自体外周血干细胞移植治疗难治性天疱疮一例

Autologous peripheral hematopoietic stem cell transplantation in a patient with refractory pemphigus

目的探讨自体外周血干细胞移植治疗天疱疮的可能性。病历资料男性患者，35岁，全身反复大疱4年余，根据临床表现、组织病理和免疫荧光检查确诊为天疱疮。经糖皮质激素和免疫抑制剂治疗效果不佳，2月前出现髋关节疼痛，经X线和CT检查诊断为股骨头无菌性坏死。采取环磷酰胺及粒细胞集落刺激因子作为动员剂，利妥昔单抗联合净化。用环磷酰胺联合抗胸腺细胞球蛋白、利妥昔单抗进行预处理，同时碱化和水化尿液，保护心、肝和肾功能。观察移植后临床表现、造血和免疫指标等的变化。结果患者移植结束即停用糖皮质激素。3周后自觉双侧髋关节疼痛减轻，复查CT示股骨头缺血性改变减轻。移植6周后直接免疫荧光和间接免疫荧光检查转阴并持续阴性。经一年复诊，临床及免疫学检查均无复发迹象。结论本研究结果提示自体外周血干细胞移植治疗天疱疮近期疗效显著。可能是治疗存在治疗抵抗的重症天疱疮潜在的“根治”方法．但其风险收益比尚需进一步评价。

Objective To explore the possibility of autologous peripheral hematopoietic stem cell transplantation in treatment with refractory pemphigus. Patient and Intervention A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities. The diagnosis of pemphigus was made on the basis of the clinical, histologic, and immunofluorescence findings. The patient showed resistance to conventional therapy with glucocorticoid and immunosuppressive agents. Two months before admission, he complained of hip joint pain, and X-ray and CT scan revealed amicrobic necrosis of the femoral head. Stem-cell mobilization was achieved by treatment with cyclophosphamide, granulocyte colony-stimulating factor （ G-CSF ）, and rituximab. Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use. Immunoablation was accomplished using cyclophosphamide （ 200 mg/kg; divided 50 mg/kg on days -5, -4, -3, and -2 ）, antithymocyte globulin （ ATG; 10 mg/kg; divided 2.5 mg/kg on days -6, -5, -4, and -3 ）, and rituximab （ 1200 rag/d; divided 600mg/d on days 0 and 7 ）. Autolognus peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system, which was monitored by flow cytometry. Results The glucocorticoid was withdrawn immediately after transplantation. His pemphigns titer turned negative at 6 weeks post-transplantation and remained negative. The patient was in complete drug-free remission with no evidence for residual clinical or serological activity of pemphigus during 1 year of follow-up. Conclusions The patient＇s response suggests that autolognus peripheral hematopoietic stem cell transplantation may be a potential ＂cure＂ for refractory pemphigns. Therefore, this approach deserves further studies to evaluate the risk-benefit ratio in patients with pemphigns showing resistance to conventional therapy.