儿童白血病化疗后合并播散性曲霉菌病三例并文献复习

Disseminated aspergillosis in children with leukemia after chemotherapy： report of three cases and review of literature

目的探讨儿童白血病化疗后合并播散性曲霉菌病的临床特征、诊断、治疗及预后。方法回顾性分析3例白血病化疗后合并播散性曲霉菌病患儿的临床特征及诊治过程。结果3例患儿的基础疾病均为白血病，存在多个侵袭性真菌病的高危因素，临床特征包括：反复发热而抗生素治疗无效，皮下硬性结节，肺部CT提示结节影、空洞，磁共振成像提示肝、脾、肾散在低密度灶（T2加权），血清半乳甘露聚糖（GM）试验阳性，均通过病理组织学检查确诊。确诊后，2例予两性霉素B脂质体抗真菌治疗超过4周，并在临床症状好转、中性粒细胞恢复及影像学提示病灶好转或无进展情况下恢复化疗，同时予口服伏立康唑维持治疗，随访6-12个月，播散性曲霉菌病达治愈标准。1例白血病持续完全缓解，截至随访结束仍生存；1例因家属要求暂停化疗，白血病复发死亡；1例因治疗无效或严重药物不良反应，多次调整抗真菌治疗方案后感染仍无法控制，且因长时间暂停化疗，白血病复发，最终死亡。结论白血病患儿化疗后反复发热，并有多发皮下硬性结节、肺部结节或空洞、肝脾肾散发性低密度灶、GM试验阳性，应考虑合并播散性曲霉菌病。有效且足疗程的抗真菌治疗，并在适当时机兼顾化疗，有望改善患者预后。

Objective To investigate the clinical features, diagnosis, treatment and prognosis of disseminated aspergillosis in children with leukemia after chemotherapy. Methods The clinical features and treatment of 3 leukemia children after chemotherapy complicated with disseminated aspergillosis were retrospectively analyzed. Results The underlying diseases of all recruited cases were leukemia, which occurred many high-risk predisposing factors for invasive fungal diseases. The major clinical features of disseminated aspergillosis in children with leukemia were prolonged and antibiotics uncontrollable fever, subcutaneous solid nodules, nodules or cavities in pulmonary CT, spread low density lesions in hepatosplenic and kidney in abdominal MR （T2 weighted） and positive serum aspergillus galactomannan （GM）. The diagnosis of iuvasive fungal disease was proven by histopathologic examination. Amphotericin B lipid complex was selected in antifungal therapy for 2 patients and the course of treatment was more than 4 weeks. Moreover, chemotherapy was advised for the 2 patients when clinical manifestations of disseminated aspergillosis improved significantly, neutrophil counts recovered and images did not deteriorate. The patients received voriconazole treatment with follow-up from 6 months to 12 months, and then disseminated aspergillosis was cured up to the standard. 1 case received complete remission and was still alive until follow-up period, 1 case was died of leukemia relapse because of suspension demand from the family members, and the other I case was died of no response or serious adverse drug reactions, uncontrolled infection, and leukemia relapse because of long-term chemotherapy suspension. Conclusions Patients with leukemia after chemotherapy may present with the following manifestations, including fever, subcutaneous solid nodules, pulmonary nodules or cavities, spread low density lesions in hepatosplenic and kidney and serum aspergillus GM antigen positive, which may indicate disseminated aspergillosis. The improvement of prognosis depends on effective and adequate antifungal treatment and chemotherapy for leukemia at the right time.