Non-Hodgkin’s
Lymphoma
Treatment Guidelines for Patients
Version II/ December 2004
The goal of the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) partnership is to provide patients and the general public with state-of-the-art cancer treatment information in an easy to understand language. This information, based on the NCCN’s Clinical Practice Guidelines, is meant to assist you in a discussion with your doctor. It is not intended to replace the expertise and judgment of your doctor.
Non-Hodgkin’s
Lymphoma
Treatment Guidelines for Patients
NCCN Clinical Practice Guidelines, the professional versions, were developed by a diverse panel of experts. The guidelines are a statement of consensus of its authors regarding the scientific evidence and their views of currently accepted approaches to treatment. These guidelines are updated as new significant data become available. The Patient Information version will be updated accordingly and will be available on-line through the NCCN and the American Cancer Society Web sites. To ensure you have the most recent version, you may contact the American Cancer Society at 1-800-ACS-2345 or the NCCN at 1-888-909-NCCN. ©2005 by the American Cancer Society (ACS) and the National Comprehensive Cancer Network. All rights reserved. The information herein may not be reprinted in any form for commercial purposes without the expressed written permission of the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.
Contents
Introduction . . . .5
Making Decisions About Non-Hodgkin’s Lymphoma Treatment . . . .5
What Is Non-Hodgkin’s Lymphoma? . . . .6
Types of Non-Hodgkin’s Lymphoma . . . .8
How Is Non-Hodgkin’s Lymphoma Diagnosed? . . . .11
Non-Hodgkin’s Lymphoma Stages . . . .15
Types of Treatment for Non-Hodgkin’s Lymphoma . . . .16
Other Things to Consider During and After Treatment . . . .22
Clinical Trials . . . .23
Treatment Guidelines . . . .25
Decision Trees Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) . . . .26
Follicular Lymphoma (Small or Mixed Cell) . . . .32
Gastric MALT Lymphoma . . . .40
Nongastric MALT Lymphoma/Marginal Zone Lymphoma . . . .46
Mantle Cell Lymphoma . . . .48
Diffuse Large B-Cell Lymphoma . . . .52
Burkitt’s Lymphoma . . . .62
Lymphoblastic Lymphoma . . . .66
AIDS-Related B-Cell Lymphoma . . . .70
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University
City of Hope Cancer Center
Dana-Farber/Partners CancerCare Duke Comprehensive Cancer Center Fox Chase Cancer Center
Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance
H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida
Huntsman Cancer Institute at the University of Utah The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Memorial Sloan-Kettering Cancer Center Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Roswell Park Cancer Institute
St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute
Stanford Hospital and Clinics
UCSF Comprehensive Cancer Center
University of Alabama at Birmingham Comprehensive Cancer Center
University of Michigan Comprehensive Cancer Center The University of Texas M. D. Anderson Cancer Center UNMC/Eppley Cancer Center at the Nebraska Medical Center
Introduction
With this booklet, patients have access to information on the way non-Hodgkin’s lymphoma is treated at the nation’s leading cancer centers. Originally developed for cancer specialists by the National Comprehensive Cancer Network (NCCN), these treatment guidelines have now been translated for the public by the American Cancer Society (ACS).
Since 1995, doctors have looked to the NCCN for guidance on the highest quality, most effective advice on treating cancer. For more than 85 years, the public has relied on the American Cancer Society for information about cancer. The Society’s books and brochures provide reliable cancer informa-tion to hundreds of thousands of patients, their families, and friends. This collaboration between the NCCN and ACS provides an authoritative and understandable source of cancer treatment information for the public.
These patient guidelines will help you better understand your cancer treatment and your doctor’s advice. We urge you to discuss them with your doctor. To make the best possible use of this information, you might ask your doctor the following questions:
• What type of non-Hodgkin’s lymphoma do I have?
• What stage is it?
• Is it a fast growing lymphoma?
• How do the stage and type of lymphoma affect my outlook for cure?
• What are my treatment options?
• What are the risks or side effects associated with each treatment and how will they affect my quality of life?
• What can I do to prepare myself for treatment, reduce side effects, and hasten my recovery?
• When will I be able to return to my normal activities?
Making Decisions About
Non-Hodgkin’s Lymphoma
Treatment
In the United States, about 54,370 people (28,850 men and 25,520 women) will be diag-nosed with non-Hodgkin’s lymphoma this year. These figures include both adults and children. It is the fifth most common cancer in the United States, excluding nonmelanoma skin cancers.
Although some types of non-Hodgkin’s lymphoma are among the most common childhood cancers, over 95% of non-Hodgkin’s lymphoma cases occur in adults. The average age at diagnosis is in the 60s. The risk of developing most types of non-Hodgkin’s lymphoma increases throughout life, and the elderly have the highest risk.
Although non-Hodgkin’s lymphoma is a serious disease, it can be treated and, in some cases, cured. Care should be provided by a team of health care professionals who are experienced in treating non-Hodgkin’s lym-phoma. This team may include a surgeon, medical oncologist, radiation oncologist,
pathologist, oncology nurse, radiologist, and social worker often along with your primary care doctor.
This information is written to help you understand your options for treatment of non-Hodgkin’s lymphoma so that you and your cancer care team can work together to decide which treatment best meet your needs. On the following pages you’ll find flow-charts that doctors call ”decision trees.” The charts represent the most common types of non-Hodgkin’s lymphoma, and each one shows how you and your doctor can arrive at the choices you need to make about your treatment. There are other types of non-Hodgkin’s lymphoma. They are discussed along with treatment on the ACS Website at www.cancer.org.
To reach an informed decision, you will need to understand some of the medical terms that your doctors use. You will find information on what is non-Hodgkin’s lym-phoma, the different types of non-Hodgkin’s lymphoma, how lymphoma is diagnosed, staging, and treatment. We’ve also provided a glossary of medical terms.
What Is Non-Hodgkin’s
Lymphoma?
Non-Hodgkin’s lymphoma is cancer that starts in lymphoid tissue (also called lym-phatic tissue). Lymphoid tissue is the main part of the immune system. It is formed by several different types of cells that work together to fight infections. These cells also react to foreign tissue (such as a transplanted
organ). Most of the time they are found in bean shaped organs called lymph nodes.
Other types of cancer can develop in other organs and then spread to lymphoid tissue. But these cancers are not lymphomas. For example, cancer that develops in the lungs and then spreads to the lymph nodes is still called lung cancer. Lymphomas start from lymphocytes in either lymph nodes or other sites of lymphoid tissue such as the bone marrow and can spread from there.
There are 2 main types of lymphomas. Hodgkin’s lymphoma (or Hodgkin’s disease) is named after Dr. Thomas Hodgkin, who first described it. All other types of lymphoma are called Hodgkin’s lymphoma. The non-Hodgkin’s lymphomas are very different from Hodgkin’s disease in how they develop and spread and in how they are treated. The information here refers only to the different types of non-Hodgkin’s lymphoma. Each type varies in how it is treated and how it responds to treatment.
Lymphoid Tissue
The main cell type found in lymphoid tissue is the lymphocyte. The 2 main types of lymphocytes are B lymphocytes (or B cells) and T lymphocytes (or T cells). Although both types can develop into lymphomas, B-cell lymphomas are more common. B-cell lym-phomas account for 85% of cases of non-Hodgkin’s lymphoma; T-cell lymphomas make up the other 15%.
