Drugs Expert

Lymphoma is a cancer that begins in the lymphatic cells of the immune system and presents as a solid tumor of lymphoid cells. It is treatable with chemotherapy, and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage of the disease. These malignant cells often originate in lymph nodes, presenting as an enlargement of the node (a tumor). Lymphomas are closely related to lymphoid leukemias, which also originate in lymphocytes but typically involve only circulating blood and the bone marrow (where blood cells are generated in a process termed haematopoesis) and do not usually form static tumors.  There are many types of lymphomas, and in turn, lymphomas are a part of the broad group of diseases called hematological neoplasms.

Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him, Hodgkin’s lymphoma. Since then, many other forms of lymphoma have been described, grouped under several proposed classifications. The 1982 Working formulation classification became very popular. It introduced the category non-Hodgkin lymphoma (NHL), divided into 16 different diseases. However, because these different lymphomas have little in common with each other, the NHL label is of limited usefulness for doctors or patients and is slowly being abandoned. The latest classification by the WHO (2001) lists 43 different forms of lymphoma divided in four broad groups.

Although older classifications referred to histiocytic lymphomas, these are recognized in newer classifications as of B, T or NK cell lineage. True histiocytic malignancies are rare and are classified as sarcomas.

What causes Lymphoma?

The exact causes of lymphoma are not known. 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.
• Infections
  • Infection with HIV
  • Infection with Epstein-Barr virus (EBV), one of the etiologic factors in mononucleosis
  • 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
  • Diseases requiring 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
  • Black hair dye, which for more than 20 years has been linked to higher rates of NHL
• 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.

What are the Symptoms of Lymphoma?

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

• Lymph nodes or tissues elsewhere in the body may also swell. The spleen, for example, often becomes 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 may cause abdominal pain or discomfort.
• Many people have no other symptoms.

Symptoms of lymphoma may include the following:

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

These symptoms are nonspecific. This means that they 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.

Classification

A number of various different classification systems exist for lymphoma. As an alternative to the American Lukes-Butler classification, in the early 1970s, Karl Lennert of Kiel, Germany, proposed a new system of classifying lymphomas based on cellular morphology and their relationship to cells of the normal peripheral lymphoid system.

Some forms of lymphoma are categorized as indolent (e.g. small lymphocytic lymphoma), compatible with a long life even without treatment, whereas other forms are aggressive (e.g. Burkitt’s lymphoma), causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The prognosis therefore depends on the correct classification of the disease, established by a pathologist after examination of a biopsy.

Working Formulation and Non-Hodgkin lymphoma

The 1982 Working Formulation is a classification of non-Hodgkin lymphoma. It excluded the Hodgkin lymphomas and divided the remaining lymphomas into four grades (Low, Intermediate, High, and Miscellaneous) related to prognosis, with some further subdivisions based on the size and shape of affected cells. This purely histological classification included no information about cell surface markers, or genetics, and it made no distinction between T-cell lymphomas or B-cell lymphomas.

The Working Formulation was widely accepted at the time of its publication but is now obsolete. It was superseded by subsequent classifications (see below) but it is still used by cancer agencies for compilation of lymphoma statistics and historical comparisons.

REAL

In the mid 1990s,the Revised European-American Lymphoma (REAL) Classification attempted to apply immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin’s lymphoma. REAL has been superseded by the WHO classification.

World Health Organization (WHO)

The WHO Classification, published in 2001 and updated in 2008, is the latest classification of lymphoma and is based upon the foundations laid within the “Revised European-American Lymphoma classification” (REAL). This system attempts to group lymphomas by cell type (i.e. the normal cell type that most resembles the tumor) and defining phenotypic, molecular or cytogenetic characteristics. There are three large groups: the B cell, T cell, and natural killer cell tumors. Other less common groups, are also recognized. Hodgkin’s lymphoma, although considered separately within the World Health Organization (and preceding) classifications, is now recognized as being a tumor of, albeit markedly abnormal, lymphocytes of mature B cell lineage.

Mature B cell neoplasms

DNA-microarray analysis of Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in lymphoma cells (as compared to normal cells), whereas red indicates genes that are overexpressed in lymphoma cells.

• Chronic lymphocytic leukemia/Small lymphocytic lymphoma
• B-cell prolymphocytic leukemia
• Lymphoplasmacytic lymphoma (such as Waldenström macroglobulinemia)
• Splenic marginal zone lymphoma
• Plasma cell neoplasms:
  • Plasma cell myeloma
  • Plasmacytoma
  • Monoclonal immunoglobulin deposition diseases
  • Heavy chain diseases
• Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
• Nodal marginal zone B cell lymphoma (NMZL)
• Follicular lymphoma
• Mantle cell lymphoma
• Diffuse large B cell lymphoma
• Mediastinal (thymic) large B cell lymphoma
• Intravascular large B cell lymphoma
• Primary effusion lymphoma
• Burkitt lymphoma/leukemia

