Synergistic Effect of Anti-Thymocyte Globulin Combined with Post-Transplant Cyclophosphamide for Dual T Cell Modulation in Haploidentical Stem Cell Transplantation for Poor Prognosis Acute Leukemia.

Abstract Background: In the evolution of haploidentical stem cell transplantation (haplo-SCT), the implementation of anti-thymocyte globulin (ATG)-based and high-dose posttransplant cyclophosphamide (PTCy)-based regimens has improved patient outcomes. We hypothesized that the combination of ATG and PTCy in the correct sequence and with proper timing has a synergistic effect on immune tolerance. The purpose of the study was to discover whether the concomitant use of ATG and PTCy would be advantageous for haplo-SCT and which subgroup of patients would receive the most benefit.Methods: This cohort was conducted on 119 patients with poor prognosis acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who underwent haplo-SCT with peripheral blood stem cell (PBSC) sources and myeloablative conditioning (MAC) regimens using a uniform protocol in our center from 2010 to 2019. The outcomes of patients who received a combination of rabbit ATG (2.5 mg/kg/d for three days) plus modified PTCy (40 mg/kg/d on days +3 and +4) (n=100) was compared with those of patients who received an ATG-only regimen (n=19). The median follow-up was 35.8 months. Both arms shared similar characteristics, except for the median donor age, the distribution of relationships, and the median time between diagnosis and transplantation.Results: The cumulative incidence of acute graft versus host disease (aGvHD) grade II-IV was significantly lower in the ATG-PTCy group (P < 0.0001), although the incidence of 30-day neutrophil engraftment was higher in the ATG group (P = 0.036). The overall outcome was not significantly different between the two arms. Subgroup analyses stratified by disease status separately for AML and ALL indicated 3-year leukemia-free survival rates of 72% and 24.6% for the first remission of intermediate-high risk AML and ALL; 34.4% and 34.5% for recurrent disease; and 46% and 33.3% for refractory disease.Conclusion: Our experience indicates that the combination of ATG +PTCy in the context of MAC and PBSC sources offers satisfactory outcomes for patients with intermediate-high risk AML receiving haplo-SCT during the first remission; however, some modifications are recommended to improve the results of other subgroups.