Genetics Predicts Toxicity Following Blood And Marrow Transplantation

The outlook for cancer patients treated with blood and marrow transplantation (BMT) for fatal blood cancers is much brighter today based on research conducted at Roswell Park Cancer Institute (RPCI), Theresa E. Hahn, PhD, Department of Medicine, explained at the 48th Annual Meeting & Exposition of the American Society of Hematology, in Orlando, FL.

BMT is used to cure leukemia, lymphoma and multiple myeloma; however, the therapy can be associated with high levels of toxicity. "Mortality due to conditioning regimen-related toxicity has decreased over the past decade," notes Dr. Hahn, "but it is still a major limitation for both autologous and allogeneic BMT."

Dr. Hahn, in collaboration with Christine B. Ambrosone, PhD (Epidemiology/ Prevention), and Philip L. McCarthy, Jr., MD (Medicine), found that the genetic makeup of patients can predict who develops toxicity following the high doses of chemotherapy and/or radiation given prior to BMT, and whether their toxicity is likely to be moderate, severe or fatal. This finding has the potential to improve outcomes by allowing individualized conditioning regimens.

The research team performed a genotype analysis of blood and bone marrow samples from 268 BMT patients to determine whether the presence or absence of two glutathione-S-transferase isoenzymes could predict which patients would develop toxicity.

"These enzymes metabolize and detoxify many chemotherapeutic drugs and radiation," explains Dr. Hahn. "Genotype analysis demonstrated that genetic variability affecting the activity of these enzymes in patients can predict which patients will develop toxicity."