GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

Overview

Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. Additional immunosuppression could be added for mismatched grafts.

Conditions