early and frequent mammograms.

Although HD is highly curable, it can have many psychologic consequences. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Fatigue persists in the majority of patients for years. Still, many survivors have an excellent quality of life.

Staging and Treatment Guidelines

Multiple treatment approaches are available for patients with Hodgkin's disease at nearly every stage, often resulting in similar rates of cure. Ultimately, the choice of treatment is based on a consideration of various prognostic factors as well as treatment side effects, both short and long term. Treatment decisions are individualized, and patients should discuss the pros and cons of various approaches with their doctors.

Staging the disease according to how far the cancer has spread (I through IV) is a primary method for determining both treatment options and prognosis. There are two levels of staging: Clinical staging and pathological staging.

Clinical stages are determined by conducting a thorough examination, which may include blood tests and different kinds of x-rays.
Pathologic staging is conducted after a laparotomy and biopsy of the tissue to help determine treatment options. It involves a much more detailed examination, but is not required as often as in the past for making treatment decisions.

In general, the prognosis according to stage is as follows:

If the disease is treated in stages I or II, the cure rates are as high as 90%. (Slightly more than half of all patients are diagnosed in these stages.)
Patients in stages III or IV are usually diagnosed with advanced Hodgkin's disease. (Even in such stages, survival at 5 years can be as high as 85%.)

The staging system can be further refined according to other features or factors that indicate a more or less severe condition and can help determine whether treatments should be more or less aggressive.

Presence or Absence of B Symptoms. For example, stages I through III are further categorized as either A or B according to whether certain widespread symptoms are absent (A) or present (B). The presence of B symptoms increases the risk of relapse.

The patient is classified as B if they have unexplained weight loss of more than 10% within 6 months, unexplained fever, and drenching night sweats. Fever and weight loss are the most important indications of B symptoms; night sweats alone do not always mean that such symptoms are present. Itching by itself is not considered a reliable B symptom.
If the patient has none of these symptoms, the disease is considered at A, which is less severe than the B form at any stage.
Another letter used to further refine a stage is E, which indicates that the malignancy is still local but has gone beyond the lymph node into surrounding tissue.

Indicators for Aggressive Treatments. Certain factors are indicators of a more serious case at any stage and the need for aggressive treatment:

The malignancy is "bulky" (a large mass)
Blood tests show high levels of erythrocyte sedimentation rates
Multiple tumors in the spleen
Greater involvement in the abdomen

Even if a patient has stage II disease, the presence of a bulky tumor or multiple tumors in the spleen indicates the patient may be treated as if they had advanced Hodgkin's disease.

Cell Types. The cell type of Hodgkin's disease may also influence treatment. For example, those with mixed cellularity type might require more aggressive therapy in certain cases than those with a slower-growing form, such as lymphocyte-predominant Hodgkin's disease (LPHD). In fact, some studies suggest that LPHD is the mildest form of Hodgkin's disease and that patients with LPHD are more likely to die of treatment-related disease than from Hodgkin's itself. Some experts are investigating the role of limiting radiation doses in such patients, although the most optimal approach is not yet known.

Other Prognostic Risk Factors. The International Prognostic Factors Project on Advanced Hodgkin’s Disease has developed seven factors that help determine which patients with advanced Hodgkin's disease would benefit from more or less aggressive chemotherapy. They are also useful to help determine success in patients with relapsed or persistent HD who are undergoing stem cell transplantation. The score is determined by the number of yes answers to the following questions. The more yes answers, the more likely the patient needs to be treated aggressively:

Is the patient male?
Is the patient older than 45?
Does the patient have stage IV disease?
Does the patient have blood tests showing lower than normal albumin levels? (Albumin is a protein found throughout the body.)
Does the patient have abnormally low hemoglobin levels? (Hemoglobin is the oxygen-carrying compound in red blood cells, so low levels suggest anemia.)
Does the patient have an abnormally high white blood cell count (15,000 or more)?
Does the patient have abnormally low levels of lymphocytes?

To avoid putting patients through unnecessary treatments that may actually be as or even more lethal than the disease itself over time, doctors are attempting to identify more specifically those patients who would or would not benefit from aggressive therapy.

Preventing Infection. Both the disease and some of the treatments suppress the immune system, increasing the risk for infections. Widespread, life-threatening infection is a particular danger if the spleen has been removed and both radiation and chemotherapy are administered. A week before any treatment, patients are often vaccinated against three bacteria: pneumococcus, meningococci, and Haemophilus influenza.

