Evidence map›Paper›PMID 40965326›Full record

ArticleActa oncologica (Stockholm, Sweden)2025

Balancing benefit and burden: treatment intensification in paediatric KMT2A rearrangements acute myeloid leukaemia.

Hend Fayez, Mariam Elsherif, Sherine Salem, Nahla Elsharkawy, Amr Elnashar, Mohamed Kamal, Reham Khedr, Leslie Lehmann, Sonia Ahmed, Alaa Elhaddad

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Article in Acta oncologica (Stockholm, Sweden), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

10 authors.

Hend FayezDepartment of Pediatric Oncology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Mariam ElsherifDepartment of Pediatric Oncology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Sherine SalemDepartment of Clinical Pathology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt; Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
Nahla ElsharkawyDepartment of Clinical Pathology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt; Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
Amr ElnasharDepartment of Research and Biostatistics, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Mohamed KamalDepartment of Research and Biostatistics, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Reham KhedrDepartment of Pediatric Oncology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
Leslie LehmannPediatric Stem Cell Transplantation Unit, Dana-Farber Cancer Institute, Boston, MA, USA.
Sonia AhmedDepartment of Pediatric Oncology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt. a.ahmed@nci.cu.edu.eg, d.ORCID 0000-0002-8322-4194
Alaa ElhaddadDepartment of Pediatric Oncology, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeChromosomal rearrangements involving KMT2A (KMT2A-r) occur in 20% of paediatric acute myeloid leukaemia (AML). Previous studies reported that the outcome depends on the specific fusion partner. The study aimed to report the outcomes of paediatric KMT2A-r AML patients and to assess the impact of different fusion partners. Patient/material and methods: We retrospectively analysed 610 paediatric patients with intermediate-risk (IR) AML diagnosed at Children's Cancer Hospital Egypt, from January 2008 to December 2021. Patients were assigned to four groups based on fusion partner.

resultsOf 610 patients diagnosed with IR-AML, 150 (24.6%) had KMT2A rearrangements. KMT2A-r was significantly associated with hyperleukocytosis (P = 0.029), central nervous system (CNS) disease (P = 0.003), monocytic differentiation (P = 0.001), additional cytogenetic abnormalities (ACA) (P = 0.04), and complex karyotype (P = 0.001). Fusion partner, t(9;11) (p22;q23) (9p22/KMT2A::MLLT3 fusion) was most prevalent (40.8%). KMT2A-r was an independent predictor of relapse with a cumulative incidence of relapse (CIR) of 46% versus 30% in KMT2A negative group (P = 0.006). Within the KMT2A-r group, ACA and complex karyotype adversely affected the outcome with 5-year overall survival (OS) of 34% versus 53% (P = 0.027) and 26% versus 51% (P = 0.004), respectively. Outcome varied depending on fusion partner. Event-free survival (EFS) ranged from 50% to 17%, OS from 54% to 27%, and CIR from 75% to 38%.

interpretationKMT2A-r is an independent prognostic factor for relapse, and presence of ACA and a complex karyotype in KMT2A-r patients is associated with poorer outcomes, emphasising the need for aggressive and innovative therapeutic strategies.

Indexed as

Histone-Lysine N-MethyltransferaseLeukemia, Myeloid, AcuteMyeloid-Lymphoid Leukemia ProteinAdolescentChildChild, PreschoolFemaleGene RearrangementHumansInfantMaleOncogene Proteins, FusionPrognosisRetrospective StudiesTranslocation, GeneticHistone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, Fusion

Identifiers

PMID40965326
PMCPMC12452033

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