Single-Dose vs. Divided-Dose G-CSF for Stem Cell Mobilization in Healthy Allogeneic Donors

Randomized Controlled Trial Comparing Single-dose and Divided-dose G-CSF for Peripheral Blood Stem Cell Mobilization in Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation.

National and international guidelines/consensus recommend G-CSF (granulocyte colony-stimulating factor) at 10 μg/kg/day as a single daily dose or divided into two daily doses for mobilization in healthy donors for allogeneic hematopoietic stem cell transplantation. However, there is no consensus or standard regarding single versus divided dosing, and high-quality evidence is lacking. Existing randomized controlled trials have small sample sizes and inconsistent conclusions, and none have focused on Asian population characteristics (e.g., body weight and drug metabolism differences). This study aims to provide level I evidence to optimize donor experience and define the optimal administration strategy.

Inclusion criteria: Healthy allogeneic stem cell donors aged 18-60 years, meeting institutional standard donor screening criteria (HLA matching, normal blood counts, normal liver and kidney function, negative infection screening), and providing written informed consent.

Primary endpoint: The rate of achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor body weight) after 5 days of G-CSF mobilization.

Secondary endpoints: The rate of achieving ≥ 2 × 10⁶ CD34⁺ cells/kg with at most one apheresis; time to myeloid, platelet, and erythroid engraftment in recipients; the proportion and composition of immune cells (CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product; donor adverse events; donor-reported outcomes; and the difference in CD34⁺ stem cell yields between single-dose and divided-dose mobilization.

Intervention: G-CSF will be administered at a total dose of 10 μg/kg/day, either as a single daily injection or divided into two equal daily injections.

This study is designed to investigate whether single-dose or divided-dose G-CSF administration is superior for mobilizing healthy donors in allogeneic hematopoietic stem cell transplantation.

National and international guidelines/consensus recommend G-CSF (granulocyte colony-stimulating factor) at 10 μg/kg/day as a single daily dose or divided into two daily doses for mobilization in healthy donors for allogeneic hematopoietic stem cell transplantation. However, there is no consensus or standard regarding single versus divided dosing, and high-quality evidence is lacking. Existing randomized controlled trials have small sample sizes and inconsistent conclusions, and none have focused on Asian population characteristics (e.g., body weight and drug metabolism differences). This study aims to provide level I evidence to optimize donor experience and define the optimal administration strategy.

Inclusion criteria: Healthy allogeneic stem cell donors aged 18-60 years, meeting institutional standard donor screening criteria (HLA matching, normal blood counts, normal liver and kidney function, negative infection screening), and providing written informed consent.

Primary endpoint: The rate of achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor body weight) after 5 days of G-CSF mobilization.

Secondary endpoints: The rate of achieving ≥ 2 × 10⁶ CD34⁺ cells/kg with at most one apheresis; time to myeloid, platelet, and erythroid engraftment in recipients; the proportion and composition of immune cells (CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product; donor adverse events; donor-reported outcomes; and the difference in CD34⁺ stem cell yields between single-dose and divided-dose mobilization.

Intervention: G-CSF will be administered at a total dose of 10 μg/kg/day, either as a single daily injection or divided into two equal daily injections.

Weight-based mobilization: G-CSF 10 μg/kg/day × 5 days, SC, once daily or in two divided doses (max 7 days). Apheresis begins on day 5; subsequent dosing and collections are guided by the CD34⁺ yield, not to exceed 7 days.

This study is designed to investigate whether single-dose or divided-dose G-CSF administration is superior for mobilizing healthy donors in allogeneic hematopoietic stem cell transplantation.

Inclusion Criteria:

1. Age 18-65 years.
2. Provision of written informed consent.
3. White blood cell (WBC) count > 2.5 × 10⁹/L.
4. Absolute neutrophil count (ANC) > 1.5 × 10⁹/L and platelet count > 100 × 10⁹/L.
5. Deemed suitable as a donor by the investigator based on donor physical examination and HLA matching.
6. Body weight ≥ 40 kg for females and ≥ 45 kg for males.

Exclusion Criteria:

1. Currently having any disease or condition that, in the judgment of the investigator, would make the donor unsuitable for participation in this study, such as severe neurological, hepatic, renal, endocrine, cardiovascular, hematologic, gastrointestinal, respiratory, or metabolic diseases; malignancies; myeloproliferative disorders; or psychiatric illnesses.
2. Currently having an active infection requiring systemic therapy.
3. Allergy to the study drug.
4. Presence of a malignant tumor.
5. Untreated HBV infection with HBV-DNA above the lower limit of detection.
6. HIV infection.
7. Addition of any new medication within 2 weeks prior to entry into this study.
8. Female donors who are pregnant or breastfeeding.