Normal T cells and B cells do different jobs within the immune system. B cells help protect the body against bacteria by produc-ing immunoglobulins (also called antibodies).
The antibodies attach to certain substances on the surface of bacteria and attract certain immune system cells that kill the antibody-coated bacteria.
T cells help protect the body against viruses, fungi, and some bacteria. They recognize specific substances found in virus-infected cells and destroy these cells. T cells can also release substances called cytokinesthat attract certain other types of white blood cells, which then digest the infected cells. T cells are also thought to destroy some types of cancer cells, as well as the cells of transplanted organs. Some types of T cells play a role in helping or blocking the work of other immune system cells.
There are several types of T cells, each with a special job, and there are also several stages of B-cell and T-cell development. Each type of lymphoma tends to look like one of the normal lymphocytes at a certain level of development.
This information is helpful because know-ing the type of lymphoma a person has is the first step in considering treatment options. So, learning about lymphocytes is the first step in understanding lymphomas, their diagnosis, and their treatment.
Organs That Contain
Lymphoid Tissue
Lymph nodesare small, bean-shaped organs found throughout the body and connected by a system of lymphatic vessels. These vessels are like veins, except that instead of carrying blood, they carry lymph (a clear fluid containing waste products and excess fluid from tissues). They also carry immune system cells traveling to lymph nodes from other tissues.
Lymph nodes increase in size when they fight an infection. Lymph nodes that grow in reaction to infection are called reactive nodes (or hyperplastic nodes) and are often tender to the touch. An enlarged lymph node is not usually serious. People with sore throats or colds often have enlarged lymph nodes in the neck. But a large lymph node is also the most common sign of lymphoma.
The spleenis found under the lower part of the rib cage, on the left side of the body. An average adult spleen weighs about 5 ounces. The spleen contains lymphocytes and other immune system cells to help fight infection. It stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste. The thymus glandis located in the front of the chest at the base of the neck. While a fetus is growing in the mother’s uterus, the thymus plays a vital role in producing T lymphocytes. The thymus gland’s size (about 1 ounce) and activity peak between 1 and 20 years of age. Although its size and role decline with age, the thymus continues to function throughout life as part of the immune system.
Adenoids and tonsils are collections of lymphoid tissue located at the back of the throat. They produce antibodies against germs that are breathed in or swallowed. They are easy to see when they become enlarged dur-ing an infection or if they become cancerous. The stomach and intestinal tract also contain lymphatic tissue.
The bone marrow(the soft inner part of bones) produces red blood cells, blood platelets, and white blood cells, including lymphocytes. Red blood cells carry oxygen from the lungs to the rest of the body.
caused by cuts or scrapes. The main job of white blood cells is fighting infections. In addition to lymphocytes, the other main type of white blood cells is the neutrophil (also known as granulocytes, or “polys”).
Types of Non-Hodgkin’s
Lymphoma
Because there are so many types of non-Hodgkin’s lymphoma, several different systems have been developed to classify this disease. Most doctors now use the REAL/WHO classi-fication (Revised European-American Lymphoma/World Health Organization). The REAL/WHO system sorts the types of lym-phoma by the appearance of the lymlym-phoma cells, presence of proteins on the surface of the cells, and genetic features. Although there are many kinds of lymphomas, only the most common types are discussed below.
To simplify discussion of non-Hodgkin’s lymphomas, the many specific types are some-times grouped together into slow growing (or indolent), aggressive, or highly aggressive categories (see Table 1). Aggressive and highly aggressive lymphomas grow more rapidly and spread through the body quickly. Without treatment, most patients live only a short time. Fortunately, most aggressive and highly aggressive lymphomas respond well to chemotherapy, and many can be cured.
Table 1. Lymphoma Types (based on how they grow)
Slow-growing • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Follicular Lymphoma • MALT Lymphoma Aggressive • Diffuse Large B Cell
Lymphoma
• Mantle Cell Lymphoma* Highly Aggressive • Burkitt’s Lymphoma
• Lymphoblastic Lymphoma • AIDS-Related Lymphoma
* Although mantle cell lymphoma is not very fast growing, it responds poorly to standard treatment
B-Cell Lymphomas
Chronic lymphocytic leukemia/small lymphocytic lymphoma: Although one disease is a leukemia and one is a lymphoma, these two diseases are related and account for 7% of all lymphomas. In both kinds, the same type of cell, the small lymphocyte, is involved. The only difference is in where the cancer occurs. It is mostly in the blood in leukemia, and it is mainly in the lymph nodes in lymphoma. Both are slow-growing diseases although leukemia, which is much more common, tends to be slower. They are not considered curable with standard treat-ments. But depending on the stage and growth rate of the disease, patients can live well over 10 years with this lymphoma.
Recently it has become clear that there are 2 kinds of chronic lymphocytic leukemia. One is very slow growing and rarely needs treatment. The other kind grows faster and almost always needs to be treated. Doctors can tell them apart by testing for a substance
called ZAP-70 in the leukemia cells. This is a new test that is not available everywhere. Cells that contain this substance are usually the faster growing kind. Sometimes, these slow-growing lymphomas can change (trans-form) over time into a more aggressive type of lymphoma.
Follicular lymphoma: About 22% of all lymphomas are follicular lymphomas. These cells tend to grow in a nodular pattern similar to the normal patterns in lymph nodes. This is a slow growing lymphoma. It mostly arises in many lymph node sites in the body, as well as in the bone marrow. The average age for people with this lymphoma is 60. It is rare in very young people. In advanced stages it is not considered curable by standard treatment. The percentage of patients who live at least 5 years after their cancer is diagnosed is about 60% to 70%. In time, many follicular lym-phomas transform into a fast growing diffuse large B-cell lymphoma.
Extranodal marginal zone B-cell lym-phomas - mucosa-associated lymphoid tissue (MALT) lymphomas:This type makes up 8% of lymphomas. Most MALT lymphomas start in the stomach. They are thought to stem from an infection by bacteria called Helicobacter pylori. This lymphoma can also develop in other sites like lung, skin, thyroid, salivary gland, small or large intestine, breast, and tissues surrounding the eye. In those cases, the cancer is called nongastric MALT lymphoma. Usually MALT lymphomas are confined to the area where they began and are not widespread. The average age for patients with this lym-phoma is 60. It is a slow-growing lymlym-phoma and often can be put into prolonged remission and possibly cured in its early stages.
Mantle cell lymphoma: About 6% of lymphomas are this type. When diagnosed, it is usually widespread and will involve lymph nodes, bone marrow, and, very often, the spleen. Men are most often affected; the average age of patients is in the early 60s. Although this is not a very fast growing lymphoma, it is a serious one. Only 20% of patients survive at least 5 years.
Diffuse large B-cell lymphoma: This kind makes up 31% of all lymphomas. It is a fast-growing lymphoma. The usual symptoms are a rapidly growing mass in the body or in a lymph node that can be felt. About one-third of these lymphomas are confined to one part of the body (localized). Although this lymphoma usually starts in lymph nodes, it can grow in other areas such as the intestines, bone, and the brain or spinal cord. When it is localized this type of lymphoma is considered to be more curable than when it has spread to other parts of the body. It can affect any age group but mostly occurs in older people. The average age of patients is the mid-60s. About 40% to 50% of people with this lymphoma are cured with treatment.
