Calcineurin inhibitors (CNI) form the foundation of current GVHD prophylaxis regimens. We hypothesized that a CNI-free regimen consisting of post-transplant cyclophosphamide (PTCy) and brief-course sirolimus would reduce chronic GVHD and non-relapse mortality (NRM) following reduced intensity allogeneic peripheral blood stem cell transplant (PBSCT). Twenty-six patients, median age 61 years, received an unmanipulated PBSCT from an 8/8 locus matched donor; MRD=17, MUD=9. GVHD prophylaxis consisted of PTCy and brief-course sirolimus. Donor engraftment occurred in all patients. The cumulative incidence (CI) of grade II-IV acute GVHD, grade III-IV acute GVHD, and chronic GVHD was 46%, 15%, and 31% respectively. One year NRM was 4%. Median time to immunosuppression discontinuation was day +138. With a median follow-up of 20 months, the estimated 2-year overall survival, disease-free survival, and relapse incidence was 71%, 64%, and 32% respectively. In patients with lymphoid malignancies (CLL, NHL, HD), 2-yr DFS and relapse was 100% and 0%, respectively. Good immune reconstitution was evidenced by low CMV reactivation rates, occurring in only 4 of 19 at-risk patients (21%). GVHD prophylaxis with PTCy and sirolimus achieves consistent donor engraftment, low rates of chronic GVHD and NRM, and excellent outcomes in recipients of HLA-identical related and unrelated donor allogeneic PBSCT.
PMID: 25064745 [PubMed - as supplied by publisher]