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  • van Weelderen, Romy E.Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, Netherlands (author)

Measurable residual disease and fusion partner independently predict survival and relapse risk in childhood KMT2A-rearranged acute myeloid leukemia : a study by the international Berlin-Frankfurt-Münster study group

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • American Society of Clinical Oncology (ASCO),2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-209194
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-209194URI
  • https://doi.org/10.1200/JCO.22.02120DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

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  • Klein, KimPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, Netherlands (author)
  • Harrison, Christine J.Leukemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom (author)
  • Jiang, YilinPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands (author)
  • Abrahamsson, JonasDepartment of Pediatrics, Institute of Clinical Sciences, Salgrenska University Hospital, Gothenburg, Sweden (author)
  • Arad-Cohen, NiraPediatric Hemato-Oncology Department, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel (author)
  • Bart-Delabesse, EmmanuelleIUC Toulouse-Oncopole, Laboratoire d'Hématologie secteur Génétique des Hémopathies, Toulouse, France (author)
  • Buldini, BarbaraPediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, Padua University, Padua, Italy (author)
  • De Moerloose, BarbaraDepartment of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium (author)
  • Dworzak, Michael N.St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, St Anna Children's Cancer Research Institute, Vienna, Austria (author)
  • Elitzur, SarahDepartment of Pediatric Hematology and Oncology, Schneider Children's Medical Center and Tel Aviv University, Tel Aviv, Israel (author)
  • Fernández Navarro, José MPediatric Oncohematology Unit, Hospital Universitari i Politècnic la Fe, Valencia, Spain (author)
  • Gerbing, Robert B.Department of Statistics, Children's Oncology Group, CA, Monrovia, United States (author)
  • Goemans, Bianca F.Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands (author)
  • de Groot-Kruseman, Hester A.Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; DCOG, Dutch Childhood Oncology Group, Utrecht, Netherlands (author)
  • Guest, ErinChildren's Mercy Kansas City, MO, Kansas City, United States (author)
  • Ha, Shau-YinDepartment of Pediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong (author)
  • Hasle, HenrikPediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark (author)
  • Kelaidi, CharikleiaDepartment of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece (author)
  • Lapillonne, HélènePediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France (author)
  • Leverger, GuyPediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France (author)
  • Locatelli, FrancoDepartment of Pediatric Hematology and Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy (author)
  • Masetti, RiccardoPediatric Oncology and Hematology, University of Bologna, Bologna, Italy (author)
  • Miyamura, TakakoDepartment of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan (author)
  • Norén-Nyström, UlrikaUmeå universitet,Pediatrik(Swepub:umu)kagr0007 (author)
  • Polychronopoulou, SophiaDepartment of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece (author)
  • Rasche, MareikeDepartment of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany (author)
  • Rubnitz, Jeffrey E.Department of Oncology, St Jude Children's Research Hospital, TN, Memphis, United States (author)
  • Stary, JanDepartment of Pediatric Hematology and Oncology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (author)
  • Tierens, AnneDepartment of Pathobiology and Laboratory Medicine, Toronto General Hospital, University Health Network, ON, Toronto, Canada (author)
  • Tomizawa, DaisukeChildren's Cancer Center, National Center for Child Health and Development, Tokyo, Japan (author)
  • Zwaan, C MichelPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands (author)
  • Kaspers, Gertjan J LPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, Netherlands (author)
  • Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsPrincess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Pediatric Oncology, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, Netherlands (creator_code:org_t)

Related titles

  • In:Journal of Clinical Oncology: American Society of Clinical Oncology (ASCO)41:16, s. 2963-29740732-183X1527-7755

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