Prospective Open-Label Phase II Trial of Individualized Anti-Thymocyte Globulin for Improved T-Cell Reconstitution after Pediatric Allogeneic Hematopoietic Cell Transplantation: The Parachute-Study

Abstract

Introduction Rabbit anti-thymocyte globulin (ATG) is used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host-disease (GvHD) and graft failure (GF). Its main and unpredictable toxicity includes poor immune reconstitution associated with increased relapse, viral reactivations and subsequently higher mortality. Early ( Methods We performed an open label, phase II historically controlled non-randomized prospective clinical trial investigating individualized versus fixed dosing of ATG (Thymoglobulin). Individualized dosing was based on the results from a previous validated population PKPD model1,2 with cumulative doses varying between 2 to 10 mg/kg starting based on weight, recipient lymphocyte counts before first dose of ATG and stem cell source, starting day -9. Primary endpoint was successful CD4+ T-cell reconstitution (CD4+ >50/mm3 at 2 consecutive timepoints within 100 days after HCT1) in patients alive without relapse or graft failure Results We included 58 patients between 2015-2018, and compared to 112 historical controls (table 1). CD4+ reconstitution was significantly better in the individualized dosing group: 83% versus 54% in the fixed dosing group; HR 2.4 (95% CI 1.6-3.6), p Conclusions Individualized ATG dosing significantly increases the chance of rapid immune reconstitution without affecting the incidence of aGvHD and graft failure. Together, this is an important step towards predictable CD4+ T cell reconstitution and improved survival changes.