High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis
High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis
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DOI：
10.1182/blood-2002-12-3908
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发表时间：
2003-10-01
期刊：
影响因子：
20.3
通讯作者：
Kraft, GH
中科院分区：
文献类型：
--
作者：
Nash, RA;Bowen, JD;Kraft, GH
有26名患者参加了一项针对严重多发性硬化症（MS）的大剂量免疫抑制治疗（HDIT）的初步研究。中位基线扩展残疾状态量表（EDSS）为7.0（范围：5.0-8.0）。HDIT包括全身照射，环磷酰胺和抗胸腺细胞球蛋白（ATG），然后移植自体，粒细胞集落刺激因子（G-CSF）动员的CD 34选择的干细胞。方案相关毒性为轻度。由于膀胱功能障碍，有8例下尿路感染事件。1例患者死于EB病毒（EBV）相关的移植后淋巴组织增生性疾病（PTLD），与HDIT方案中马源性ATG变为兔源性ATG相关。在最初的18例患者中，有13例发生了以非感染性发热伴或不伴皮疹为特征的植入综合征，在某些情况下与神经系统症状的短暂恶化相关。发生了2起显著的神经系统不良事件，包括动员期间MS发作和HDIT后不可逆的神经系统恶化伴发热。中位随访时间为24（范围：3-36）个月，Kaplan-Meier估计的3年进展（大于或等于1.0分EDSS）为27%。在12例基线时脊髓液中有寡克隆条带的患者中，9例在HDIT后持续存在。HDIT后，4例患者在脑磁共振成像上出现新的增强病变。3年生存率估计为91%。在使用HDIT和干细胞移植治疗MS的重要临床问题被确定;然而，最初方法的修改似乎可以降低治疗风险。这是一个异质性高风险组，计划进行一项III期研究以全面评估疗效。(C)2003年，美国血液学会。
There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (greater than or equal to 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebro-spinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy. (C) 2003 by The American Society of Hematology.