Outcomes after a second allogeneic haematopoietic stem cell transplant for relapsed paediatric acute myeloid leukaemia improved over time: A study from the EBMT Paediatric Diseases Working Party.

Evolution of acute myeloid leukaemia (AML) treatments and transplantation procedures may affect outcomes after second haematopoietic stem cell transplantation (HSCT2) for relapsed paediatric AML. We analysed 345 paediatric patients reported to the European Society for Bone Marrow Transplantation (EBMT) registry for HSCT2 performed for AML relapse post-HSCT between 2000 and 2022. Multivariable analyses were adjusted for sex, age, transplant period, donor, disease status pre-HSCT2, cytogenetics, conditioning, total body irradiation (TBI) and post-first haematopoietic stem cell transplantation (HSCT1) remission duration. At three years leukaemia-free survival (LFS), overall survival (OS), non-relapse mortality (NRM), relapse incidence (RI) and graft-versus-host disease (GVHD)/relapse-free survival (GRFS) were 30.2%, 37.5%, 19.1%, 50.7% and 20.7% respectively. Compared with the 2000-2013 period, HSCT2 performed in 2014-2022 had better LFS (hazard ration [HR]: 0.66, 95% confidence interval [95% CI]: 0.48-0.90; 3-year: 34.3% vs. 26.3%), OS (HR: 0.60, 95% CI: 0.42-0.84; 3-year: 42.9% vs. 32.8%), RI (HR: 0.66, 95% CI: 0.46-0.98; 3-year: 46.0% vs. 54.7%) and GRFS (HR: 0.65, 95% CI: 0.48-0.90; 3-year: 25.3% vs. 16.1%) while NRM and GVHD incidence were stable. Relapse >6 months post-HSCT1 and remission pre-HSCT2 were associated with better LFS, OS and RI. Conditioning and cytogenetics did not influence outcomes. Mismatched unrelated donor negatively affected OS. These results highlight the improving survival after HSCT2 and support it in selected patients, particularly those relapsing later and in remission at HSCT2.