单倍体相合造血干细胞移植联合间充质干细胞输注治疗异染性脑白质营养不良

Haploidentical Hematopoietic Stem Cell Transplantation and Mesenchymal Stem Cell Infusion for the Treatment of Metachromatic Leukodystrophy

目的探讨单倍体相合造血干细胞移植联合间充质干细胞输注治疗异染性脑白质营养不良的疗效。方法 7岁患儿,采用单倍体相合造血干细胞移植联合间充质干细胞输注的方法,经氟达拉滨、马利兰、环磷酰胺和抗人胸腺细胞球蛋白方案进行预处理,供者应用G-CSF动员和联合免疫抑制剂(包括环胞菌素A、氨甲喋呤、霉酚酸酯、CD25单抗)预防移植物抗宿主病。造血重建后,每周输注脐带来源的间充质干细胞1次,连续4周。结果患儿造血重建迅速,11 d时中性粒细胞>0.5×109/L、血小板>20×109/L;14 d时血白细胞芳基硫酸酯酶A水平明显上升;28 d时达正常水平。患者无急性GVHD发生。移植后1个月经植入证据检测,证实为完全供者造血,神经系统症状逐渐恢复。结论单倍体相合造血干细胞移植,联合间充质干细胞输注,治疗异染性脑白质营养不良,安全、有效,血白细胞芳基硫酸酯酶A水平回升迅速。这种新型疗法可能是治疗缺乏HLA全相合供者的异染性脑白质营养不良疾病患者的可靠选择。

Objective To investigate the effect of haploidentical hematopoietic stem cell transplantation and mesenchymal stem cell infusion in the treatment of metachromatic leukodystrophy.Methods A 7-year-old girl with metachromatic leukodystrophy received hematopoietic stem cell transplantation and mesenchymal stem cells infusion.The pretreatment regimen consisted of fludarabine,cyclophosphamide,and busulfan.The prophylaxis of acute graft-versus-host disease was performed by the administration of anti-CD25 monoclonal antibody,cyclosporine A,methotrexate,mycophenolate mofetil,anti-thymocyte globulin and G-CSF-mobilized bone marrow.After hematopoietic reconstruction,mesenchymal stem cells derived from umbilical cord were intravenously infused once a week for 4 consecutive weeks.Results The patient achieved rapid hematopoietic engraftment of donor origin.Neutrophil（ 0.5 × 10^9 / L） and platelet（ 20 × 10^9 / L） recovery was achieved on ＋11 day.On day 14,arylsulfatase A level in peripheral blood leukocytes was significantly increased and it reached to the normal range on ＋28 day.No acute graft-versus-host disease was observed.One month after transplantation,finger-printing analysis indicated an achievement of complete donor-type hematopoiesis.Neurological symptoms gradually recovered.Conclusion Haploidentical hematopoietic stem cell transplantation and mesenchymal stem cell infusion for the treatment of metachromatic leukodystrophy were safe,effective and leukocyte arylsulfatase A level rises rapidly.The novel regimen described here might be one of the options patients with metachromatic leukodystrophy and lack of HLA-matched sources.