Hodgkin's Disease

Description

Transplantation

Patients with relapsed or progressive HD are often treated with high-dose chemotherapy followed by stem cell transplantation procedures. (It does not appear to offer an advantage compared to standard chemotherapy as initial treatment for patients with high-risk advanced HD.)

This treatment involves removal and replacement of stem cells, which are produced in the bone marrow. This allows the patient to receive high-dose chemotherapy without destroying these important cells. 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, usually using the patients own cells (called an autologous procedure) or, less commonly, from a donor (allogeneic procedure).

Collecting the Stem Cells

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

• Directly from blood (peripheral blood stem cell transplantation).
• From bone marrow (bone marrow transplantation).

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

• 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, however, so at this time its use is limited to children and sometimes adults with low weight. (A small 2001 study on adults suggested it might also be useful for adults with normal weights.)

Current evidence suggests that the stem cell and bone marrow procedure produce similar benefits in terms of survival. However, because stem cell transplantation seems to be superior in terms of cost, quality of life, and the need for less supportive care, it is 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):

• An autologous transplant is one in which marrow or blood cells used are the patient's own. Autologous stem cell transplantation is the current preferred choice for HD patients who need these procedures. The advantage to an autologous procedure is that the patient is not at risk for rejection by the immune system. There is some danger, however, that the cells used may contain tumor cells and the cancer can regrow. There is also a higher risk for leukemia (This risk is lower in peripheral stem cells transplants than in bone marrow transplants.) A number of studies, however, are reporting good success with this transplant.
• An allogeneic transplant is one in which bone marrow or stem cells are taken from a donor. The 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. Siblings are the best possibility.

The Blood Stem Cell Collection Procedure

• The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim) 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 patients 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 three to four 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. Agents used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning to reduce toxicity includes total-body radiation plus one agent.
• A few days after treatment, the patient is rescued using the stored stem cells, which are administered through a vein. This may take several hours. Patients may experience 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. Because this increases immune factors, there is some concern that it might also heighten the immune attack against the donor cells, but studies to date have been encouraging and are reporting a low risk. (Adding another substance, thrombopoietin, may prove to enhance stem cell production.)
• The patient is kept in a protected environment to minimize infection, and he or she usually needs blood cell replacement and nutritional support.

Candidates and Success Rates

The following patients may be appropriate transplantation candidates:

• Patients with advanced or relapsed Hodgkin's disease, particularly for young patients with a poor outlook.
• Some studies suggest benefits using stem cell transplantation for early-stage patients who do not respond to initial therapy. (This includes those who achieve an initial partial remission, those who progress during therapy, and those who have evidence of residual disease on biopsy.)

Patients with B symptoms or those who are in poor condition at the time of the procedure are more likely to experience poorer results.

Overall, studies report five-year survival rates of between 30% and 93%, with the rates being higher or lower depending on different factors. The success rates appear to be the same in children, adolescents, and adults. Prognosis is best in the following:

• If the patient has had only one relapse that occurred more than 12 months after the completion of previous treatment, and
• If the cancer recurred within a lymph node, not outside it.

In such patients, the four-year survival rate was 93% in one study. Even when these factors were not present, the survival rate, with equivalent treatment, was 43%, and experts suggest it could be higher with more aggressive therapies. (It should be noted that there was a 6% mortality rate from the treatment itself.)

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% to 25% morality rates. Now mortality rates are below 5%. Potentially serious complications are the following:

• Infection resulting from a weakened immune system. This 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 is can become chronic, which usually develops after the third month following the transplant but may not develop for a year or more. GVHD can cause 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 (Sandimmune), 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 agents, however, may not pose as high a danger as older treatments.
• Bleeding because of reduced platelets. This risk is highest within the first four weeks after BMT.
• Infertility.
• Organ complications to the liver, heart, kidney, or lungs.
• Failure of the transplant. The marrow graft may fail or new marrow cells may now grow.