无关供体外周血干细胞和骨髓移植治疗白血病的比较研究

A comparative study of unrelated donor bone marrow transplantation and peripheral blood stem cell transplantation for their therapeutic effects on leukemia

目的评价无关供体外周血干细胞和骨髓移植的造血重建、T细胞重建、感染、GVHD及疗效的差异。方法46例患者接受无关供体造血干细胞移植(URD-HSCT),其中16例患者接受无关供者外周血干细胞移植(外周血组),30例患者接受无关供者骨髓移植(骨髓组)。流式细胞仪测定移植后1年内不同时间点患者的T细胞免疫重建。统计分析两组患者移植后白细胞(WBC)和血小板(BPC)重建时间,T细胞重建,感染发生率,移植物抗宿主病(GVHD)、白血病复发、无病生存(DFS)情况。结果除1例骨髓干细胞移植患者未造血重建外,其余45例均获得造血重建。外周血组和骨髓组WBC重建时间分别为+(12.81±4.15)和+(16.21±3.09)d(P=0.003);白细胞重建时间分别为+(15.50±6.91)和+(20.31±7.19)d(P=0.035),外周血组白细胞和血小板重建时间均快于骨髓组。外周血组和骨髓组患者移植后1、3、6、9、12月的T细胞重建无显著性差异。外周血组和骨髓组的移植后早期感染发生率分别为37.50%和50.00%,二者无显著性差异(P=0.644)。外周血组与骨髓组急性GVHD(aGVHD)的发生率分别为56.25%和70.00%,其中Ⅲ-Ⅳ°aGVHD的发生率在二组分别为18.75%和13.79%;在可统计的患者中,慢性GVHD(cGVHD)的发生率外周血组为30.77%(4/13),骨髓组为36.36%(8/22),aGVHD和cGVHD发生率二组比较均无差异(P值分别为0.456和0.413)。非白血病复发移植相关死亡率外周血组和骨髓组分别为18.75%和33.33%,二者无显著性差异(P=0.295)。外周血组与骨髓组移植后分别有3例和2例复发,二者的复发率无显著性差异(P=0.226);移植后2年DFS在外周血组与骨髓组分别为62.19%和56.23%,二者无显著性差异(P=0.615)。结论无关供体外周血干细胞移植后的造血重建比骨髓移植迅速,但两者间移植后T细胞重建、感染发生率、GVHD及DFS并无显著性差异。

Objective To compare the effect of unrelated donor bone marrow （BM） transplantation and peripheral blood stem cell （PBSC） transplantation in light of hemopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease （GVHD） and other complications in patients with leukemia. Methods The clinical outcomes of 16 patients receiving unrelated PBSC graft mobilized by granulocyte colony-stimulating factor （G-CSF） were compared with 30 patients receiving unrelated BM transplantation. Results Engraftment was achieved in 97.83% of the total patients. Compared with BM transplantation group, PBSC graft contained significantly more nucleated cells （P=0.000）, resulting in a significantly shorter time-to-neutrophil （16.21±3.09 vs 12.81±4.15 days, P=0.003） and platelet engraftment （20.31±7.19 vs 15.50±6.91 days, P=0.035）. T cell reconstitution differed little between the two groups at different time points after transplantation. The incidences of early-stage infection were 37.50% and 50.00% （P=0.644） in the PBSC and BM groups, respectively. In PBSC and BM groups, the incidences of grades I to IV acute GVHD （aGVHD） were 56.25% and 70.00% （P=0.456）, 18.75% and 13.79% （P=0.661） for grades Ⅲ to Ⅳ aGVHD, and 30.77% and 36.36% （P=0.413） for chronic GVHD（cGVHD）, respectively. The nonrelapse transplant-related mortality （TRM） rates were 18.75% in PBSC group and 33.33% in BM group （P=0.295）. The relapse occurred in 18.75% and 6.90% （P=0.226） of the patients in the two groups, respectively, and the 2-year disease-free survival （DFS） rates were 62.19% and 56.23% （P=0.615）, respectively. Conclusion G-CSF-mobilized PBSCs allow more rapid engraftment in unrelated donor recipients in comparison with conventional BM, but T cell reconstitution and the incidence of infection between the two groups differ little, nor are there significant differences in the incidence or severity of aGVHD and cGVHD, nonrelapse TRM or 2-year DFS rates between the two groups.