High-dose cyclophosphamide without stem cell rescue in 207 patients with aplastic anemia and other autoimmune diseases.
High-dose cyclophosphamide without stem cell rescue in 207 patients with aplastic anemia and other autoimmune diseases.
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DOI：
10.1097/md.0b013e318210e685
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发表时间：
2011-03
期刊：
影响因子：
1.6
通讯作者：
Brodsky RA
中科院分区：
文献类型：
--
作者：
DeZern AE;Petri M;Drachman DB;Kerr D;Hammond ER;Kowalski J;Tsai HL;Loeb DM;Anhalt G;Wigley F;Jones RJ;Brodsky RA
大剂量环磷酰胺长期以来一直被用作抗癌剂、造血干细胞移植的预处理方案以及包括再生障碍性贫血在内的自身免疫性疾病的有效免疫抑制剂。高剂量环磷酰胺对淋巴细胞有高毒性，但对造血干细胞无毒性，因为它们含有大量醛脱氢酶，这是环磷酰胺灭活的主要机制。大剂量环磷酰胺治疗可使大多数获得性再生障碍性贫血患者获得持久缓解。此外，没有造血干细胞救援的高剂量环磷酰胺在各种其他严重的自身免疫性疾病中显示出活性。在这里，我们回顾了环磷酰胺的历史，因为它适用于再生障碍性贫血（AA）和其他自身免疫性疾病。本文包括早期接受AA治疗的患者的历史数据以及在一家三级医院进行的观察性回顾性研究。后一部分旨在评估难治性自身免疫性疾病患者在无干细胞拯救的情况下接受大剂量环磷酰胺治疗的安全性和有效性。我们充分分析了140例严重的，进行性自身免疫性疾病的治疗。本文讨论的所有患者均接受环磷酰胺，50 mg/kg/天，连续4天。测量反应、复发和总生存率。缓解定义为疾病活动性降低，同时免疫调节药物减少或消除。复发定义为疾病活动性恶化和/或需要增加免疫抑制药物剂量或给予新的免疫抑制药物。所有患者的血液学均恢复。总体缓解率为95%，其中44%的患者保持无进展，140例患者的中位随访时间为36个月（范围1-120）。60个月时所有疾病的总体精算和无事件生存率分别为90.7%和20.6%。在严重自身免疫性疾病中，高剂量环磷酰胺（无干细胞救援）耐受性良好，缓解率高。
High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20.6%, respectively. High- dose cyclophosphamide without stem cell rescue is well-tolerated and induces a high rate of remissions in severe autoimmune diseases.