Measures for Infertility. People who wish to have children should discuss the possibility for receiving treatments that may lessen the risk for infertility. Examples include the following:

Men with Hodgkin's disease may want to consider sperm freezing and assisted reproductive techniques. One encouraging study on male survivors of childhood Hodgkin's disease, reported that although treatments had reduced their sperm count and quality, the actual genetic material was healthy. Such men, then, would still be good candidates for assisted reproductive techniques.
Women should ask their doctors about the possibility for preserving fertility by taking hormonal drugs called GnRH analogs before and during chemotherapy.

[For more information on fertility preservation treatments, see In-Depth Report #67: Male infertility and In-Depth Report #22: Female infertility.]

Considerations During Pregnancy. Women who are pregnant need special preparation and treatments.

Periodic examination for recurrent Hodgkin's disease is necessary for years after treatment, since relapse is not uncommon, even after treatment for early stages, and can occur a decade or more after treatment. Chest x-rays and CT scans of the abdomen are useful for detecting relapsed disease. Relapse is more likely to occur in early-stage disease, probably because limited radiation normally used in such cases did not destroy all malignancies. Patients who had large tumors in the chest are also at higher risk for recurrence. Patients also need to be monitored for long-term effects of the treatments themselves. Conditions to watch for include inflammation in the lungs and thyroid disease from radiation in the chest and heart disease and cancers from combined treatments, chemotherapy (particularly the use of MOPP), and blood stem cell transplantation.

Because Hodgkin's disease often occurs in young adults, treatment for pregnant women is of particular concern. Therapy must be effective enough to protect the mother without hurting the fetus. Treatment choice must be individualized, taking into consideration the mother's wishes, the severity and pace of the disease, and the length of the remaining pregnancy. The treatment plan may need to be changed as the pregnancy progresses.

Early in the Term. Unfortunately, an abortion may sometimes be the most prudent approach if the disease occurs in the first trimester. Chemotherapy is rarely used during that period, because it poses a risk for birth defects. Deciding on a course of action when Hodgkin's disease occurs in the first trimester is very difficult and emotionally wrenching. Prospective parents should not be shy about consulting with more than one doctor if they are uncertain about how to proceed.

Later in the Term. If the disease develops in the second half of the pregnancy, it may be possible to postpone therapy until after an early induced delivery. Alternatively, some evidence suggests that chemotherapy in pregnant women after the first trimester may be beneficial without harming the fetus. If full-dose standard chemotherapy is not deemed possible, vinblastine alone may be beneficial; this drug is not usually associated with fetal abnormalities in the second half of pregnancy.

Steroids may also be used late in the pregnancy both because of their antitumor effect and their effect in hastening fetal lung maturity. As an alternative, a short course of radiation (with extensive shielding of the fetus) can sometimes be considered prior to delivery if the mother is experiencing lung problems because of a rapidly enlarging mass in the chest. Combination chemotherapy may also be safe in the second half of pregnancy.

In one study, the 20-year survival rate of pregnant women with Hodgkin's disease was no different from that of nonpregnant women matched for similar stage of disease and age at diagnosis.

Treatment Options by Stage

Treatment is guided by the stage of the disease and usually relies on the location and extent of the disease. Treatment may vary within a stage, depending on whether it is categorized as either A or B. (Systemic symptoms are absent in "A" and present in "B.”) The presence of B symptoms increases the risk of relapse, and so may require more aggressive treatments for that stage.

Early Stages (I or II). For disease in stages I or II, the following treatments may be used:

Treatment in Adults. Doctors usually recommend radiation first for adults with HD. It provides excellent remission rates, although studies have reported a number of serious long-term complications in some patients. Selected patients in early stages may also be candidates for radiation limited only to areas above the diaphragm (called the mantle field), which can also have excellent results although still pose a considerable risk for late serious complications.
Treatment in Children. Chemotherapy and low-dose radiation is the standard treatment for most children and adolescents who have not reached full growth. Specific chemotherapy combinations have been developed to reduce the risks for infertility, leukemia, and toxic effects on the heart and lungs. Researchers are studying the use of chemotherapy alone in this group.

Later Stages. For stage III disease, chemotherapy, often with radiation, is a standard treatment. For stage IV disease, chemotherapy alone is generally recommended. The latest chemotherapy regimens are achieving survival rates that reach 90%.

Relapse. Relapse after treatment occurs in 20 - 35% of patients. Treatments for relapse include chemotherapy, radiation, and bone marrow or blood stem cell transplantation. Many patients respond favorably to such treatments, although another relapse is still possible.

