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血液系统恶性肿瘤成年患者外周血异基因造血细胞移植后CD34细胞剂量与5年总生存率的相关性

Association of CD34 Cell Dose with 5-Year Overall Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies.

作者信息

Gauntner Timothy D, Brunstein Claudio G, Cao Qing, Weisdorf Daniel, Warlick Erica D, Jurdi Najla El, Maakaron Joseph E, Arora Mukta, Betts Brian C, Bachanova Veronika, Holtan Shernan G, He Fiona C

机构信息

Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.

出版信息

Transplant Cell Ther. 2022 Feb;28(2):88-95. doi: 10.1016/j.jtct.2021.11.004. Epub 2021 Nov 10.

Abstract

Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT) but also may increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results. In this study, we sought to clarify the prognostic impact of CD34 cell dose by examining a large contemporary cohort of patients undergoing alloHCT with a matched sibling peripheral blood stem cell (PBSC) donor. We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality, relapse, acute GVHD grade II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with a PBSC graft source from a matched sibling donor at the University of Minnesota between 2002 and 2015. The patients were classified into 3 groups based on the tertile (T) of CD34 cell dose received: T1, <5 × 10 cells/kg; T2, 5 to 7.5 × 10 cells/kg; and T3, ≥7.5 × 10 cells/kg. Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR], 0.57; P = .01) and more rapid platelet engraftment (HR, 1.70; P < .01). Higher CD34 cell dose also was associated with improved absolute neutrophil count engraftment (T2: HR, 1.54; T3: HR, 1.52; P < .01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell dose was not associated with acute GVHD grade II-IV, it was associated with chronic GVHD (T2: HR, 1.68; T3: HR, 1.50; P = .04). Our data indicate that higher CD34 cell dose (>7.5 × 10/kg) is associated with superior OS at 5 years and improved engraftment but carries an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5 × 10/kg for sibling PBSC graft donors.

摘要

较高的CD34细胞剂量与异基因外周血造血干细胞移植(alloHCT)后植入改善相关,但也可能增加长期并发症的风险,如移植物抗宿主病(GVHD)。先前研究CD34细胞剂量与长期生存结果之间关系的研究结果相互矛盾。在本研究中,我们试图通过研究一大群接受alloHCT且供者为匹配同胞外周血干细胞(PBSC)的当代患者,来阐明CD34细胞剂量的预后影响。我们回顾性研究了2002年至2015年间在明尼苏达大学接受来自匹配同胞供者的PBSC移植物来源的alloHCT的377例连续患者中,CD34细胞剂量对总生存(OS)、中性粒细胞植入、血小板植入、治疗相关死亡率、复发、急性GVHD II-IV级和III-IV级以及慢性GVHD的影响。根据接受的CD34细胞剂量三分位数(T)将患者分为3组:T1,<5×10细胞/kg;T2,5至7.5×10细胞/kg;T3,≥7.5×10细胞/kg。多变量分析表明,高CD34细胞剂量与5年OS更佳(风险比[HR],0.57;P = 0.01)和血小板植入更快(HR,1.70;P < 0.01)相关。较高的CD34细胞剂量还与绝对中性粒细胞计数植入改善相关(T2:HR,1.54;T3:HR,1.52;P < 0.01)。CD34细胞剂量与5年时的治疗相关死亡率或复发之间无关联。虽然较高的CD34细胞剂量与急性GVHD II-IV级无关,但与慢性GVHD相关(T2:HR,1.68;T3:HR,1.50;P = 0.04)。我们的数据表明,较高的CD34细胞剂量(>7.5×10/kg)与5年时更佳的OS和植入改善相关,但慢性GVHD风险增加。这些数据支持同胞PBSC移植物供者的目标CD34细胞剂量目标为7.5×10/kg。

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