Guidelines for determining the best possible time to receive bone marrow transplants

Bone marrow transplant, the only cure for patients with myelodysplastic syndrome (MDS), is a life-saving procedure but carries with it many risks and potential side effects.

Guidelines for determining the best possible time to receive this vital treatment will be published in a new study in the July 15, 2004, issue of Blood, the official journal of the American Society of Hematology.

“Many MDS patients enjoy a long period after diagnosis without obvious disease progression. For these patients, the risks associated with bone marrow transplantation are unacceptably high,” according to Corey Cutler, M.D., M.P.H., F.R.C.P.C., of the Dana-Farber Cancer Institute, the senior author of the study. “The challenge is to determine the optimal timing of bone marrow transplantation to reduce the risks while extending survival as much as possible.”

In patients with MDS, the bone marrow produces poorly functioning blood cells instead of healthy ones. By American Cancer Society estimates, 14,000 people in the United States and 87,000 worldwide are diagnosed with MDS each year. The survival time for these patients, depending on the severity of their disorder, is typically only about six months to six years.

A team of researchers from several prestigious institutions studied 260 patients who were diagnosed with MDS and received bone marrow transplants; 230 patients whose MDS had progressed into acute myeloid leukemia (AML), a cancer of the white blood cells, and who also received bone marrow transplants; and 184 patients who were diagnosed with MDS but did not receive transplants.

The MDS patients were categorized into four risk groups based on their prognosis at the time of diagnosis: Low, Intermediate-1, Intermediate-2, and High. The researchers analyzed the patient outcomes for each of these risk groups for three different scenarios: the patient receiving a bone marrow transplant at diagnosis of MDS, a transplant after the MDS had progressed to AML, and a transplant at an interval between these two occurrences.

It was found that for the Low and Intermediate-1 groups, the best time for a bone marrow transplant was after diagnosis, but before development of AML. Delaying the transplant resulted in the greatest increase in life expectancy, especially in patients under the age of 40. The researchers theorize that the ideal timing of the transplant corresponds to certain clinical events for the MDS patient, such as developing a dependence on blood transfusions or the development of a cytogenetic abnormality.

For the High and Intermediate-2 groups, transplantation immediately following diagnosis maximized overall survival.

"The timing of bone marrow transplantation is challenging in patients with myelodysplasia due to the unpredictability of the natural history of the underlying disease as well as the significant risk of morbidity and mortality from the procedure. Prospective clinical trials that will address this issue are unlikely to be performed,” says Richard T. Maziarz, Medical Director of the Center for Hematologic Malignancies at Oregon Health & Science University. “This study is valuable to the hematology community because it supports a widespread practice in which low-risk myelodysplasia patients are monitored for disease evolution, while high-risk patients are referred for early transplant. The authors have utilized sophisticated statistical tools to perform a retrospective data analysis to draw their conclusions, which may quite possibly become the future established guidelines for the management of myelodysplasia patients."