Department of Hematology, Shanghai Jiao Tong University School of Medicine Affiliated Shanghai General Hospital, Shanghai, China.
Cell Transplant. 2023 Jan-Dec;32:9636897231157054. doi: 10.1177/09636897231157054.
The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 10/kg) that separated the risk of II-IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II-IV aGvHD, and III-IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, < 0.0001, = 0.002, and = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD ( = 0.005, = 0.018, and = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/μL vs 338 cells/μL, = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.
淋巴细胞亚群组成对单倍体外周血造血干细胞移植(haploPBSCT)后结局的影响尚不完全清楚。我们回顾性分析了 2016 年至 2020 年在我中心接受 haploPBSCT 的 314 例血液系统恶性肿瘤患者。我们获得了 CD3+T 细胞剂量(2.96×10^6/kg)的截止值,该值将急性移植物抗宿主病(aGvHD)的风险分开,并将患者分为低 CD3+T 细胞剂量组(CD3+低)和高 CD3+T 细胞剂量组(CD3+高)。CD3+高组患者的 I-IV 级 aGvHD、II-IV 级 aGvHD 和 III-IV 级 aGvHD 发生率明显较高(高组为 50.8%、19.8%和 8.1%,低组为 23.1%、6.0%和 0.9%, < 0.0001、=0.002 和=0.02)。我们发现移植物中 CD4+T 细胞及其幼稚和记忆亚群对 aGvHD 有显著影响(=0.005、=0.018 和=0.044)。此外,我们发现与低剂量组相比,高剂量组在移植后第一年 NK 细胞的重建明显较差(239 个/μL 比 338 个/μL,=0.0003)。两组之间在植入、慢性移植物抗宿主病(cGvHD)、复发率、移植相关死亡率(TRM)和总生存率(OS)方面均无差异。总之,我们的研究发现,高 CD3+T 细胞剂量导致 haploPBSCT 中 aGvHD 风险增加和 NK 细胞重建不良。在未来,仔细操纵移植物淋巴细胞亚群的组成可能会降低 aGvHD 的风险并改善移植结果。