University of Virginia Health System

U.VA. RESEARCHERS DISCOVER POSSIBLE HINDRANCE TO BLOOD PLATELET REGENERATION IN BONE MARROW TRANSPLANT PATIENTS

Researchers at the University of Virginia Health System are closer to understanding why patients who receive bone marrow transplants are unable to effectively produce blood platelets-sticky cell fragments that cause blood to clot. They discovered a mechanism that blocks megakaryocytes, bone marrow cells that are needed to make platelets, from doing their job. The findings will be published in the March 1 edition of Blood.

"The goal at the end of the rainbow is to find some sort of therapy that we can administer to a patient that will cause rapid regeneration of megakaryocytes after high dose chemotherapy," said Dr. Adam Goldfarb, the study's principal investigator and associate professor in the Department of Pathology and associate director of the Clinical Hematology Laboratory at U.Va. Health System. "It will eliminate the need for platelet transfusion. It will reduce the patient's risk for excessive bleeding. It will permit that patient to be discharged sooner. It will improve the overall management of the patient."

Patients needing a bone marrow transplant first receive high doses of chemotherapy in order to kill off their own sick marrow. These drugs inhibit their body's ability to produce megakaryocytes. When they receive a bone marrow transplant, they are often unable to regenerate new platelets for up to a half a year or more. According to the researchers, stromal cells, non-blood cells derived from bone marrow, blocked the ability of bone marrow stem cells to develop into megakaryocytes by jamming a specific signal transduction pathway. Using a molecular approach to force the activation of this jammed pathway, the researchers were able to override the inhibitory effects of the stromal cells.

Currently, patients who receive high doses of chemotherapy require platelet transfusions. This is a process where platelets are separated from blood products of a donor and administered to patients who need them. According to Goldfarb, a better procedure to help does not exist.

"It's hard to keep up the supply of platelets in stock, it's expensive to transfuse the number of platelets that a single patient needs," said Goldfarb. "Patients also have the possibility of making antibodies from being exposed to too much donor tissue. This could make a person resistant to transfusions when they really need them."

Goldfarb adds that bone marrow transplantation is broadening and being used to treat things that it was not used to treat in the past. Therefore the number of patients who get high dose chemotherapy is going up, increasing the need for therapies to improve megakaryocyte regeneration.

February 24, 2003