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Annals of Hematology
Erschienen in: Annals of Hematology 3/2018

21.12.2017 | Original Article

CTLA-4 polymorphisms are associated with treatment outcomes of patients with multiple myeloma receiving bortezomib-based regimens

verfasst von: Xiao-Ying Qin, Jin Lu, Guo-Xuan Li, Lei Wen, Yang Liu, Lan-Ping Xu, Ying-Jun Chang, Kai-Yan Liu, Zheng-Fan Jiang, Xiao-Jun Huang

Erschienen in: Annals of Hematology | Ausgabe 3/2018

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Abstract

Single-nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte antigen-4 (CTLA-4) are important risk factors associated with autoimmune diseases and malignancies. This study explored the association of CTLA-4SNPs with the development of myeloma and evaluated the outcome of patients receiving bortezomib-based regimens in relation to CTLA-4SNPs. Peripheral blood samples from 86 patients with multiple myeloma (MM) and 154 healthy controls were obtained to investigate CTLA4 polymorphisms. Five SNP genotypes of CTLA-4, namely, −1772 (rs733618), −1661 (rs4553808), −318 (rs5742909), CT60 (rs3087243), and +49 (rs231775), were evaluated through TaqMan SNP genotyping assays (Applied Biosystems). Some of the CTLA-4 polymorphisms displayed frequencies that vary among ethnic groups. Kaplan–Meier analysis revealed that patients with rs733618 GG showed a significantly lower disease-free survival (0 vs. 57.4%, P = 0.020) and overall survival (46.3 vs. 83.3%, P = 0.026) than those with GA+AA following bortezomib-based therapy. Multivariate analyses showed that rs733618 GG was a risk factor for OS (HR = 0.012; 95% CI = 0.001–0.199; P = 0.002). The incidence of nonhematologic grade 3/4 adverse events significantly increased in the rs4553808 GG+GA group compared with that in the AA group (P = 0.036). CTLA-4 rs733618 GG reduced the progression-free survival and the overall survival of patients with MM who received bortezomib-based therapy. Information regarding CTLA-4 polymorphisms and haplotypes may be used to improve MM therapy. Future studies must determine the precise effect of CTLA-4 polymorphisms and haplotypes on MM therapy outcomes by using different cohorts with a large number of subjects.
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Metadaten
Titel
CTLA-4 polymorphisms are associated with treatment outcomes of patients with multiple myeloma receiving bortezomib-based regimens
verfasst von
Xiao-Ying Qin
Jin Lu
Guo-Xuan Li
Lei Wen
Yang Liu
Lan-Ping Xu
Ying-Jun Chang
Kai-Yan Liu
Zheng-Fan Jiang
Xiao-Jun Huang
Publikationsdatum
21.12.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 3/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-3203-7

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