Burkitt’s lymphoma:This type makes up about 2% of all lymphomas. It is named after the doctor who first described this disease in African children and young adults. Another kind of lymphoma called Burkitt’s-like lym-phoma looks like Burkitt’s lymlym-phoma but the cells are slightly larger. Because they are hard to tell apart, the REAL/WHO classification combines them. In the African type, it often starts as tumors of the jaws or other facial bones. In the more common types seen in the United States, the lymphoma usually starts in the abdomen, where it forms a large tumor
mass. It can also spread to the brain and spinal fluid. The average age of patients is about 30, and close to 90% of patients are male. Although this is a fast-growing lymphoma, about half of patients are cured by aggressive chemotherapy.
AIDS-related B-cell lymphoma: The major types of non-Hodgkin’s lymphoma seen in people with AIDS are diffuse large B-cell lymphoma, Burkitt’s lymphoma, and primary central nervous system lymphoma. The first two are discussed above. The main difference in treating these lymphomas in people with AIDS is that often their outcome depends on how well the AIDS is responding to treatment. Also, these patients are very sensitive to the side effects of chemotherapy, especially the effect on blood counts. This is becoming less of a problem because of advances in treating the HIV infection that causes AIDS. Also, the number of people developing these lym-phomas has decreased in the last few years because of the improved HIV treatment.
Primary central nervous system lym-phoma:This lymphoma usually involves the brain (then called primary brain lymphoma), but it also can be found in the spinal cord and in tissues around the spinal cord and inside the eye. In time, it spreads throughout the central nervous system. In the past, this was a rare tumor, but it has become more common with the AIDS epidemic. Most people develop headache and confusion. They can also have vision problems and, rarely, paralysis. The outlook for people with this condition is poor. About 30% of people can live 5 years with modern treatments.
T-Cell Lymphomas
Anaplastic large T/null-cell lymphoma:
About 2% of lymphomas are this kind. The cells are large. It is more common in young people. It usually starts in lymph nodes and can also spread to skin. There is one form that begins in the skin. Although this type of lymphoma appears to be fast growing, treat-ment with chemotherapy or radiotherapy is often successful, especially if the tumor cells contain a protein called ALK-1. Many patients with this lymphoma are cured. It is generally treated like a diffuse large B-cell lymphoma.
Peripheral T-cell lymphomas:There are several kinds of peripheral T-cell lymphomas, which, in total, account for about 7% of all lymphomas. They are mostly treated like dif-fuse large B-cell lymphomas. There are a variety of rare subtypes of these lymphomas which include:
• Histology unspecified: Extranodal natural killer/T-cell lymphoma, nasal type which often involves the upper airway passages, such as the nose and nasopharynx, but also invades the skin and gastrointestinal tract.
• Enteropathy type T-cell lymphoma which can occur in people who are sensitive to gluten, the main protein in wheat flour.
• Subcutaneous panniculitis-like T-cell lymphoma which invades the deepest layers of the skin and causes nodules to form under the skin.
Lymphoblastic lymphoma/leukemia:
This type can be either B cell or T cell. This disease can be considered either a lymphoma or leukemia, depending on whether more
(leukemia) or less (lymphoma) than 25% of bone marrow cells are lymphoma cells. Usually the lymphoma forms in the mediastinum(the area in front of the heart and behind the chest bone). About 2% of all lymphomas fall into this group. Patients are most often (75%) men, and their average age is 25. The cell is small to middle-sized. The lymphoma is fast growing, but if it hasn’t spread to the bone marrow when first diagnosed, the chance of cure with chemotherapy is quite good.
How Is Non-Hodgkin’s
Lymphoma Diagnosed?
Signs and Symptoms
Non-Hodgkin’s lymphoma may cause many different signs and symptoms, depending on where it develops in the body.
Non-Hodgkin’s lymphoma can lead to easily seen or felt lymph nodes close to the surface of the body (such as lymph nodes on the sides of the neck, in the groin or underarm areas, or above the collar bone). These enlarged nodes are usually noticed by the patient, a family member, or a health care professional. When lymphoid tissue in the abdomen is involved, the abdomen can become swollen. This may be due to large collections of fluid or a tumor. When lymphoma causes swelling of lymphoid tissue near the intestines, passage of feces through the compressed area may be blocked. The pressure or blockage can also cause discomfort or abdominal pain.
When lymphoma starts in the thymus or lymph nodes in the chest, irritation or com-pression of the nearby windpipe (trachea) can cause coughing or trouble breathing. The large
vein that carries blood from the head and arms back to the heart (called the superior vena cava) passes near the thymus and lymph nodes inside the chest. Growth of lymphoma may compress this vein. This causes swelling of the head and arms, known as SVC syndrome, which can be life threatening. Patients with SVC syndrome need to be treated as soon as possible.
Lymphomas of the stomach often cause pain in the stomach, nausea, and reduced appetite. Primary central nervous system lymphomas cause headache, trouble think-ing and movthink-ing parts of the body, personality changes, and, sometimes, epileptic seizures.
In addition to symptoms and signs caused by local effects of cancer growth, non-Hodgkin’s lymphoma can produce rather vague symp-toms, such as unexplained weight loss, fever, profuse sweating (enough to soak clothing) particularly at night, or severe itchiness. Doctors sometimes call these “B symptoms.” The presence of B symptoms is associated with a worse outlook.
The diagnosis of lymphoma may be delayed or difficult because enlarged lymph nodes are more commonly caused by infections than by non-Hodgkin’s lymphoma. Doctors often wait to see if swollen nodes change in size without or with antibiotic treatment. If the node continues to grow, either a small piece of the node or, more commonly, the entire node should be removed for examination under the microscope (biopsy) and by other laboratory tests. A biopsy may be needed right away if the node is hard or large or if its location or other symptoms strongly suggests lymphoma is present.
Medical History and
Physical Examination
The first step in making a diagnosis is for your doctor to take your medical history, which includes questions about symptoms and risk factors. The doctor will perform a thorough physical examination, especially checking lymph nodes, the adenoid and tonsil areas, the spleen, and other internal organs. The doctor will also ask about weight loss, fever, and night sweats, as well other questions about your health.
If signs or symptoms suggest that you might have non-Hodgkin’s lymphoma, more examinations and tests will be done to be certain that this disease is present and, if so, to determine the exact type of non-Hodgkin’s lymphoma.
Biopsies
A biopsy is the only way to diagnose non-Hodgkin’s lymphoma. There are several biopsy procedures, and the doctor’s choice is based on each patient’s unique situation.
Excisional or incisional biopsy:A surgeon cuts through the skin to remove the entire node (excisional biopsy) or a small part of a large tumor (incisional biopsy or core needle biopsy). If the node is near the skin surface, this is a simple operation that can be done with local anesthesia (numbing medicine). But if the node is inside the chest or abdomen, general anesthesia is used (the patient is asleep). This method almost always provides enough tissue to diagnose the exact type of non-Hodgkin’s lymphoma; it is preferred if it can be done without too much discomfort for the patient.
