Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study.

Détails

ID Serval
serval:BIB_C76A626B4003
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study.
Périodique
Blood
Auteur⸱e⸱s
Kim R., Bergugnat H., Pastoret C., Pasquier F., Raffoux E., Larcher L., Passet M., Grardel N., Delabesse E., Kubetzko S., Caye-Eude A., Meyer C., Marschalek R., Lafage-Pochitaloff M., Thiebaut-Bertrand A., Balsat M., Escoffre-Barbe M., Blum S., Baumann M., Banos A., Straetmans N., Gallego-Hernanz M.P., Chalandon Y., Graux C., Soulier J., Leguay T., Hunault M., Huguet F., Lhéritier V., Dombret H., Boissel N., Clappier E.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
23/11/2023
Peer-reviewed
Oui
Volume
142
Numéro
21
Pages
1806-1817
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
KMT2A-rearranged (KMT2A-r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is widely recognized as a high-risk leukemia in both children and adults. However, there is a paucity of data on adults treated in recent protocols, and the optimal treatment strategy for these patients is still a matter of debate. In this study, we set out to refine the prognosis of adult KMT2A-r BCP-ALL treated with modern chemotherapy regimen and investigate the prognostic impact of comutations and minimal residual disease (MRD). Of 1091 adult patients with Philadelphia-negative BCP-ALL enrolled in 3 consecutive trials from the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), 141 (12.9%) had KMT2A-r, with 5-year cumulative incidence of relapse (CIR) and overall survival (OS) rates of 40.7% and 53.3%, respectively. Molecular profiling highlighted a low mutational burden in this subtype, reminiscent of infant BCP-ALL. However, the presence of TP53 and/or IKZF1 alterations defined a subset of patients with significantly poorer CIR (69.3% vs 36.2%; P = .001) and OS (28.1% vs 60.7%; P = .006) rates. Next, we analyzed the prognostic implication of MRD measured after induction and first consolidation, using both immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements and KMT2A genomic fusion as markers. In approximately one-third of patients, IG/TR rearrangements were absent or displayed clonal evolution during the disease course, compromising MRD monitoring. In contrast, KMT2A-based MRD was highly reliable and strongly associated with outcome, with early good responders having an excellent outcome (3-year CIR, 7.1%; OS, 92.9%). Altogether, our study reveals striking heterogeneity in outcomes within adults with KMT2A-r BCP-ALL and provides new biomarkers to guide risk-based therapeutic stratification.
Mots-clé
Child, Humans, Adult, Neoplasm, Residual/genetics, Prognosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy, Recurrence, Immunoglobulins, Risk Assessment
Pubmed
Web of science
Création de la notice
19/09/2023 11:57
Dernière modification de la notice
20/01/2024 7:12
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