Granulocyte colony stimulating factor(Lipoxen Technologies Ltd.)

We retrospectively evaluated the impacts of using granulocyte colony‐stimulating factor (G‐CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single‐unit cord blood transplantation (CBT). Multivariate analysis showed that G‐CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II–IV acute graft‐versus‐host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G‐CSF administration in BMT and CBT patients, but not in PBSCT patients. G‐CSF administration significantly improved overall survival (OS) and leukemia‐free survival (LFS) only following CBT. Regarding the timing of G‐CSF, in comparison with late initiation of G‐CSF (Days 5–10), early initiation (Days 0–4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II–IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G‐CSF administration accelerated neutrophil recovery and increased the risk of grades II–IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G‐CSF should be considered for CBT in adult patients with AML.

Granulocyte colony‐stimulating factor (G‐CSF) mobilizes peripheral blood (PB) progenitor cells from bone marrow (BM) into circulation for PB stem cell transplantation (PBSCT). This study aimed to develop a population pharmacokinetic–pharmacodynamic (PK‐PD) model of filgrastim in healthy subjects to optimize PB CD34+ cell collection. Plasma filgrastim concentrations and CD34+ cell count data were obtained from a clinical study involving healthy Korean subjects. A total of 1378 plasma concentration measurements and 982 CD34+ cell count data collected from 53 subjects were used in the PK‐PD model. Filgrastim PKs were adequately described by a one‐compartment linear disposition model with an additional transit compartment for absorption. Log‐transformed body weight was the only significant covariate affecting the volume of distribution and clearance. CD34+ cell mobilization was best captured by a modified Friberg model, assuming continual entry of proliferating BM stem cells into PB via a single transit compartment. Simulation results suggested that the 5 μg/kg twice‐daily dosing regimen may yield higher CD34+ cell counts compared to the 10 μg/kg once‐daily regimen for achieving target CD34+ cell counts of 20/μL and 50/μL. We successfully developed a robust PK‐PD model of G‐CSF that optimizes the yield of CD34+ cells during allogeneic PBSCT. This model can guide the efficient determination of optimal G‐CSF dosing regimens and CD34+ cell harvesting strategies.