Fine needle aspiration (FNA) biopsy:
FNA uses a very thin needle and a syringe to withdraw a small amount of tissue from the tumor mass. The doctor can aim the needle while feeling an enlarged node near the sur-face of the body. If the tumor is deep inside the body, the doctor can guide the needle while viewing a computed tomography (CT) scan (see discussion of imaging tests later in this section). It is especially useful for finding out whether there is lymphoma in a lymph node of a patient who already has been diagnosed. The main advantage of FNA is that it does not require surgery. The disadvantage is that in some cases the thin needle cannot remove enough tissue for a definite diagnosis of non-Hodgkin’s lymphoma. It is not recommended to make the first diagnosis of lymphoma. However, advances in performing lab tests (discussed later in this section) and the grow-ing experience of many doctors with FNA have improved the accuracy of this procedure. FNA is also very useful in diagnosing other cancers that spread to lymph nodes.
Bone marrow aspiration and biopsy:In bone marrow aspiration, a needle and syringe are used to remove small amounts of bone marrow. For a bone marrow biopsy, a larger needle is used to remove a cylinder of bone and marrow, about 1⁄
16inch across and 1 inch long. Both samples are usually taken from marrow at the back of the hip after the area has been numbed with local anesthesia. These tests can be used for the initial diagnosis and for see-ing how far the cancer has spread (stagsee-ing).
Lumbar puncture: In some instances when involvement of the central nervous sys-tem (brain and spinal cord) is suspected, a
thin needle is inserted into the spinal cavity in the lower back (below the level of the spinal cord) to withdraw some cerebrospinal fluid, which is examined for lymphoma cells. This test is often called a “spinal tap.”
Laboratory Tests
All biopsy specimens are examined under a microscope by a doctor with special training in recognizing cells from blood and lymphoid tis-sue diseases. The doctor, a pathologist, looks at the size and shape of the cells and how the cells are arranged in the lymph node. Pathologists who specialize in diagnosing lymphoma can often tell best which type of lymphoma a patient has. In addition to pathology, special laboratory tests like immunohistochemistry and flow cytometry are needed to accurately diagnose the type of non-Hodgkin’s lymphoma.
To simplify discussion of non-Hodgkin’s lymphomas, the many specific types are sometimes grouped together into low-grade, intermediate-grade, or high-grade categories. High-grade lymphomas grow more rapidly and spread through the body quickly. Without treatment, most patients live only a short time. The term “aggressive” is often used to describe intermediate and high-grade lymphomas. Most high-grade lymphomas respond well to chemotherapy, and many can be cured.
Immunohistochemistry: In this test, a part of the biopsy sample is treated with special laboratory antibodies. The cells are treated so that certain types of them change color. The color change can be seen under a microscope. This test may be helpful in identifying different
types of non-Hodgkin’s lymphoma from one another and from other diseases.
Flow cytometry:The cells being examined by this test are treated with special laboratory antibodies and passed in front of a laser beam. Each antibody sticks only to cells with certain types of molecules on their surface. If the cells contain those molecules, the laser will cause them to give off light of a different color, which is measured and analyzed by a computer. This test can help determine whether lymph node swelling is due to non-Hodgkin’s lymphoma, some other cancer, or some other disease. It has become very useful in helping doctors determine the exact type of non-Hodgkin’s lymphoma so that they can choose the right treatment.
Cytogenetics: This technique uses a microscope to examine cells to see if part of one chromosome is abnormally attached to part of a different chromosome (translocation), as happens in certain types of lymphoma. Normal human cells each contain 46 chro-mosomes (giant DNA molecules that control the cells’ growth and metabolism). In addition to translocations, some lymphoma cells may have too many chromosomes.
Molecular genetic studies:Tests of lym-phoma cell DNA can also detect transloca-tions that are not visible under a microscope in cytogenetic tests. And DNA tests can also find some translocations involving parts of chromosomes too small to be seen under a microscope. In the future, as we learn more about lymphomas, this may become the most useful test for determining what kind of lymphoma is present.
Imaging Tests
Imaging testsare used to find tumors inside the body. These tests are an important part of staging.
Chest x-ray:An x-ray is done to look for enlarged lymph nodes inside the chest. It can also detect fluid and any tumors in the lungs.
Ultrasound:Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. A small microphone-like instrument called a transducer emits sound waves. These high-frequency sound waves are transmitted into the area of the body being studied and echoed back. The sound wave echoes are picked up by the transducer and converted by a computer into an image that is displayed on a computer screen. This test uses no radiation, which is why it is often used to look at developing fetuses. To have an ultrasound examination, you simply lie on a table and a technician moves the transducer over the part of your body being examined. Usually, the skin is first lubricated with oil. Sometimes an ultrasound can be used to find masses in the abdomen.
Computed tomography (CT):The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, as does a conventional x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine will create multiple images of the part of your body that is being studied. A CT scan is useful for looking at lymphoma in the abdomen, pelvis, chest, head, and neck. Often after the first set of pictures is taken, you will get an intravenous injection of a “dye,” or contrast agent, that helps better
outline structures in your body. A second set of pictures is then taken.
A special kind of CT, the spiral CT, uses a rapid scanner that diminishes organ move-ment from the patient taking breaths and can provide greater detail.
CT scans can also be used to precisely guide a biopsy needle into an enlarged lymph node. For this procedure, called a CT-guided needle biopsy, the patient remains on the CT scanning table while a radiologist advances a biopsy needle toward the mass. CT scans are repeated until the doctors are sure that the needle is within the mass. A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about 1⁄2inch long and less than 1⁄8inch in diameter) is removed and examined under a microscope.
Magnetic resonance imaging (MRI):
MRI scans use radio waves and strong mag-nets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. A contrast material might be injected just as with CT scans but is used less often. MRI scans are helpful in examining the brain and spinal cord.
Positron emission tomography (PET):
PET uses glucose (a form of sugar) that con-tains a radioactive atom. A special camera can detect the radioactivity. Cancer cells absorb high amounts of the radioactive sugar because of their high rate of metabolism. PET is used to look for lymphoma throughout your body. A PET scan can be more helpful than several
different x-rays because it scans your whole body. It may also tell if an enlarged lymph node contains lymphoma or is noncancerous (benign). PET is also used after treatment to help decide if an enlarged lymph node still contains lymphoma or is merely scar tissue. Although this test is relatively new, it is becoming widely used to examine people with lymphomas.
Gallium scan: The radiologist injects radioactive gallium into a vein. It is attracted to areas of lymphoma in the body. A special camera can detect the radioactivity, showing the location of the radioactive gallium. These tests can find tumors that might be non-Hodgkin’s lymphoma in bones and other organs. The gallium scan will not detect most slow-growing lymphomas but will recognize aggressive lymphomas.
Bone scan: A different radioactive sub-stance is used for bone scans. After it is injected, it travels to areas of the bone that are damaged. If there is lymphoma in bone, it often causes bone damage, and a bone scan will find it. But a bone scan will also pick up noncancerous problems, such as arthritis and fractures. It is not generally used in the early staging process for non-Hodgkin’s lymphoma.
