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单倍体相合干细胞联合脐带血移植治疗B细胞急性淋巴细胞白血病患者的临床结局

Clinical Outcomes of B Cell Acute Lymphoblastic Leukemia Patients Treated with Haploidentical Stem Cells Combined with Umbilical Cord Blood Transplantation.

作者信息

Zhou Biqi, Xu Mimi, Lu Shenqi, Liu Yujie, Qi Lijuan, Liu Tianhui, Tian Hong, Chen Jia, Wu Depei, Xu Yang

机构信息

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Transplant Cell Ther. 2022 Mar;28(3):173.e1-173.e6. doi: 10.1016/j.jtct.2021.12.010. Epub 2021 Dec 22.

Abstract

Clinical outcomes of hematopoietic stem cell transplantation (HSCT) using a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) for the treatment of B cell acute lymphoblastic leukemia (B-ALL) remain unclear. This study was conducted to explore the clinical outcomes of haplo-cord HSCT in patients with B-ALL. A total of 112 B-ALL patients who underwent haplo-cord HSCT and 64 B-ALL patients who underwent haploidentical HSCT (haplo-HSCT) at our center between 2010 and 2020 were retrospectively included in this study, and clinical outcomes and prognostic factors were further analyzed. Of the 112 haplo-cord HSCT recipients, 106 (94.6%) achieved complete haploidentical chimerism and 6 (5.4%) had mixed cord blood chimerism. No differences in neutrophil and platelet recovery or in the incidences of graft-versus-host disease, cytomegalovirus/Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis were observed between the haplo-cord HSCT and haplo-HSCT groups. Compared with the haplo-HSCT group, the haplo-cord HSCT group had a higher absolute number of CD3 cells (P = .029) and a lower ratio of CD3CD4 /CD3CD8 cells (P = .049) at 1 month post-transplantation. Moreover, the haplo-cord HSCT group had lower minimal residual disease (MRD) levels at 1 month (P = .020) and 100 days (P = .038) post-transplantation and a better 3-year prognosis (overall survival, P = .016; disease-free survival, P = .041; cumulative incidence of relapse [CIR], P = .016). The CIRs in patients with adverse genomic features (P = .040) or flow cytometry-based MRD (FCM-MRD) ≥1 × 10 (P = .033) were improved by haplo-cord HSCT. Multivariate analysis revealed that haplo-cord HSCT could independently improve the 3-year OS, DFS, and CIR of B-ALL patients (OS, P = .029; DFS, P = .024; CIR, P = .024). In addition, allo-HSCT at first complete remission was an independent parameter associated with 3-year OS for B-ALL patients (P = .014). An FCM-MRD ≥1 × 10 pre-HSCT could independently predict unfavorable 3-year DFS and CIR (DFS, P = .020; CIR, P = .036) in B-ALL patients. Our data suggest that the use of haplo-cord HSCT can independently improve survival in patients with B-ALL.

摘要

使用单倍体相合干细胞移植物和无关脐血单位进行造血干细胞移植(haplo-cord HSCT)治疗B细胞急性淋巴细胞白血病(B-ALL)的临床结果仍不清楚。本研究旨在探讨haplo-cord HSCT治疗B-ALL患者的临床结果。本研究回顾性纳入了2010年至2020年期间在本中心接受haplo-cord HSCT的112例B-ALL患者和接受单倍体相合HSCT(haplo-HSCT)的64例B-ALL患者,并进一步分析了临床结果和预后因素。在112例haplo-cord HSCT受者中,106例(94.6%)实现了完全单倍体相合嵌合,6例(5.4%)具有混合脐血嵌合。haplo-cord HSCT组和haplo-HSCT组在中性粒细胞和血小板恢复、移植物抗宿主病、巨细胞病毒/爱泼斯坦-巴尔病毒血症、血流感染或出血性膀胱炎的发生率方面未观察到差异。与haplo-HSCT组相比,haplo-cord HSCT组在移植后1个月时CD3细胞绝对数更高(P = 0.029),CD3CD4/CD3CD8细胞比例更低(P = 0.049)。此外,haplo-cord HSCT组在移植后1个月(P = 0.020)和100天时(P = 0.038)微小残留病(MRD)水平更低,3年预后更好(总生存,P = 0.016;无病生存,P = 0.041;复发累积发生率[CIR],P = 0.016)。haplo-cord HSCT改善了具有不良基因组特征(P = 0.040)或基于流式细胞术的MRD(FCM-MRD)≥1×10的患者的CIR(P = 0.033)。多变量分析显示,haplo-cord HSCT可独立改善B-ALL患者的3年总生存、无病生存和CIR(总生存,P = 0.029;无病生存,P = 0.024;CIR,P = 0.024)。此外,首次完全缓解时进行异基因HSCT是B-ALL患者3年总生存的独立相关参数(P = 0.014)。移植前FCM-MRD≥1×10可独立预测B-ALL患者不良的3年无病生存和CIR(无病生存,P = 0.020;CIR,P = 0.036)。我们的数据表明,使用haplo-cord HSCT可独立改善B-ALL患者的生存。

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