GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia
Status:
Completed
Trial end date:
2020-11-01
Target enrollment:
Participant gender:
Summary
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.