TY - JOUR
T1 - TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens
AU - Kanagal-Shamanna, Rashmi
AU - Jain, Preetesh
AU - Takahashi, Koichi
AU - Short, Nicholas J.
AU - Tang, Guilin
AU - Issa, Ghayas C.
AU - Ravandi, Farhad
AU - Garcia-Manero, Guillermo
AU - Yin, Cameron C.
AU - Luthra, Rajyalakshmi
AU - Patel, Keyur P.
AU - Khoury, Joseph D.
AU - Montalban-Bravo, Guillermo
AU - Sasaki, Koji
AU - Kadia, Tapan M.
AU - Borthakur, Gautam
AU - Konopleva, Marina
AU - Jain, Nitin
AU - Garris, Rebecca
AU - Pierce, Sherry
AU - Wierda, William
AU - Estrov, Zeev
AU - Cortes, Jorge
AU - O'Brien, Susan
AU - Kantarjian, Hagop M.
AU - Jabbour, Elias
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - acute lymphoblastic leukemia (ALL)
KW - hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD)
KW - next-generation sequencing
KW - tumor protein 53 (TP53)
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U2 - 10.1002/cncr.30810
DO - 10.1002/cncr.30810
M3 - Article
C2 - 28608976
AN - SCOPUS:85020393013
SN - 0008-543X
VL - 123
SP - 3717
EP - 3724
JO - Cancer
JF - Cancer
IS - 19
ER -