Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China
This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.7 years, 58.4 % male, 16.9 % children (<18 years)]. The most common hematological diseases were acute myeloid leukemia (AML, 28.5 %), non-Hodgkin lymphoma (NHL, 26.3 %), and acute lymphoblastic leukemia (ALL, 20.2 %). Severe neutropenia (absolute neutrophil count [ANC] <500/mm3) occurred after one third (1,633/4,889, 33.4 %) of chemotherapy courses. Incidence of proven/probable IFI was 2.1 % per chemotherapy course and higher in patients with myelodysplastic syndrome (MDS, 4.94 %), acute hyperleukocytic leukemia (AHL, 4.76 %), AML (3.83 %), or induction chemotherapy. Risk factors included ANC <500/mm3 [odds ratio (OR) 3.60], AML or MDS (OR 1.97), induction chemotherapy (OR 2.58), previous IFI (OR 3.08), and being male (OR 1.74). Antifungal agents, prescribed in one quarter (1,211/4,889, 24.8 %) of chemotherapy courses, included primary/secondary prophylaxis (n = 827, 16.9 %) and/or treatment (n = 655, 13.4 %; 86.9 % triazoles), which was empirical (84.3 %), pre-emptive (8.6 %), or targeted (7.1 %). Overall mortality following each chemotherapy course (1.5 %) increased in proven/probable (11.7 %) and possible IFI (8.2 %). In summary, IFI was more common in MDS, AHL, AML, or induction chemotherapy, and substantially increased mortality. Neutropenic patients receiving induction chemotherapy for AML or MDS and those with previous IFI were at particular risk. Antifungal prophylaxis showed an independent protective effect but was not commonly used, even in high-risk patients. By contrast, empiric antifungals were widely used.
KeywordsIFI Chemotherapy Hematological cancer Mortality Antifungal
The authors would like to thank the patients and investigators at each study site, without whom this study would not have been possible. CAESAR study group investigators not listed as authors were: Yu Ji, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing; Li Yu and Zhanxiang Liu, Chinese PLA General Hospital (301 Hospital), Beijing; Huisheng Ai and Jianhui Qiao, Chinese PLA 307 Hospital, Beijing; Daobin Zhou and Haiyan Xie, Peking Union Medical College Hospital, Beijing; Hanyun Ren and Mangju Wang, The First Hospital of Peking University, Beijing; Ting Liu and Juan Xu, West China Hospital, Sichuan University, Chengdu; Tingbo Liu, Fujian Medical University Union Hospital, Fuzhou; Fanyi Meng and Guopan Yu, Nanfang Hospital, Nanfang Medical University, Guangzhou; Huo Tan and Runhui Zheng, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou; Xin Du and Chengwei Luo, Guangdong General Hospital, Guangzhou; Waiyi Zou, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou; Jin Zhou and Liming Li, The First Hospital of Harbin Medical University, Harbin; Keyu Liu, Harbin Hematologic Tumor Institution, Harbin; Xiaoyan Zhang, Jiangsu Province Hospital, Nanjing; Jian Ouyang and Yong Xu, Nanjing Drum Tower Hospital, Nanjing; Jun Yang and Yu Cai, The First People’s Hospital of Shanghai, Shanghai; Xianmin Song, Changhai Hospital of the Second Military Medical University, Shanghai; Zhixiang Shen and Ling Wang, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai; Ran Gao, The First Affiliated Hospital of China Medical University, Shengyang; Zhuogang Liu and Ying Yang, The Second Affiliated Hospital of China Medical University, Shengjing Hospital, Shenyang; Yonghua Li, The General Hospital of Guangzhou Military Command of PLA, Guangzhou; Jun Wang, The First Affiliated Hospital of Soochow University, Suzhou; Jianxiang Wang, Mingzhe Han and Guixin Zhang, Institute of Hematology & Blood Diseases Hospital,Chinese Academy of Medical Sciences, Tianjin; Zonghong Shao and Chen Tong, General Hospital of Tianjin Medical University, Tianjin; Xudong Hu and Xingzhou Ren, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou; Ping Zou and Yong You, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan; Guohui Li, Tangdu Hospital, Fourth Military Medical University, Xi’an; Hai Bai and Chunbang Wang, The General Hospital of Lanzhou Military Area, Lanzhou; Liansheng Zhang and Lingling Yue, The Second Affiliated Hospital of Lanzhou University, Lanzhou; Yongping Song and Yuewen Fu, Henan Tumour Hospital affiliated to Zhengzhou University, Zhengzhou; Xinghua Chen and Lei Gao, Xinqiao Hospital, The Second Affiliated Hospital of Third Military Medical University, Chongqing; Lin Liu and Li Wang, The First Affiliated Hospital of Chongqing Medical University, Chongqing; Yongmin Tang and Heping Shen, Children’s Hospital of Zhejiang University Medical schoool, Hangzhou; Xia Qin, Shanghai Children’s Medical Center, Shanghai; Liya Ma and Wangzhuo Xie, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou China. This work was supported by Merck Sharp & Dohme China, who sponsored the study. Support for manuscript development was provided by Merck & Co., Inc, USA. The authors accept direct responsibility for this paper and are grateful for the contribution made by Esther Nathanson, MD, and Izabel James, at Watermeadow Medical (supported by Merck & Co., Inc, Whitehouse Station, NJ, USA) in developing a first draft from an agreed outline, collating comments and providing editorial assistance.
Conflicts of interest
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