Burt R K, Traynor A E, Pope R, Schroeder J, Cohen B, Karlin K H, Lobeck L, Goolsby C, Rowlings P, Davis F A, Stefoski D, Terry C, Keever-Taylor C, Rosen S, Vesole D, Fishman M, Brush M, Mujias S, Villa M, Burns W H
Departments of Medicine, Neurology, Nephrology, and Rheumatology, Division of Hematology/Oncology & Lurie Comprehensive Cancer Center, Northwestern University Medical School and Robert H. Lurie Cancer Center, Chicago, IL, USA.
Blood. 1998 Nov 15;92(10):3505-14.
Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.
多发性硬化症、系统性红斑狼疮和类风湿性关节炎都是免疫介导性疾病，对免疫系统的抑制或调节有反应。对于重症患者，免疫抑制可能会强化到骨髓抑制或造血功能消除的程度。然后通过回输CD34(+)祖细胞可迅速重建造血功能和免疫功能。在10例患有这些自身免疫性疾病的患者中，自体造血干细胞从骨髓中采集，或通过粒细胞集落刺激因子（G-CSF）或环磷酰胺与G-CSF从外周血中动员出来。使用CD34(+)分选法在体外富集干细胞，并在接受环磷酰胺（200 mg/kg）、甲泼尼龙（4 g）和抗胸腺细胞球蛋白（ATG；90 mg/kg）进行骨髓抑制预处理或全身照射（1200 cGy）、甲泼尼龙（4 g）和环磷酰胺（120 mg/kg）进行清髓预处理后回输。6例多发性硬化症患者、2例系统性红斑狼疮患者和2例类风湿性关节炎患者接受了造血干细胞移植。绝对中性粒细胞计数大于500/μL（0.5×10⁹/L）和未输血血小板计数大于20,000/μL（20×10⁹/L）的平均植入时间分别为第10天和第14天。与治疗方案相关的非造血毒性极小。所有患者病情均有改善和/或稳定，随访时间为5至17个月（中位数为11个月）。我们得出结论，强化免疫抑制预处理和自体T细胞清除的造血移植被安全地用于治疗这10例重症自身免疫性疾病患者。尽管反应的持久性尚不清楚，但所有患者均已表现出病情稳定或改善。
