Liping Wan1, Yicheng Zhang1, Yongrong Lai1, Ming Jiang1, Yongping Song1, Jianfeng Zhou1, Zhongming Zhang1, Xianlin Duan1, Yuewen Fu1, Lianming Liao1, Chun Wang2. 1. 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. 2. 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.
Abstract
PURPOSE: 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). PATIENTS AND METHODS: We randomly assigned 206 patients undergoingalloHSCT 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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: Prashanth K Kandalla; Sandrine Sarrazin; Kaaweh Molawi; Carole Berruyer; David Redelberger; Anne Favel; Christophe Bordi; Sophie de Bentzmann; Michael H Sieweke Journal: J Exp Med Date: 2016-10-10 Impact factor: 14.307