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TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper‐CVAD‐based regimens
- Kanagal‐Shamanna, Rashmi;
- Jain, Preetesh;
- Takahashi, Koichi;
- Short, Nicholas J;
- Tang, Guilin;
- Issa, Ghayas C;
- Ravandi, Farhad;
- Garcia‐Manero, Guillermo;
- Yin, Cameron C;
- Luthra, Rajyalakshmi;
- Patel, Keyur P;
- Khoury, Joseph D;
- Montalban‐Bravo, Guillermo;
- Sasaki, Koji;
- Kadia, Tapan M;
- Borthakur, Gautam;
- Konopleva, Marina;
- Jain, Nitin;
- Garris, Rebecca;
- Pierce, Sherry;
- Wierda, William;
- Estrov, Zeev;
- Cortes, Jorge;
- O'Brien, Susan;
- Kantarjian, Hagop M;
- Jabbour, Elias
Abstract
Background
Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.Methods
TP53 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.Results
TP53 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.Conclusions
Hyper-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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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