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- Title
TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens.
- Authors
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
- Abstract
<bold>Background: </bold>Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
LYMPHOBLASTIC leukemia treatment; LYMPHOBLASTIC leukemia; P53 protein; CYCLOPHOSPHAMIDE; VINCRISTINE; TREATMENT effectiveness; GENETIC mutation; CANCER remission; GENETICS; THERAPEUTICS
- Publication
Cancer (0008543X), 2017, Vol 123, Issue 19, p3717
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.30810