异基因造血干细胞移植治疗恶性血液病20例临床疗效观察

 【摘要】　目的　探讨异基因造血干细胞移植（allo-HSCT）治疗恶性血液病的疗效，观察造血重建、移植物抗宿主病（GVHD）发生、移植相关并发症及疾病的转归。方法　回顾性分析allo-HSCT治疗恶性血液病患者20例，男15例，女5例，中位年龄39岁（8～59岁）。供者于移植前3 d采用重组人粒细胞集落刺激因子（rhG-CSF）行干细胞动员；预处理方案：人类白细胞抗原（HLA）亲缘全相合移植患者采用改良Bu／Cy方案；HLA亲缘不全相合者采用改良Bu／Cy+ATG方案；急性T淋巴细胞白血病（T-ALL）和多发性骨髓瘤（MM）患者采用Flu+Bu／Cy方案。GVHD预防方案：麦考酚酸酯+环孢素+短疗程甲氨蝶呤。结果　20例患者均成功获得造血重建，中性粒细胞计数＞0.5×109／L的中位时间为13 d（12～17 d），血小板＞20×109／L的中位时间为16 d（12～23 d），且供者CD+34 细胞采集量＞2.5×106／kg（受者体质量）或单个核细胞采集量＞5.0×108／kg（受者体质量）所移植的患者造血重建较快。12例供受者血型不合，移植后未出现严重溶血反应；11例（55 %）发生急性GVHD（aGVHD），包括Ⅰ度4例，Ⅱ度4例，Ⅲ度2例，Ⅳ度1例，均经治疗后好转。移植后所有患者均达到完全缓解（CR），中位随访6个月（2～14个月），1例白血病患者移植后5个月复发死亡，1例移植后4个月因自行停用环孢素发生自身免疫性溶血、慢性GVHD（cGVHD）、多器官衰竭死亡，其余患者仍处于CR状态。结论　allo-HSCT是治疗恶性血液病的有效方法。造血重建与采集物中造血干细胞的数量密切相关。ABO血型不合不是移植的障碍。复发、GVHD、感染是移植后死亡的重要原因。

Clinical observation of allogeneic hematopoietic stem cell transplantation for 20 patients with hematologic malignancies

Objective To evaluate the efficacy of allogeneic stem cell transplantation （allo-HSCT） in treatment of hematologic malignancies and observe hcmatopoietic reconstitution, graft versus host disease （GVHD） occurrence, transplant-related complications and the outcome of disease. Methods 20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39 （8-59） years. Mobilization of donor＇ s stem cells using rhG-CSF program 3 days before transplantation. Conditioning regimen： the patients with HLA-matched used modified Bu/Cy programs, the patients with HLA-mismatched （with 1 to 3 loci mismatched） used the modified Bu/Cy＋ ATG program; the patient with T-ALL and the patient with MM used Flu＋Bu/Cy program. GVHD prevention programs： mycophenolate mofetil ＋ cyclosporine ＋ short course methotrexate. Results 20 patients were successfully engrafted, the median time of absolute neutrophil count （ANC） 〉 0.5×10^9/L was 13 （12-17） days, the median time of Ph 〉 20×10^9/L was 16 （12-23） days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CD34^＋ ceils 〉 2.5× 10^6/kg （recipient body weigh） or the collected amount of mononuclear cell 〉 5.0×10^8/kg （recipient body weigh）. No severe hemolytic reaction occun＇ed in 11 cases of blood group incompatibility between donor and recipient after transplantation, 11 cases （55 %） developed acute GVHD （aGVHD）： 4 cases I degree aGVHD, 4 cases Ⅱ degree aGVHD, 2 cases Ⅲ degree aGVHD, 1 case Ⅳ degree aGVHD, all patients were improved after treatment. All patients attained complete remission （CR） after transplantation. Follow-up 6 （2-14） months,1 patient died in 5 months after transplantation because of leukemia relapse, l case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD （cGVHD） and multiple organ failure, the remaining patients still were in CR state. Conclusion Allo-I-ISCT is the effective way to treat hematologic malignancies. Engraftment is closely related with the quantity of hematopoietic stem cells from donor. Blood group incompatibility was not an obstacle for transplantion. Relapse, GVHD, infection are the major cause of death after transplantation.