Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy: China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study
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Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n = 3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0–10, ~1.2%), intermediate (11–15, 6.4%), and high risk ( > 15, 17.5%) of IFD. In the validation set (n = 1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, P = 0.007) and high-risk patients (8.4% vs. 23.3%, P = 0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.
Keywordsinvasive fungal diseases hematological malignancies chemotherapy risk score prophylaxis
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Jiong Hu and Xiaojun Huang contributed to the conception and design of the study. Ling Wang, Ying Wang, and Jiong Hu interpreted the data and drafted the paper. Yuqian Sun, He Huang, Jing Chen, Jianyong Li, Jun Ma, Juan Li, Yingmin Liang, Jianmin Wang, Yan Li, Kang Yu, Jianda Hu, Jie Jin, Chun Wang, Depei Wu, and Yang Xiao were involved in the development of the methodology and participated in the analysis. All authors contributed in the writing, review, and revision of the article and final approval for submission.
The authors would like to thank the patients and investigators at each study site, without whom this study would not have been possible. The CAESAR study group investigators not listed as authors were as follows: Zhixiang Shen, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai; Waiyi Zou, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou; Jun Yang and Yu Cai, The First People’s Hospital of Shanghai, Shanghai; Yonghua Li, The General Hospital of Guangzhou Military Command of PLA, Guangzhou; Yongping Song and Yuewen Fu, Henan Tumor Hospital Affiliated to Zhengzhou University, Zhengzhou; Xudong Hu and Xingzhou Ren, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou; Huisheng Ai and Jianhui Qiao, Chinese PLA 307 Hospital, Beijing; Xianmin Song, Changhai Hospital of the Second Military Medical University, Shanghai; Hai Bai and Chunbang Wang, The General Hospital of Lanzhou Military Area, Lanzhou; Yongmin Tang and Heping Shen, Children’s Hospital of Zhejiang University Medical School, Hangzhou; Xiaoyan Zhang, Jiangsu Province Hospital, Nanjing; Xin Du and Chengwei Luo, Guangdong General Hospital, Guangzhou; Jian Ouyang and Yong Xu, Nanjing Drum Tower Hospital, Nanjing; Huo Tan and Runhui Zheng, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou; Ting Liu and Juan Xu, West China Hospital, Sichuan University, Chengdu; Jin Zhou and Liming Li, The First Hospital of Harbin Medical University, Harbin; Zhuogang Liu, Shengjing Hospital of China Medical University, Shenyang; Ping Zou and Yong You, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan; Lin Liu and Li Wang, The First Affiliated Hospital of Chongqing Medical University, Chongqing; Ran Gao, The First Affiliated Hospital of China Medical University, Shenyang; Zhanxiang Liu, Chinese PLA General Hospital (301 Hospital), Beijing; Mangju Wang, The First Hospital of Peking University, Beijing; Guopan Yu, Nanfang Hospital, Nanfang Medical University, Guangzhou; Jun Wang, The First Affiliated Hospital of Soochow University, Suzhou; Guixin Zhang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin; 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. The support for the manuscript development was provided by Merck & Co., Inc. (Whitehouse Station, NJ, USA). The authors are grateful for the contribution made by Bo-Jing Cai (Merck & Co., Inc.) in the data management and statistical analysis.
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