Characteristics and prognosis of paediatric normal karyotype acute myeloid leukaemia: A NOPHO-DBH AML study.

Fecha de publicación: 01/10/2025 Fecha Ahead of Print: 18/08/2025

Autores de IIS La Fe

José María Fernández Navarro

Autor

Participantes ajenos a IIS La Fe

Herlin MK
Kjeldsen E
Abrahamsson J
Arad-Cohen N
Cheuk D
De Moerloose B
Jahnukainen K
Jónsson ÓG
Kaspers GJL
Kovalova Z
Noren-Nyström U
Palle J
Pasauliene R
Saks K
Zeller B
Holmfeldt L
Hasle H
Juul-Dam KL

Grupos

Investigación Clínica y Traslacional en Cáncer

Abstract

Normal karyotype acute myeloid leukaemia (NK-AML) in children is a heterogeneous subgroup with scarce data on characteristics and prognosis. We investigated NK-AML in a large paediatric AML cohort from four trials of the Nordic Society for Paediatric Haematology and Oncology-Dutch Belgian Hongkong (NOPHO-DBH) group. Among 1476 AML patients, we identified 316 NK-AML patients (21%). NK-AML was characterized by high frequencies of FLT3 internal tandem duplications (ITD, 33%), mutated NPM1 (28%), WT1 (25%) and CEBPA (21%). Five-year event-free survival (EFS) and overall survival (OS) in NK-AML were 52% (95% confidence interval [CI]: 46-58) and 70% (CI: 65-75) respectively. Restricted to NPM1(wt) cases only (n = 959), NK-AML was associated with unfavourable outcome (relative risk [RR] of EFS = 0.80, p = 0.014; RR of OS = 0.87, p = 0.022). NK-AML with mutated NPM1 had excellent EFS (79%, CI: 66-88) and OS (97%, CI: 88-99), which was not influenced by concomitant FLT3-ITD. In multivariable analysis, mutated NPM1 in NK-AML was associated with favourable EFS (hazard ratio [HR]: 0.24, CI: 0.13-0.43, p < 0.001) and OS (HR: 0.10, CI: 0.03-0.35, p < 0.001). FLT3-ITD was associated with inferior EFS (HR: 1.56, CI: 1.03-2.35, p = 0.035) and OS (HR: 1.91, CI: 1.11-3.31, p = 0.02). We conclude that prognosis in paediatric NK-AML is independently affected by NPM1 and FLT3-ITD status. Further molecular characterization of NK-AML is needed, especially for NPM1(wt) NK-AML.

Datos de la publicación

ISSN/ISSNe:: 0007-1048, 1365-2141
Tipo:: Article
Páginas:: 1454-1463
DOI:: 10.1111/bjh.70094
PubMed:: 40826900
Enlace a otro recurso:: www.scopus.com
Factor de Impacto:: 1,677 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Herlin MK:: Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Kjeldsen E:: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Department of Haematology, Aarhus University Hospital, Aarhus, Denmark
Abrahamsson J:: Department of Paediatrics, Institution for Clinical Sciences, Queen Silvia Children's Hospital, Gothenburg, Sweden
Arad-Cohen N:: Department of Paediatric Haemato-Oncology, Rambam Medical Centre, Haifa, Israel
Cheuk D:: Hong Kong Paediatric Haematology and Oncology Study Group (HKPHOSG), Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong, China
De Moerloose B:: Department of Paediatric Haematology-Oncology, Ghent University Hospital, Ghent, Belgium
Jahnukainen K:: New Children's Hospital, Paediatric Research Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Jónsson ÓG:: Department of Paediatrics, Landspitalinn, Reykjavik, Iceland
Kaspers GJL:: Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands
Kovalova Z:: Department of Paediatric Oncology/Haematology, Children's Clinical University Hospital, Riga, Latvia
Navarro JMF:: Hospital Universitario y Politécnico La Fe, Valencia, Spain
Noren-Nyström U:: Department of Paediatrics, Umeå University Hospital, Umeå, Sweden
Palle J:: Department of Woman's and Children's Health, Uppsala University, Uppsala, Sweden
Pasauliene R:: Centre of Oncohaematology, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
Saks K:: Department of Paediatrics, Tallinn, Estonia
Zeller B:: Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Holmfeldt L:: Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
Hasle H:: Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Juul-Dam KL:: Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

Keywords

acute myeloid leukaemia; childhood; cytogenetics of leukaemia; prognostic factors

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