PURPOSE: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. METHODS: A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS: The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. CONCLUSION: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

Children's Cancer Center National Center for Child Health and Development Tokyo Japan

Children's Mercy Kansas City Kansas City MO

DCOG Dutch Childhood Oncology Group Utrecht the Netherlands

Department of Clinical Sciences Pediatrics Umeå University Umeå Sweden

Department of Oncology St Jude Children's Research Hospital Memphis TN

Department of Pathobiology and Laboratory Medicine University Health Network Toronto General Hospital Toronto ON Canada

Department of Pediatric Hematology and Oncology Aghia Sophia Children's Hospital Athens Greece

Department of Pediatric Hematology and Oncology and Cell and Gene Therapy IRCCS Ospedale Pediatrico Bambino Gesù Catholic University of the Sacred Heart Rome Italy

Department of Pediatric Hematology and Oncology Schneider Children's Medical Center and Tel Aviv University Tel Aviv Israel

Department of Pediatric Hematology and Oncology University Hospital Essen Essen Germany

Department of Pediatric Hematology and Oncology University Hospital Motol and 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent Belgium

Department of Pediatric Oncology Erasmus MC Sophia Children's Hospital Rotterdam the Netherlands

Department of Pediatrics and Adolescent Medicine Hong Kong Children's Hospital Kowloon Hong Kong

Department of Pediatrics Institute of Clinical Sciences Salgrenska University Hospital Gothenburg Sweden

Department of Pediatrics Osaka University Graduate School of Medicine Suita Japan

Department of Statistics The Children's Oncology Group Monrovia California

IUC Toulouse Oncopole Laboratoire d'Hématologie secteur Génétique des Hémopathies Toulouse France

Leukemia Research Cytogenetics Group Translational and Clinical Research Institute Newcastle University Centre for Cancer Newcastle upon Tyne United Kingdom

Pediatric Hemato Oncology Department Ruth Rappaport Children's Hospital Rambam Health Care Campus Haifa Israel

Pediatric Hematology and Oncology Department Hôpital Armand Trousseau Paris France

Pediatric Hematology Oncology and Stem Cell Transplant Division Maternal and Child Health Department Padua University Padua Italy

Pediatric Oncohematology Unit Hospital Universitari i Politècnic la Fe Valencia Spain

Pediatric Oncology and Hematology IRCCS Azienda Ospedaliero Universitaria di Bologna University of Bologna Bologna Italy

Pediatric Oncology Emma Children's Hospital Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam the Netherlands

Pediatrics and Adolescent Medicine Aarhus University Hospital Aarhus Denmark

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

St Anna Children's Hospital Department of Pediatrics Medical University of Vienna and St Anna Children's Cancer Research Institute Vienna Austria

Wilhelmina Children's Hospital University Medical Center Utrecht Utrecht the Netherlands

Transl Pediatr. 2023 Oct 30;12(10):1920-1925. doi: 10.21037/tp-23-360. PubMed

Transl Pediatr. 2023 Dec 26;12(12):2099-2102. doi: 10.21037/tp-23-436. PubMed

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Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

Cytogenetic abnormalities predict survival after allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia: a PDWP/EBMT study