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第二次自体干细胞移植:复发多发性骨髓瘤的有效治疗方法

Second autologous stem cell transplant: an effective therapy for relapsed multiple myeloma.

作者信息

Singh Abbi Kamal Kant, Zheng Junting, Devlin Sean M, Giralt Sergio, Landau Heather

机构信息

Division of Hematology, Oncology and Bone Marrow Transplantation, University of Iowa Hospitals and Clinic, Iowa City, Iowa.

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.

出版信息

Biol Blood Marrow Transplant. 2015 Mar;21(3):468-72. doi: 10.1016/j.bbmt.2014.11.677. Epub 2014 Dec 18.

Abstract

Therapeutic options for patients with multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (ASCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second ASCT, with no clear standard of care. We retrospectively analyzed the outcomes of 75 patients who underwent salvage melphalan-based ASCT for relapsed MM at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Conditioning was performed with melphalan 200 mg/m(2) (n = 43), 180 mg/m(2) (n = 1), 140 mg/m(2) (n = 22), and 100 mg/m(2) (n = 9). The median age at second ASCT was 59 years (range, 36 to 75), and 58% (n = 35) were men. Of those with available data, 19% had high-risk cytogenetics (including t (4;14), p53 loss, or del 13q by karyotype) at the time of second ASCT. Median interval between first and salvage ASCT was 37.5 months (range, 6.9 to 111.4). Of 72 assessable patients, 57% had chemotherapy-sensitive disease before to salvage ASCT and 43% were chemoresistant. Four patients died within 100 days of ASCT. Response was assessed at 2 to 3 months post-ASCT, and of 71 assessable patients, 82% achieved at least a partial response, 15% had stable disease, and 3% progressed despite salvage ASCT. After salvage ASCT, 38 patients received maintenance therapy and 14 went on to allogeneic ASCT. The median progression-free survival (PFS) after second autograft was 10.1 months (95% confidence interval [CI], 7.6 to 13.4) and median overall survival (OS) 22.7 months (95% CI, 19.2 to 41.2). Patients with chemosensitive relapse had a trend toward better PFS (hazard ratio [HR], .60 [95% CI, .36 to 1.02]; P = .058) and significantly longer OS (HR, .49 [95% CI, .27 to .88]; P = .017) than patients with resistant relapse. Those with high-risk cytogenetics at the time of second ASCT had higher risk of death (HR, 2.98 [95% CI, 1.28 to 6.97]; P = .012) compared with patients with standard-risk cytogenetics. Salvage ASCT is an effective strategy for relapsed MM with chemosensitive disease and results in comparable PFS and OS to other salvage strategies.

摘要

对于多发性骨髓瘤(MM)患者,若其疾病在先前自体干细胞移植(ASCT)后复发,治疗选择包括越来越多的新型药物,通常与传统化疗联合使用,或进行第二次ASCT,但尚无明确的标准治疗方案。我们回顾性分析了1995年至2012年间在纪念斯隆凯特琳癌症中心接受基于美法仑的挽救性ASCT治疗复发MM的75例患者的结局。预处理采用美法仑200mg/m²(n = 43)、180mg/m²(n = 1)、140mg/m²(n = 22)和100mg/m²(n = 9)。第二次ASCT时的中位年龄为59岁(范围36至75岁),58%(n = 35)为男性。在有可用数据的患者中,19%在第二次ASCT时具有高危细胞遗传学特征(包括t(4;14)、p53缺失或核型分析显示13q缺失)。首次和挽救性ASCT之间的中位间隔为37.5个月(范围6.9至111.4个月)。在72例可评估患者中,57%在挽救性ASCT前患有化疗敏感疾病,43%为化疗耐药。4例患者在ASCT后100天内死亡。在ASCT后2至3个月评估缓解情况,在71例可评估患者中,82%至少达到部分缓解,15%疾病稳定,3%尽管进行了挽救性ASCT仍进展。挽救性ASCT后,38例患者接受维持治疗,14例继续进行异基因ASCT。第二次自体移植后的中位无进展生存期(PFS)为10.1个月(95%置信区间[CI],7.6至13.4),中位总生存期(OS)为22.7个月(95%CI,19.2至41.2)。化疗敏感复发的患者与耐药复发的患者相比,PFS有改善趋势(风险比[HR],0.60[95%CI,0.36至1.02];P = 0.058),OS显著更长(HR,0.49[95%CI,0.27至0.88];P = 0.017)。第二次ASCT时具有高危细胞遗传学特征的患者与标准风险细胞遗传学特征的患者相比,死亡风险更高(HR,2.98[95%CI,1.28至6.97];P = 0.012)。挽救性ASCT是治疗化疗敏感的复发MM的有效策略,其PFS和OS与其他挽救策略相当。

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