Lymphoma (Hodgkin's Disease and Non-Hodgkin's Lymphoma)

Facts You Should Know About Lymphoma

1. Lymphoma (also termed lymphatic or lymphocytic cancer) is a type of cancer involving cells of the immune system, called lymphocytes. Just as cancer represents many different diseases, lymphoma represents many different cancers of lymphocytes -- about 35-60 different subtypes, in fact, depending upon which group of experts is categorizing the subtypes.
2. Seek medical attention for unexplained swellings in an arm or leg, fever, night sweats, unexplained weight loss, or itching that lasts for a few days.
3. Treatment of lymphoma may involve radiation, chemotherapy, biological therapy, and occasionally stem cell transplantation.

Lymphoma is a group of cancers that affect the cells that play a role in the immune system and primarily represents cells involved in the lymphatic system of the body.

• The lymphatic system is part of the immune system. It consists of a network of vessels that carry a fluid called lymph, similar to the way that the network of blood vessels carry blood throughout the body. Lymph contains white blood cells called lymphocytes that are also present in blood and tissues. Lymphocytes attack a variety of infectious agents as well as many cells in the precancerous stages of development.
• Lymph nodes are small collections of lymph tissue that occur throughout the body. The lymphatic system involves lymphatic channels that connect thousands of lymph nodes scattered throughout the body. Lymph flows through the lymph nodes, as well as through other lymphatic tissues including the spleen, the tonsils, the bone marrow, and the thymus gland.
• These lymph nodes filter the lymph, which may carry bacteria, viruses, or other microbes. At infection sites, large numbers of these microbial organisms collect in the regional lymph nodes and produce the local swelling and tenderness typical of a localized infection. These enlarged and occasionally confluent collections of lymph nodes (so-called lymphadenopathy) are often called "swollen glands." In some areas of the body (such as the anterior part of the neck), they are often visible when swollen.

Lymphocytes recognize infectious organisms and abnormal cells and destroy them. There are two major subtypes of lymphocytes: B lymphocytes and T lymphocytes, also referred to as B cells and T cells.

• B lymphocytes produce antibodies (proteins that circulate through the blood and lymph and attach to infectious organisms and abnormal cells). Antibodies essentially alert other cells of the immune system to recognize and destroy these intruders (also known as pathogens); the process is known as humoral immunity.
• T cells, when activated, can kill pathogens directly. T cells also play a part in the mechanisms of immune system control to prevent the system from inappropriate overactivity or underactivity.
• After fighting off an invader, some of the B and T lymphocytes "remember" the invader and are prepared to fight it off if it returns.

Cancer occurs when normal cells undergo a transformation whereby they grow and multiply uncontrollably. Lymphoma is a malignant transformation of either B or T cells or their subtypes.

• As the abnormal cells multiply, they may collect in one or more lymph nodes or in other lymph tissues such as the spleen.
• As the cells continue to multiply, they form a mass often referred to as a tumor.
• Tumors often overwhelm surrounding tissues by invading their space, thereby depriving them of the necessary oxygen and nutrients needed to survive and function normally.
• In lymphoma, abnormal lymphocytes travel from one lymph node to the next, and sometimes to remote organs, via the lymphatic system.
• While lymphomas are often confined to lymph nodes and other lymphatic tissue, they can spread to other types of tissue almost anywhere in the body. Lymphoma development outside of lymphatic tissue is called extranodal disease.

Lymphomas fall into one of two major categories: Hodgkin's lymphoma (HL, previously called Hodgkin's disease) and all other lymphomas (non-Hodgkin's lymphomas or NHLs).