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Disease is limited to a single node region (I) or has involved one neighboring area or a single nearby organ (IE). The standard treatment for stage I disease is usually radiation for adult patients who have determined the stage using pathologic staging with laparotomy. Chemotherapy with low-dose radiation is now the standard approach for children and adolescents. Cure rates can be greater than 90%.

Stage IA. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Radiation therapy to the mantle field (chest, neck, and arm pits) and to the lymph nodes in the upper abdomen and spleen
Radiation therapy to a mantle field in certain patients -- best candidates are females with nodular sclerosis or lymphocyte predominant cell types, who are no older than 40 years, have no "B" symptoms, and have erythrocyte sedimentation rate (ESR) levels less than 50
Radiation therapy to a mantle field, the lymph nodes in the upper abdomen, and the spleen (subtotal node irradiation)
Chemotherapy alone is under investigation

If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation. Radiation therapy may be directed to the lymph nodes in the upper abdomen and pelvis, and sometimes the spleen or groin. Total nodal irradiation is an option which includes these regions plus the mantle field.

Stage IB. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Chemotherapy plus radiation therapy to a mantle field (in patients who have severe symptoms and did not undergo laparotomy to determine the extent of the disease below the diaphragm)
Radiation therapy to the mantle field and to the lymph nodes in the upper abdomen is sometimes considered, but relapse rate can be high if significant B symptoms are present
Chemotherapy alone under investigation for children

If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, to the areas that contain cancer, or to the spleen. Total nodal irradiation or radiation to lymph nodes in the upper abdomen and pelvis is another option.

Disease is limited to two or more lymph nodes on the same side of the diaphragm (II) or involvement of a single neighboring organ or area and one or more nearby lymph nodes; other lymph nodes on the same side of the diaphragm may be involved (IIE).

There are few differences between treatments for stage IIA and IIB, and the approach for both depends on the extent and location of the disease:

Non-bulky disease:

Radiation alone for adult and possibly adolescent (especially male) patients
Chemotherapy with low-dose radiation is used for children

For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Radiation therapy to a mantle field and to the lymph nodes in the upper abdomen
Radiation therapy to a mantle field only (See Stage I Hodgkin's Disease section above)

Chemotherapy alone or with radiation therapy (combined modality) is being evaluated for those with non-bulky stage IIA. Also under investigation is radiation therapy to a mantle field only in patients with lymphocyte predominant cell types, who are no older than 40 years.

If the malignancy is above the diaphragm and does involve a large part of the chest, chemotherapy plus radiation therapy to a mantle field is the common approach.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, and possibly the spleen. Total nodal irradiation is another option.

Disease is in lymph nodes on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated organ or site outside the lymph node (IIIE), by involvement of the spleen (IIIS), or by both (IIIE+S). In addition, stage III may be further categorized by the extent of its spread into the spleen or where it has spread in the abdominal area. Survival rates in some cases can be as high as 90%.

Stage IIIA. Chemotherapy is the most common treatment approach for most adults and children. Radiation may be added under certain circumstances, especially to provide localized treatment of bulky areas. (Radiation does not appear to offer any survival advantage for patients whose disease is in complete remission after chemotherapy.)

For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Chemotherapy alone
Chemotherapy with radiation therapy (combined modality)
Total or subtotal nodal radiation therapy alone -- for adults if disease is only in the upper abdomen and fewer than five nodes in the spleen are affected

If the malignancy involves a large part of the chest, the following may be used:

Standard chemotherapy alone
Chemotherapy plus radiation therapy (combined modality)
Investigative treatments

Stage IIIB. Chemotherapy alone is the standard treatment for most adults and children. Radiation is often added to treat areas of bulky tumor.

Disease has spread to organs outside the lymph system, such as liver, lung, or bone marrow. Even in this population, high long-term survival rates of over 85% are possible, including in children.

Treatment may include:

Chemotherapy alone
Chemotherapy with limited radiation to places of bulky disease
A clinical trial of investigational chemotherapy regimens or of stem-cell transplantation

Click the icon to see an image of liver involvement in Hodgkin's disease.

When disease recurs or persists after initial treatment either in the same area or in another part of the body, the next round of therapy depends on where the disease returns and the previous treatment used.

If the previous treatment was radiation therapy without chemotherapy, salvage chemotherapy is the usual choice.
If the patient was previously treated with chemotherapy, the choice may be radiation therapy to the lymph nodes with or without salvage chemotherapy.
In some patients, if the disease has persisted or if relapse has occurred after chemotherapy with or without radiation, high-dose chemotherapy and stem cell transplantation may be given.

