Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial.

"Competing interests The authors declare no competing interests."

"Funding PHRC-K 2015 (Ministry of Health)."

"With 80 analyzable patients, the study design had 60% power to identify PTCy as superior to ATG when the GRFS at 1 year was 20% better than ATG at the one-sided significance level of 5% (two-sided level of 10%). The full analysis set included all patients who underwent HSCT for whom GRFS could be estimated. We also compared OS and DFS from time of randomization, in an intent-to-treat analysis. Probabilities of GRFS, DFS and OS were calculated using Kaplan–Meier estimates. Univariate analyses were performed using Gray’s test for CI and the log-rank test for GRFS, DFS and OS. The follow-up was censored at 1 year for 1-year comparisons. We also updated the follow-up of all patients in order to give the estimates at 3 years. Results of QoL after scoring were compared at each time point using the Mann-Whitney test and a generalized linear model was used to compare the evolution with time. Statistical analyses were performed with R version 4.0.1 (R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/). This study was registered with ClinicalTrials.gov, identifier number: NCT02876679. The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679."