title: Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Prevention and Treatment of Invasive Fungal Disease in Recipients of Allogeneic Stem-Cell Transplantation: A Prospective Multicenter Randomized Phase IV Trial.
abstract: OBJECTIVE
  For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD).
  
  
  METHODS
  We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 μg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 μg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 μg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 10(9)/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment.
  
  
  RESULTS
  For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients.
  
  
  CONCLUSIONS
  For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality.
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wan
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Yongrong
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China.
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.affiliation: Liping Wan and Chun Wang, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai; Yicheng Zhang and Jianfeng Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yongrong Lai and Zhongming Zhang, First Affiliated Hospital of Guangxi Medical University, Nanning; Ming Jiang and Xianlin Duan, Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi; Yongping Song and Yuewen Fu, Henan Cancer Hospital, Zhengzhou; and Lianming Liao, Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China. wangchun2@medmail.com.cn.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006402:Hematologic Diseases / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor