The prognostic implications of CDKN2A/2B deletion in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

This review aimed to evaluate the impact of cyclin-dependent kinases 2 A/2B (CDKN2A/2B) deletion on survival in pediatric acute lymphoblastic leukemia (ALL). We pooled hazard ratios (HRs) and risk ratios (RRs) with 95% CIs, which were calculated using random-effects models. Individual patient data (IPD) were extracted from published survival curves of included studies, and combined HR was estimated. Fourteen studies (n = 2532 subjects) were included. CDKN2A/2B deletion was found to be associated with poor event/disease/relapse-free survivals at both study levels (HR 2.18; 95% CI: 1.46-3.27; I² 51%) and IPD level (HR 3.45; 95% CI 2.76-4.32 and p < 0.001); and poor overall survival at the IPD level (HR 3.22; 95% CI: 1.78-5.84 and p < 0.001). CDKN2A/2B deletion was also associated with a higher risk of poor prednisolone response (RR 1.38; 95% CI: 1.09-1.74; I² 7%) and relapse rates (RR 3.83; 95% CI: 2.76-5.3; I² -0%). The meta-analysis highlights the negative impact of CDKN2A/2B deletions on disease outcome and treatment response. Hence, incorporating these alterations should improve risk stratification and risk-adapted treatment strategies for childhood ALL.