Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) represents a diverse group of diseases that are distinguished by the characteristics of the cancer cells associated with each disease type.
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The reasons for the development of NHL are not known. Immune suppression plays a role in certain cases.
People infected with the human immunodeficiency virus (HIV) have a higher risk of developing lymphoma. There is a higher incidence of NHL in farming communities. Studies suggest that specific ingredients in herbicides and pesticides such as organochlorine, organophosphate and phenoxyacid compounds are linked to lymphoma. The number of lymphoma cases caused by such exposures has not been determined.
Exposure to certain viruses and bacteria is associated with NHL. It is thought that infection with a virus or bacterium can lead to intense lymphoid cell proliferation, increasing the probability of a cancer-causing event in a cell. Some examples include
Epstein-Barr virus (EBV) infection—in patients from specific geographical regions—is strongly associated with African Burkitt lymphoma. The role of the virus is unclear since African Burkitt lymphoma also occurs among people who have not been infected with EBV. Epstein-Barr virus infection may play a role in the increased risk of NHL in persons whose immune systems are suppressed as a result of organ transplantation and its associated therapy.
Human T-lymphotropic virus (HTLV) is associated with a type of T-cell lymphoma in patients from certain geographic regions in Southern Japan, the Caribbean, South America and Africa.
The bacterium Helicobacter pylori causes ulcers in the stomach and is associated with the development of mucosa-associated lymphoid tissue (MALT) lymphoma in the stomach wall.
About a dozen inherited syndromes can predispose individuals to later development of NHL. These inherited disorders are uncommon, but the concept of predisposition genes is under study to determine if they play a role in the sporadic occurrence of NHL in otherwise healthy individuals.
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Types of Non-Hodgkin Lymphoma
There are many types of non-Hodgkin lymphoma. Most people with NHL have a B-cell type of NHL (about 85 percent). The others have a T-cell type or an NK-cell type of lymphoma.
NHL that is
Slow-Growing or Indolent NHL
Follicular lymphoma - the most common slow-growing NHL
Chronic lymphocytic leukemia
Cutaneous T-cell lymphoma
Lymphoplasmacytic lymphoma
Marginal zone lymphoma
Mucosa-associated lymphoid tissue (MALT) lymphoma
Small cell lymphocytic lymphoma
Waldenström macroglobulinemia
Fast-growing or Aggressive NHL
Diffuse large B-cell lymphoma - the most common fast-growing NHL
AIDS-associated lymphoma
Anaplastic large cell lymphoma
Burkitt lymphoma
Central nervous system (CNS) lymphoma
Follicular lymphoma
Lymphoblastic lymphoma
MALT lymphoma (transformed)
Mantle cell lymphoma (most types)
Peripheral T-cell lymphoma (most types)
There are treatments for every type of NHL. Some patients with fast-growing NHL can be cured. For patients with slow-growing NHL, treatment may keep the disease in check for many years.
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Signs and Symptoms
The most common sign of NHL is one or more enlarged lymph nodes in the neck, armpit or groin. Enlarged lymph nodes also can be near the ears or elbow.
Signs and symptoms of NHL may include
- Swollen lymph nodes
- Fever
- Night sweats
- Feeling tired
- Loss of appetite
- Weight loss
- Rash.
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Diagnosis and Staging
Having the correct diagnosis is important for getting the right treatment. Some patients may need to get a second medical opinion about the diagnosis before they begin treatment. Talk to the doctor about the tests used to make the diagnosis.
Doctors do a test called a lymph node biopsy to determine if a patient has non-Hodgkin lymphoma. To do the biopsy, a surgeon removes all or part of an enlarged lymph node. The lymph node is examined under a microscope by a pathologist. It may be important to get another opinion about the biopsy results from a second pathologist.
Immunophenotyping is done to find out if the patient's NHL cells are B cells or T cells. This is a lab test that can be done using the sample of cells from the lymph node biopsy or with blood or bone marrow biopsy samples.
