Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation

目的 探讨静脉应用伏立康唑对异基因造血干细胞移植(allo-HSCT)后侵袭性真菌病(IFD)一级预防的疗效及耐受性.方法 移植前无真菌感染的allo-HSCT患者从预处理开始应用伏立康唑注射液,直至患者的中性粒细胞恢复至0.5× 109/L以上,以口服氟康唑者为对照组,分析两组间IFD易感因素有无差异,比较两组IFD发生率及药物不良反应的差异.结果 227例患者在移植后3个月内有33例(14.54％)发生IFD,中位随访38(5～76)个月,发生IFD患者累计死亡13例(33.96％),20例存活,总生存率60.61％;194例未发生IFD患者,累计死亡40例(19.89％),154例(79.38％)存活,两组间总生存率差异有统计学意义(P=0.029).227例患者中,83例应用伏立康唑行一级预防,发生IFD者7例(8.43％),对照组144例患者发生IFD 26例(18.06％),两组IFD发生率差异有统计学意义(P=0.048).对两组间的性别、年龄、既往有无慢性病、移植时是否为进展期血液病、移植方式、预处理方案、粒细胞缺乏时间、有无急性移植物抗宿主病、有无CMV感染等因素逐一进行比较,结果显示两组上述因素差异无统计学意义(P＞0.05).伏立康唑和氟康唑两组间转氨酶升高患者比例差异无统计学意义(P＞0.05).应用伏立康唑出现幻听或视觉障碍等不良反应的比例不高.结论 应用静脉伏立康唑对allo-HSCT患者行IFD的一级预防的效果明显优于氟康唑,且患者对治疗的耐受性良好.To investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).At the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10?/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.Of the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.Intravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)07577-5803