Effect of Different Administration Timing of G-CSF on Peripheral Blood CD34+ Cell Mobilization in Healthy Donors: A Prospective Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 3
- 主要终点
- Pre-Apheresis Peripheral Blood CD34+ Cell Count
研究概览
简要总结
Healthy donors are commonly mobilized with granulocyte colony-stimulating factor (G-CSF) to collect peripheral blood stem cells for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the efficiency of mobilization varies among donors, and suboptimal mobilization may require additional collection procedures or rescue strategies.
This prospective, multicenter, randomized trial evaluates whether the timing of daily G-CSF administration (morning vs evening) affects the level of circulating CD34+ cells prior to apheresis in healthy donors. Participants will be randomly assigned to receive subcutaneous G-CSF 10 μg/kg once daily for 5 consecutive days either at 08:00 (±15 minutes) or at 20:00 (±15 minutes). The primary endpoint is the peripheral blood CD34+ cell count measured approximately 12 hours after the last G-CSF dose and within 60 minutes before the start of the first apheresis session. Secondary endpoints include collection efficiency and CD34+ yield metrics, the proportion of donors achieving the target CD34+ dose on the first collection day, the need for a second collection day, and donor safety outcomes.
The goal of the study is to identify a practical dosing schedule that may improve stem cell mobilization and streamline donor collection procedures.
详细描述
Background and Rationale
Peripheral blood stem cell collection after G-CSF mobilization is the most widely used donation approach for allo-HSCT. Donor mobilization outcomes exhibit inter-individual variability, and donors with lower circulating CD34+ levels may require longer processing volumes, additional collection days, or rescue mobilization. Circadian biology may influence hematopoietic cell trafficking and cytokine responses, suggesting that the administration timing of G-CSF could affect mobilization intensity and collection efficiency. This trial tests whether a simple, operational change in dosing time can improve pre-apheresis CD34+ levels in healthy donors.
Objectives
Primary Objective: To compare the pre-apheresis peripheral blood CD34+ cell count between donors receiving G-CSF in the morning versus the evening.
Secondary Objectives: To compare collection efficiency and CD34+ yield measures, the need for additional collection days, target attainment on day 1, and donor safety outcomes between study groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-55 years
- •HLA matching appropriate for intended allo-HSCT recipient and meets donor medical evaluation criteria
- •Body weight ≥35 kg and adequate blood volume/BSA for apheresis
- •Karnofsky score ≥80
- •Screening labs meet thresholds (Hb/platelets/ANC, liver/renal/coagulation), no splenomegaly, pregnancy test negative if applicable
- •Written informed consent
- •Stable circadian rhythm before mobilization (no night shift/no ≥3 time-zone travel; avoid melatonin/sedatives or other agents affecting sleep/circadian rhythm)
排除标准
- •Prior/current hematologic or immune diseases (e.g., aplastic anemia, leukemia, lymphoma, autoimmune disease)
- •Significant cardiovascular/structural heart disease, uncontrolled hypertension, uncontrolled diabetes
- •Neurologic/psychiatric disorders affecting adherence
- •Sleep/circadian disorders; recent night shift or ≥3 time-zone travel
- •Prohibited medications (e.g., beta-blockers, systemic steroids >10 mg prednisone-equivalent ≥7 days, melatonin/psychotropics; recent G-CSF/GM-CSF/CXCR4 inhibitor use)
- •Severe allergy to G-CSF or components
研究组 & 干预措施
Evening G-CSF Dosing
10 μg/kg subcutaneous once daily for 5 days at 20:00 ± 15 min
干预措施: G-CSF (Granulocyte colony-stimulating factor) (Drug)
Morning G-CSF Dosing
10 μg/kg subcutaneous once daily for 5 days at 08:00 ± 15 min
干预措施: G-CSF (Granulocyte colony-stimulating factor) (Drug)
结局指标
主要结局
Pre-Apheresis Peripheral Blood CD34+ Cell Count
时间窗: On the day of first apheresis: approximately 12 (±1) hours after the final G-CSF dose and within 60 minutes prior to apheresis start.
Peripheral blood CD34+ cell count (cells/µL) measured by flow cytometry (ISHAGE single-platform method). Blood is drawn approximately 12 (±1) hours after the last G-CSF dose and within 60 minutes before the start of the first apheresis session.
次要结局
未报告次要终点
研究者
Yanmin Zhao
professor
First Affiliated Hospital of Zhejiang University