Interplay between acute graft-versus-host disease and graft-versus-leukemia effect in pediatric acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: implications for relapse incidence and survival - an EBMT PDWP retrospective study

The interplay between graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect in children with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains complex. This EBMT Pediatric Diseases Working Party (PDWP) retrospective analysis of 2374 pediatric AML patients evaluated the impact of aGVHD on relapse incidence (RI), non-relapse mortality (NRM), overall survival (OS), and leukemia-free survival (LFS). Grade III/IV aGVHD significantly reduced RI (HR: 0.61, p = 0.01) while significantly increasing NRM (HR: 4.51, p < 0.001), offsetting any benefits in OS and LFS. Grade II aGVHD increased NRM (HR: 2.07, p = 0.002) without affecting RI or OS, while grade I aGVHD had no significant impact on these outcomes. Patients with Grade II or higher aGVHD were at greater risk of both chronic (c)GvHD (HR: 1.98 for Grade II; HR: 4.33 for Grade III/IV, p < 0.001) and extensive cGVHD (HR: 2.52 for Grade II; HR: 4.91 for Grade III/IV, p < 0.001). These findings highlight the challenge of mitigating NRM while preserving the GVL effect to optimize disease control and long-term survival in pediatric AML. This study provides critical insights for refining post-transplant strategies in this population.