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序贯移植单倍体相合造血干细胞和无关脐带血联合使用 ATG/PTCY 可提高复发/难治性血液系统恶性肿瘤的生存率。

Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies.

机构信息

Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.

Translational Medicine Center on Hematology, Fujian Medical University, Fuzhou, China.

出版信息

Front Immunol. 2021 Nov 4;12:733326. doi: 10.3389/fimmu.2021.733326. eCollection 2021.

Abstract

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 56.5%), >0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175-0.691; =0.0025), DFS (HR 0.402, 95% CI, 0.208-0.779; =0.0069), and GRFS (HR 0.235, 95% CI, 0.120-0.457, <0.0001) compared to the single cord group. The 2-year's probability in OS, DFS, and GRFS was 64.9 31.6%, 64.5 31.6%, and 60.8 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 6.2%, chronic GVHD 25.8 13.7%, and extensive chronic GVHD 5.3 1.8% were shown in corresponding group, >0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.

摘要

异基因单倍体相合造血干细胞移植(haplo-HSCT)和非血缘脐带血移植(UCBT)用于缺乏 HLA 完全相合的同胞供者或无关供者的患者。我们采用清髓性预处理方案,使用低剂量 ATG 和移植后环磷酰胺(PTCY)进行 GVHD 预防,进行了一项前瞻性临床试验。2015 年 2 月至 2019 年 12 月,研究共纳入 122 例符合条件的患者,其中 113 例患者入组。48 例患者接受序贯单倍体-脐带血移植(haplo-cord HSCT),65 例患者接受单份 UCBT。2 年无病生存(DFS)是两组患者的主要终点,无统计学差异(64.1% vs. 56.5%,>0.05)。对复发/难治患者的亚组分析显示,haplo-cord HSCT 与更好的 OS(HR 0.348,95%CI,0.175-0.691;=0.0025)、DFS(HR 0.402,95%CI,0.208-0.779;=0.0069)和 GRFS(HR 0.235,95%CI,0.120-0.457,<0.0001)相关。haplo-cord 组和单份脐带血组 2 年 OS、DFS 和 GRFS 的概率分别为 64.9% vs. 31.6%、64.5% vs. 31.6%和 60.8% vs. 15.0%。两组患者 III-IV 级急性移植物抗宿主病(GVHD)发生率分别为 8.3% vs. 6.2%、慢性 GVHD 发生率分别为 25.8% vs. 13.7%、广泛性慢性 GVHD 发生率分别为 5.3% vs. 1.8%,>0.05。持续 UCB 植入的患者生存结局更好。我们采用 ATG/PTCY 的序贯单倍体相合造血干细胞移植改善了患者的生存,可能为复发/难治性血液系统恶性肿瘤患者提供了一种可供选择的移植方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9864/8599442/e6455685ebdb/fimmu-12-733326-g001.jpg

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