Sparing effect by montelukast treatment for chronic graft versus host disease: A pilot study
Sparing effect by montelukast treatment for chronic graft versus host disease: A pilot study
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DOI：
10.1097/01.tp.0000255575.03795.df
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发表时间：
2007-03-15
期刊：
影响因子：
6.2
通讯作者：
Shapira, Michael Y.
中科院分区：
文献类型：
--
作者：
Or, Reuven;Gesundheit, Benjamin;Shapira, Michael Y.
背景慢性移植物抗宿主病（GvHD）是异基因造血干细胞移植（SCT）后的主要并发症，通常由急性GvHD发展而来。慢性GvHD是SCT后长期存活者严重发病和死亡的主要原因。半胱氨酰白三烯（cysteinyl leukotrienes，cysLTs）和嗜酸性粒细胞在GvHD的发病机制中起重要作用，这是联合使用孟鲁司特（montelukast，Mk）治疗GvHD的理论基础。除了标准的免疫抑制方案外，还向19名符合条件的难治性慢性GvHD患者给予MK。MK口服给药（10 mg，每日一次），平均持续10个月（范围，2 - 21个月）。器官特异性反应由美国国立卫生研究院共识项目建立的新评分标准确定。基于器官受累终点，在19例患者中的15例（79%）中观察到Mk联合治疗的总体缓解。皮肤、肝脏和胃肠道的显著改善分别为53%、62%和46%。一般来说，Mk在GvHD的较轻阶段中是显著有益的，这导致更早地停用其他免疫抑制剂。没有记录Mk给药的副作用，也没有基础疾病复发的病例。我们的初步前瞻性研究支持MK作为慢性GvHD患者标准治疗的安全和毒性保留补充的潜在疗效。未来的临床研究是必要的，以建立最佳剂量的Mk和它的症状和预防性治疗的急性和慢性GvHD的作用。
Background. Chronic graft versus host disease (GvHD) is a major complication after allogeneic stem cell transplantation (SCT), which is usually progression from acute GvHD. Chronic GvHD is the main cause of severe morbidity and mortality in long-term survivors after SCT. The cysteinyl leukotrienes (cysLTs) and eosinophils play an important role in the pathogenesis of GvHD, which is the rationale for the combined use of montelukast (Mk) in the treatment of this illness.Methods. Mk was administrated to 19 eligible patients with refractory chronic GvHD, in addition to their standard immunosuppressive regimens. Mk was given orally (10 mg once daily) for a mean period of 10 months (range, 2-21 months). Organ-specific response was determined by the new scoring criteria established by the National Institutes of Health consensus project.Results. Based on organ involvements endpoints, overall response to the combined therapy with Mk was observed in 15 of 19 (79%) patients. Significant improvement of skin liver and gastrointestinal was observed in 53%, 62%, and 46%, respectively. Generally, Mk was notably beneficial in milder stages of GvHD, which lead to earlier withdrawal of other immunosuppressive agents. Side effects of Mk administration were not documented, nor were cases of relapse of the basic disease.Conclusions. Our preliminary prospective investigation supports the potential efficacy of Mk as a safe and toxicity-sparing supplement to standard therapy for patients with chronic GvHD. Future clinical studies are necessary to establish the optimal dose of Mk and its role in the symptomatic and prophylactic treatment of acute and chronic GvHD.