The doctor will do other tests to stage the disease (see how widespread the disease is). A physical exam, lab and imaging tests help the doctor stage the NHL . The doctor will check
- The number of lymph nodes that are affected
- Where the affected lymph nodes are (for example, in the abdomen or the chest or in both parts of the body)
- Whether any cancer cells are in other parts of the body besides the lymph nodes or lymphatic system, such as the lungs or liver.
The tests for staging include
- Blood tests - to check red cell, white cell and platelet counts; blood tests are also done to check for other signs of disease
- Bone marrow tests (bone marrow aspiration and bone marrow biopsy) - to look for NHL cells in the marrow.
- Imaging tests - to create pictures of the chest and abdomen and see if there are lymphoma masses in the lymph nodes, liver, spleen or lungs. Examples of imaging tests are
- Chest x-ray
- CT (computed tomography) scan
- MRI (magnetic resonance imaging)
- PET (positron emission tomography) scan.
Other staging tests may be done for some types of NHL.
Non-Hodgkin Lymphoma Stages
NHL may be described as
- Stage I: Involvement of one lymph node group
- Stage IE: Involvement of one area or organ other than the lymph nodes ("E" stands for "extranodal," meaning that NHL is found in an area or organ other than the lymph nodes or has spread to tissues beyond, but near, the major lymphatic areas)
- Stage II: Involvement of two or more lymph node groups on the same side of the diaphragm (a thin muscle below the lungs)
- Stage IIE: Involvement of an area or organ other than the lymph nodes and of lymph nodes near that area or organ, and possibly including other lymph node groups on the same side of the diaphragm
- Stage III: Involvement of lymph node groups on both sides of the diaphragm
- Stage IIIE: Involvement of lymph node groups on both sides of the diaphragm and in an area or organ other than the lymph nodes
- Stage IV: Involvement of one or more organs other than the lymph nodes and possibly of the lymph nodes.
Patients are also divided into either "A" or "B" categories.
- "A" patients don't have fever, excessive sweating and weight loss.
- "B" patients have fever, a lot of sweating and weight loss. Patients in the B category often require more aggressive treatment.
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Treatment
The doctor has to take into account many factors to make a treatment plan for a patient with NHL, including
- The type of NHL
- The stage and category of the disease
- The patient's overall health.
Treatments for NHL include
- Chemotherapy - the main type of treatment for NHL
- Drug therapy - Rituxan® (rituximab) and certain other drugs are used to treat some types of NHL
- Radiation therapy - an important added treatment given along with chemotherapy for some types of NHL
- Stem cell transplantation - a procedure for some types of NHL
- Watch and wait - an approach for some types of NHL
- New types of treatment - now under study in clinical trials.
Chemotherapy is given in cycles, usually several weeks apart. Patients need a number of cycles. The treatment may last from six to 10 months. High doses of chemotherapy may also kill normal blood-forming cells in the marrow. Chemotherapy may cause very low counts of red cells, white cells or platelets. A red cell transfusion or drugs called blood cell growth factors may be needed until the side effects of chemotherapy wear off.
Examples of growth factors are:
- Aranesp® (Darbepoetin alfa) and Procrit® (epoetin alfa) - these can increase the red cell count
- Neupogen® or Neulasta®(also called G-CSF ) and Leukine®(also called GM-CSF) - these can increase the number of neutrophils (white cells).
Most treatment for NHL usually takes place in an outpatient setting. Some patients may need to stay in the hospital for a short time - for example, if they develop a fever or have other signs of infection. Some patients who need antibiotics may stay in the hospital until the infection is gone.
Drug Therapy
Many drug combinations are used to treat NHL The drug choice depends on the type of NHL and the stage of treatment. A number of drug combinations include Rituxan - a monoclonal antibody therapy. Monoclonal antibody therapies kill certain types of cancer cells. They can cause side effects but do not cause many of the side effects caused by chemotherapy.