• These two types occur in the same places, may be associated with the same symptoms, and often have similar appearance on physical examination (for example, swollen lymph nodes). However, they are readily distinguishable via microscopic examination of a tissue biopsy sample because of their distinct appearance under the microscope and their cell surface markers.
• Hodgkin's disease develops from a specific abnormal B lymphocyte lineage. NHL may derive from either abnormal B or T cells and are distinguished by unique genetic markers.
• There are five subtypes of Hodgkin's disease and about 30 subtypes of non-Hodgkin's lymphoma (not all experts agree on the numbers and names of these NHL subtypes).
• Because there are so many different subtypes of lymphoma, the classification of lymphomas is complicated (it includes both the microscopic appearance as well as genetic and molecular markers).
• Many of the NHL subtypes look similar, but they are functionally quite different and respond to different therapies with different probabilities of cure. For example, the subtype plasmablastic lymphoma is an aggressive cancer that arises in the oral cavity of HIV-infected patients, the follicular subtype is composed of abnormal B lymphocytes, while anaplastic subtype is comprised of abnormal T cells and cutaneous lymphomas localize abnormal T cells in the skin. As previously mentioned, there are over 30 subtypes of NHL with unusual names such as Mantle cell lymphoma, mucosa associated lymphoid tissue (MALT) lymphoma, hepatosplenic lymphoma, angioimmunoblastic T-cell lymphoma, Waldenstrom's macroglobulinemia, and hereditary lymphomas. However, the World Health Organization (WHO) suggests there at least 61 types of NHL; subtyping is still a work in progress. However, no matter how many subtypes experts suggest exist, there are too many to discuss in detail in this article. HL subtypes are microscopically distinct, and typing depends upon the microscopic differences as well as extent of disease.

Lymphoma is the most common type of blood cancer in the United States. It is the seventh most common cancer in adults and the third most common in children. Non-Hodgkin's lymphoma is far more common than Hodgkin's lymphoma.

• In the United States, about 74,680 new cases of NHL and 8,500 new cases of HL were expected to be diagnosed in 2018.
• About 19,910 deaths due to NHL were expected in 2018, as well as 1,050 deaths due to HL, with the survival rate of all but the most advanced cases of HL greater than that of other lymphomas.
• Lymphoma can occur at any age, including childhood. Hodgkin's disease is most common in two age groups: young adults 16-34 years of age and in older people 55 years of age and older. Non-Hodgkin's lymphoma is more likely to occur in older people.

The exact causes of lymphoma are unknown. Several factors have been linked to an increased risk of developing lymphoma, but it is unclear what role they play in the actual development of lymphoma. These risk factors include the following:

• Age: Generally, the risk of NHL increases with advancing age. HL in the elderly is associated with a poorer prognosis than that observed in younger patients. In the 20-24-year age group, the incidence of lymphoma is 2.4 cases per 100,000 while it increases to 46 cases per 100,000 among individuals 60-64 years of age.
• Infections
  • Infection with HIV
  • Infection with Epstein-Barr virus (EBV), one of the causative factors in mononucleosis, is associated with Burkitt lymphoma, a NHL that most often occurs in children and young people (ages 12 to 30).
  • Infection with Helicobacter pylori, a bacterium that lives in the digestive tract
  • Infection with hepatitis B or hepatitis C virus
• Medical conditions that compromise the immune system
  • HIV
  • Autoimmune disease
  • Use of immune suppressive therapy (often used following organ transplant)
  • Inherited immunodeficiency diseases (severe combined immunodeficiency, ataxia telangiectasia, among a host of others)
• Exposure to toxic chemicals
  • Farm work or an occupation with exposure to certain toxic chemicals such as pesticides, herbicides, or benzene and/or other solvents
  • Hair dye use has been linked to higher rates of lymphoma, especially in patients who started to use the dyes before 1980.
• Genetics: Family history of lymphoma

The presence of these risk factors does not mean a person will actually develop lymphoma. In fact, most people with one or several of these risk factors do not develop lymphoma.

Often, the first sign of lymphoma is a painless swelling of lymph nodes in the neck, under an arm, or in the groin.

