米卡芬净治疗急性白血病和造血干细胞移植后患儿合并肺侵袭性真菌病的临床分析

A clinical analysis of micafungin treatment of pulmonary invasive fungal infection in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation

目的 观察米卡芬净（MCF）治疗恶性血液病和造血干细胞移植后患儿合并肺侵袭性真菌病（PIFD）的效果和安全性.方法 回顾性选取2012年1月至2015年6月中山大学孙逸仙纪念医院儿科收治的25例粒细胞缺乏合并PIFD患儿为研究对象,其中男12例,女13例;年龄2~15岁,平均（6.2＆#177;2.0）岁.包括急性白血病化疗患儿12例,急性白血病异基因造血干细胞移植术后患儿4例,重型β-地中海贫血异基因造血干细胞移植术后9例.MCF剂量为3~4 mg/（kg＆#183;d）,1次/d,7 d为一疗程,治疗2~6个疗程.同时动态监测外周血1,3-β-D-葡聚糖试验（G试验）和半乳甘露聚糖抗原（GM试验）、高分辨肺CT及各脏器功能指标.结果 25例患儿中确诊2例,临床诊断6例,拟诊17例;25例中病理证实曲霉菌1例,血培养白色念珠菌生长1例.G试验阳性者5例,GM试验阳性者2例.25例患儿胸部高分辨CT均有明显病变,新月形空气征及空洞改变4例,双肺磨玻璃改变9例,双肺散在斑片状、小结节、条索状密度增高影7例,单侧或双侧贴胸壁的楔形实变边5例;25例患儿中5例伴胸腔积液.MCF治疗PIFD有效率为68%（17/25）,其中痊愈13例,显效4例,进步4例,无效4例.MCF单药治疗12例,有效8例,联合治疗13例,有效9例.本组患儿未发现过敏、胃肠道不良反应、电解质紊乱、肝肾功能损害等不良反应.结论 MCF是治疗儿童恶性血液病和造血干细胞移植后合并PIFD安全且有效的抗真菌药物.

Objective To investigate the efficacy and safety of micafungin （MCF） for pulmonary invasive fungal disease （PIFD） in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation. Method Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 （average 6.2＆#177;2.0） years. There were 12 cases of acute leukemia （AL） after chemotherapy, 4 cases of acute leukemia （AL） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and 9 cases of β-thalassemia major after allo-HSCT. All children received MCM for the treatment of PIFD, the dosage of MCM was 3-4 mg/（kg ＆#183; d）, once a day. The children received 2 to 6 courses of treatment, individually with a course of 7 days.1,3-β-D glucan assay （G test）, galactomannan antigen test （GM test）, high-resolution CT and the biochemical indexes for organ functions were closely monitored. Result Twenty-five cases were diagnosed as PIFD, including 2 patients diagnosed as proven, 6 as probable and 17 as possible. Of the 25 cases, 1 was confirmed aspergillus by biopsy pathology and 1 was candida albicans by blood culture. The G and GM test with positive results was 5 and 2 respectively. Chest CT scans of the 25 cases had obvious lesions：air crescent sign and cavitation in 4 cases, diffuse ground glass change in 9 cases, double lung scattered patchy, small＆amp;nbsp;nodules and cord like high density shadow in 7 cases, unilateral or bilateral chest wall wedge-shaped consolidation edge in 5 cases and pleural effusion in 5 patients. The effective rate of MCF in treatment of PIFD was 68%（17/25）, including 13 cases cured,4 cases improved,4 cases were improved clinically and in 4 cases the treatment was ineffective. Eight cases were effective in MCF monotherapy group （12 cases） and nine were effective in MCF combined therapy group（13 cases）, respectively. Side-effects including allergies, gastrointestinal side effects, electrolyte disturbances, impairment of liver and kidney function, and myelosuppression were not found in those children treated with MCF.Conclusion Micafungin is effective and safe in the treatment of pulmonary invasive fungal disease in pediatric patients with acute leukemia or post hematopoietic stem cell transplantation.