TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper‐CVAD‐based regimens

Abstract

BackgroundTumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.MethodsTP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing.ResultsTP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5.6%-93.8%). The majority of mutations were single-nucleotide variants of missense type and involved the DNA-binding domain. TP53-mutated (TP53mut ) ALL was found to be significantly associated with older age, lower median white blood cell and platelet counts, lower frequency of Philadelphia chromosome and a higher frequency of low hypodiploid karyotype compared with ALL with wild-type TP53 (TP53wt ). To evaluate the prognostic effect of TP53 mutations, the authors selected 146 patients with B-cell immunophenotype ALL (24 with TP53mut and 122 with TP53wt ) who were uniformly treated with frontline hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD)-based regimens; >90% of these individuals also received a monoclonal antibody. Over a median follow-up duration of 15 months, there was no significant difference in the median overall survival, event-free survival, and duration of complete remission noted between patients with TP53mut ALL and those with TP53wt ALL.ConclusionsHyper-CVAD-based regimens appear to negate the poor prognostic impact of TP53 mutations in patients with adult B-cell immunophenotype ALL. Cancer 2017;123:3717-24. © 2017 American Cancer Society