• Lymph nodes and/or tissues elsewhere in the body may also swell. The spleen, for example, may become enlarged in lymphoma.
• The enlarged lymph node sometimes causes other symptoms by pressing against a vein or lymphatic vessel (swelling of an arm or leg), a nerve (pain, numbness, or tingling), or the stomach (early feeling of fullness).
• Enlargement of the spleen (splenomegaly) may cause abdominal pain or discomfort.
• Many people have no other symptoms.

Symptoms of lymphoma may vary from patient to patient and may include one or more the following:

• Fevers
• Chills
• Unexplained weight loss
• Night sweats
• Lack of energy
• Itching (up to 25% of patients develop this itch [pruritus], most commonly in the lower extremity but it can occur anywhere, be local, or spreading over the whole body)
• Loss of appetite
• Shortness of breath
• Lymphedema
• Back or bone pain
• Neuropathy
• Blood in the stool or vomit
• Blockage of urine flow
• Headaches
• Seizures

These symptoms are nonspecific, and not every patient will have all of these potential symptoms. This means that a patient's symptoms could be caused by any number of conditions unrelated to cancer. For instance, they could be signs of the flu or other viral infection, but in those cases, they would not last very long. In lymphoma, the symptoms persist over time and cannot be explained by an infection or another disease.

Swelling in the neck, armpit, or groin, or unexplained swelling in an arm or leg should prompt one to seek medical attention. Such swellings may have many causes or have nothing to do with lymphoma, but they should be checked.

If any of the following symptoms persist for more than a few days, seek medical attention:

• Fevers
• Chills
• Unexplained weight loss
• Night sweats
• Lack of energy
• Itching

If a person has swelling or symptoms described in the Symptoms section, his or her health care provider will ask many questions about the symptoms (when they began, recent illnesses, past or current medical problems, any medications, workplace, health history, family history, and habits and lifestyle). A thorough examination follows these questions.

If, after an initial interview and examination, the health care provider suspects that a patient may have lymphoma, the patient will undergo a series of tests designed to provide further clarification. At some point in this workup, the patient might be referred to a specialist in blood diseases and cancer (hematologist/oncologist).

Blood tests

Blood is drawn for various tests.

• Some of these tests evaluate the function and performance of blood cells and important organs, such as the liver and kidneys.
• Certain blood chemicals or enzymes (lactate dehydrogenase [LDH]) may be determined. High levels of LDH in cases in which NHL is suspected may indicate a more aggressive form of the disorder.
• Other tests may be done to learn more about lymphoma subtypes.

Biopsy

If there is a swelling (also called lump or mass), a sample of tissue from the swelling will be removed for examination by a pathologist. This is a biopsy. Any of several methods can be used to obtain a biopsy of a mass.

• Masses that can be seen and felt under the skin are relatively easy to biopsy. A hollow needle can be inserted into the mass and a small sample removed with the needle (called a core-needle biopsy). This is usually done in the health care provider's office with a local anesthetic.
• Core-needle biopsy does not always obtain a good-quality sample. For that reason, many health care providers prefer a surgical biopsy. This involves removal of the entire swollen lymph node through a small incision in the skin. This procedure often is done with a local anesthetic, but it sometimes requires a general anesthetic.
• If the mass is not immediately under the skin but is instead deep inside the body, access is somewhat more complicated. The tissue sample is usually obtained via laparoscopy. This means making a tiny incision in the skin and inserting a thin tube with a light and a camera on the end (a laparoscope). The camera sends pictures of the inside of the body to a video monitor, and the surgeon can see the mass. A small cutting tool on the end of the laparoscope can remove all or part of the mass. This tissue is withdrawn from the body with the laparoscope.
• A pathologist (a physician who specializes in diagnosing diseases by looking at cells and tissues) examines the tissue sample with a microscope. The pathologist's report will specify whether the tissue is lymphoma and the type and subset of lymphoma. For example, Reed-Sternberg cells (large, often multinucleated cells) are hallmark cells for Hodgkin lymphoma while Sézary cells that contain pathological amounts of mucopolysaccharides are seen in cutaneous lymphoma.

