Childhood Acute B-Lineage Lymphoblastic Leukemia With CDKN2A/B Deletion Is a Distinct Entity With Adverse Genetic Features and Poor Clinical Outcomes
Jing Feng, Ye Guo, Wenyu Yang, Yao Zou, Li Zhang, Yumei Chen, Yingchi Zhang, Xiaofan Zhu, Xiaojuan Chen
Abstract
To further emphasize the clinical–genetic features and prognosis of CDKN2A/B deletions in childhood acute lymphoblastic leukemia (ALL), we retrospectively analyzed 819 consecutive B-ALL patients treated with the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol, and fluorescence in situ hybridization (FISH) analysis on CDKN2A/B deletion was available for 599 patients. The prevalence of CDKN2A/B gene deletions was 20.2% (121/599) of B-ALL. CDKN2A/B deletions were significantly associated with older age, higher leukocyte counts, a higher percentage of hepatosplenomegaly, and a higher frequency of BCR-ABL ( p < 0.05). Those patients achieved similar minimal residual disease (MRD) clearance and complete remission compared to patients without CDKN2A/B deletion. The CDKN2A/B deletions were correlated with inferior outcomes, including a 3-year event-free survival (EFS) rate (69.8 ± 4.6 vs. 89.2 ± 1.6%, p = 0.000) and a 3-year overall survival (OS) rate (89.4% ± 2.9% vs. 94.7% ± 1.1%, p = 0.037). In multivariable analysis, CDKN2A/B deletion was still an independent prognostic factor for EFS in total cohorts ( p < 0.05). We also detected a multiplicative interaction between CDKN2A/B deletions and TP53 deletion on dismal prognosis ( p -interaction < 0.05). In conclusion, CDKN2A/B deletion is associated with distinct characteristics and serves as a poor prognostic factor in pediatric ALL, especially in TP53 deletion carriers.