Immune reconstitution and infections with ATG versus post-transplant cyclophosphamide as GvHD prophylaxis after nonmyeloablative matched unrelated donor hematopoietic stem cell transplantation.

INTRODUCTION: Anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) are both used as in-vivo lymphodepleting treatment in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in the matched unrelated donor (MUD) setting. METHODS: In this retrospective study, we compared the incidences of infections and viral reactivations and evaluated immune cell reconstitution in the first-year post-transplant between ATG- and PTCy-based conditioning regimens in nonmyeloablative MUD transplantations. Infection incidence was evaluated for the periods 0-100 vs. 101-365 days post-transplant. RESULTS: A total of 185 patients (ATG=95, PTCy=90), transplanted between 2014 and 2021, were included. In the first 100 days after transplantation, the cumulative incidence of bacterial infections was higher in the PTCy group (ATG 17% vs. PTCy 32%, p=0.01) while CMV reactivations were more frequent in the ATG group (36% vs. 16%, p<0.001). Beyond 100-days post-transplant, incidence of bacterial infections was higher in the ATG group (18% vs. 1%, p<0.001). Fungal infection incidence was similar in both groups/periods. The 1-year densities of viral infections (3.54 vs. 1.89, p<0.01) and CMV reactivations (2.21 vs. 0.68, p<0.01) were higher in the ATG compared to the PTCy group. After 1-year, circulating CD4+ T-cell counts were significantly lower in the ATG than in the PTCy group (p<0.001). DISCUSSION: In conclusion, this study shows that overall PTCy is associated with better immune reconstitution and reduced rate of viral infections/CMV reactivations compared to ATG-based conditioning. Together with our previous findings of a lower risk of acute GvHD following PTCy compared to ATG-based conditioning, these data may favor PTCy over ATG as GvHD prophylaxis.