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Non-Hodgkin's lymphoma

Description

An in-depth report on the causes, diagnosis, and treatment of non-Hodgkin's lymphoma.

Alternative Names

Lymphoma - non-Hodgkin's; NHL; B-cell lymphomas

Transplantation

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

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

Collecting the Stem Cells

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

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

Some evidence suggests that both stem cell and bone marrow procedures produce similar benefits in terms of response rates and duration of remission. However, in a 2002 study, stem cell transplantation was associated with better overall survival rates. It also seems to be superior in terms of cost, quality of life, and the need for less supportive care, so is the procedure discussed here.

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

• In an autologous transplant, the marrow or blood cells used for replacement are taken from the patient. There is some danger, however, that these cells may contain tumor cells and that the cancer can regrow. It is unclear if this approach improves survival compared to standard chemotherapy for newly diagnosed disease. However, it clearly has benefits in the treatment of some forms of relapsed non-Hodgkin's lymphomas. There is also a higher risk for leukemia. (This risk is lower in peripheral stem cells transplants than in bone marrow transplants.)
• In an allogeneic transplant, bone marrow or stem cells are taken from a donor. Siblings are the best donors. Relapse rates can be very low with this approach and cure may be possible in some cases. However, it is highly toxic and donor and recipient must be matched as closely as possible to avoid rejection by the immune system, a serious complication called graft-versus-host disease. Advances in techniques are reducing the toxicities associated with this approach.

The Blood Stem Cell Collection Procedure.

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

The Transplantation Procedure

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

Candidates and Success Rates

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

Success Rates. Success rates vary depending on many factors. The following are survival rates reported by a few 2000 and 2001 studies of patients with different lymphomas:

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

Side Effects and Complications

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

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

Infection resulting from a weakened immune system is the most common side effect and can persist for several months after the transplant. Because the stem cell procedure is done more swiftly, the risk period is shorter than with bone marrow transplantation. Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. Acute GVHD occurs in over half of allogeneic transplants, usually within 90 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). In some cases, it can become chronic, which usually develops after the third month following the transplant but may not develop for a year or more. GVHD can causes gastrointestinal problems, severe skin reactions, hair loss, mouth and throat ulcers, and liver damage. Careful matching of the donor and preventive immunosuppressive drugs, such as corticosteroids, methotrexate, and cyclosporine, may reduce the risk. T-lymphocyte depletion is another approach for preventing GVHD, which involved reducing the number T cells infused with the stem cells.

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

Other potentially serious complications include:

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

• Review Date: 1/17/2007
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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