TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based re... - PubMed - NCBI
Cancer. 2017 Oct 1;123(19):3717-3724. doi: 10.1002/cncr.30810. Epub 2017 Jun 13.
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 R1,
Jain P2,
Takahashi K2,
Short NJ2,
Tang G1,
Issa GC2,
Ravandi F2,
Garcia-Manero G2,
Yin CC1,
Luthra R1,
Patel KP1,
Khoury JD1,
Montalban-Bravo G1,
Sasaki K2,
Kadia TM2,
Borthakur G2,
Konopleva M2,
Jain N2,
Garris R2,
Pierce S2,
Wierda W2,
Estrov Z2,
Cortes J2,
O'Brien S3,
Kantarjian HM2,
Jabbour E2.
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. © 2017 American Cancer Society.
KEYWORDS:
acute lymphoblastic leukemia (ALL); hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD); next-generation sequencing; tumor protein 53 (TP53)
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