Pediatric Oncology/Coagulation Section, Karolinska University Hospital, Solna, Sweden.
Department of Clinical Research Center, Karolinska Institute, Stockholm, Sweden.
Clin Transplant. 2019 Jun;33(6):e13537. doi: 10.1111/ctr.13537. Epub 2019 May 7.
Graft-versus-host disease (GVHD) and relapse remain majobstacles ftreatment success in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the immune cell profile of the graft to outcome after HSCT.
Flow cytometry data of graft cell subsets [CD34 , CD3 , CD19 , CD4 , CD8 , CD3-CD56 CD16 , CD4 CD127 CD25 ] from G-CSF primed peripheral blood stem cell (PBSC) donors was collected retrospectively from 299 patients with hematological malignancies undergoing HSCT between 2006 and 2013. The association to overall survival, transplant-related mortality (TRM), GVHD and probability of relapse was analyzed. Patients outcome from HLA-identical sibling (Sib) (n = 97) and unrelated donors (URD) (n = 202) were analyzed separately as all URD patients received anti-thymocyte globulin (ATG).
Five-year overall survival was similar in the two cohorts (68% (Sib) vs 65% (URD)). The relapse incidence was significantly lower in the Sib cohort (24% vs 35%, P = 0.04). Multivariate analysis in the URD group revealed an association between a higher CD8 dose and less relapse (HR, 0.94; 95%CI, 0.90-0.98; P = 0.006) as well as an association between higher CD34 dose and both higher TRM (HR, 1.09; 95%CI, 1.02-1.20; P = 0.02) and relapse (HR, 1.09; 95%CI, 1.01-1.17; P = 0.025). The Sib analysis showed an association between a higher graft CD19 dose and more severe acute GVHD (HR, 1,09; 95%CI, 1.03-1.15; P = 0.003) and TRM (HR, 1.09; 95%CI, 1.01-1.17; P = 0.036). In addition, a higher CD4 graft content was associated to an increased risk for chronic GVHD (HR, 1.02; 95%CI 1.00-1.04; P = 0.06).
These data indicate an importance of PBSC dongraft composition in patients with a hematological malignancy.
移植物抗宿主病（GVHD）和复发仍然是异基因造血干细胞移植（HSCT）治疗成功的主要障碍。在本研究中，我们评估了移植物的免疫细胞谱与 HSCT 后的结果。
回顾性收集了 2006 年至 2013 年间接受 HSCT 的 299 例血液系统恶性肿瘤患者的 G-CSF 诱导外周血干细胞（PBSC）供者移植物细胞亚群[CD34、CD3、CD19、CD4、CD8、CD3-CD56 CD16、CD4 CD127 CD25]的流式细胞术数据。分析了其与总生存、移植相关死亡率（TRM）、GVHD 和复发概率的关系。分别分析了 HLA 同基因供体（Sib）（n=97）和无关供体（URD）（n=202）患者的结果，因为所有 URD 患者均接受了抗胸腺细胞球蛋白（ATG）治疗。
两组 5 年总生存率相似（Sib 为 68%，URD 为 65%）。Sib 组的复发率明显较低（24% vs 35%，P=0.04）。URD 组的多变量分析显示，较高的 CD8 剂量与较低的复发率相关（HR，0.94；95%CI，0.90-0.98；P=0.006），较高的 CD34 剂量与较高的 TRM 相关（HR，1.09；95%CI，1.02-1.20；P=0.02）和复发（HR，1.09；95%CI，1.01-1.17；P=0.025）。Sib 分析显示，较高的移植物 CD19 剂量与更严重的急性 GVHD（HR，1.09；95%CI，1.03-1.15；P=0.003）和 TRM（HR，1.09；95%CI，1.01-1.17；P=0.036）相关。此外，较高的 CD4 移植物含量与慢性 GVHD（HR，1.02；95%CI，1.00-1.04；P=0.06）的风险增加相关。
这些数据表明，PBSC 供体移植物组成在血液系统恶性肿瘤患者中具有重要意义。
