NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients.

Autor:	Simonin M; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France.; Department of Pediatric Hematology and Oncology, Armand Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France., Vasseur L; Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation, INSERM U1153, Université Paris Cité, Paris, France.; Adolescent and Young Adult Hematology Unit, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Lengliné E; Institut de Recherche Saint-Louis, EA-3518, Université Paris Cité, Paris, France.; Department of Hematology, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France., Lhermitte L; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France., Cabannes-Hamy A; Department of Hematology, Versailles Hospital, Le Chesnay, France., Balsat M; Clinical Hematology Department, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France., Schmidt A; Hematology Department, Angers University Hospital, Angers, France.; PRES LUNAM, INSERM U 892, Angers University, Angers, France., Dourthe ME; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France.; Department of Pediatric Hematology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Touzart A; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France., Graux C; Department of Hematology, Université Catholique de Louvain, CHU UCL Namur-site Godinne, Yvoir, Belgium., Grardel N; Department of Hematology, University Hospital Claude Huriez, Lille, France., Cayuela JM; Institut de Recherche Saint-Louis, EA-3518, Université Paris Cité, Paris, France.; Laboratory of Hematology, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France., Arnoux I; Laboratory of Hematology, La Timone University Hospital, Assitance Publique des Hôpitaux de Marseille, Marseille, France., Gandemer V; Department of Pediatric Hematology and Oncology, University Hospital of Rennes, Rennes, France., Huguet F; Department of Hematology, Toulouse University Hospital, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France., Ducassou S; Department of Pediatric Oncology and Hematology, Bordeaux University Hospital, Bordeaux, France., Lhéritier V; Coordination of the Group for Research on Adult Acute Lymphoblastic Leukemia, Hospices Civils de Lyon, Hôpital Lyon Sud, Lyon, France., Chalandon Y; Department of Oncology, Hematology Service, Geneva University Hospitals and Medical School, University of Geneva, Geneva, Switzerland.; Swiss Group for Clinical Cancer Research, Bern, Switzerland., Ifrah N; Hematology Department, Angers University Hospital, Angers, France.; PRES LUNAM, INSERM U 892, Angers University, Angers, France., Dombret H; Institut de Recherche Saint-Louis, EA-3518, Université Paris Cité, Paris, France.; Department of Hematology, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France., Macintyre E; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France., Petit A; Department of Pediatric Hematology and Oncology, Armand Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France., Rousselot P; Department of Hematology, Versailles Hospital, Le Chesnay, France., Lambert J; Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation, INSERM U1153, Université Paris Cité, Paris, France.; Biostatistics and Medical Information Department, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Baruchel A; Department of Pediatric Hematology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France., Boissel N; Adolescent and Young Adult Hematology Unit, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut de Recherche Saint-Louis, EA-3518, Université Paris Cité, Paris, France., Asnafi V; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.; Institut Necker-Enfants Malades, INSERM U1151, Paris, France.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Oct 10; Vol. 144 (15), pp. 1570-1580.
DOI:	10.1182/blood.2023023754
Abstrakt:	Abstract: We previously reported a better outcome in adult and pediatric T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 mutations without alterations of K-N-RAS and PTEN genes. Availability of high-throughput next-generation sequencing (NGS) strategies led us to refine the outcome prediction in T-ALL. Targeted whole-exome sequencing of 72 T-ALL-related oncogenes was performed in 198 adults with T-ALLs in first remission from the GRAALL-2003/2005 protocols and 242 pediatric patients with T-ALLs from the FRALLE2000T. This approach enabled the identification of, to our knowledge, the first NGS-based classifier in T-ALL, categorizing low-risk patients as those with N/F, PHF6, or EP300 mutations, excluding N-K-RAS, PI3K pathway (PTEN, PIK3CA, and PIK3R1), TP53, DNMT3A, IDH1/2, and IKZF1 alterations, with a 5-year cumulative incidence of relapse (CIR) estimated at 21%. Conversely, the remaining patients were classified as high risk, exhibiting a 5-year CIR estimated at 47%. We externally validated this stratification in the pediatric cohort. NGS-based classifier was highly prognostic independently of minimal residual disease (MRD) and white blood cell (WBC) counts, in both adult and pediatric cohorts. Integration of the NGS-based classifier into a comprehensive risk-stratification model, including WBC count at diagnosis and MRD at the end of induction, enabled the identification of an adverse-risk subgroup (25%) with a 5-year CIR estimated at 51%, and a favorable-risk group (32%) with a 5-year CIR estimated at 12%. NGS-based stratification combined with WBC and MRD sharpens the prognostic classification in T-ALL and identifies a new subgroup of patients who may benefit from innovative therapeutic approaches. The GRAALL-2003/2005 studies were registered at www.ClinicalTrials.gov as #NCT00222027 and #NCT00327678. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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