粒细胞集落刺激因子动员的异基因骨髓与外周血干细胞混合移植治疗血液系统恶性疾病

A pilot study of G-CSF mobilized allogeneic bone marrow cells plus peripheral blood stem cells transplantation for malignant 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治疗血液系统疾病的可行性与疗效。方法 供者给予G CSF连续 4～ 6天皮下注射 ,注射后第 3天从髂后上嵴抽取G CSF动员的骨髓血 ,第 4天开始取外周血干细胞。并立即输给受者——— 14例血液系统恶性疾病患者 (恶性肿瘤 10例 ,重症再生障碍性贫血 4例 )接受了G CSF动员的异基因骨髓与外周血干细胞混合移植 ,分析其植活率、植活速度以及急性、慢性移植物抗宿主病 (aGVHD ,cGVHD)的发生率。结果 14例患者均获得异体植活 ,白细胞数恢复至≥ 1× 10 9/L ,血小板≥ 2 0× 10 9/L的中位时间分别为移植后的 14d(12～ 18d)和 13d (11～ 6 5d)。有 4例发生了Ⅰ度aGVHD ,3例发生了Ⅱ度aGVHD ,但无一例重度aGVHD发生。在可评估的 9例患者中有 3例出现了广泛的cGVHD。有 2例患者因白血病复发而死亡 ,另 1例因植活不良 ,再次输注供者外周血干细胞 (PBSC)后出现IV度aGVHD死亡 ,其余 11例中位随访时间 4 5 5d(84～ 715d) ,均无病生存。结论 G CSF动员的异基因骨髓与外周血干细胞混合移植可以用于血液系统恶性疾病的治疗 ,能保证持久、稳定的植活 ,植活速度快 ,急、慢性GVHD的发生率与异基因骨髓移植相比并没有增加。

Objective To study the feasibility and clinical outcome of granulocyte-colony stimulating factor (G-CSF) mobilized allogeneic bone marrow (G-BM) plus G-CSF mobilized peripheral blood stem cells (G-PBSC) transplantation for malignant hematological disease. Methods G-BM plus G-PBSC transplantation was conducted between siblings or between parent and child. G-CSF was injected hypodermically into 14 stem cell donors 5 μg·kg -1·d -1 for 4～6 days. On the 3rd day after beginning of G-CSF injection bone marrow blood was extracted from the posterior superior iliac spine of the donors; on the 4th day G-PBSCs were collected. The collected stem cells were transplanted immediately into the bodies of the 14 patients with hematological disease, including acute myelocytic leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndrome and severe aplastic anemia. The clinical outcomes, including the rate of engraftment, speed of engraftment, and the occurrence of acute graft versus host disease (aGVHD and chronic graft versus host disease (cGVHD) were investigated. Results All patients got endurable engraftment. The median time of recovery of neutrophil count to ≥1×109/L was 14 days (range 12～18 days). The median time to achieve a platelet count ≥20×109/L without transfusion was 13 days (range 11～65 days). Seven of the 14 patients developed aGVHD, 4 being in the grade I and 3 being in grade II. Three of the evaluable 9 patients developed extensive chronic GVHD. Two patients died of relapsed leukemia. One patient received secondary PBSCT from hte same donor because of ill engraftment and developed grade IV GVHD and died. The other 11 patients were still alive and event-free with a median follow-up duration of 455 days (range 84～715 days). Conclusion An effective treatment for malignant hematological disease, G-CSF mobilized allogeneic bone marrow plus peripheral blood stem cells transplantation provides rapid and sustained engraftment without increase in incidence of aGVHD and cGVHD.