两种异基因造血干细胞移植治疗白血病的临床观察

Cli, ical observation of HLA.haploidentical related or unrelated donors allogeneic hematopoietic stem cell transplantation for leukemia

目的比较HLA单倍型供者造血干细胞移植（HLA—haploidenticalRD—HSCT）和非血缘供者造血干细胞移植（URD—HSCT）治疗白血病的疗效。方法分析93例接受异基因造血干细胞移植（allo-HSCT）白血病患者的资料，其中51例患者接受HLA-haploidenticalRD．HSCT，42例接受URD—HSCT。HLA-haploidenticalRD．HSCT组中42例患者予氟达拉滨（Flu）＋白消安（Bu）＋阿糖胞苷（Am-C）预处理方案，9例子全身照射（TBI）＋nu＋Am—C预处理方案；URD—HSCT组患者中35例接受改良白消安／环磷酰胺（Bu／Cy）方案预处理，7例予TBI＋Flu方案。结果HLA—haploidenticalRD．HSCT和URD—HSCT组中性粒细胞数〉0．5×10^9／L时间分别为移植后12．5d（11—17d）和16．2d（12-21d），血小板计数〉20×10^9／L时间分别为移植后17．5d（16—25d）和20．3d（17-28d），两组中性粒细胞和血小板重建时间差异均有统计学意义（P值分别为0．008、0．023）。HLA—haploidenticalRD—HSCT组与URD．HSCT组2～4度急性移植物抗宿主病（GVHD）发生率分别为46．0％（23／50）和51．2％（21／41），慢性GVHD总发生率分别为46．0％（23／50）和63．4％（26／41），GVHD致死率分别为6．0％（3／50）和17．1％（7／41），差异均无统计学意义（P值分别为0．773、0．529、0．113）。两组移植后复发率分别为17．6％（9／51）和11．9％（5／42）（P=0．653）。3年总生存率分别为（56．3±7．0）％和（63．1±5．8）％（P=0．318），无病生存率分别为（48．2±7．7）％和（62．3±9．4）％（P=0．661）。结论采用加强预处理及免疫抑制剂的HLA—haploidenticalRD．HSCT治疗白血病，在不增加感染和GVHD发生率的基础上，可取得与URD-HSCT近似的疗效。

Objective To compare the effects of HLA-haploidentical related donors （RD） and unrelated donors （URD） hematopoietic stem cell transplantations （HSCTs） for leukemia. Methods Ninety-three leukemia patients who underwent allogenic HSCT were divided into two groups including 51 cases of HLA- haploidentical RD-HSCT and 42 cases of URD-HSCT. In the RD-HSCT group, a preconditioning regimen with fludarabine （Flu）＋busulfan （Bu）＋cytosine arabinoside （Ara-C） was employed for 42 cases and total body irradiation （TBI）＋Flu＋Ara-C for the rest of the 9 cases. In the URD-HSCT group, the modified preconditioning regimen with Bu＋cyclophosphamide （Cy） was employed in 35 cases, while the other 7 cases underwent the treatment of TBI＋Flu. Results After transplantation, the mean time of reaching the neutrophil count of more than 0.5x109/L was 12.5 and 16.2 days, while the mean time of attaining platelet count of more than 20x109/L was 17.5 and 20.3 days in the RD- and URD-HSCT groups, respectively. The occurrence rates of grade II -IV acute graft-versus-host disease （aGVHD） were 46.0 % （23/50） and 51.2 % （21/41） in the RD- and URD-HSCT groups, respectively, and the rates of chronic GVHD （cGVHD） were 46.0 % （23/50） and 63.4 % （26/41）, respectively. Furthermore, the mortality rates of GVHD were 6.0 % （3/50） and 17.1% （7/41） in the RDand URD-HSCT groups, respectively. No significant difference in the occurrence of aGVHD （P = 0.773）,cGVHD （P = 0.529） and mortality of GVHD （P = 0.113） was detected between the two groups. The recurrence rate after transplantation, three-year survival rate and disease-free survival rate were 17.6 %, （56.3±7.0） % and （63.1±5.8） % in HLA-haploidentical RD-HSCT group, and 11.9 %, （48.2±7.7） % and （62.3±9.4） % in URD-HSCT group, respectively. There were no significant differences between the two groups （P = 0.653, P = 0.318 and P = 0.661）. Conehrsion HLA-haploidentical RD-HSCT with enhanced preconditioning and administration of immunosuppressants shows the similar clinical efficacy to URD-HSCT in the battle against leukemia, without the risk of increasing infection and GVHD incidence.