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多发性骨髓瘤患者异基因干细胞移植后的长期生存和多克隆免疫球蛋白重建。

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma.

机构信息

Department of Medicine A, University Hospital Münster, Münster, Germany.

出版信息

Ann Hematol. 2020 Aug;99(8):1907-1915. doi: 10.1007/s00277-020-04068-5. Epub 2020 May 22.

Abstract

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.

摘要

尽管在过去十年中,多发性骨髓瘤(MM)患者的治疗取得了重大进展,但对于早期复发或疾病快速进展的高危患者,异体造血干细胞移植(SCT)可能是一种能够实现长期生存的选择。在此,我们回顾性分析了 1999 年至 2017 年期间在我们中心接受异体 SCT 的 90 例 MM 患者的结果。我们特别评估了体液免疫重建受损(称为免疫缺陷)与移植后生存之间的关联。64 例患者在接受 2-7 线治疗后复发时接受了异体 SCT;26 例患者接受了 upfront tandem 自体-异体 SCT。中位随访 76 个月后,2 年和 5 年的 OS 和 PFS 分别为 52.6%(95%CI 42.9-64.3)和 36.4%(95%CI 27.6-47.9),38.6%(95%CI 29.2-51.1)和 25.3%(95%CI 17.5-36.4)。移植前接受超过两线治疗是 OS(HR 3.68,95%CI 2.02-6.70)和 PFS(HR 3.69,95%CI 2.09-6.50)的独立危险因素。在第 200 天的里程碑分析中,长期免疫缺陷与 OS 降低相关(HR 3.22,95%CI 1.14-9.11)。异体干细胞移植提供了一种额外的治疗手段,可能会使预后较差的选定患者获得长期缓解,可能利用移植物抗骨髓瘤效应。免疫缺陷可能是异体移植后生存受损的一个潜在指标,这一观察结果需要进一步前瞻性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/7340674/448cd0fcfef7/277_2020_4068_Fig1_HTML.jpg

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