Imaging studies

If there is no palpable mass in the presence of persistent symptoms, imaging studies will likely be carried out in order to determine whether a mass is present and, if so, how then to direct a biopsy.

• X-rays: In certain parts of the body, such as the chest, a simple X-ray can sometimes detect lymphoma.
• CT scan: This test provides a three-dimensional view and much greater detail and may detect enlarged lymph nodes and other masses anywhere in the body.
• MRI scan: Similar to the CT scan, MRI gives three-dimensional images with excellent detail. MRI provides better definition than CT scan in certain parts of the body, especially the brain and the spinal cord.
• Positron-emission tomographic (PET) scan: PET scan is a newer alternative to lymphangiogram and gallium scan for detecting areas in the body that are affected by lymphoma. A tiny amount of a radioactive substance is injected into the body and then traced on the PET scan. Sites of radioactivity on the scan indicate areas of increased metabolic activity, which implies the presence of a tumor.

Bone marrow examination

Most of the time, an examination of the bone marrow is necessary to see if the marrow is affected by the lymphoma. This is done by collecting a biopsy of the bone marrow.

• Samples are taken, usually from the pelvis bone.
• A pathologist examines the blood-forming bone marrow cell types under a microscope.
• Bone marrow containing certain types of abnormal B or T lymphocytes confirms a B-cell lymphoma or a T-cell lymphoma.
• Bone marrow biopsy can be an uncomfortable procedure, but it can usually be performed in a medical office. Most people receive pain medication prior to the procedure to make them more comfortable.

Staging is the classification of a cancer type by its size and whether and how much it has spread around the body. Determining a cancer's stage is very important because it tells the oncologist which treatment is most likely to work and what are the chances of remission or a cure (prognosis).

Staging of lymphomas depends on the results of imaging studies and related tests that reveal the extent of the cancer involvement.

HL is often described as being "bulky" or "nonbulky." Nonbulky means the tumor is small; bulky means the tumor is large. Nonbulky disease has a better prognosis than bulky disease.

NHL is a complicated set of diseases with a complex classification system. In fact, the classification system is continuously evolving as we learn more about these cancers. The newest classification system takes into account not only the microscopic appearance of the lymphoma but also its location in the body and genetic and molecular features.

Grade is also an important component of the NHL classification.

• Low grade: These are often called "indolent" or low-grade lymphomas because they are slow growing. Low-grade lymphomas are often widespread when discovered, but because they grow slowly, they usually do not require immediate treatment unless they compromise organ function. They are rarely cured and can transform over time to a combination of indolent and aggressive types.
• Intermediate grade: These are rapidly growing (aggressive) lymphomas that usually require immediate treatment, but they are often curable.
• High grade: These are very rapidly growing and aggressive lymphomas that require immediate, intensive treatment and are much less often curable.

The "staging," or evaluation of extent of disease, for both HL and NHL, are similar.

• Stage I (early disease): Lymphoma is located in a single lymph node region or in one lymphatic area.
• Stage IE: Cancer occurs in one area or organ outside the lymph node.
• Stage II (early disease): Lymphoma is located in two or more lymph node regions all located on the same side of the diaphragm.
• Stage IIE: As II, but cancer grows outside the lymph nodes in one organ or area on the same side of the diaphragm as the involved lymph nodes. (The diaphragm is a flat muscle that separates the chest from the abdomen.)
• Stage III (advanced disease): Lymphoma affects two or more lymph node regions, or one lymph node region and one organ, on opposite sides of the diaphragm.
• Stage IV (widespread or disseminated disease): Lymphoma is outside the lymph nodes and spleen and has spread to another area or organ such as the bone marrow, bone, or central nervous system.

If the cancer is also found in the spleen, an "S" is added to the classification.

