A phase II study of sirolimus, tacrolimus, and rabbit anti-thymocyte globulin as graft-versus-host prophylaxis after unrelated-donor peripheral blood stem cell transplant

We report on a prospective phase II trial of 32 patients who underwent unrelated donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute GVHD, with 80% power to detect a 30% decrease compared to institutional historical controls. Median age at transplant was 60 (19-71). Twenty-three patients (72%) received reduced-intensity conditioning, while the remainder received full-intensity regimens. Median follow up for surviving patients was 35 months (range: 21 - 49). The cumulative incidence of acute GVHD was 37.3% and the 2-year cumulative incidence of cGVHD was 63%. We observed TMA in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four patients of 32 (12.5%) failed to engraft, and three of these four died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year overall survival was 65.5% and event-free survival was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates; however, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen.