移植物细胞组分对异基因造血干细胞移植预后的影响

Effect of graft composition on the prognosis of allogeneic hematopoietic stem cell transplantation

目的:探讨移植物中单个核细胞(mononuclear cell,MNC)、CD34^(+)细胞及T淋巴细胞亚群剂量对移植后生存的影响。方法:回顾性分析121例行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo⁃HSCT)的血液系统恶性疾病患者,研究回输移植物中MNC、CD34^(+)细胞、CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、调节性T细胞(regulatory T cell,Treg)剂量及CD4^(+)/CD8^(+)T细胞比值对移植后造血重建及生存的影响。结果:中性粒细胞成功植入120例,高剂量CD34^(+)T细胞(≥6.90×10^(6)个/kg)(P<0.001)、CD3^(+)T细胞(≥6.24×10^(8)个/kg)(P=0.042)和CD8^(+)T细胞(≥1.05×10^(8)个/kg)(P=0.021)与中性粒细胞更快植入相关。血小板成功植入119例,高剂量CD34^(+)细胞与血小板更快植入相关(P=0.001)。53例(43.8%)患者发生急性移植物抗宿主病,28例发生慢性移植物抗宿主病。1年和3年总体生存(overall survival,OS)率为83.5%和68.0%,1年和3年无进展生存(progression⁃free survival,PFS)率为75.0%和64.4%。单因素分析中,高剂量MNC(≥9.79×10^(8)个/kg)、高剂量CD3^(+)T细胞和CD4^(+)/CD8^(+)T细胞比值<3.57患者有更好的OS,高剂量MNC患者有更好的PFS(P=0.061)。多因素分析显示,CD4^(+)/CD8^(+)T细胞比值<3.57患者有更好的OS(HR=0.288,95%CI:0.084~0.988,P=0.048)。1年和3年累积复发率分别为18.2%和26.8%,高剂量MNC和CD8^(+)T细胞患者有更低的累积复发率。结论:移植物细胞组分对异基因造血干细胞移植预后有重要影响,高剂量CD34^(+)细胞可促进血小板更快植入,回输移植物中CD4^(+)/CD8^(+)T细胞比值<3.57的患者有更好的OS和更低的累积复发率。

Objective:To investigate the impact of the graft content including mononuclear cells(MNC),CD34^(+)cells and T⁃lymphocyte subsets on post⁃transplant survival.Methods:A retrospective analysis of 121 patients with hematologic malignant diseases undergoing allogeneic hematopoietic stem cell transplantation(allo⁃HSCT)was performed to investigate the effects of the doses of MNC,CD34^(+)cells,CD3^(+)T cells,CD4^(+)T cells,CD8^(+)T cells and regulatory T(Treg)cells in the grafts on hematopoietic reconstitution and survival.Results:Neutrophils were successfully engrafted in 120 patients,and patients with high doses of CD34^(+)cells(≥6.90×10^(6)/kg)(P<0.001),CD3^(+)T cells(≥6.24×10^(8)/kg)(P=0.042)and CD8^(+)T cells(≥1.05×10^(8)/kg)(P=0.021)had more rapid engraftment of neutrophils.Platelets were successfully engrafted in 119 cases,and high dose CD34^(+)cells were associated with faster platelet reconstruction(P=0.001).Acute graft⁃versus⁃host disease(aGVHD)occurred in 53(43.8%)patients and 28 patients had chronic graft⁃versus⁃host disease(cGVHD).One and 3⁃year overall survival(OS)rates were 83.5%and 68.0%,and one and 3⁃year progression⁃free survival(PFS)rates were 75.0%and 64.4%.In univariate analysis,the patients with high MNC dose(≥9.79×10^(8)/kg),high CD3^(+)T cells dose and CD4^(+)/CD8^(+)T cells<3.57 had better OS and the high MNC group had better PFS(P=0.061).Multivariate analysis showed that the CD4^(+)/CD8^(+)T⁃cell<3.57 group had better OS(HR=0.288,95%CI:0.084~0.988,P=0.048).One and 3⁃year cumulative incidence of relapse(CIR)were 18.2%and 26.8%,respectively.Patients in the higher MNC and CD8^(+)T⁃cell groups had lower CIR.Conclusion:Graft components has an important impact on the prognosis of allo⁃HSCT.High doses of CD34^(+)cells promote faster platelet implantation,and patients with a CD4^(+)/CD8^(+)T⁃cell ratio<3.57 in the graft have better OS and lower CIR.