Effect of tresperimus on in vitro human cord blood CD34+ cell differentiation

Tresperimus, an analogue of 15-deoxyspergualin (15-DSG), is immunosuppressi ve and prevents lethal graft-versus-host disease following allogeneic bone marrow transplantation in mice. Here, we present an in vitro dose response study examining the ability of tresperimus to support clonogenesis in cultu red CD34+ cord blood stem cells. Our findings revealed that only the lowest dose examined, 0.5 mug tresperimus/ml, supports normal myelopoiesis, eryth ropoiesis and megakaryopoiesis. Greater concentrations of the drug induced dose-dependent inhibition of clonogenesis. This latter effect was not due t o apoptosis and was reversible by drug withdrawal. We conclude that tresperimus at 0.5 mug/ml supports the clonogenic potentia l of cord blood CD34+ cells. Dose-dependent inhibition of clonogenesis was completely reversible following drug withdrawal. These results may be of cl inical interest as tresperimus is currently used in phase I-III studies for the prevention of graft versus host disease in recipients of allogeneic bo ne marrow.