Other tests
Endoscopy:This procedure uses a very flex-ible lighted tube with a video camera on the end. The camera is connected to a television set, allowing the doctor to clearly see any masses in the lining of the digestive organs. If something that shouldn’t be there is seen, small pieces of tissue can be removed through the endoscope (biopsy). The tissue
can be examined under the microscope to determine if cancer is present and what kind of cancer it is. For upper endoscopy, the tube is passed down through the mouth to view the esophagus, stomach, and first part of the small bowel.
Non-Hodgkin’s
Lymphoma Stages
Staging is a process of finding out how far a cancer has spread. Once non-Hodgkin’s lym-phoma is diagnosed, tests are done to deter-mine the stage of the disease (extent of spread). The treatment and prognosis (outlook) for a patient with non-Hodgkin’s lymphoma depend on the exact type and the stage of the lymphoma.
Tests used to gather information for stag-ing often include:
• physical examination
• blood tests
• bone marrow aspiration and biopsy
• a lumbar puncture (spinal tap) (this is not always done)
• imaging tests, including a chest x-ray, chest/abdomen/pelvis CT or MRI scan, and PET scan and/or gallium scan. The staging system most often used to describe the spread of non-Hodgkin’s lym-phoma in adults is called the Ann Arbor staging system. The stages are represented by Roman numerals I through IV. The letter “B” is added (stage IIIB, for example) if B symptoms (unexplained weight loss, soaking sweats, high fever,) are present. For patients without these symptoms, the letter “A” is added to their
stage. Lymphomas that grow into organs from lymph nodes have “E” added to their stage ( for example, stage IIE).
• Stage I:The lymphoma is in a lymph node or nodes in only one region, such as the neck, groin, or underarm.
• Stage II:The lymphoma is in two groups of lymph nodes, and these are on the same side of the diaphragm(the breathing muscle that aids breathing and separates the chest and abdomen). For example, this might include nodes in the underarm and neck area, but not the combination of underarm and groin nodes.
• Stage III:The lymphoma is only in lymph nodes but on both sides of the diaphragm.
• Stage IV:The lymphoma is widespread in an organ or organs, skin, or bone marrow.
International Prognostic Index
This index was developed to help predict the outcome of people with large cell lymphoma. The index depends on 5 factors. In the list below, the unfavorable prognostic factor is in bold type.
• age (below or above 60)
• stage (I and II vs. III and IV)
• absence or presence of lymphoma outside of lymph nodes
• performance status(able to function normally or needing lots of help with daily activities)
• serum LDH(a protein found in the blood that goes up in the presence of fast-growing tumors — the index looks for whether the LDH is normal or elevated)
For each unfavorable prognostic factor, 1 point is assigned. The index divides people with lymphomas into 4 categories. The low category (0 or 1 point) means that the person with lymphoma has mostly good factors (is young, has stage I disease, is able to work, and so on). The highest category (4 or 5 points) means mostly or all unfavorable factors (high stage, high LDH, can’t get out of bed, and so on). No matter what the type of lymphoma, more than 75% of people in the lowest group will live longer than 5 years, whereas only 30% of people in the highest group live 5 years.
The prognostic index lets a doctor plan treatment better than he or she could from just the pathology report and staging information. This has become more important as new, more effective treatments — but sometimes with more side effects — have been developed. The index tells us whether these treatments are needed.
Types of Treatment for
Non-Hodgkin’s Lymphoma
In recent years, much progress has been made in treating non-Hodgkin’s lymphoma.The treatment options depend on the type of lymphoma and its stage, as well as the prognostic index. Of course, no 2 patients are exactly alike, and standard treatment options are often tailored to each patient’s unique situation.
It is important to know and understand all treatment options. It is often a good idea to seek a second opinion. This can give you more information and help you feel more confident about the treatment plan that is chosen.
Surgery
Surgery is often used to get a tissue sample to diagnose and classify lymphoma, but it is very rarely used as treatment because lymphoma is considered a systemic disease, involving the lymphatic system that circulates lymphatic fluid throughout the body. However, surgery is sometimes used to treat lymphomas that start in certain extranodal organs, such as the thyroid or stomach, and have not spread beyond these organs.
Radiation Therapy
Radiation therapy uses high-energy rays to kill cancer cells. Radiation focused on a cancer from a source outside the body is called external beam radiation. This is the type of radiation therapy most often used to treat non-Hodgkin’s lymphoma. Radiation might be used as the main (primary) treatment of early (stage I or II) non-Hodgkin’s lymphomas. More often, it is used along with chemotherapy. Radiation therapy can also be used to ease (palliate) symptoms caused by lymphoma when it affects internal organs, such as the brain or spinal cord, or causes pain by pressing on nerves.
Side effects of radiation therapy may include mild skin problems or fatigue. Radiation of the abdomen may cause upset stomach and diarrhea. These usually go away after radiation is finished. Chest radiation ther-apy may damage the lungs and lead to trouble breathing. Side effects of brain radiation therapy usually become most serious 1 or 2 years after treatment and may include headaches and difficulty thinking. Radiation may also make the side effects of chemotherapy worse.
Chemotherapy
Chemotherapy uses drugs that are injected into a vein or a muscle or taken by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment very useful for lymphoma. Depending on the type and the stage of the lymphoma, chemo-therapy may be used alone or in combination with radiation therapy. In some cases, chemo-therapy is given by injection into the spinal fluid (intrathecal injection) to kill lymphoma cells on the surface of the brain and spinal cord. Many drugs are useful in the treatment of patients with lymphoma. Usually, several drugs are combined. (See Table 2 for examples of combination chemotherapy treatments for lymphoma.) The treatments all have different schedules, but they are usually repeated several times in cycles given 3 or 4 weeks apart. Sometimes a patient may take one chemotherapy combination for several cycles and later switch to a different one if the first combination does not seem to be working.
Table 2. Combination Chemotherapy Treatments
CHOP cyclophosphamide, doxorubicin, vincristine, prednisone
ICE ifosfamide, carboplatin, etoposide DHAP dexamethasone, cisplatin, cytarabine MIME mitoguazone, ifosfamide, methotrexate,
etoposide
Chemotherapy drugs kill lymphoma cells, but they can also damage normal cells. For this reason, some side effects occur. These depend on the type of drugs, the amount taken,
and the length of treatment. Temporary side effects might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores. Because chemotherapy can damage the blood-producing cells of the bone marrow, patients may have low blood cell counts. This can result in an increased chance of infection (due to low white blood cells), easy bleeding or bruising after minor cuts or injuries (due to low platelet counts), and fatigue (due to low red blood cell counts).
There are often ways to lessen these side effects. For example, antinausea drugs can be given to prevent or reduce nausea and vomit-ing. Drugs known as growth factors(G-CSF or GM-CSF, for example) are sometimes given to keep the white blood cell counts higher and thus reduce the chance of infection. Another type of growth factor, erythropoietin, helps prevent anemia (too few red blood cells).
If a patient’s white blood cell counts are very low, the risk of infection can be reduced by:
• avoiding exposure to people with known or suspected bacteria, fungi, or virus infections
• paying special attention to washing hands
• wearing a surgical mask or having visitors wear a mask, a gown, and surgical gloves
• not eating fresh, uncooked fruit and other foods that might carry germs
• avoiding contact with children because they are more likely than adults to carry infections
Another way to protect patients with low white blood cell counts against infection is treatment with powerful antibiotics. These
may be given before signs of infection appear but most often are given at the earliest sign of an infection, such as fever. If platelet counts are very low, the patient may receive platelet transfusions to protect against bleeding. Likewise, fatigue caused by very low red blood cell counts is treated with red blood cell transfusions. White blood cell transfusions are not useful because these cells exist in such low numbers in the donor blood.
