供者活化型KIR2DS5在单倍体相合造血干细胞移植预后中的意义

Impact of Donor KIR2DS5 Genotype on Outcome Following Haploidentical Hematopoietic Stem Cell Transplantation

本研究探讨供者杀伤细胞免疫球蛋白样受体(KIR)和受者人类白细胞抗原(HLA)基因型在单倍体相合造血干细胞移植(HSCT)预后中的意义。26例患者接受单倍体相合HSCT,均未进行体外T细胞去除(TCD)。采用序列特异性引物聚合酶链式反应(PCR-SSP)分型技术对供、受者HLA和供者KIR基因型进行检测。根据供者KIR和受者HLA-Bw4组、-C1组、-C2组等位基因分析结果进行供受者KIR/HLA分组。对KIR/HLA不合与相合组、Bw4不合与相合组、C2不合与相合组、Bw4和C2均不合组与至少其一相合组在造血重建、移植物抗宿主病(GVHD)、无病生存(DFS)、移植后感染及移植相关死亡(TRM)等方面的差异进行比较;并就供者活化型KIR对单倍体相合HSCT预后的影响进行评价。结果表明:各组在造血重建、急性或慢性GVHD发生率、DFS、移植后感染及TRM等方面均无显著性差异(p均>0.05),但C2不合组发生严重GVHD4例。供者活化型KIR2DS5阳性组2年DFS明显优于阴性组,分别为(85.7±13.2)%、(31.2±12.8)%,p<0.05〕。结论:供者KIR及受者HLA基因型对单倍体相合HSCT预后有影响,供者携带活化型KIR2DS5可能有助于提高患者的DFS。

The aim of this study was to evaluate the impact of donor killer cell immunoglobulin-like receptor （KIR） and recipient HLA genotypes on outcome following haploidenticai hematopoietic stem cell transplantation （HSCT）. 26 patients with hematologic diseases received non T-cell-depleted （ TCD ） in vitro transplant from haploidentical donor. Donor/recipient HLA and donor KIR genotypes were determined by polymerase chain reaction- sequence-specific primer （PCR-SSP）. Donor/recipient KIR/HLA subgroup was assessed by donors KIR and recipients HLA-Bw4, Cwl group and Cw2 group alleles. Hematopoietic reconstitution , incidence of graft versus host disease （ GVHD ）, disease-free survival（ DFS ）, infection and transplant-related mortality （TRM）were analyzed between every two groups. The influence of donor activating KIR on outcome follwing haploidenticai HSCT also has been studied. The results showed that hematopoietic reconstitution, incidence of GVHD, DFS, infection and TRM were not significantly different between every two groups（p 〉 0.05 ）. There were 4 cases of severe GVHD in C2 mismatched group. The donor activating KIR2DS5 positive group had higher 2-year DFS compared with the negative group [（85.7 ± 13.2）% vs （31.2 ± 12,8）%, p〈0.05 ]. It is concluded that KIR/HLA genotypes between donor and recipient influence the outcome following haipoidenticai HSCT. Donor activating KIR2DS5 may improve DFS in non TCD haploidenticai HSCT.