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.