Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease
Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease
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DOI：
10.7326/0003-4819-129-12-199812150-00007
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发表时间：
1998-12-15
影响因子：
39.2
通讯作者：
Jones, RJ
中科院分区：
文献类型：
--
作者：
Brodsky, RA;Petri, M;Jones, RJ
目的：确定大剂量环磷酰胺对各种难治性、重症自身免疫性疾病的疗效。设计：第二阶段前瞻性研究。地点：约翰霍普金斯大学(马里兰州巴尔的摩)和哈内曼大学(费城，宾夕法尼亚州)。患者：8例难治性严重自身免疫性疾病患者。干预：连续4天大剂量环磷酰胺(50 mg/kg体重)。测量：自身免疫性疾病的临床和实验室变量。结果：7名患者改善：5名患者显著缓解，2名患者部分缓解。4例患者持续完全缓解3~21个月，2例部分缓解患者经过14个月和19个月的随访后继续好转。大剂量环磷酰胺耐受性良好，中性粒细胞计数达到0.5×10(9)个/L的中位时间为17天，血小板输注中位时间为16天。结论：免疫清除性大剂量环磷酰胺治疗难治性重症自身免疫性疾病可获得完全缓解。骨髓功能的恢复与自体移植后相似，不存在自体移植物回输自体侵袭性淋巴细胞的风险。
Background: Immunoablative high-dose cyclophosphamide without stem-cell rescue induces durable, complete remission in most patients with aplastic anemia.Objective: To determine the efficacy of high-dose cyclophosphamide in various refractory, severe autoimmune diseases.Design: Prospective phase II study.Setting: Johns Hopkins University (Baltimore, Maryland) and Hahnemann University (Philadelphia, Pennsylvania).Patients: Eight patients with refractory, severe autoimmune disease.Intervention: Immunoablative high-dose cyclophosphamide (50 mg/kg of body weight per day) for 4 consecutive days.Measurements: Clinical and laboratory variables of autoimmune disease.Results: Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continuous complete remission for 3 to 21 months, and two patients in partial remission continue to improve after 14 and 19 months of follow-up. High-dose cyclophosphamide was well tolerated; median times to a neutrophil count of 0.5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days, respectively.Conclusions: Immunoablative high-dose cyclophosphamide without stem-cell rescue can induce complete remission in patients with refractory, severe autoimmune disease. Reemergence of marrow function is similar to that seen after autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.