CHRONO-MOBILIZE: Chronotherapy of G-CSF for CD34+ Mobilization in Healthy Donors

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.

Inclusion Criteria: 1. Age 18-55 years 2. HLA matching appropriate for intended allo-HSCT recipient and meets donor medical evaluation criteria 3. Body weight ≥35 kg and adequate blood volume/BSA for apheresis 4. Karnofsky score ≥80 5. Screening labs meet thresholds (Hb/platelets/ANC, liver/renal/coagulation), no splenomegaly, pregnancy test negative if applicable 6. Written informed consent 7. Stable circadian rhythm before mobilization (no night shift/no ≥3 time-zone travel; avoid melatonin/sedatives or other agents affecting sleep/circadian rhythm) Exclusion Criteria: 1. Prior/current hematologic or immune diseases (e.g., aplastic anemia, leukemia, lymphoma, autoimmune disease) 2. Significant cardiovascular/structural heart disease, uncontrolled hypertension, uncontrolled diabetes 3. Neurologic/psychiatric disorders affecting adherence 4. Sleep/circadian disorders; recent night shift or ≥3 time-zone travel 5. Prohibited medications (e.g., beta-blockers, systemic steroids \>10 mg prednisone-equivalent ≥7 days, melatonin/psychotropics; recent G-CSF/GM-CSF/CXCR4 inhibitor use) 6. Severe allergy to G-CSF or components