R-CHOP: Rituxan, cyclophosphamide, doxorubicin (hydroxydoxorubicin), Oncovin® (vincristine) and prednisone
R-FCM: Rituxan, fludarabine, cyclophosphamide and mitoxantrone
R-CVP or F-CVP: Rituxan or fludarabine, plus cyclophosphamide, vincristine and prednisone
R-HCVAD: Rituxan, cyclophosphamide, vincristine, Adryamicin® (doxorubicin) and dexamethasone alternating with R-MTXAraC: Rituxan, methotrexate, cytarabine (ara-C)
Radioimmunotherapy is used to treat some patients with certain types of NHL. Ibritumomab (Zevalin®) and tositumomab and iodine I 131 tositumomab (Bexxar®) are radioimmunotherapies that link an anti-CD20 monoclonal antibody to a radioactive isotope (either radioactive yttrium or radioactive iodine) to deliver radiation directly to cancer cells.
Radiation Therapy
Radiation therapy uses high-energy rays to kill lymphoma cells in one area. Radiation can be used along with chemotherapy when there are very large masses of lymphoma cells in a small area of the body. Radiation can also be used when large lymph nodes are pressing on an organ (such as the bowel) and chemotherapy cannot control the problem. Radiation usually isn't the only treatment for NHL because the lymphoma cells are likely to be in many areas of the body.
Allogeneic Stem Cell Transplantation
Stem cells from a donor are transfused into the patient's blood after treatment with chemotherapy is completed. Sometimes the donor can be a brother or a sister. A person has about a 1 in 4 chance of having stem cells that "match" his or her brother's or sister's stem cells. When there is no related donor, the donor can be an unrelated person with stem cells that "match" the patient's. High-dose chemotherapy is given to patients to kill lymphoma cells in the body before a stem cell transplant.
The transplanted stem cells go from the patient's blood to the marrow. The stem cells start a new supply of red cells, white cells (including immune cells) and platelets. The donated stem cells make immune cells that do not totally match the patient's cells. A goal of this therapy is for the donor immune cells to recognize that the patient's lymphoma cells do not belong in the patient's body and to kill them. This desired effect is called graft versus lymphoma. Allogeneic stem cell transplantation can be a high-risk treatment.
The decision to do a transplant depends on
- The patient's age
- The patient's overall health
- How well the donor cells and patient cells match
- The patient's response to drug therapy.
The decision also depends on the patient's understanding of the benefits and risks of the transplant. If the doctor thinks a patient might benefit from a transplant, he or she will talk about these factors with the patient. Allogeneic stem cell transplant is most successful in younger patients. Patients up to about 60 years of age who have a matched donor may be considered.
Watch and Wait for Slow-Growing NHL
In most cases, a patient begins treatment for NHL right away. But when a patient has NHL that is widespread throughout the body, that is not growing or is slow-growing, the doctor may recommend a watch and wait approach.
The watch and wait approach means that a doctor watches a patient's condition but does not treat with drugs or radiation therapy. Patients may think that they should have treatment right away. But for patients with slow-growing disease and no symptoms, it is common not to start treatment. This allows the patient to avoid side effects of therapy until treatment is needed.
Patients in watch and wait need follow-up visits with the doctor. At each office visit the doctor will check for any health changes. The results of exams and lab tests over time will help the doctor advise the patient about
- When to start treatment
- The type of treatment to have.
Treatment will begin if a patient develops symptoms or there are signs that the NHL is starting to grow. Patients may be treated with one to five drugs. The goal of treatment is a series of remissions - each lasting a number of years. This can be true even when tests show disease remains in some parts of the body. Many patients lead active, good-quality lives.
Maintenance for Slow-Growing NHL
Patients with some types of slow-growing lymphoma may stay in treatment to keep their remission. This is called maintenance treatment.
Relapsed or Refractory NHL
Disease can come back months or years after treatment ends. This is called relapsed NHL. Or, some patients may not respond to treatment for newly diagnosed or relapsed NHL. This is called refractory NHL.
Doctors can change the patient's treatment or give added treatment. There are many drug choices and approaches to treatment. If relapse occurs long after treatment, the same drugs that were used for the patient before may be effective. In other cases, new drugs or treatment approaches are used. Patients with refractory NHL should talk with the doctor about the risks and benefits of participating in a clinical trial.
