Characteristics and prognosis of paediatric normal karyotype acute myeloid leukaemia: A <scp>NOPHO</scp>‐<scp>DBH AML</scp> study
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<sup>wt</sup> 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<sup>wt</sup> NK-AML.
Authors
- Linda Holmfeldt (ORCID: https://orcid.org/0000-0003-4140-3423)
- Bernward Zeller (ORCID: https://orcid.org/0000-0001-9008-4495)
- Zhanna Kovalova
- Morten Krogh Herlin (ORCID: https://orcid.org/0000-0001-7179-4643)
- Kristian Løvvik Juul-Dam (ORCID: https://orcid.org/0000-0003-0028-8115)
- Eigil Kjeldsen (ORCID: https://orcid.org/0000-0003-0897-7361)
- Josefine Palle (ORCID: https://orcid.org/0000-0001-7431-2865)
- Nira Arad‐Cohen (ORCID: https://orcid.org/0000-0002-2801-7600)
- Gertjan J.L. Kaspers (ORCID: https://orcid.org/0000-0001-7716-8475)
- Daniel KL Cheuk
- Ulrika Norén‐Nyström (ORCID: https://orcid.org/0000-0001-5606-5442)
- Kadri Saks (ORCID: https://orcid.org/0000-0002-1632-8727)
- Jonas Abrahamsson (ORCID: https://orcid.org/0000-0002-9240-3522)
- Barbara De Moerloose (ORCID: https://orcid.org/0000-0002-2449-539X)
- Henrik Hasle (ORCID: https://orcid.org/0000-0003-3976-9231)
- Kirsi Jahnukainen
- Ramunė Pasaulienė
- José María Fernández Navarro
- Ólafur Gísli Jónsson
Institutions
- Uppsala University (SE)
- Oslo University Hospital (NO)
- University of Helsinki (FI)
- Vilnius University (LT)
- Aarhus University (DK)
- Helsinki University Hospital (FI)
- Ghent University Hospital (BE)
- Rambam Health Care Campus (IL)
- Aarhus University Hospital (DK)
- Hospital Universitari i Politècnic La Fe (ES)
- Helsinki Children's Hospital (FI)
- Duchess of Kent Children's Hospital (CN)
- East Tallinn Central Hospital (EE)
- Emma Kinderziekenhuis (NL)
- University Hospital of Umeå (SE)
- Drottning Silvias barn- och ungdomssjukhus (SE)
- National University Hospital of Iceland (IS)
- Tallinn Health Care College (EE)
- Children's Clinical University Hospital (LV)
- Princess Máxima Center (NL)
- Amsterdam University Medical Centers (NL)
- Vilnius University Hospital Santariskiu Klinikos (LT)
- Vrije Universiteit Amsterdam (NL)
- Umeå University (SE)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1111/bjh.70094
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Børnecancerfonden
- Region Midtjylland
- Kom op tegen Kanker
- Graduate School of Health, University of Technology Sydney