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.

Cansearch Research Platform for Pediatric Oncology and Hematology Faculty of Medicine Department of Pediatrics Gynecology and Obstetrics University of Geneva Geneva Switzerland

CHU Bordeaux Groupe Hospitalier Pellegrin Enfants Bordeaux France

Clinica di Oncoematologia Pediatrica Dipartimento di Pediatria Padova Italy

Département Hématologie Oncologie Pédiatrique Hôpital de la Timone Marseille France

Department of Paediatric Haematology and Oncology University Hospital Motol Prague Czech Republic

Department of Paediatric Haematology Bone Marrow Unit Royal Manchester Children's Hospital Manchester UK

Department of Paediatric Oncology BMT Bristol Royal Hospital for Children Bristol UK

Department of Pediatric Hematology and Oncology IRRCS Ospedale Pediatrico Bambino Gesù Catholic University of the Sacred Heart Rome Italy

Department of Pediatric Hematology Oncology BMT Wroclaw Medical University Wroclaw Poland

Division of Pediatric Oncology and Hematology Department of Women Child and Adolescent University Geneva Hospitals Geneva Switzerland

EBMT Paris Study Unit Saint Antoine Hospital INSERM UMR S 938 Sorbonne University Paris France

Federal Research Center for Pediatric Hematology Moscow Russian Federation

Fondazione IRCCS Policlinico San Matteo Pediatric Hematology Oncology Pavia Italy

Niño Jesus Children's Hospital Stem Cell Transplant Unit Madrid Spain

Onco Ematologia Pediatrica Centro Trapianti Cellule Staminali Ospedale Infantile Regina Margherita Torino Italy

Princess Maxima Center University Hospital for Children Stem Cell Transplantation Utrecht The Netherlands

RM Gorbacheva Research Institute Pavlov University Saint Petersburg Russian Federation

Service d'Immuno Hémato Oncologie Pédiatrique Hôpital Charles Nicolle Rouen France

Stem Cell Transplantation Unit St Anna Kinderspital Vienna Austria

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