Prognostic factors

Health researchers have extensively evaluated several risk factors shown to play a role in treatment outcome. For HL, the International Prognostic Index includes the following seven risk factors:

1. Male sex
2. Age 45 years or older
3. Stage IV disease
4. Albumin (blood test) less than 4.0 g/dL
5. Hemoglobin (red blood cell level) less than 10.5 g/dL
6. Elevated white blood cell (WBC) count of 15,000/mL
7. Low lymphocyte counts less than 600/mL or less than 8% of total WBC

The absence of any of the above risk factors is associated with an 84% rate of control of Hodgkin's disease, whereas the presence of a risk factor is associated with a 77% rate of disease control. The presence of five or more risk factors was associated with a disease control rate of only 42%.

The treatment these patients received, which occurred primarily in the 1980s, determined their outcomes. Newer treatments for Hodgkin's lymphoma may improve these predicted outcomes. Furthermore, new treatments are being developed for patients with greater risk factors.

The International Prognostic Index for NHL includes five risk factors:

1. Age older than 60 years
2. Stage III or IV disease
3. High LDH
4. More than one extranodal site
5. Poor performance status (as a measure of general health): From these factors, the following risk groups were identified:

• Low risk: no or one risk factor, has a five-year overall survival of approximately 73%
• Low-intermediate risk: two risk factors, has a five-year overall survival of approximately 50%
• High-intermediate risk: three risk factors, has a five-year overall survival of approximately 43%
• High risk: four or more risk factors, has a five-year overall survival of approximately 26%

The prognostic models were developed to evaluate groups of patients and are useful in developing therapeutic strategies. It is important to remember that any individual patient might have significantly different results than the above data, which represent statistical results for a patient group. There are specific IPIs for certain types of lymphoma, such as follicular or diffuse large B-cell.

Although the patient's primary care doctor or pediatrician can help manage the patient's care, other specialists are usually involved as consultants. Oncologists, hematologists, pathologists, and radiation oncologists are usually involved in making treatment plans and caring for the patient. Occasionally, other specialists may need to be involved depending upon what organs may be at risk in the individual's disease process.

General health care providers rarely undertake the sole care of a cancer patient. The vast majority of cancer patients receive ongoing care from oncologists but may in fact be referred to more than one oncologist should there be any question about the disease. Patients are always encouraged to gain second opinions if the situation so warrants this approach.

• One may choose to speak with more than one oncologist to find the one with whom he or she feels most comfortable.
• In addition to one's primary care physician, family members or friends may offer information. Also, many communities, medical societies, and cancer centers offer telephone or Internet referral services.

Once one settles in with an oncologist, there is ample time to ask questions and discuss treatment regimens.

• The doctor will present types of treatment options, discuss the pros and cons, and make recommendations based on published treatment guidelines and his or her own experience.
• Treatment for lymphoma depends on the type and stage. Factors such as age, overall health, and whether one has already been treated for lymphoma before are included in the treatment decision-making process.
• The decision of which treatment to pursue is made with the doctor (with input from other members of the care team) and family members, but the decision is ultimately the patients.
• Be certain to understand exactly what will be done and why and what can be expected from these choices.

As in many cancers, lymphoma is most likely to be cured if it is diagnosed early and treated promptly.

• The most widely used therapies are combinations of chemotherapy and radiation therapy.
• Biological therapy, which targets key features of the lymphoma cells, is used in many cases nowadays.

The goal of medical therapy in lymphoma is complete remission. This means that all signs of the disease have disappeared after treatment. Remission is not the same as cure. In remission, one may still have lymphoma cells in the body, but they are undetectable and cause no symptoms.

• When in remission, the lymphoma may come back. This is called recurrence.
• The duration of remission depends on the type, stage, and grade of the lymphoma. A remission may last a few months, a few years, or may continue throughout one's life.
• Remission that lasts a long time is called durable remission, and this is the goal of therapy.
• The duration of remission is a good indicator of the aggressiveness of the lymphoma and of the prognosis. A longer remission generally indicates a better prognosis.

Remission can also be partial. This means that the tumor shrinks after treatment to less than half its size before treatment.