Mature T cell and natural killer (NK) cell neoplasms

• T cell prolymphocytic leukemia
• T cell large granular lymphocytic leukemia
• Aggressive NK cell leukemia
• Adult T cell leukemia/lymphoma
• Extranodal NK/T cell lymphoma, nasal type
• Enteropathy-type T cell lymphoma
• Hepatosplenic T cell lymphoma
• Blastic NK cell lymphoma
• Mycosis fungoides / Sezary syndrome
• Primary cutaneous CD30-positive T cell lymphoproliferative disorders
  • Primary cutaneous anaplastic large cell lymphoma
  • Lymphomatoid papulosis
• Angioimmunoblastic T cell lymphoma
• Peripheral T cell lymphoma, unspecified
• Anaplastic large cell lymphoma

Hodgkin lymphoma

• Classical Hodgkin lymphomas:
  • Nodular sclerosis
  • Mixed cellularity
  • Lymphocyte-rich
  • Lymphocyte depleted or not depleted
• Nodular lymphocyte-predominant Hodgkin lymphoma

Immunodeficiency-associated lymphoproliferative disorders

• Associated with a primary immune disorder
• Associated with the Human Immunodeficiency Virus (HIV)
• Post-transplant
• Associated with methotrexate therapy
• Primary central nervous system lymphoma occurs most often in immunocomprimised patients,in particular those with AIDS,but it can occur in the immunocompetent as well.It has a poor prognosis,particularly in those with AIDS.Treatment can consist of corticosteroids, radiotherapy,and chemotherapy,often with methotrexate.

Diagnosis

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). These questions are followed by a thorough examination.

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 will likely 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 called 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.

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.
• Lymphangiogram: This approach, which provides an image of the lymphatic system by tracing a dye that moves though the system, has essentially been replaced by either CT scan, MRI, or PET (see below).
• Gallium scan: Lymphomas tend to collect a substance called gallium when injected into the body. For this test, a tiny amount of radioactive gallium is injected into the body. A scan is then done to find areas where the gallium has collected. Collections of gallium suggest a tumor.
• 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 a hip bone.
• A pathologist examines the bone marrow under a microscope.
• Bone marrow containing certain types of abnormal B or T lymphocytes confirms 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.

Other tests

• Lumbar puncture: This test, sometimes called a spinal tap, is a method for collecting a sample of the fluid surrounding the brain and spinal cord. This fluid is called cerebrospinal fluid. If the lymphoma has affected the central nervous system, the cerebrospinal fluid will likely contain lymphoma cells.
• Organ function tests: These tests are usually done before starting treatment to make sure that one’s organs are healthy enough to withstand the side effects of therapy. Examples include an echocardiogram or MUGA scan (a test that provides a movie-like image of the working heart) for the heart and pulmonary function tests for the lungs.

Staging

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 is based on the microscopic examination and 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” lymphomas because they grow slowly. Low-grade lymphomas are often widespread when discovered, but because they grow slowly, they usually do not require immediate treatment unless organ function is compromised. 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 area or organ outside the lymph node.
• Stage II (locally advanced disease): Lymphoma is located in two or more lymph node regions all located on the same side of the diaphragm or in one lymph node region and a nearby tissue or organ. (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.

Both HL and NHL are further classified with letters.

• An “A” or “B” designation indicates whether the person with lymphoma had symptoms such as fevers and/or weight loss at the time of diagnosis. “A” indicates no such symptoms, and “B” indicates symptoms.
• An “E” designation indicates that the tumor spread directly from a lymph node into an organ or that a single organ outside the lymphatic system is affected with no apparent lymphatic involvement.

Prognostic factors

Several risk factors have been extensively evaluated and 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 then 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 count 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 outcomes for these patients were also determined by the treatment they received, which occurred primarily in the 1980s. 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: one risk factor, five-year lymphoma-free survival (LFS) of 70%
• Intermediate risk: two to three risk factors, five-year LFS of 49%-50%
• Poor risk: four to five risk factors, five-year LFS of 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.

Methods of Treatment

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.

• Although medical treatments are fairly standardized, not all physicians behave similarly.
• 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 each type of treatment, 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 patient’s.
• 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 takes advantage of the body’s innate cancer-fighting ability, is used in some cases.

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.

Medical Treatment

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 increasingly being used in addition to or as an alternative to these standard therapies.

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), 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 therapy

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.

Other therapies under continuing development include drugs that target cancer cells on a molecular level, various new monoclonal antibodies, and other biologic therapies.

Other Therapy

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 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 blind studies and cannot be considered a part of any planned therapeutic endeavor.

Drugs rating:

	Title	Votes	Rating
1	Leukeran (Chlorambucil)	2		(10.0/10)
2	Adriamycin (Doxorubicin)	11		(8.9/10)
3	Velcade (Bortezomib)	16		(8.4/10)
4	Arranon (Nelarabine)	0		(0/10)
5	Folotyn (Pralatrexate)	0		(0/10)
6	Vinblastine	0		(0/10)
7	Ontak (Denileukin Diftitox)	0		(0/10)
8	Thioplex (Thiotepa)	0		(0/10)
9	Trexall (Methotrexate)	0		(0/10)
10	Thiotepa	0		(0/10)
11	Velban (Vinblastine)	0		(0/10)

Prognosis

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.

As a result 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 63% for adults and up to 90% for children. The addition of immunotherapy to standard treatment for NHLs may further improve survival rates.

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

Follow-up

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.