G-CSF动员后异基因骨髓联合外周血干细胞移植治疗血液病

Clinical study of G-CSF mobilized allogeneic bone marrow cells plus peripheral blood stem cells transplantation for hematological diseases

目的探讨粒细胞集落刺激因子（G-CSF）动员的异基因骨髓与外周血干细胞混合移植后造血重建、移植物抗宿主病（GVHD）、复发及生存情况。方法45例血液病患者进行了动员后的异基因骨髓联合外周血干细胞混合移植,人白细胞抗原（HLA）全合37例,1-3个位点不合8例。38例恶性病中32例采用清髓性预处理,6例为减低强度预处理;7例重型再生障碍性贫血（SAA）均采用环磷酰胺联合兔抗人胸腺细胞球蛋白（ATG）及甲泼尼龙预处理。采用环孢素联合霉酚酸酯预防移植物抗宿主病,HLA不全相合患者加用ATG。供者给予G-CSF连续5天皮下注射,注射后第5天采集外周血干细胞,第7天采取骨髓血。结果45例患者均获得快速造血重建,中性粒细胞绝对计数≥0.5×10^9/L,血小板≥20×10^9/L的中位时间分别为移植后的12（8-18）天和16（10-28）天。10例发生了急性GVHD（22%）,Ⅱ度以上1例。可评估的42例患者中16例出现了慢性GVHD,7例为广泛型（16%）。复发9例,死亡11例,其余34例中位随访时间16月（10-46月）,可评估的2年无病生存率为75%。结论G-CSF动员后的异基因骨髓联合外周血干细胞移植治疗血液病可获快速造血重建,移植相关死亡率及重度急、慢性GVHD的发生率低,复发率不增高。

Objective To study the clinical outcome about hematopoetic reconstitution、graft-versus-host disease、relapse and survival of granulocyte colony stimulating factor（G-CSF） mobilized allogeneic bone marrow（G-BM） plus peripheral blood stem cells（G-PBSC） transplantation for hematological disease.Methods 45 patients undergone allogeneic G-BM plus G-PBSC transplantation for hematological diseases.37 cases were matched for HLA antigens,8 cases were one～three loci mismatched.Among 38 patients with malignant diseases,32 cases conditioned with myeliablative regimen,others with reduced intensity regimen;7 cases with severe aplastic anemia conditioned with cyclophosphamide,antihuman thymocyte immunoglobin（ATG）,and methylprednisolone.All the patients received cyclosporine A and mycophenolate mofetil to prevent GVHD,HLA mismatched cases plus ATG.All donor were mobilized with G-CSF 7.5 to 10 μg/kg of subcutaneous for 5 to 6 days,PBSC were collected on day 5,BM cells were harvested on day 7.Results The hematopoetic reconstitution was accelerated,The median number of days of granulocyte count exceeding 0.5×10^9/L and platelet count exceeding 20×10^9/L was 12 d （range 8-18 d） and 16 d （range 10-28 d）,respectively.The cumulative incidence of aGVHD was 22%,only one case with greater than grade II aGVHD.16 of 42 evaluatable patients developed cGVHD,extensive cGVHD was 16%.9 cases relapsed,11 cases died.The estimate probability of disease free survival at 2 years was 75%.Conclusion Allogeneic G-BM plus G-PBSC transplantation can accelerate hematopoietic recovery,reduce the incidence of severe GVHD and transplant related mortality,relapse rate did not increase.