单倍体相合外周血造血干细胞移植治疗恶性血液病

Clinical Study of Haploidentical Peripheral Blood Stem Cell Transplantation without Ex Vivo T-cell Depletion for High-risk Hematological Malignancies

为了探讨单倍体相合外周血造血干细胞移植(hi-PBSCT)治疗恶性血液病的疗效和相关并发症,对15例高危患者进行体外不去除T细胞的hi-PBSCT。预处理采用改良的Bu/Cy或TBI/Cy方案,用抗胸腺细胞球蛋白(ATG)、环孢素A(CsA)、霉酚酸酯(MMF)和短程甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD),4例加用抗CD25单克隆抗体。回输G-CSF动员的外周血干细胞,输注MNC中位数为8.16(3.92-10.86)×108/kg,CD34+细胞中位数为4.51(1.27-5.95)×106/kg。结果显示:所有患者均植入成功,ANC≥0.5×109/L的中位时间为14(11-19)天,Plt≥20×109/L的中位时间为22(11-52)天。Ⅰ-Ⅱ度急性GVHD6例,慢性GVHD2例。移植后100天内均出现感染,病原学确诊为细菌感染8例,CMV感染6例。5例患者出现复发。中位随访213(42-589)天,死亡8例,存活7例。结论:hi-PBSCT治疗无HLA相合供者的恶性血液病患者是可行而且有效的,进一步降低移植相关并发症是主要问题。

This study was aimed to explore the efficacy and associated complications of haploidentical peripheral blood stem cell transplantation （hi-PBSCT） without ex vivo T-cell depletion in treatment of hematological malignancies. 15 high-risk patients received HLA 1 - 3 loci （ A, B, or DRB1 ） mismatched hi-PBSCT. The modified Bu/Cy or TBI/ Cy regimen was used for preconditioning of patients. The anti-thymocyte globulin, cyclosporin A, methotrexate and mycophenolate mofetil were used for GVHD prophylaxis. 4 cases were administrated with anti-CD25 monclonal antibody. G-CSF-mobilized peripheral blood stem cells were infused, with the median number of infused nucleated cells was 8.16 （3.92 - 10.86） × 10^8/kg and that of CD34^ ＋ ceils was 4.51 （ 1.27 -5.95 ） × 10^6/kg. The results showed that the rapid engraftment was observed in all cases. The median times of neutrophil recovery ≥0.5 x 109/L and platelet recovery 〉120 x 109/L were 14 （ 11 - 19 ） and 22 （ 11 - 52 ） days after transplantation respectively. 6 cases developed acute GVHD of grade I - II , and 2 cases experienced chronic extensive GVHD. Infection within 100 days after hi-PBSCT was documented in all cases. 8 cases were subjected to bacterial infection, and six got cytomegalovirus infection. Relapse occurred in five cases. Overall survival of patients was 46.7% （7/15）, with a median follow-up of 213 （42 - 589 ） days. In conclusion, hi-PBSCT provides an effective alternative treatment for high-risk patients in lack of matched donors, and to reduce the high transplantation-related mortality.