Key Points

  • Adding sirolimus to standard GVHD prophylaxis reduces acute GVHD after nonmyeloablative HLA antigen mismatched donor transplantation

  • Compared to historical controls the reduced incidence of acute GVHD translates into a better overall survival

This trial aimed to evaluate the efficacy of sirolimus in addition to cyclosporine and mycophenolate mofetil for GVHD prophylaxis after nonmyeloablative conditioning for HLA class I or II mismatched Hematopoietic cell transplantation (HCT). Eligible patients had hematological malignancies treatable by allogeneic HCT. Conditioning consisted of fludarabine (90 mg/m2) and 2-3 Gy total body irradiation. GVHD prophylaxis was with cyclosporine, mycophenolate mofetil and sirolimus. The primary objective was to determine whether the cumulative incidence of grade II-IV acute GVHD could be reduced to less than 70%, in HLA class I or II mismatched HCT. The study was closed on December 20, 2018. This study was registered with, number NCT01251575. Seventy-seven participants were recruited between April 14, 2011, and December 12, 2018 of whom 76 completed the study intervention. Median follow-up was 47 months (range, 4-94). The cumulative incidence of grade 2-4 acute GVHD at day 100 was 36% (95% CI, 25-46) meeting the primary endpoint. The cumulative incidences of nonrelapse morality, relapse/progression and overall survival were 18% (95% CI, 9-27), 30% (IQR, 19-40) and 62% (95% CI, 50-73%) after 4 years. In conclusion the addition of sirolimus to cyclosporine and mycophenolate mofetil resulted in a lower incidence of acute GVHD, thus translating into a superior overall survival compared to historical results.

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