Radiation Treatments

High-dose radiation therapy, which shrinks the tumors, has been used for more than 50 years for treating Hodgkin's disease. High-dose radiation is generally reserved for adults. Radiation treatments are highly toxic for children and appear to add little benefit. In such young age groups radiation is mostly used if there are large areas of disease in the chest; otherwise, chemotherapy with possibly low-dose radiation is the best option with excellent survival rates.

Radiation is directed to specific areas depending on the location of the disease:

If HD is above the diaphragm, “extended field radiation” is delivered to the neck, chest, and under arms (called the mantle field). Extended-field radiation is sometimes expanded to include lymph nodes in the upper abdomen.
If cancer is below the diaphragm, an "inverted Y" field is sometimes used, in which radiation is directed at lymph nodes in the upper abdomen, spleen, and pelvis.
Inverted Y-field radiation therapy combined with mantle-field radiation is called “total nodal radiation.”
"Involved field radiation" targets only lymph node regions that are known to have cancer. By contrast, extended-field radiation targets lymph node regions with cancer as well as adjacent, uninvolved lymph node regions. Involved-field radiation is usually given after several rounds of chemotherapy.

A 2006 study indicated that radiation therapy alone, without chemotherapy, may help older patients with early-stage Hodgkin’s disease. If chemotherapy is given, another 2006 study suggested that involved-field is a better option than extended-field radiation for elderly adults with early-stage unfavorable Hodgkin’s lymphoma.

In general, recent research suggests that extended-field radiation adds little survival advantage and carries a greater risk of serious side effects. Involved-field radiation is now becoming the preferred method. Some researchers recommend that involved-field radiation therapy plus chemotherapy should become the standard treatment for patients with early-stage Hodgkin’s disease who have a good prognosis. More research is needed before standard practice guidelines can be implemented.

It is very important that radiation treatments cover the entire diseased area and that the radiation therapy be powerful enough to destroy the malignant cells' capacity to grow and divide. Unfortunately, this means that normal cells are also affected, which can cause serious side effects. Different approaches may be used to prevent complications.

Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.
Long-term complications generally occur at higher radiation doses (over 35 Gy). Investigators are studying the doses as low as 20 Gy (in children). Studies indicate that radiation alone in doses under 35 Gy can control the disease as well as higher doses in most stage I and II patients, although some patients may require more aggressive treatment.
To protect ovaries, a technique called ovarian transposition may sometimes be performed. The procedure uses a laparoscope (a thin tube containing tiny instruments and cameras) that is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Infections. Infections may be a particular problem with radiation combined with chemotherapy. All patients should be vaccinated against pneumonia and influenza.

Inflammation in the Lungs. With carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.

Click the icon to see an image of the lungs.

Infertility. Radiation therapy to the pelvic area can adversely affect later fertility in women and men. Such negative effects may be worse in women; sperm usually recover within 5 years.

Heart Disease and Stroke. Radiation is associated with a future risk of heart disease, which includes atherosclerosis (hardening of the arteries) and diseases of the heart valves. Lower doses pose less risk. Recent research suggests that adults who survived childhood Hodgkin’s disease have a four times higher risk of having a stroke than healthy patients.

Fatigue. Fatigue is significant and chronic in many survivors. It is more highly associated with intensive chemotherapy, but it also may be a late response to radiation treatment.

Secondary Cancers. Second cancers (such as breast, stomach, lung, melanoma) may develop later in areas within or at the edge of the radiation area. Thyroid, respiratory tract, and digestive tract secondary cancers may affect patients who were treated as children. The risks are twice as high with treatments that are combined with chemotherapy.

Lung cancer in survivors is highly associated with smoking after treatment, and no survivor should smoke. The risk for breast cancer increases significantly in young women after treatment, particularly with high radiation doses and combined chemotherapy and radiation. The risk can persist for 25 years or more after radiotherapy, and lifetime monitoring (including frequent mammograms) is essential.

Thyroid Disorders. Hypothyroidism (underactive thyroid) occurs in a number of patients treated with radiation treatments. There is also a 5% chance for hyperthyroidism (overactive thyroid).

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of hyperthyroidism.

Impaired Growth in Children. Children and adolescents are at special risk for impaired bone growth.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. The drugs are called cytotoxic medications. Chemotherapy is referred to as body-wide, or systemic, therapy because the drugs travel throughout the entire body.

