Copy Number Alterations are Associated with the Risk of Very Early Relapse in Pediatric B-lineage Acute Lymphoblastic Leukemia: A Nested Case-control MIGICCL Study

Abstract

Background: Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population.

Aim of the study: The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL.

Methods: A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted.

Results: The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR = 4.94, 95% CI = 1.87-13.07 and HR = 7.42, 95% CI = 2.37-23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant.

Conclusions: Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.

Keywords: Acute lymphoblastic leukemia; Copy number alterations; Deletions; Relapse; Risk stratification.