Childhood NHL
Burkitt lymphoma is the most common type of NHL subtype in children aged 5 through 14 years. Diffuse large B-cell lymphoma is the most common type in 15- to 29-year-olds. Children and teens with NHL should be treated at medical centers that have a pediatric oncology team.
It is important for young adults and parents of children to talk to members of the oncology team about the
Stage of the disease
Type of NHL
Lab test results.
Doctors use this information about the patient's disease in order to determine the most effective therapy. Treatments used for children with NHL may be different from those used for adults with NHL.
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Treatment Side Effects
There are many possible side effects of treatment for NHL.
Patients react to treatment in different ways. Most side effects are mild and last only a short time. Other side effects may be serious or last a long time. When side effects occur, most
- Can be helped with treatment
- Do not last long
- Clear up when treatment ends.
The number of red cells may decrease (anemia) in patients treated with chemotherapy. Blood transfusions or growth factors to increase red cells may be needed. Aranesp® and Procrit® may be given to increase the red cell count.
A severe drop in white cells may lead to an infection. Infections caused by bacteria or fungi are treated with antibiotics. To help a patient's white cell count to improve:
- The amount of chemotherapy drugs may be reduced
- The time between treatments may be increased
- Growth factors such as G-CSF (Neupogen® or Neulasta®) and GM-CSF (Leukine®) may be given to increase neutrophil counts.
Some common side effects from treatment for NHL are
- Mouth sores
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Bladder irritation
- Blood in the urine.
Other side effects from treatment may include
- Extreme tiredness
- Fever
- Cough
- Rash
- Hair loss
- Weakness
- Tingling sensation
- Lung, heart or nerve problems.
Fertility (the ability to conceive a baby) may be affected by lymphoma treatment in both men and women. Patients who are concerned about fertility should talk to their doctors about this before treatment begins. For example, men who plan to have children in the future may want to consider banking sperm before starting treatment. If a couple's ability to have children is not affected by treatment, their chance of having a healthy baby is the same as that for the general population.
Patients should talk with their health care providers about any long-term effects of treatment. For more information, order the free LLS booklet, Understanding Drug Therapy and Managing Side Effects, and the free fact sheets, Cancer-Related Fatigue Facts, Long-Term and Late Effects of Treatment for Childhood Leukemia or Lymphoma and Long-Term and Late Effect of Treatment in Adults.
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Clinical trials are used to study new drugs, new treatments or new uses for approved drugs or treatments. Doctors are testing new drugs and new combinations of drugs in clinical trials to treat all types of lymphoma. A growing number of clinical trials include older adults.
There are clinical trials for
- Newly diagnosed non-Hodgkin lymphoma patients
- Patients who do not get a good response to treatment
- Patients who relapse after treatment
- Patients who continue treatment after remission (maintenance).
Some clinical trials test new ways to use drugs that are already approved. For example, changing the amount of the drug or giving the drug along with another type of treatment might be better.
Doctors are also studying the types of stem cell transplantation called autologous stem cell transplantation and reduced-intensity transplantation in clinical trials for NHL. These may be helpful for some patients
Autologous Stem Cell Transplantation
Many patients with lymphoma cannot have an allogeneic stem cell transplant. Doctors are studying the use of autologous stem cell transplantation in clinical trials to treat certain NHL patients. This type of transplant is used to treat patients with other kinds of blood cancer. In these cases, it is not a cure, but it can give patients longer disease-free periods than standard-dose chemotherapy without stem cell transplantation.
The goal of autologous stem cell transplantation is to help the body start a new supply of blood cells after high-dose chemotherapy. With an autologous transplant
The patient's own stem cells are collected from the patient's blood or marrow and stored after the first cycles of drug therapy are completed.
Then, the patient is given high-dose chemotherapy to kill the lymphoma cells. This treatment also kills normal stem cells in the marrow.
Next, the stem cells collected before chemotherapy are infused back into the patient's blood through a central line.
Reduced-Intensity Transplantation
The reduced-intensity transplant (also called a nonmyeloablative transplant) is also under study. It uses lower doses of chemotherapy in combination with an allogeneic stem cell transplant. Older and sicker patients may be able to be helped by this treatment.
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