Allogeneic hematopoietic stem cell transplantation improves the prognosis of p16-deleted adult patients with acute lymphoblastic leukemia

Abstract

Aim: The prognostic value of CDKN2A inactivation in adult patients with acute lymphoblastic leukemia (ALL) is still under debate, and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult ALL with p16 deletion remains to be evaluated. Materials & methods: This study analyzed the clinical implications of p16 deletion in adult ALL and investigated the efficacy of allo-HSCT in patients with p16 deletion. Results: Deletion of p16 was identified in 38.4% of the adult ALL patients, and the prevalences of hemizygous deletion, homozygous deletion and mixed hemi/homozygous of p16 were 22.1, 11.6 and 5.5%, respectively. The prevalence of p16 deletion was 39.7% in B-lineage ALL and 33.3% in T-lineage ALL. Deletion of p16 was significantly associated with higher white blood cell count (p = 0.032) and lower platelets (p = 0.023) but was not related to age, sex, percentage of bone marrow blasts, hepatosplenomegaly, CNS leukemia rate, first complete remission and relapse rate (p > 0.05). Deletion of p16 was significantly correlated with poor outcome in terms of event-free survival (EFS; p = 0.028) and overall survival (OS; p = 0.033). Twenty-two of the 33 patients with p16 deletion received allo-HSCT treatment. Patients with p16 deletion after allo-HSCT experienced higher EFS and OS than those without (52.9 vs 0%, p < 0.001; 46.8 vs 29.1%, p = 0.01, respectively). Multivariate analysis found CNS leukemia and poor response to induction chemotherapy to be the risk factors for EFS and OS, whereas no deletions of p16 and allo-HSCT were favorable factors. Conclusion: Deletion of p16 is a strong adverse prognostic factor in adult ALL. Testing for p16 alterations at diagnosis may help in risk stratification, and we propose to implement testing for p16 deletion in future treatment protocols.