Chronic Graft-Versus-Host-Disease Improves Survival of Multiple Myeloma Patients

Chronic Graft-Versus-Host-Disease Improves Survival of Multiple Myeloma Patients Receiving Stem Cell Transplants

Results of a Canadian study published in Bone Marrow Transplantation, indicates that multiple myeloma patients are more likely to achieve long-term, cancer-free survival from an allogeneic stem cell transplant if the procedure causes chronic graft-versus-host-disease (GVHD).

There are approximately 40,000 people in the United States living with multiple myeloma. With 14,000 new cases of multiple myeloma diagnosed each year in the U.S., it is the second most common blood cancer. Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, thereby suppressing the normal formation and function of other cells necessary for optimal production of blood cells and immune functions. The excessive accumulation of cancer cells in bone marrow ultimately leads to the formation of tumors within the bone and to its breakdown.

Standard treatment for multiple myeloma is chemotherapy and may be followed with stem cell transplantation (SCT). High-dose chemotherapy and/or radiation tend to be more effective at killing cancer cells than lower doses of therapy. However, the high doses also kill blood-forming cells (stem cells) that are produced in the bone marrow, leaving patients susceptible to infection, anemia and uncontrolled bleeding. In order to rescue low levels of blood cells caused by high-dose therapy, stem cells are collected from either blood or bone marrow, stored and then infused into the patient after completion of high-dose therapy. In an allogeneic transplant, stem cells are collected from a related or unrelated donor. Although high-dose therapy and SCT may be very effective at curing some cancers, the high incidence of severe side effects leaves some physicians and patients hesitant to utilize this treatment option.

GVHD is a common complication of allogeneic SCT. In GVHD, lymphocytes contained in donated marrow or blood stem cells attack cells in the body of the recipient, especially in the skin, gastrointestinal tract and liver. The common symptoms of GVHD are skin rashes, jaundice, liver disease and diarrhea, but GVHD also increases a patient's susceptibility to infection. Interestingly, GVHD can also have an anti-cancer effect because donor lymphocytes can kill cancer cells as well as normal cells. When donor lymphocytes kill cancer cells, it is known as graft-versus-cancer effect. There are ongoing studies attempting to control this graft-versus-cancer reaction for therapeutic purposes.

To better identify which patients are most likely to benefit from an allogeneic SCT, Canadian researchers collected data from 37 patients with advanced multiple myeloma who had undergone an allogeneic SCT between 1990 and 2000. The patients averaged five cycles of high-dose chemotherapy prior to transplant, with an average of 9.3 months between diagnosis and transplant. The probability of patients achieving a complete disappearance of cancer (remission) one year following the transplant was 57%. Forty months following the transplant, cancer progression occurred in 52% of patients and the overall survival was 32%. Importantly, patients with chronic GVHD experienced significantly more complete remissions than did other patients. The data also implied that patients who had undergone more chemotherapy cycles prior to SCT were more likely to fail treatment and die early.

Results of a Canadian study suggest that patients with chronic GVHD benefit most from allogeneic SCT and that treatment with an allogeneic SCT early in the disease may increase the likelihood of survival. Individuals with multiple myeloma may wish to speak with their physician regarding the risks and benefits of allogeneic SCT or about participating in a clinical trial. (Bone Marrow Transplantation, Vol 28, No 9, pp 841-848, 2001)

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