Tumor lysis syndrome is a side effect of the rapid breakdown of cells during very effective chemotherapy for some bulky (large) lymphomas. When the lymphoma cells are destroyed, they release normal cellular components in large amounts into the blood-stream, which may damage, in particular, the kidneys and heart. This condition can be pre-vented by giving extra fluids and certain drugs, such as sodium bicarbonate, allopurinol, or rasburicase, which help the body get rid of these substances.
Organs that could be directly damaged by chemotherapy drugs include the kidneys, liver, testes, ovaries, brain, heart, and lungs. Some effects occur during and shortly after treatment while others may not occur until much later. While being treated, patients are watched closely so serious side effects are avoided. If serious side effects occur, the chemotherapy may have to be reduced or stopped, at least for a short time. Careful monitoring and adjustment of drug doses are important to avoid long-term side effects to organs. One of the most serious late compli-cations of successful chemotherapy is the possibility of developing leukemia. This affects a small percentage of lymphoma patients.
Patients who are to receive chemotherapy may be concerned about the effects of the treatment on their ability to have children. The doctor and patients should discuss fertility before treatment begins. Questions that might be asked include:
Will this treatment have any short- or long-term effect on my reproductive system? If so, what is the effect and how long will it last?
• Is infertility a possible side effect of treatment (including ovarian failure)?
• Is there anything that can be done to prevent infertility before treatment?
• Do any of the fertility preservation options interfere with my cancer treatment?
• If I become infertile, what are my options for having a family?
• Can you refer me to a fertility specialist?
• Once I finish treatment, how will I know if I am infertile?
• How long is it safe to wait to pursue fertility options before beginning treatment for my cancer?
• Is my infertility short term or permanent?
Immunotherapy
Immunotherapies use natural substances produced by the immune system. These sub-stances may kill lymphoma cells, slow their growth, or activate the patient’s immune sys-tem to fight the lymphoma more effectively.
Interferon:Interferon is a hormone-like protein naturally produced by white blood cells to help the immune system fight infections. Some studies have suggested that interferon can cause some types of non-Hodgkin’s lym-phomas to shrink or delay disease progression.
Side effects of this treatment include moder-ate to severe fatigue, fever, chills, headaches, muscle and joint aches, and mood changes.
Monoclonal antibodies:Antibodies are normally produced by the immune system to help fight infections. Similar antibodies called monoclonal antibodies can be made in the laboratory. Instead of attacking germs as usual antibodies do, some monoclonal antibodies can be designed to attack lymphoma cells. One product is called rituximab. Rituximab recognizes and attaches to a substance called CD20 that is found on the surface of some types of lymphoma cells. This attachment kills the lymphoma cell. Patients usually receive 4 intravenous infusions over a period of about 3 weeks. Common side effects are usually minor and limited to the time of infusion, and may include chills, fever, nausea, rashes, fatigue, and headaches.
Another man-made molecule approved by the FDA is called denileukin diftitox. It is used to treat T-cell skin lymphomas. It is made by combining interleukin-2 (a protein that attaches to some kinds of lymphocytes) and diphtheria toxin, which kills cells.
Alemtuzumab is an antibody that is useful in chronic lymphocytic leukemia (CLL) and even T-cell leukemias of the skin.
Other new monoclonal antibodies are being studied in clinical trials.
Radioimmunotherapy: Newer forms of monoclonal antibodies similar to rituximab but with radioactive molecules attached to them have also been developed for use in lymphomas. The first to be approved by the FDA was ibritumomab tiuxetan, which is an antibody that has radioactive yttrium attached to it. It is used in patients with low grade or
follicular lymphoma that has returned after treatment, and is also being studied in other types of lymphoma. The second drug approved was tositumomab, which is an antibody with radioactive iodine attached. It is also used against low grade or follicular lymphoma after initial treatments no longer work. Both these drugs are being used for lymphomas that do not respond to other treatments. Their one disadvantage is they cannot be used along with chemotherapy because they lower blood counts.
Stem Cell Transplants
Stem cell transplantsare used to treat lym-phoma patients when standard treatment does not work. Although only a small number of patients with NHL receive this treatment, this number is growing. Blood-forming stem cells are the earliest form of bone marrow cells. They can develop into normal blood cells such as red blood cells, white blood cells, and platelets. They are given to patients after they have had high-dose chemotherapy to replenish the bone marrow.
Stem cells can be taken from several bone marrow aspirates, or they can be separated from the circulating (peripheral) blood by a method known as apheresis. Recent studies have shown that there may be an advantage to using stem cells obtained by apheresis instead of bone marrow aspiration. This has become the usual way that doctors get stem cells.
The 2 main kinds of stem cell transplants are allogeneic and autologous. In an allogeneic
stem cell transplant, the stem cells come from a donor whose cells are almost identical
with those of the patient. The donor is often a brother or sister, or it can be a matched unrelated donor. Allogeneic transplantation is limited, however, because of the need for a matched donor. Also, the side effects of this treatment are too severe for most people over 55 to 60 years old.
In an autologous stem cell transplant, a patient’s own stem cells are removed from his or her bone marrow or bloodstream. With some types of lymphoma that tend to spread to the bone marrow or blood, it may be hard to collect stem cells alone without the presence of lymphoma cells. Even after treating the stem cells in the lab to kill or remove lymphoma cells (purging), some remaining lymphoma cells may be returned with the stem cell transplantation. Stem cells collected from a donor or the patient are frozen and stored. The patient then receives high-dose chemotherapy, and sometimes whole body radiation treatment as well. This destroys remaining cancer cells, but it also kills all or most normal cells in the bone marrow. After treatment, the frozen stem cells are thawed and returned to the body through an intravenous infusion. They then make their way through the blood system to the bone marrow where they grow and divide to become the patient’s new blood-forming system.
A blood stem cell transplant is a complex treatment that can be life-threatening. If the doctors think the patient may benefit from a transplant, the best place to have it done is at a nationally recognized cancer center where the staff has experience with the procedure and with managing the recovery period. Patients should not hesitate to ask the doctor about
the number of times he or she has done this procedure and their results with cases such as theirs. Experience and knowledge are key factors in providing the best care.
A stem cell transplant is very expensive and can require a lengthy hospital stay. Side effects from a stem cell transplant are gener-ally divided into early and long-term effects. The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy. They are caused by damage to the bone marrow and other rapidly growing tissues of the body. Complications and side effects that can last for a long time or not occur until years after the transplant include:
• radiation damage to the lungs, causing shortness of breath
• graft-versus-host disease, which occurs only in allogeneic (donor) transplants
• damage to the ovaries that can cause infertility and loss of menstrual periods
• damage to the thyroid gland that can cause problems with metabolism
• cataracts (damage to the lens of the eye that can affect vision)
• bone damage called aseptic necrosis. If damage is severe, the patient will need to have part of the affected bone and the joint replaced.