The following terms are used to describe the lymphoma's response to treatment:

• Improvement: The lymphoma shrinks but is still greater than half its original size.
• Stable disease: The lymphoma stays the same.
• Progression: The lymphoma worsens during treatment.
• Refractory disease: The lymphoma is resistant to treatment.

The following terms to refer to therapy:

• Induction therapy is designed to induce a remission.
• If this treatment does not induce a complete remission, new or different therapy will be initiated. This is usually referred to as salvage therapy.
• Once in remission, one may be given yet another treatment to prevent recurrence. This is called maintenance therapy.

Standard first-line therapy (primary therapy) for lymphoma includes radiation therapy for most early-stage lymphomas, or a combination of chemotherapy and radiation. For later-stage lymphomas, chemotherapy is primarily used, with radiation therapy added for control of bulky disease. Biological therapy, or immunotherapy, is routinely used alongside chemotherapy.

Radiation therapy

Radiation therapy uses high-energy rays to kill cancer cells. It is considered a local therapy, meaning that it should be used to target areas of the body involved by tumor masses. A radiation oncologist will plan and supervise therapy.

• The radiation is targeted at the affected lymph node region or organ. Occasionally, nearby areas are also irradiated to kill any cells that might have spread there undetected.
• Depending on how and where the radiation is administered, it may cause certain side effects such as fatigue, loss of appetite, nausea, diarrhea, and skin problems. Radiation of lymph node areas may result in suppression of the immune system to varying degrees. Irradiation of the underlying bone and the marrow within the bone may result in suppression of the blood counts.
• The radiation is usually administered in short bursts on five days a week over the course of several weeks. This keeps the dose of each treatment low and helps prevent or lessen side effects.

Chemotherapy

Chemotherapy is the use of powerful drugs to kill cancer cells. Chemotherapy is a systemic therapy, meaning that it circulates through the bloodstream and affects all parts of the body.

Unfortunately, chemotherapy also affects healthy cells; this accounts for its well-known side effects.

• The side effects of chemotherapy depend partly on the drugs used and the doses.
• Some people, because of variability in metabolism of chemotherapy drugs, tolerate chemotherapy better than other people.
• The most common side effects of chemotherapy include suppression of blood counts, which could result in increased susceptibility to infection (low white blood cell count), anemia (low red blood cell count that may require a blood transfusion), or blood-clotting problems (low platelet count). Other side effects may include nausea and vomiting, loss of appetite, hair loss, sores in the mouth and digestive tract, fatigue, muscle aches, and changes in fingernails and toenails.
• Medications and other treatments are available to help people tolerate these side effects, which can be severe.
• It is very important to discuss and review the potential side effects of each chemotherapy drug in the treatment with the oncologist, pharmacist, or oncology nurse. Medications to lessen the side effects should also be reviewed.

Chemotherapy may be given in pill form, but it is typically a liquid infused directly into the bloodstream through a vein (intravenous).

• Most people who receive intravenous chemotherapy will have a semi-permanent device placed in a large vein, usually in the chest or arm.
• This device allows the medical team quick and easy access to the blood vessels, both for administering medications and for collecting blood samples.
• These devices come in several types, usually referred to as a "catheter," "port," or "central line."

Experience has shown that combinations of drugs are more efficient than monotherapy (use of a single medication).

• Combinations of different drugs both increase the chance that the drugs will work and lower the dose of each individual drug, reducing the chance of intolerable side effects.
• Several different standard combinations are used in lymphoma. Which combination one receives depends on the type of lymphoma and the experiences of the oncologist and the medical center where a person is receiving treatment.
• The combinations of drugs are usually given according to a set schedule that must be followed very strictly.
• In some situations, chemotherapy can be given in the oncologist's office. In other situations, one must stay in the hospital.

Chemotherapy is given in cycles.

