Table_1_Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies.pdf

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 vs. 56.5%), p>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; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p<0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>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.

异基因单倍体相合造血干细胞移植（Allogeneic haploidentical HSCT, haplo-HSCT）与无关供者脐血移植（unrelated umbilical cord blood transplantation, UCBT）适用于缺乏HLA相合同胞供者或无关供者的患者。本研究采用清髓性预处理方案，联合低剂量抗胸腺细胞球蛋白（ATG）与移植后环磷酰胺（PTCY）进行移植物抗宿主病（GVHD）预防，开展了一项前瞻性临床试验。2015年2月至2019年12月期间，本研究共纳入符合入组标准的122例患者，最终113例患者入组。其中48例患者接受序贯单倍体-脐血造血干细胞移植（sequential haplo-cord HSCT, haplo-cord HSCT），65例患者接受单纯脐血移植（single UCBT）。两组的主要终点——2年无病生存率（disease-free survival, DFS）无统计学差异（64.1% vs. 56.5%，p>0.05）。对复发/难治性亚组患者的分析显示，与单纯脐血移植组相比，序贯单倍体-脐血造血干细胞移植组的总生存率（overall survival, OS）、无病生存率（DFS）及无移植物抗宿主病无复发生存率（GRFS）均更优，风险比（HR）分别为0.348（95%置信区间[CI]：0.175~0.691，p=0.0025）、0.402（95%CI：0.208~0.779，p=0.0069）与0.235（95%CI：0.120~0.457，p<0.0001）。序贯单倍体-脐血移植组与单纯脐血移植组的2年总生存率、无病生存率及无移植物抗宿主病无复发生存率分别为64.9% vs. 31.6%、64.5% vs. 31.6%与60.8% vs. 15.0%。两组Ⅲ~Ⅳ级急性移植物抗宿主病发生率分别为8.3% vs. 6.2%，慢性移植物抗宿主病发生率为25.8% vs. 13.7%，广泛性慢性移植物抗宿主病发生率为5.3% vs. 1.8%，组间比较均无统计学差异（p>0.05）。持续植入脐血的患者生存结局更优。本研究所采用的联合ATG/PTCY的序贯单倍体-脐血造血干细胞移植可改善患者生存，有望成为复发/难治性血液系统恶性肿瘤患者的替代移植方案。