A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after nonmyeloablative unrelated donor transplantation.

Publication Type:

Journal Article


Haematologica, Volume 99, Issue 10, p.1624-31 (2014)


2014, August 2014, Center-Authored Paper, Clinical Research Division, Research Trials Office Core Facility - Biostatistics Service


The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after nonmyeloablative (90 mg/m2 fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: Arm 1- tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2-tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3- tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at day 150, respectively (arm 3 vs. 1 (hazard ratio 0.62, P =.04). Owing to the decreased incidence of acute graft-versus-host disease systemic steroid use was lower at day 150 in arm 3 (32% versus 55% in arm 1 and 49% in arm 2; P =.009). The day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=.002 by hazard ratio analysis). The nonrelapse mortality was comparable in the 3 arms at 2 years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. The study was registered with clinicalTrials.gov (NCT00105001).