• One cycle includes the period of actual treatment, usually several days, followed by a period of rest for several weeks to allow recovery from side effects caused by the chemotherapy, particularly anemia and low white blood cells.
• Standard treatment typically includes a set number of cycles, such as four or six.
• Spreading the chemotherapy out this way allows a higher cumulative dose to be given, while improving the person's ability to tolerate the side effects.

Biological therapies are sometimes referred to as immunotherapy because they take advantage of the body's natural immunity against pathogens. These therapies are attractive because they offer anticancer effects without many of the undesirable side effects of standard therapies. There are many different types of biological therapies. The following are some of the most promising for treating lymphoma:

• Monoclonal antibodies: Antibodies are substances produced by our body to fight pathogens. Every cell, organism, or pathogen within our body carries markers on its surface that antibodies may recognize. These surface markers are called antigens. A monoclonal antibody is an antibody that is made in a laboratory to find and attach itself to a specific antigen. Monoclonal antibodies can be used to help one's own immune systems kill tumor cells and other pathogens directly, or they can deliver cancer-killing therapies (such as radiation or chemotherapy) directly to a specific antigen found on cancer cells.
• Cytokines: These naturally occurring chemicals are produced by the body to stimulate the cells in the immune system and other organs. They can also be produced artificially and administered in large doses to patients with greater effect. Examples include interferons and interleukins, which stimulate the immune system, and colony-stimulating factors, which stimulate the growth of blood cells.
• Vaccines: Unlike the more familiar vaccines for infectious diseases such as polio and flu, cancer vaccines do not prevent the disease. Rather, they are designed to stimulate the immune system to mount a specific response against the cancer. They also create a "memory" of the cancer so that the immune system activates very early in cases of recurrence, thus preventing the development of a new tumor.
• Radioimmunotherapy combines a radioactive substance with a monoclonal antibody that reacts with antigens on lymphoma cells and can disrupt these cells.

Other therapies that are primary or supportive medications are undergoing continuing development and refinement; they include drugs that target cancer cells on a molecular level, various new monoclonal antibodies, and other biologic therapies such as steroids and bone marrow stimulants. For example, CAR T-cell therapy uses the body's own immune cells that are modified to recognize and fight cancer cells. It treats many hematologic malignancies in clinical trials and is approved for the treatment of DLBCL (diffuse large B-cell lymphomas).

Watchful waiting means choosing to observe and monitor the cancer rather than treat it right away. This is strategy is sometimes used for indolent recurrent tumors. Treatment is given only if the cancer starts to grow more rapidly or to cause symptoms or other problems.

Stem cell transplantation is usually not used as a primary therapy in lymphoma.

• Stem cell transplantation is usually reserved for lymphoma that has been previously treated into remission but has recurred.
• Stem cell therapy as primary therapy has been used for aggressive T-cell NHL in first remission, usually as part of a clinical trial. Stem cell therapy is also considered when standard primary treatment is unable to control the lymphoma and achieve remission.
• This procedure, which requires a lengthy hospital stay, involves very high doses of chemotherapy to kill the aggressive cancer cells.
• The chemotherapy doses are so high that the chemotherapy also stops the patient's bone marrow from producing healthy new blood cells.
• The patient then receives a transfusion of healthy bone marrow or blood stem cells, either from previously collected stem cells from the patient himself or herself (called autologous transplantation or autotransplantation) or from a donor (called allogeneic transplantation), to "kick start" the bone marrow into producing healthy blood cells.
• This is a very intensive therapy with a lengthy recovery period.

Clinical trials

An oncologist may belong to a network of investigators who offer novel treatments for various types of cancers. These novel therapies are newer agents that have been recently developed, and extensive data on treatment results are not yet known. Such new agents can be offered in the context of a clinical trial. Usually, a consent form that explains the drug, its known side effects, its potential side effects, and alternatives to the drug treatment are presented to the patient. If the treatment seems promising for the particular subtype of lymphoma, and the patient is fully educated about the potential benefits and risks associated with such treatment and is interested in receiving such treatment, then the consent form is signed by the patient and the managing physician, and possibly other involved parties. The patient is then enrolled in a treatment protocol that specifies exactly how a patient is to be treated with the new therapy.

