Prognostic impact of copy number alterations in pediatric B-cell precursor acute lymphoblastic leukemia: A collaborative data from two major oncology centers of North India

Abstract

In current study, copy number alteration (CNA) status and CNA risk profiles of IKZF1plus, UK-ALL CNA risk groups and MRplus score, were evaluated for clinical and prognostic impact in a cohort of 493 B-ALL cases diagnosed and treated under ICICLE trial at two major oncology centres of Northern India. Overall CNA frequency was 59% with 60% of cases showing 2-loci deletion. CDKN2A/B deletion was the most common CNA (36.3%), while IKZF1 deletion and IKZF1plus profile were noted in 19.5% and 13.4% of cases respectively. IKZF1 deletions and other CNA risk profiles were all signifcantly associated with poor/high risk clinical and genetic profile parameters (p-<0.001). In addition, the 3-year OS, EFS was significantly poor with high RR of 38.6%, 46.5% and 35.2% for IKZF1 deletions, IKZF1plus profile and UK-ALL CNA –IR+PR risk group respectively (p-<0.001). Integrated evaluation of UK-ALL CNA risk profile with ICICLE trial risk stratification groups also revealed a worse OS, EFS and RR of 63.3%, 43.2% and 35.2% for combined ICICLE groups with CNA-IR±PR profile compared to CNA-GR profile (81.3%,65.0% and 21.0% ; p-<0.001). Hence, routine CNA testing in our setting is must to identify SR and IR cases likely to benefit from high risk treatment.