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1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响

OBJECTIVE: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. METHODS: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogene...

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Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editorial office of Chinese Journal of Hematology 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342892/
https://www.ncbi.nlm.nih.gov/pubmed/29779352
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.05.013
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collection PubMed
description OBJECTIVE: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. METHODS: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. RESULTS: ①In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105–3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090–5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. CONCLUSION: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
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spelling pubmed-73428922020-07-16 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响 Zhonghua Xue Ye Xue Za Zhi 论著 OBJECTIVE: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. METHODS: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. RESULTS: ①In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105–3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090–5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. CONCLUSION: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q. Editorial office of Chinese Journal of Hematology 2018-05 /pmc/articles/PMC7342892/ /pubmed/29779352 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.05.013 Text en 2018年版权归中华医学会所有 http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution 3.0 License (CC-BY-NC). The Copyright own by Publisher. Without authorization, shall not reprint, except this publication article, shall not use this publication format design. Unless otherwise stated, all articles published in this journal do not represent the views of the Chinese Medical Association or the editorial board of this journal.
spellingShingle 论著
1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title_full 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title_fullStr 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title_full_unstemmed 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title_short 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
title_sort 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
topic 论著
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342892/
https://www.ncbi.nlm.nih.gov/pubmed/29779352
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.05.013
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