1例高龄慢性淋巴细胞白血病合并侵袭性曲霉菌感染

Elderly Chronic Lymphocytic Leukemia Combined with Invasive Aspergillosis Infection in One Case

目的:本研究通过分析1例高龄慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)患者的治疗过程,探讨高龄CLL合并侵袭性曲霉菌(invasive aspergillosis,IA)感染患者的骨髓形态学、免疫表型、细胞遗传学和临床特点及治疗经验。方法:应用显微镜观察骨髓细胞形态改变;流式细胞术检测骨髓细胞的免疫表型;常规染色体核型分析及荧光原位杂交(fluorescence in situ hybridization,FISH)检测细胞遗传学变化。结果:患者初诊为慢性淋巴细胞白血病Rai II期,B细胞性,给予1疗程RF方案(氟达拉滨50 mg×5,利妥昔单抗600 mg×5)化疗,完全缓解5年后疾病复发,再次给予多疗程化疗,疾病维持在稳定状态。于2012年7月末次化疗后出现发热,体温波动在37.2-38.7℃,肺CT发现团块状阴影,多次1,3-β-D-葡聚糖(G试验)阳性,考虑为侵袭性曲霉菌感染,给予伏立康唑抗真菌治疗2个月,肺CT提示感染明显好转。2013年3月因白血病持续进展,血象三系极低,肺部真菌感染复发,再次给予伏立康唑治疗效果差,最终因白血病快速进展和多器官侵袭性曲霉菌感染死亡。尸检提示:慢性淋巴细胞白血病多发转移及多器官侵袭性曲霉菌感染、曲菌性败血症。结论:侵袭性曲霉菌感染是CLL严重的并发症,一旦发生预后极差,因此早期诊断及预防性应用抗真菌药物有可能会减少真菌感染的发生。

Objective： This study was aimed to investigate the morphological, i mmunophenotype, cytogenetic char- acteristics, clinical and therapy features in one elderly patient with chronic lymphocytic leukemia （CLL） combined with invasive aspergillose infection（IAI）. Methotls, The morphological features of bone marrow cells from patient were observed by light microscope, the immunophenotype were detected by flow cytometry, the cytogenetic characteristics were assayed by conventional chromosomal analysis and fluorescence in situ hybridization （FISH）. Results ： at onset of disease, the patient was diagnosed as B-CLL, Rai stage is H. He was treated with a course of RF（ fludarabine 50 mg × 5, rituximab 600 nag × 5） chemotherapy, and achived complete remission（CR） lasting for five years, then the patient was treated with multiple courses of chemotherapy and maintained at a steady state of disease. After the last chemotherapy, this patient developed a fever, his temperature fluctuated at 37.2 -38.7℃, the lung CT showed the presence of massive shadow,repeated 1-3-B-D-glucan test was positive, and he was considered as invasive aspergillosis infection, voriconazole was intravenously injected him for 2 months, his lung CT showed better efficacy. However, the leukemia continued progress, his hemogram was extremely low, invasive aspergillosis infection relapsed, voriconazole treatment was poor effect, ultimately this patient died of the rapid progress of leukemia and multiple organ invasive aspergillosis. Autopsy showed chronic lymphocytic leukemia with multiple metastases and multiple organ invasive aspergillosis. Conclusion： invasive aspergillosis is a serious complication for CLL patients, once occurs, the prognosis is poor, so early diagnosis and prophylactic antifungai therapy may reduce fungal infection complication.