Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Autor: Rigaud C; Department of Children and Adolescents Oncology, Gustave Roussy Cancer, Paris-Saclay University, Villejuif, France., Forster VJ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Al-Tarrah H; Division of Hematology and Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada., Attarbaschi A; St Anna Children's Hospital, Medical University, Vienna, Austria.; St Anna Children's Cancer Research Institute, Vienna, Austria., Bianchi V; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Burke A; Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK., Burkhardt B; NHL-BFM Study Center and Pediatric Hematology, Oncology and BMT, University Hospital Muenster, Muenster, Germany., Colas C; Department of Genetics, Institut Curie, University Paris Sciences Lettres, Paris, France., Devalck C; Hemato-Oncology Department, HUB, ULB, HUDERF, Brussels, Belgium., Edwards M; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Elitzur S; Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Garthe AK; NHL-BFM Study Center and Pediatric Hematology, Oncology and BMT, University Hospital Muenster, Muenster, Germany., Goldberg Y; Raphael Recanati Genetics Institute, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.; Sackler School for Faculty, Tel Aviv University, Tel Aviv, Israel., Guerrini-Rousseau L; Department of Children and Adolescents Oncology, Gustave Roussy Cancer, Paris-Saclay University, Villejuif, France., Horpaopan S; Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria., Januszkiewicz-Lewandowska D; Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland., Kabíčková E; Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic., Kratz CP; Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany., Loeffen J; Princess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands., Pérez-Alonso V; Pediatric Oncology Unit, University Hospital Doce de Octubre, Madrid, Spain., Pineda M; Hereditary Cancer Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), ONCOBELL Program, Barcelona, Spain.; Consortium for Biomedical Research in Cancer, CIBERONC, Carlos III Institute of Health, Madrid, Spain., Minard-Colin V; Department of Children and Adolescents Oncology, Gustave Roussy Cancer, Paris-Saclay University, Villejuif, France., Rueda D; Hereditary Cancer Genetic Diagnostic Laboratory, University Hospital Doce de Octubre, Madrid, Spain., Ruiz-Ponte C; Fundación Publica Galega de Medicina Xenómica, SERGAS, Grupo de Medicina Xenómica - Universidad de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain., Trinquand A; National Children's Research Centre at Children's Health Ireland, Dublin, Ireland., Uyttebroeck A; Department of Oncology, KU Leuven, Pediatric Hemato-Oncology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium., Wimmer K; Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria., Auperin A; Biostatistics and Epidemiology Departement, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Paris-Saclay University, Villejuif, France., Tabori U; Division of Hematology and Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada., Brugieres L; Department of Children and Adolescents Oncology, Gustave Roussy Cancer, Paris-Saclay University, Villejuif, France.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2024 Dec; Vol. 71 (12), pp. e31302. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1002/pbc.31302
Abstrakt: Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome.
Methods: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first.
Findings: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%.
Interpretation: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.
(© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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