Alternatively, an oncologist may refer a patient to another institution to receive investigational treatment or intensive treatment, such as a stem cell transplant.

Complementary/alternative therapies

Several alternative therapies have undergone preliminary testing in lymphoma. None has been found to work better than or as well as standard medical therapies. A few therapies, still felt to be experimental, have been found to be potentially helpful as complements to medical therapy, however.

• Acupuncture has been helpful in relieving musculoskeletal symptoms, as well as in controlling nausea and vomiting associated with chemotherapy.
• The supplements coenzyme Q10 and polysaccharide K (PSK) are undergoing further evaluation to determine their effects on treatment outcome. Both drugs have immune enhancing properties. PSK has been used more extensively in Japan as part of an anticancer therapy.
• Neither of these therapies has undergone extensive blinded studies and cannot be considered a part of any planned therapeutic endeavor.
• Do not use these therapies unless you first discuss them with your doctor.

Numerous chemotherapy and biological drug combinations may be prescribed by an oncologist. Which type and combination of therapy depends on many factors, including the type and stage of lymphoma, the age of the patient, the ability to tolerate chemotherapy side effects, and if any previous treatment for the lymphoma has occurred. Oncologists often work together regionally to decide which combination of chemotherapy and biological drugs are currently working best for their patients. Because of this regional collaboration, the drug combinations often vary and are able to change rapidly when improved results occur.

After completion of primary therapy for lymphoma, all appropriate tests will be repeated to see how well the therapy worked.

• The results of these tests will tell the oncologist whether the patient is in remission.
• If the patient is in remission, the oncologist will recommend a schedule of regular testing and follow-up visits to monitor the remission and to catch any recurrence early.
• Keeping up with these visits and tests is very important in order to avoid advanced or widespread disease.

If lymphoma recurs after treatment, the oncologist will likely recommend further treatment.

The outlook for HL is very good. It is one of the most curable cancers. The five-year survival rate after treatment is greater than 80% for adults and greater than 90% for children.

Because of refinements in and more aggressive approaches to therapy, the outlook for NHL has improved significantly in the last few decades. The five-year survival rate after treatment is 69% for adults and up to 90% for children; the 10-year relative survival rate is 59%. The addition of immunotherapy to standard treatment for NHLs may further improve survival rates so that life expectancy may move toward normal.

Many people live with lymphoma in remission for many years after treatment.

There is no known way to prevent lymphoma. A standard recommendation is to avoid the known risk factors for the disease. However, some risk factors for lymphoma are unknown, and therefore impossible to avoid. Infection with viruses such as HIV, EBV, and hepatitis are risk factors that can be avoided with frequent hand washing, practicing safe sex, and by not sharing needles, razors, toothbrushes, and similar personal items that might be contaminated with infected blood or secretions.

Living with lymphoma presents many new challenges for an individual and his or her family and friends.

• There may be many worries about how the lymphoma will affect one's ability to "live a normal life," that is, to care for family and home, to hold a job, and to continue the friendships and activities one enjoys.
• Many people feel anxious and depressed. Some people feel angry and resentful; others feel helpless and defeated.

For most people with lymphoma, talking about their feelings and concerns can be helpful.

• Friends and family members can be very supportive. They may be hesitant to offer support until they see how the affected person is coping. If the affected person wishes to talk about his or her concerns, it is important to let them know to do so.
• Some people don't want to "burden" their loved ones, or they prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if one wishes to discuss their feelings and concerns about having lymphoma. The treating hematologist or oncologist should be able to recommend someone.
• Many people with lymphoma are helped profoundly by talking to other people who have lymphoma. Sharing such concerns with others who have been through the same thing can be remarkably reassuring. Support groups of people with lymphoma may be available through the medical center where one is receiving treatment. The American Cancer Society also has information about support groups all over the United States.