Rappeport J M, Parkman R, Newburger P, Camitta B M, Chusid M J
Am J Med. 1980 Apr;68(4):605-9. doi: 10.1016/0002-9343(80)90312-5.
Allogeneic bone marrow transplantation has been unsuccessful as therapy for genetically determined bone marrow disorders. In patients prepared for transplantation with drugs alone long-term hematopoietic engraftment is not achieved due to the overgrowth of the infused donor bone marrow cells by residual recipient hematopoietic stem cells. Utilizing a combination of total body irradiation and antihuman thymocyte serum, the successful eradication of the abnormal hematopoietic stem cells of patients with the Wiskott-Aldrich syndrome and now infantile agranulocytosis has been achieved. Following preparation with total body irradiation and antihuman thymocyte serum a 20 month old patient with infantile agranulocytosis has complete donor hematopoietic and lymphoid engraftment one year after a histocompatible allogeneic bone marrow transplant. Prior to transplantation, this patient had no circulating or bone marrow granulocytes; following transplantation he has normal numbers of circulating granulocytes with normal in vivo and in vitro function. This therapeutic result demonstrates that genetic disorders of myeloid function can be corrected by allogeneic bone marrow transplantation following preparation with total body irradiation and antihuman thymocyte serum, and suggests that infantile agranulocytosis is due to an intrinsic defect of the pluripotent hematopoietic stem cell and not to a micro-environmental defect.
同种异体骨髓移植作为治疗遗传性骨髓疾病的方法并不成功。在仅用药物准备进行移植的患者中，由于残留的受体造血干细胞使注入的供体骨髓细胞过度生长，无法实现长期造血植入。通过全身照射和抗人胸腺细胞血清联合使用，成功根除了患有维斯科特-奥尔德里奇综合征以及现在的婴儿粒细胞缺乏症患者的异常造血干细胞。在接受全身照射和抗人胸腺细胞血清准备后，一名患有婴儿粒细胞缺乏症的20个月大患者在进行组织相容性同种异体骨髓移植一年后实现了完全的供体造血和淋巴植入。移植前，该患者没有循环或骨髓粒细胞；移植后，他的循环粒细胞数量正常，体内和体外功能也正常。这一治疗结果表明，在经过全身照射和抗人胸腺细胞血清准备后，同种异体骨髓移植可以纠正髓系功能的遗传性疾病，并表明婴儿粒细胞缺乏症是由于多能造血干细胞的内在缺陷，而非微环境缺陷。
