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.

Fecha de publicación: 30/03/2023 Fecha Ahead of Print: 30/03/2023

Autores de IIS La Fe

José María Fernández Navarro

Autor

Participantes ajenos a IIS La Fe

van Weelderen, Romy E
Klein, Kim
Harrison, Christine J
Jiang, Yilin
Abrahamsson, Jonas
Arad-Cohen, Nira
Bart-Delabesse, Emmanuelle
Buldini, Barbara
De Moerloose, Barbara
Dworzak, Michael N
Elitzur, Sarah
Gerbing, Robert B
Goemans, Bianca F
de Groot-Kruseman, Hester A
Guest, Erin
Ha, Shau-Yin
Hasle, Henrik
Kelaidi, Charikleia
Lapillonne, Helene
Leverger, Guy
Locatelli, Franco
Masetti, Riccardo
Miyamura, Takako
Noren-Nystrom, Ulrika
Polychronopoulou, Sophia
Rasche, Mareike
Rubnitz, Jeffrey E
Stary, Jan
Tierens, Anne
Tomizawa, Daisuke
Zwaan, C Michel
Kaspers GJL

Grupos

Investigación Clínica y Traslacional en Cáncer

Leader

José Gómez Codina

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 0732-183X, 1527-7755
Tipo:: Article
Páginas:: 2202120-2202120
DOI:: 10.1200/JCO.22.02120
Factor de Impacto:: 9,378 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

van Weelderen, Romy E:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
Klein, Kim:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
Harrison, Christine J:: Leukemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom
Jiang, Yilin:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
Abrahamsson, Jonas:: Department of Pediatrics, Institute of Clinical Sciences, Salgrenska University Hospital, Gothenburg, Sweden

Department of Pediatrics, Institute of Clinical Sciences, Salgrenska University Hospital, Gothenburg, Sweden
Arad-Cohen, Nira:: Pediatric Hemato-Oncology Department, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel

Pediatric Hemato-Oncology Department, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
Bart-Delabesse, Emmanuelle:: IUC Toulouse-Oncopole, Laboratoire d'Hématologie secteur Génétique des Hémopathies, Toulouse, France

IUC Toulouse-Oncopole, Laboratoire d'Hématologie secteur Génétique des Hémopathies, Toulouse, France
Buldini, Barbara:: Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, Padua University, Padua, Italy

Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, Padua University, Padua, Italy
De Moerloose, Barbara:: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium

Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
Dworzak, Michael N:: St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, and St Anna Children's Cancer Research Institute, Vienna, Austria

St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, and St Anna Children's Cancer Research Institute, Vienna, Austria
Elitzur, Sarah:: Department of Pediatric Hematology and Oncology, Schneider Children's Medical Center and Tel Aviv University, Tel Aviv, Israel

Department of Pediatric Hematology and Oncology, Schneider Children's Medical Center and Tel Aviv University, Tel Aviv, Israel
Fernandez Navarro, Jose M:: Pediatric Oncohematology Unit, Hospital Universitari i Politècnic la Fe, Valencia, Spain

Pediatric Oncohematology Unit, Hospital Universitari i Politècnic la Fe, Valencia, Spain
Goemans, Bianca F:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
de Groot-Kruseman, Hester A:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
Ha, Shau-Yin:: Department of Pediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong

Department of Pediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
Hasle, Henrik:: Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Kelaidi, Charikleia:: Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece

Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece
Lapillonne, Helene:: Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France

Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France
Leverger, Guy:: Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France

Pediatric Hematology and Oncology Department, Hôpital Armand Trousseau, Paris, France
Locatelli, Franco:: 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 and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy
Masetti, Riccardo:: Pediatric Oncology and Hematology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy

Pediatric Oncology and Hematology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy
Miyamura, Takako:: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan
Noren-Nystrom, Ulrika:: Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
Polychronopoulou, Sophia:: Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece

Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece
Rasche, Mareike:: Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany

Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany
Stary, Jan:: Department of Pediatric Hematology and Oncology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

Department of Pediatric Hematology and Oncology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
Tierens, Anne:: Department of Pathobiology and Laboratory Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada

Department of Pathobiology and Laboratory Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
Tomizawa, Daisuke:: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan

Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
Zwaan, C Michel:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
Kaspers GJL:: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands