Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Blood, 2014-06, Vol.123 (24), p.3739-3749

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.