Cytotoxic drugs may be taken by mouth or given by injection. Treatment may be administered at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drug can be monitored.

Patients may receive 4 - 8 cycles of chemotherapy, depending on the stage. A cycle is usually 28 days and consists of several doses of drug administration followed by a period of rest.

The standard chemotherapy regimens for Hodgkin’s disease are ABVD and Stanford V.

ABVD consists of a 4-drug combination:

Doxorubicin (Adriamycin)
Bleomycin
Vinblastine
Dacarbazine

Stanford V consists of a 7-drug combination:

Doxorubicin (Adriamycin)
Mechlorethamine (nitrogen mustard)
Vincristine
Vinblastine
Bleomycin
Etoposide
Prednisone

BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is a chemotherapy regimen reserved for high-risk patients. This regimen is proving to be extremely effective, particularly in advanced stages, with studies reporting remission rates of over 95% in patients with advanced Hodgkin's. However, this regimen also increases the risk for developing secondary cancers such as leukemia. Patients who are treated with BEACOPP should receive long-term follow-up care to monitor for side effects from this therapy.

Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment, though some trials suggest that toxicities can be reduced by administering the drugs for shorter duration without loss of cancer-killing effects.

Common Side Effects. Common side effects include the following:

Nausea and vomiting -- drugs known as serotonin antagonists, including ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
Diarrhea
Hair loss
Weight loss
Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days a month.

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used. They include:

Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta) can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to only treat anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
Infection. Patients must take precautions against infections (see "Infection Prevention" in Transplant section).
Liver and kidney damage
Abnormal blood clotting (thrombocytopenia)
Allergic reaction

Long-Term Complications.

Fatigue and general aches and pains are called somatic symptoms. Fatigue is especially common after chemotherapy and can even last for years.
Many women stop menstruating after chemotherapy. The risk for infertility is highest for women with advanced stage Hodgkin’s disease who are treated after age 30. Studies indicate that the risk for infertility is higher with BEACOPP than with ABVD. Researchers are studying whether taking oral contraceptives during chemotherapy can reduce the risk.
Bone thinning (osteoporosis) may be related to steroid treatments such as prednisone.
Heart failure may occur with the use of anthracyclines (such as doxorubicin).
Bleomycin (Blenoxane), an antibiotic, is particularly toxic to the lungs. Vinblastine may also pose a risk when used in combination with radiation therapy.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Regimens. Chemotherapy (usually ABVD) plus radiation, referred to as combined modality, is a common treatment approach for patients with more advanced-stage disease and for those who have early-stage bulky (large mass) disease.

Chemotherapy with low-dose radiation is being used in children with excellent results, even for late stage cancer. In one study, 82% of the children were still disease free at 5 years. Some chemotherapy drugs or high doses of radiation may be more deleterious to a boy's future fertility than to a girl's. A gender-specific combined regimen for pediatric Hodgkin's reduces the amount of radiation given to boys and also substitutes etoposide for procarbazine in the chemotherapy mixture (procarbazine, vincristine, prednisone, and doxorubicin).

Side Effects and Long-Term Complications. Side effects of combination treatments can be very serious. Examples include:

Combined modality poses a higher risk for secondary cancers than the use or radiation or chemotherapy alone. They include breast, lung, thyroid, melanoma, and gastrointestinal cancers, which usually develop in near or in the areas treated with radiation. Of note, the risk for breast cancer is lower when chemotherapies using alkylated drugs or radiation treatments damage the ovaries, suggesting that hormone stimulation plays a role in this higher risk. Newer drugs used in combined modalities may reduce the risk, at least for breast cancer.
ABVD and other regimens containing bleomycin increase the risk for severe effects on the lungs when used before or after mantle-field radiation. EVA (etoposide, vinblastine, and doxorubicin) is considered to be an effective substitute in patients with lung disease for whom bleomycin and radiation present an unacceptable risk.

Transplantation

Patients with relapsed or progressive HD are often treated with high-dose chemotherapy followed by stem cell transplantation procedures. (Transplantation does not appear to offer an advantage compared to standard chemotherapy as initial treatment for patients with high-risk advanced HD.)

This treatment involves removal and replacement of stem cells, which are produced in the bone marrow. This allows the patient to receive high-dose chemotherapy without destroying these important cells. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them.