• development of new cancers, mainly leukemia several years later.
• infertility in male patients and early menopause in female patients.
Nonmyeloablative transplants:This is a special kind of transplant that takes advan-tage of the donor cells’ immune response to
kill the lymphoma. Only low doses of chemotherapy (usually a drug called fludara-bine, which lowers a patient’s immunity) are given. Then stem cells from a matched donor are given. Over time the donor cells take over the bone marrow and develop an immune response to the lymphoma cells and destroy them. The problem with this procedure is the graft-versus-host disease, which harms the patient. Researchers are looking for ways to stop the graft-versus-host response while keeping the graft-versus-lymphoma effect.
Supportive Care
Most of this document discusses ways to cure people with non-Hodgkin’s lymphoma or to help them live longer. However, another important goal is to help you feel as well as you can and continue to do the things in life that you want to do. Don’t hesitate to discuss your symptoms or how you are feeling with your cancer care team. There are effective and safe ways to treat symptoms you may be hav-ing, as well as most of the side effects caused by treatment for non-Hodgkin’s lymphoma.
Pain is a concern for patients with advanced cancer. Growth of the cancer around certain nerves may cause severe pain. It is important that you tell your doctors if you are having pain. For most patients, treatment with morphine or other so-called opioids (medicines related to opium) will reduce the pain considerably. For more information on the treatment of cancer pain, contact the ACS or NCCN to request a copy of the Cancer Pain Treatment Guidelines for Patients.
Complementary and
Alternative Therapies
If you are considering any alternative or complementary treatments, please discuss this openly with your cancer care team and request information from the ACS or the National Cancer Institute. Some alternative treatments can cause serious side effects.
Other Things to Consider
During and After Treatment
During and after treatment, you may be able to hasten your recovery and improve your quality of life by taking an active role. Learn about the benefits and disadvantages of each of your treatment options, and ask questions if there is anything you do not understand. Learn about and look out for side effects of treatment, and report these promptly to your cancer care team so that they can take steps to reduce them or make them go away.Remember that your body is as unique as your personality and your fingerprints. Although understanding your cancer’s stage and learning about your treatment options can help predict what health problems you may face, no one can say precisely how you will respond to cancer or its treatment.
You may have special strengths such as a history of excellent nutrition and physical activity, a strong family support system, or a deep faith, and these strengths may make a difference in how you respond to cancer. There are also experienced professionals in mental health services, social work services, and pastoral services who may assist you in coping with your illness.
You can also help in your own recovery from cancer by making healthy lifestyle choices. If you use tobacco, stop now. Quitting will improve your overall health, and the full return of the sense of smell may help you enjoy a healthy diet during recovery. If you use alcohol, limit how much you drink. Have no more than 1 or 2 drinks per day. Good nutrition can help you get better after treatment. Eat a nutritious diet, with plenty of fruits, vegetables, and whole grain foods. Ask your cancer care team if you could benefit from a special diet. They may have specific advice for people who have had radiation therapy, chemotherapy, or surgery.
If you are being treated for cancer, be aware of the battle that is going on in your body. Radiation therapy and chemotherapy add to the fatigue caused by the disease itself. To help you with the fatigue, plan your daily activities around when you feel your best. Get plenty of sleep at night. Don’t be afraid to ask others for help. And ask your cancer care team about a daily exercise program to help you feel better.
Surgery, radiation therapy, and chemo-therapy may sometimes affect your feelings about your body and may lead to specific physical problems that affect sexuality. Your cancer care team can help with these issues, so don’t hesitate to share your concerns.
A cancer diagnosis and its treatment are major life challenges, affecting you and everyone who cares for you. Before you reach the point of feeling overwhelmed, consider attending a meeting of a local support group. If you need assistance in other ways, contact your hospital’s social service department or the American Cancer Society for help in contacting counselors or other services.
Clinical Trials
The purpose of clinical trials: Studies of promising new or experimental treatments in patients are known as clinical trials. Researchers conduct studies of new treat-ments to answer the following questions:
• Is the treatment helpful?
• How does this new type of treatment work?
• Does it work better than other treat-ments already available?
• What side effects does the treatment cause?
• Are the side effects greater or less than the standard treatment?
• Do the benefits outweigh the side effects?
• In which patients is the treatment most likely to be helpful?
Types of clinical trials:A new treatment is normally studied in 3 phases of clinical trials before it is eligible for approval by the FDA (Food and Drug Administration).
Phase I clinical trials:The purpose of a phase I study is to find the best way to give a new treatment and how much of it can be given safely. The treatment has been well tested in laboratory and animal studies, but the side effects in patients are not completely known. Although doctors are hoping to help patients, the main purpose of a phase I study is to test the safety of the drug.
Phase II clinical trials:These are designed to see if the drug works. Patients are usually given the highest dose that doesn’t cause severe side effects (determined from the
phase I study) and closely observed for an effect on the cancer. The doctors will also look for side effects.
Phase III clinical trials:Phase III studies involve large numbers of patients. One group will receive the standard (most accepted) treatment. The other group will receive the new treatment. The study will be stopped if the side effects of the new treatment are too severe or if one group has had much better results than the others.
If you are in a clinical trial, you will have a team of experts looking at you and monitoring your progress very carefully. The study is espe-cially designed to pay close attention to you.
However, there are some risks. No one involved in the study knows in advance whether the treatment will work or exactly what side effects will occur. That is what the study is designed to discover. While most side effects will disappear in time, some can be permanent or even life threatening. Keep in mind, though, that even standard treatments have side effects. Depending on many factors, you may decide to enroll in a clinical trial.
Deciding to enter a clinical trial:
Enrollment in any clinical trial is completely up to you. Your doctors and nurses will explain the risks and possible benefits of the study to you in detail and will give you a form to read and sign indicating your understanding of the study and your desire to take part. Even after signing the form and after the clinical trial begins, you are free to leave the study at any time, for any reason. Taking part in the study will not prevent you from getting other medical care you may need.
To find out more about clinical trials, ask your cancer care team. Among the questions you should ask are:
• What is the purpose of the study?
• What kinds of tests and treatments does the study involve?
• What does this treatment do?
• What is likely to happen in my case with, or without, this new research treatment?
• What are my other choices and their advantages and disadvantages?
• How could the study affect my daily life?
• What side effects can I expect from the study? Can the side effects be con-trolled?
• Will I have to be hospitalized? If so, how often and for how long?
• Will the study cost me anything? Will any of the treatment be free?
• If I am harmed as a result of the research, what treatment would I be entitled to?
• What type of long-term follow-up care is part of the study?
• Has the treatment been used to treat other types of cancers?
The ACS offers a clinical trials matching service that will help you find a clinical trial that is right for you. Simply go to our web site (www.cancer.org) or call us at 1-800-ACS-2345. You also can get a list of current National Cancer Institute sponsored clinical trials by calling the NCI Cancer Information Service toll free at 1-800-4-CANCER or visiting the NCI clinical trials Web site (www.cancer.gov/ clinical_trials/).
