Posttransplant cyclophosphamide vs tacrolimus-based GVHD prophylaxis: lower incidence of relapse and chronic GVHD.

The ability of post-transplant cyclophosphamide (PTCY) to facilitate stem cell transplantation using HLA-haplotype-mismatched donors has spurred interest in whether PTCY can improve clinical outcomes in patients with HLA-matched unrelated donors undergoing peripheral blood stem cell transplantation (PBSCT). We investigated our institutional experience with 8/8 or 7/8 HLA-matched unrelated donor PBSCT using PTCY-based GVHD prophylaxis compared to conventional tacrolimus-based regimens. We compared overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality, and acute and chronic GVHD in 107 adult patients receiving a PTCY-based regimen versus 463 patients receiving tacrolimus-based regimens for GVHD prophylaxis. All patients were transplanted for hematologic malignancies. The two cohorts were well balanced for baseline characteristics except that more patients in the PTCY cohort received 7/8 matched PBSCT. There was no difference in acute GVHD. All-grade chronic GVHD and moderate-severe chronic GVHD were substantially reduced in patients receiving PTCY compared to tacrolimus-based regimens (2-year moderate-severe chronic GVHD: 12% vs 36%, p<0.0001). Recipients of PTCY-based regimens also had a lower incidence of relapse compared to recipients of tacrolimus-based regimens (25% vs. 34% at 2-years, p=0.027), primarily in patients who received reduced intensity conditioning. This led to improved PFS in the PTCY cohort (64% vs 54% at 2 years, p=0.02). In multivariable analysis, hazard ratio was 0.59 (p=0.015) for PFS and subdistribution hazard ratio was 0.27 (p<0.0001) for moderate-severe chronic GVHD and 0.59 (p=0.015) for relapse. Our results suggest that PTCY prophylaxis is associated with lower rates of relapse and chronic GVHD in patients who receive HLA-matched unrelated donor PBSCT.