For Hodgkin’s disease, the most common type of transplant is an autologous procedure, using the patient’s own cells. An allogeneic transplant, using cells from a donor, is more risky for patients with Hodgkin’s disease and is generally used only when an autologous transplant has failed. (This section provides information pertinent to autologous procedures. Detailed information on allogeneic transplants, including such complications as graft-versus-host-disease, can be found in In-Depth Report #84: Non-Hodgkin’s Lymphoma.)

Stem cells must first be collected in one of the following ways:

Directly from blood (peripheral blood stem cell transplantation)
From bone marrow (bone marrow transplantation)

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Stem cells are collected several weeks before the procedure. They are frozen and stored while the patient undergoes high-dose chemotherapy. Some patients receive high-dose whole body radiation therapy along with chemotherapy.

After the patient completes the pre-transplant therapy, the frozen cells are thawed and then infused into the patient. Within a few weeks, these cells start to generate new white blood cells and then new red blood cells.

The risk for infection greatest during the first 6 weeks following the transplant. During this period, a patient usually remains in isolation and receives antibiotics and intravenous nutrition. It takes 6 - 12 months post-transplant for a patient’s immune system to fully recover.

It is very important that patients take precautions to avoid infections. Guidelines for infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about handwashing, and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Common side effects of stem cell transplants include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.

There is a small long-term risk for leukemia after transplantation in young people. Chemotherapy itself increases the risk of secondary cancers. Recent studies suggest that transplantation after chemotherapy does not add any additional risks. In addition, use of newer chemotherapeutic drugs may not pose as high a danger as older treatments.

Other serious potential complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)

Immunotherapy

Investigational approaches to Hodgkin's disease include immunotherapies, which are drugs that take advantage of the patients' own immune factors to attack the disease.

One important approach uses genetically designed immune factors called monoclonal antibodies (MAb) that recognize and attack specific molecules found on the surface of cells associated with HD.

Rituximab (Rituxan) was the first monoclonal antibody to be approved for any cancer. It is an unconjugated MAb that targets the CD-20 antigen, which is found on most B-cell lymphomas and normal mature B cells (although not stem cells). It is used in non-Hodgkin's lymphomas, but it may have benefits for some patients with Hodgkin's disease as well.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.lymphoma.org -- Lymphoma Research Foundation
www.leukemia.org -- Leukemia and Lymphoma Society
www.canceradvocacy.org -- National Coalition for Cancer Survivorship
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.marrow.org -- National Marrow Donor Program
www.oncolink.org -- Cancer information
www.lymphomainfo.net -- Lymphoma Information Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hodgkin Disease / Lymphoma. V.1.2007.

A.D.A.M. Copyright

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Don't Let the Freshman 15 Sneak Up On You

FitSugar — Mon, 08 Sep 2008 12:00:00 -0700

Starting your first year of college is so awesome because you can do whatever you want and there's nobody around to tell you not to. You can eat candy for dinner, order a pizza at 2 a.m., and avoid all vegetable matter for three months straight. And though it's technically against the rules, most freshmen also end up drinking a lot of beer. It doesn't take long for a lifestyle of college eating to turn into the dreaded Freshman 15. Here are some things to keep in mind as you delve into your first year on campus.

Just because you can eat whatever and whenever you want - don't. Try to be sensible when it comes to food choices and how often you eat. Try to remember not to eat when you're not hungry, especially late at night. Don't let others influence your decisions either or be a victim of peer pressure when it comes to food. If you just ate dinner, don't let someone talk you into going out for Chinese.
Be wary of dining halls. These endless buffets allow you to consume well beyond your daily caloric needs in a single sitting. I know there are a ton of choices and that the soft serve machine is on all the time, but try to remember how much you used to eat at meals. Don't keep going back for more just because it's there.
Don't use food to deal with stress. If college life is getting the best of you, then exercise, take a long shower, or talk to someone about it. And I don't mean your friends Ben & Jerry.

To find out what else can help read more.

Choose healthy snacks to nosh on during late-night studying. Or better yet, instead of having a bag of snacks open all the time, take snack breaks. That way you can refuel and give your brain a break too.
Don't keep food in your room or in your desk drawer. If you can see it, you'll probably end up eating it, even if you're full.
Walk or ride your bike to class and around campus instead of taking advantage of campus transportation.
Join the campus gym. As a student, I bet your school has a superb gym complete with cardio machines, weights, classes, a track, and maybe even a pool. Make gym dates with you girlfriends, so you can help each other maintain a healthy weight. If you're not into the gym, take a fitness class for credit, or find some other way to stay active. Regular exercise will not only keep those extra pounds from settling around your middle, but it'll also strengthen your immune system.

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