Department of Pediatrics, Institute of Clinical Sciences, Salgrenska University Hospital, Gothenburg, Sweden.
Pediatric Hemato-Oncology Department, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
IUC Toulouse-Oncopole, Laboratoire d'Hématologie secteur Génétique des Hémopathies, Toulouse, France.
Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, Padua University, Padua, Italy.
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, St Anna Children's Cancer Research Institute, Vienna, Austria.
Department of Pediatric Hematology and Oncology, Schneider Children's Medical Center and Tel Aviv University, Tel Aviv, Israel.
Pediatric Oncohematology Unit, Hospital Universitari i Politècnic la Fe, Valencia, Spain.
Department of Statistics, Children's Oncology Group, CA, Monrovia, United States.
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; DCOG, Dutch Childhood Oncology Group, Utrecht, Netherlands.
Children's Mercy Kansas City, MO, Kansas City, United States.
Department of Pediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong.
Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece.
Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France.
Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France.
Department of Pediatric Hematology and Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy.
Pediatric Oncology and Hematology, University of Bologna, Bologna, Italy.
Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece.
Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.
Department of Oncology, St Jude Children's Research Hospital, TN, Memphis, United States.
Department of Pediatric Hematology and Oncology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Pathobiology and Laboratory Medicine, Toronto General Hospital, University Health Network, ON, Toronto, Canada.
Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
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.
American Society of Clinical Oncology (ASCO) , 2023. Vol. 41, no 16, p. 2963-2974