A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia (ALL)
Menée initialement sur une cohorte de 809 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë, puis validée sur une cohorte complémentaire de 742 patients, cette étude met en évidence l'intérêt de combiner données cytogénétiques et génomiques pour identifier les patients susceptibles de bénéficier d'un traitement moins intensif
tRecent genomic studies have provided a refined genetic map of acute lymphoblastic leukemia and increased the number of potential prognostic markers. Therefore we integrated copy number alteration data from the eight most commonly deleted genes, subordinately, with established chromosomal abnormalities to derive a two-tier genetic classification. The classification was developed using 809 ALL97/99 patients and validated using 742 UKALL2003 patients. Good risk genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy number status for all eight genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk. Three-quarters of UKALL2003 patients had a good risk genetic profile and a significantly improved event-free survival (94%) compared to patients with a poor risk genetic profile (79%). This difference was driven by a lower relapse rate (4% v 17%), was seen across all patient subgroups and was independent of other risk factors. Even genetic good risk patients with minimal residual disease (>0.01%) at day 29 had an event-free survival in excess of 90%. In conclusion, the integration of genomic and cytogenetic data defines two subgroups with distinct responses to treatment, and identifies a large subset of children suitable for treatment de-intensification.
Submitted March 14, 2014.Accepted June 9, 2014.Copyright © 2014 American Society of Hematology
Blood , résumé, 2013