Post-transplant cyclophosphamide, abatacept, and vedolizumab for the prevention of graft-versus-host disease after hematopoietic stem cell transplantation in children with acute leukemia: results of a prospective study

High-dose post-transplant cyclophosphamide (PTCy) is an established method for the prevention of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical donors, however data on its efficacy in the pediatric population remain limited. In this prospective study, we evaluated an improved PTCy-based GVHD prophylaxis regimen comprising the a4b7 integrin blocker vedolizumab and a co-stimulatory signal inhibitor abatacept in addition to standard treatment with PTCy and cyclosporine A. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. Allogeneic HSCT was performed in children with high-risk acute leukemia in complete remission from a haploidentical (n = 54) or unrelated (n = 4) donor. Myeloablative conditioning was based on treosulfan or total body irradiation. In 97% of cases, bone marrow was used as a graft source. The engraftment rate was 98%. The cumulative risk of acute GVHD grade II-IV and III-IV was 38% and 8.6%, respectively, of acute intestinal GVHD grade II-IV - 10%, and of chronic GVHD - 7%. Transplant-related mortality after 2 years of follow-up was 3.6%, the incidence of relapse was 16%, the overall survival rate - 91%, and the event-free survival rate - 85%. Overall, the proposed GVHD prophylaxis regimen demonstrated a favorable safety profile and good tolerability, no specific adverse events were observed.