血缘与非血缘供者异基因造血干细胞移植治疗白血病的比较研究

A comparison of the therapeutic effects between related donor and unrelated donor allogeneic hematopoietic stem cell transplantation in treatment of leukemia

目的探讨血缘供者(RD)与非血缘供者(URD)造血干细胞移植(HSCT)治疗白血病的差异。方法 115例白血病患者接受 HLA 血清学全相合异基因造血干细胞移植。流式细胞仪测定移植后1年内不同时间点患者的 T 细胞与 B 细胞重建情况。结果接受骨髓移植的 RD-HSCT 和URD-HSCT 组 WBC>1.0×10~9/L 分别为移植后(13.1±2.4)d、(16.3±3.0)d;PLT>20×10~9/L 分别为移植后(14.9±6.6)d、(20.2±7.3)d,两组 WBC 和 PLT 重建时间差异均有统计学意义(P 值分别为0.003、0.042);接受外周造血干细胞移植患者 RD-HSCT 和 URD-HSCT 组 WBC>1.0×10~9/L 分别为(12.5±2.9)d、(13.1±4.1)d(P=0.488),PLT>20×10~9/L 分别为(12.2±4.2)d、(15.7±7.1)d(P=0.020)。移植后1、3、6、9、12个月 CD_4^+CD_3^+,1个月 CD_(45)RA^+CD_4^+,3个月 CD_8^+CD_3^+重建两组差异均有统计学意义。两组Ⅱ～Ⅳ度急、慢性移植物抗宿主病(GVHD)的发生率分别为45.5%、52.3%;45.3%、63.2%;GVHD 的病死率分别为6.1%、15.9%,差异均无统计学意义。两组移植后复发率分别为18.2%、11.4%(P=0.424)。两组移植后早期感染率分别为42.4%、47.7%(P=0.696)。3年总生存率分别为(67.8±6.9)%、(61.6±7.7)%(P=0.133),无病生存率分别为(62.3±6.9)%、(56.8±7.9)%(P=0.177)。结论 URD-HSCT 治疗白血病具有和 RD-HSCT 近似的疗效。

Objective To compare the therapeutic effect for leukemia between related donor hematopeietic stem cell transplantation （RD-HSCT） and unrelated donor hematopeietic stem cell transplantation （URD-HSCT）. Methods 115 patients received allo-HSCT, of whom 68 received RD-HSCT and 47 received URD-HSCT. All patients were HLA serologically matched. Total body irradiation plus cyclophosphamide was adopted in 56 cases and busulfan, Ara-C, cyclophosphamide conditioning regimen （modified BuCY） in 59 cases. T and B cell reconstitution at different time points was assayed with flow cytometer one year after transplantation. Graft versus host disease （GVHD） and early infection were observed after transplantation. The difference of haematopeietic and immunological reconstitution between the two groups were estimated with Independent-Samples T test. Kaplan-Meier survival analysis model was used to estimate the overall survival and the disease-free survival in the two groups. Results The time in WBC 〉 1.0 × 10^9/L was （ 13. 1 ± 2. 4） d and （ 16. 3 ± 3.0） d （P = 0. 003 ）, the time in PLT 〉 20 × 10^9/L was （ 14. 9 ±6. 6） d and （20. 2 ±7.3） d （P =0. 042）, respectively, RD-BMT and URD-BMT. The time with WBC 〉 1.0 × 10^9/L was （ 12. 5 ± 2.9 ） d and （ 13. 1 ± 4. 1 ） d （ P = 0. 488 ）, the time with PLT 〉 20× 10^9/L was （ 12. 2 ± 4. 2） d and （ 15.7 ± 7. 1 ） d （P = 0. 020）, respectively, in RD-PBSCT and URD-PBSCT. The reconstitution of CD4^＋ CD3^＋ at 1st, 3rd, 6th, 9th, 12th month,CD45RA^＋ CD^＋ at 1st month and CD3^＋ CD3^＋ at 3rd month was different significantly between RD-HSCT and URD-HSCT. The incidence of Ⅱ-Ⅳ acute GVHD, chronic GVHD and lethality of GVHD was 45. 5% and 52. 3%, 45. 3% and 63. 2%, 6. 1% and 15.9%, respectively, in RD-HSCT and URD-HSCT groups. The relapse rate was 18.2% and 11.4%, respectively, in RD-HSCT and URD-HSCT groups. The incidence of early infection was 42. 4% and 47. 7% （P =0. 696）, respectively, in RD-HSCT and URD-HSCT groups. The overall survival and the disease-free survival rates at three-year follow-up were （67. 8 ± 6.9） % and （ 61.6 ± 7.7 ） % （ P = 0. 133 ）, （ 62. 3 ± 6.9）% and （56.8 ± 7.9）% （P = 0.177）, respectively, in RD-HSCT and URD-HSCT groups. Conclusion The therapeutic effect for leukemia is proximate in RD-HSCT and URD-HSCT.