Treatment Guidelines
Decision Trees
The decision trees on the following pages represent treatment options for several types of non-Hodgkin’s lymphoma. Each one shows you step-by-step how you and your doctor can arrive at the choices you need to make about your treatment. Keep in mind, this information is not meant to be used without the expertise of your own doctor, who is familiar with your situation, medical history, and per-sonal preferences. You may even want to review this booklet together with your doctor, who can show you which of the decision trees apply to you. We’ve left some blank spaces in the decision tree section for you or your doctor to add notes about the treatments. You might also use this space to write down some questions to ask your doctors about the treatments.
Participating in a clinical trial is an appropriate option for patients with most stages of non-Hodgkin’s lymphoma. Taking part in a study does not prevent you from getting other medical care you may need.
The NCCN guidelines are updated as new significant data become available. To ensure you have the most recent version, consult the Web sites of the ACS (www.cancer.org) or NCCN (www.nccn.org). You may also call the NCCN at 1-888-909-NCCN or the ACS at 1-800-ACS-2345 for the most recent information on these guidelines or on cancer in general.
Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL)
The diagnosis is made by examining the bone marrow and blood cells in the case of leukemia and by a lymph node biopsy if it appears to be lymphoma. A pathologist expe-rienced in diagnosing lymphomas should examine these samples. The diagnosis can be confirmed by studying the cell surface markers. A special test of the cells for Zap-70 can also help tell if the CLL will ever need treatment. A complete history and physical examination should be done. The doctor will want to know if the lymph nodes, spleen, or liver are
enlarged. The doctor will also examine the patient’s other organ systems and general health and ask whether there has been any fever or weight loss.
Blood tests are done to check the blood counts, liver function, kidney function, and calcium, uric acid, and LDH levels. These tests provide information about the patient’s gen-eral health and how advanced the lymphoma is. A blood test for beta-2-microglobulinmay be useful because it can sometimes also tell how advanced the lymphoma is. It can be elevated in advanced cases, as can the LDH.
Treatment Guidelines for Patients
Diagnosis
Lymph node biopsy or bone marrow biopsy for diagnosis of lymphoma or leukemia
Blood cell examination for leukemia
Review by pathologist experienced in diagnosis of leukemia and lymphoma
Special tests of blood, lymph node, or bone marrow to establish the exact type of lymphoma • Cell surface markers
Depending on a patient’s general health and symptoms other tests may be done. If there is anemia, looking for young red cells in the blood can tell if the red cells are being destroyed — something that can happen with this type of lymphoma. Often in CLL, the pro-duction of infection fighting immunoglobulins (antibodies) is defective and it is useful to measure their levels, particularly if the patient has experienced infections. X-rays and CT
scans may also be useful, particularly to look for enlarged lymph nodes and infections. Sometimes a bone marrow biopsy may be needed. Treatment such as chemotherapy can temporarily or permanently block the ability of the ovaries to make eggs and the testes to produce sperm. This should be discussed with patients who may want to have children in the future.
Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL)
Stage
Stage I or II
(Lymphoma in one lymph node group or in more than one node group on same side of diaphragm)
Stage III or IV
(Lymphoma on both sides of diaphragm or has spread out of nodes to distant sites)
Evaluation
Doctor must do: • Physical examination
• Determine general health and activity level • Determine if fever and/or weight loss is present • Complete blood count
• Blood test of liver and kidney function and LDH, calcium, and uric acid levels
Useful to do in some cases:
• Measurement of blood immunoglobulins • If patient has anemia, count of young red
blood cells • CT scan of chest
• CT scan of abdomen and pelvis or ultrasound of abdomen
• Discuss fertility issues and treatment • Blood test for beta-2-microglobulin • Chest x-ray
• Bone marrow aspiration and biopsy
©2005 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.
If the diagnosis is stage I or II small lymphocytic lymphoma (SLL), the affected lymph nodes can be treated with radiation therapy, or no treatment may be needed. If the lymphoma is more advanced or it is chronic lymphocytic leukemia (CLL), then treatment will be considered based on symptoms and amount of cancer present and the wishes of the patient. Also, certain patients may be eligible to enter a clinical trial. If the lymphoma is
causing or will soon cause serious problems such as organ damage or serious infections or there is steady growth, then treatment should be given to avoid these problems. In advanced stages where the red blood cell count and/or platelet count is low, treatment should be given.
If the decision is made to treat, drug ther-apy will be used. The drugs used most often are chlorambucil, which is given as a pill, or
Treatment Guidelines for Patients
Evaluation
Stage
Stage III or IV Stage I or II Small lymphocytic lymphomaCLL–Good risk (only high white blood cell count present)
CLL–Intermediate risk (enlarged lymph nodes, spleen, or liver present)
CLL–High risk (low red blood cell and platelet count present)
Determine whether there are reasons for treatment, such as:
• Eligible for a clinical trial
• Immune system is destroying blood cells • Frequent serious infections
• Vital organ damage • Low blood counts • Large tumor masses
• Steady tumor growth over 6 months • Lymphocyte count doubles within a year • Patient wants treatment
fludarabine, which is given intravenously. The monoclonal antibody rituximab can be added to the fludarabine. Another option is a combination of drugs, such as cyclophos-phamide and vincristine given intravenously and prednisone given as a pill. Cyclophospha-mide and fludarabine can be given together
along with rituximab. Another monoclonal antibody that can be used is alemtuzumab. If frequent infections are a problem, this will be treated with intravenous immunoglobulin. Radiation therapy may be given to help con-trol symptoms.
Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL) (continued)
Initial Treatment
Either radiation therapy to lymph nodes, or Observation only No reasons for treatment If lymph nodes are growing
Yes, there are reasons for treatment
Observation until disease progresses
Treatment with single drug
• Purine, such as fludarabine with or without rituximab
• Alkylating agent, such as cyclophosphamide or chlorambucil
OR
Treatment with combination of drugs (no anthracycline or doxorubicin), such as • Cyclophosphamide, vincristine, prednisone • Cyclophosphamide, fludarabine, rituximab OR
Radiation therapy
Continued on next pages
©2005 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.
If the lymphoma or leukemia responds to the treatment by shrinking more than 50%, then nothing further needs to be done. If the
lymphoma or leukemia doesn’t shrink, or if it shrinks and then grows back and there are reasons for treatment, then different drugs or
Treatment Guidelines for Patients
Response to Initial Treatment
Lymphoma or leukemia has shrunk at least 50% Lymphoma or leukemia has not shrunk or is growing
Determine whether there are reasons for treamtent, such as:
• Eligible for a clinical trial
• Immune system is destroying blood cells • Frequent serious infections
• Vital organ damage • Low blood counts • Large tumor masses
• Steady tumor growth over 6 months • Lymphocyte count doubles within a year • Patient wants treatment
a different monoclonal antibody may be given. Other options are simple treatment, such as radiation therapy to enlarged lymph
nodes, or more intensive therapy, such as entering a clinical trial of a new drug or stem cell transplant.
Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL) (continued)
If lymphoma or leukemia is growing Yes, there are reasons for treatment No reasons for treatment
Additional Treatment
Clinical trials (including studies of stem cell transplants in certain patients)
OR
Another treatment such as fludarabine or other purine drug; if resistant to purines, use alkylator-based treatment (such as cyclophosphamide) or combination chemotherapy OR
Local radiation therapy OR
Antibody-based treatment (such as rituximab or alemtuzumab) with or without chemotherapy
Observation Clinical trial or observation
©2005 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.
