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.
J Clin Oncol. 2015 Dec 1;33(34):3999-4006. doi: 10.1200/JCO.2014.60.5121. Epub 2015 Sep 21.
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).
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.
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.
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.
对于接受异基因造血干细胞移植（alloHSCT）的患者，我们假设在中性粒细胞减少期间预防性使用粒细胞-巨噬细胞集落刺激因子（GM-CSF）可降低侵袭性真菌感染（IFD）的发生率。
我们将 206 名接受 alloHSCT 的患者随机分为三组，分别接受每日一次皮下注射 GM-CSF（每天 5 至 7μg/kg）、粒细胞集落刺激因子（G-CSF；每天 5 至 7μg/kg）或 G-CSF 和 GM-CSF 的联合治疗（每天各 2 至 3μg/kg）。治疗于移植后第 5 天开始，持续至连续两天绝对中性粒细胞计数≥1.5×10^9/L。主要结局为 100 天内确诊和可能 IFD 的发生率以及抗真菌治疗的反应率。
在意向治疗人群中，三组患者 100 天内确诊和可能 IFD 的发生率无显著差异。从第 22 天至第 100 天，GM-CSF 组和 G-CSF+GM-CSF 组的抗真菌治疗反应优于 G-CSF 组（P=0.009）。移植后 100 天的累积死亡率在 GM-CSF 组低于 G-CSF 组（分别为 10.3%和 24.6%；P=0.037）。GM-CSF 组和 G-CSF+GM-CSF 组的 100 天移植相关死亡率低于 G-CSF 组（分别为 8.8%、8.7%和 21.7%；P=0.034）。中位随访 600 天后，与 G-CSF 组相比，接受 GM-CSF 或 G-CSF+GM-CSF 治疗的患者 IFD 相关死亡率较低（分别为 1.47%、1.45%和 11.59%；P=0.016）。三组患者的复发、移植物抗宿主病或出血相关死亡率无显著差异。
与 G-CSF 相比，alloHSCT 患者接受预防性 GM-CSF 治疗可降低 100 天移植相关死亡率、100 天累积死亡率和 600 天 IFD 相关死亡率。
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