NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients - Nantes Université
Article Dans Une Revue Blood Année : 2024

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

1 Hôpital Necker - Enfants Malades [AP-HP]
2 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
3 CHU Trousseau [APHP]
4 AP-HP - Hopital Saint-Louis [AP-HP]
5 ECSTRRA [CRESS - U1153 / UMR_A 1125] - Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé
6 IRSL - Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH)
7 CHV - Centre Hospitalier de Versailles André Mignot
8 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
9 CHU Angers - Centre Hospitalier Universitaire d'Angers
10 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
11 AP-HP Hôpital universitaire Robert-Debré [Paris]
12 UCL - Université Catholique de Louvain = Catholic University of Louvain
13 Hôpital Claude Huriez [Lille]
14 Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM]
15 Service de médecine de l'enfant et de l'adolescent [CHU Rennes]
16 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
17 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
18 CHU Bordeaux
19 Geneva University Hospitals and Geneva University
20 Swiss Group for Clinical Cancer Research (SAKK)
21 Service de biostatistiques et information médicale [Saint-Louis]
22 Service d'Hématologie Biologique [Hôpital Robert Debré, Paris]
Nathalie Grardel
Stéphane Ducassou
  • Fonction : Auteur
Arnaud Petit

Résumé

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.
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Dates et versions

hal-04752342 , version 1 (24-10-2024)

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Citer

Mathieu Simonin, Loïc Vasseur, Etienne Lengliné, Ludovic Lhermitte, Aurélie Cabannes-Hamy, et al.. NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients. Blood, 2024, 144 (15), pp.1570-1580. ⟨10.1182/blood.2023023754⟩. ⟨hal-04752342⟩
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