Demonstrator 2: HSCT Preconditioning Drugs

Toleration of HSCT Preconditioning Treatments in FA Patients

Bone Marrow Failure (BMF) is a common condition associated with Fanconi Anemia (FA), that is treated with hematopoietic stem cell transplants (HSCT). Various chemotherapeutic agents can be used to ‘pre-condition' BMF patients prior to HSCT. It is well known that FA-patients with BMF tolerate certain conditioning agents well (e.g. fludarabine), and respond poorly to other agents that pose no problems for non-FA patients (e.g. cyclophosphamide and busulfan). And even within FA patient's, response to a given condition agent can vary widely.

If we can understand what other variants may contribute to the differential response of FA patients to different conditioning drugs, we can develop and test mechanistic hypotheses, that may ultimately lead to better, personalized therapies. In this demonstrator we want to know if there are certain genetic variants (or combinations thereof) in patients with BMF that are correlated with clinical outcomes following different HSCT pre-conditioning regimens, and generate hypotheses about underlying molecular and pathophysiological mechanisms.