泊沙康唑对血液恶性肿瘤化疗患者的预防性抗真菌作用

doi:10.3969/j.issn.1674-8115.2022.06.014

摘要/Abstract

摘要：

目的·观察急性白血病（acute leukemia，AL）包括骨髓增生异常综合征（myelodysplastic syndrome，MDS）患者使用泊沙康唑预防侵袭性真菌病（invasive fungal disease，IFD）的有效性和安全性。方法·回顾性分析上海交通大学医学院附属瑞金医院2016年6月—2021年5月收治的121例AL（包括MDS）患者的临床资料。所有患者根据《泊沙康唑临床应用专家共识》进行临床预防治疗。根据中国血液病抗真菌治疗评估（China Assessment of Antifungal Therapy in Hematological Diseases，CAESAR）研究，对患者进行IFD风险分层，分为低危组、中危组和高危组。观察泊沙康唑应用于不同风险组患者的疗效。在泊沙康唑应用期间确诊或临床诊断为真菌感染视为发生突破性真菌感染，停用泊沙康唑后3个月期间无真菌感染视为有效预防。中性粒细胞缺乏期间，每日监测血常规、体温，每周3次检测肝肾功能、电解质，观察口服泊沙康唑期间患者是否出现胃肠道不适如腹胀、腹泻、恶心、呕吐等，并监测心电图。结果·共收集病例121例，其中低危组27例、中危组40例、高危组54例。突破性真菌感染的发生率为3.31%（4/121），4例均为高危组患者。肝功能异常是最常见的不良反应（20例）；其中，中、高危组13例（10.74%，13/121）患者因不耐受治疗而更换方案。因中性粒细胞缺乏时间不同，各组泊沙康唑预防用药时间也不同，其中低危组的平均应用天数为16.85 d，中危组18.90 d，高危组21.31 d。泊沙康唑的整体预防有效率为85.95%（104/121）。低危组预防有效率（100%，27/27）与中危组（95.00%，38/40）比较，差异无统计学意义（P=0.242）；低危组、中危组的预防有效率分别与高危组（72.22%，39/54）比较，差异均具有统计学意义（P=0.003，P=0.005）。结论·泊沙康唑用于AL（包括MDS）患者IFD的预防治疗有效且安全，但在高危患者预防治疗中需密切监测肝功能变化。

关键词: 泊沙康唑, 急性白血病, 化学治疗, 有效性, 安全性, 侵袭性真菌病

Abstract:

Objective·To observe the efficacy and safety of posaconazole in the prevention of invasive fungal disease (IFD) in patients with acute leukemia (AL) including myelodysplastic syndrome (MDS).

Methods·The clinical data of 121 patients with AL (including MDS) treated in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from June 2016 to May 2021 were analyzed retrospectively. All the patients received clinical prophylaxis and treatment according to the Expert Consensus on ClinicalUse of Posaconazole. According to the study of China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR), the patients were divided into three groups, including low-risk group, medium-risk group and high-risk group according to the IFD risk stratification, among which the efficacy and safety of posaconazole in different risk groups were observed. Patients proved or probable to have fungal infection while receiving posaconazole were considered to have breakthrough fungal infection. Patients who reported no fungal infection during the three-month follow-up after discontinuation were regarded as effective prophylaxis. If any fungal infection was found, it was regarded as a prevention failure. During the period of neutropenia, blood routine and body temperature were monitored daily, and liver and kidney function and electrolytes were tested three times a week. Whether the patients had gastrointestinal discomfort such as abdominal distension, diarrhea, nausea and vomiting during oral posaconazole or not was observed, and the electrocardiogram of the patients was monitored.

Results·A total of 121 cases were collected, including low-risk group (n=27), medium-risk group (n=40) and high-risk group (n=54). The incidence of breakthrough fungal infection was 3.31% (4/121), and the 4 patients were in the high-risk group. Abnormal liver function was the most common adverse reaction (20 cases); among them, 13 cases in the medium-risk group and high-risk group (10.74%, 13/121) changed the regimen because of treatment intolerance. According to the time of neutropenia, the prophylactic time of posaconazole was different among the groups. The average time of use of posaconazole was 16.85 d in the low-risk group, 18.90 d in the medium-risk group and 21.31 d in the high-risk group. The overall prevention effective rate of posaconazole was 85.95% (104 /121). There was no significant difference in the effective rate of prevention between the low-risk group (100%, 27/27) and the medium-risk group (95.00%, 38/40) (P=0.242), but the differences in the comparison of the high-risk group (72.22%, 39/54) with the low-risk group and the medium-risk group were both significant (P=0.003, P=0.005).

Conclusion·Posaconazole is effective and safe in the prophylactic treatment of invasive fungal infection in patients with AL (including MDS), but liver function should be closely monitored in moderate and high risk patients.

Key words: posaconazole, acute leukemia, chemotherapy, efficacy, safety, invasive fungal disease

中图分类号:

R730.53

金磊, 徐文彬, 叶晨静, 阎骅. 泊沙康唑对血液恶性肿瘤化疗患者的预防性抗真菌作用[J]. 上海交通大学学报（医学版）, 2022, 42(6): 792-796.

JIN Lei, XU Wenbin, YE Chenjing, YAN Hua. Prophylactic antifungal effect of posaconazole on patients with hematological malignant tumor undergoing chemotherapy[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(6): 792-796.

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