目的探讨肾移植联合造血干细胞移植诱导治疗的安全性和有效性,并总结其经验。方法2009年实施7例亲属活体肾移植联合造血干细胞移植,其中1例为供受者HLA抗原全相合,其余为半相合。肾移植前5d使用粒细胞集落刺激因子动员供者造血干细胞,术前1d采集供者造血干细胞。肾移植前3d受者开始接受全身淋巴照射,连续3d,肾移植术中给予受者抗胸腺细胞球蛋白50nag,术后第2、4、6天输注供者造血干细胞。术后常规采用三联免疫抑制方案,监测受者血常规、淋巴细胞亚型变化及移植肾功能等情况。结果全身淋巴照射后受者淋巴细胞数进行性降低,以B淋巴细胞(CD19+)的比例下降幅度最大,其他血细胞数量变化不大。HLA全相合受者诱导出30%~50%的嵌合体,其余受者仅诱导出1%~5%的嵌合体。术后随访3年,7例受者移植肾功能稳定,均未出现骨髓抑制和移植物抗宿主病,未增加感染风险。经移植肾活检证实,1例受者出现轻度急性排斥反应,其余6例受者未发生排斥发生。7例受者中,有3例减少了免疫抑制剂的用量。结论肾移植联合造血干细胞移植诱导治疗的方案安全、有效。
Objective To introduce the safety and efficacy of donor hematopoietic stem cell transplantation combined with kidney transplantation as induction therapy. Method Seven patients with end-stage renal disease, 22 to 36 years of age, were enrolled in this study. Four had parent and three had sibling donors. One was matched and six were mismatched for one HLA haplotype. The donor received a 5-day course of subcutaneous injections of granulocyte colony-stimulating factor and donor cells were harvested before transplantation. Total lymphoid irradiation (TLI) and ATG were used as induction in recipients. Intravenous infusion of donor cells was followed by kidney transplantation. Surveillance of lymphocyte, renal allograft function, biopsies, etc. was performed at regular intervals thereafter. Result The number of lymphocytes was decreased rapidly after TLI, but that of neutrophils kept stably. For the lymphocyte subset, the proportion of CD19+ B cells was decreased significantly as compared with that of CD4+ Th cells and CD8+ Ts cells. Chimerism was successfully induced in the first recipient, and the rate was about 30%to 50%. The rate of ehimerism was 1 % to 5 % in other recipients. All recipients were followed up for three years and renal function remained stable in seven recipients. Myelosuppression and GVHD were not found in all patients. Biopsy specimens showed one recipient had acute rejection (IA), while rest recipients were normal. The dose of immunosuppressant was reduced in three recipients. Conclusion Renal transplantation combined with hematopoietie stem cell transplantation was safe and effective.