Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia

With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, a...

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Bibliographic Details
Published in:Blood 2014-06, Vol.123 (24), p.3739-3749
Main Authors: Beldjord, Kheira, Chevret, Sylvie, Asnafi, Vahid, Huguet, Françoise, Boulland, Marie-Laure, Leguay, Thibaut, Thomas, Xavier, Cayuela, Jean-Michel, Grardel, Nathalie, Chalandon, Yves, Boissel, Nicolas, Schaefer, Beat, Delabesse, Eric, Cavé, Hélène, Chevallier, Patrice, Buzyn, Agnès, Fest, Thierry, Reman, Oumedaly, Vernant, Jean-Paul, Lhéritier, Véronique, Béné, Marie C., Lafage, Marina, Macintyre, Elizabeth, Ifrah, Norbert, Dombret, Hervé
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biomarkers, Tumor - genetics
DNA Mutational Analysis
Female
Humans
Male
Middle Aged
Multicenter Studies as Topic
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Prognosis
Recurrence
Retrospective Studies
Survival Analysis
Young Adult
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Summary:With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome–negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10−4and unfavorable genetic characteristics (ie, MLLgene rearrangement or focal IKZF1gene deletion in BCP-ALL and no NOTCH1/FBXW7mutation and/or N/K-RASmutation and/or PTENgene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.govas #NCT00222027 and #NCT00327678, respectively. •In adult ALL, oncogenetic markers and minimal residual disease levels are independent outcome predictors.•Both factors should be used for individual treatment stratification.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2014-01-547695