Filgrastim in the pharmaceutical name for granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim is the long-acting form of filgrastim. The excretion of exogenous G-CSF into breastmilk or its effects on breastfed infants have not been well studied. Limited data indicate that filgrastim and a similar G-CSF product, lenograstim, are poorly excreted into breastmilk and are undetectable by 3 days after an injection. Some authors recommend withholding breastfeeding for this period of time.[1] However, filgrastim has been safely given orally to neonates and is not orally absorbed by neonates, so any filgrastim that is excreted into milk is unlikely to adversely affect the breastfed infant.

Addition of polyethylene glycol (PEG), or PEGylation, is a modification that extends the half-life of drug products, thereby reducing the frequency of dosing. However, PEGylation can pose challenges for biosimilar drug development, as replicating the reference product's PEG characteristics to achieve similarity to the reference product's pharmacokinetics (PK) can be difficult. A few biosimilar product submissions have highlighted issues with PK assays, potentially contributing to failures in PK similarity assessment. With many approved PEGylated protein therapeutics soon becoming eligible for biosimilar development, developing alternative methods for PK assessment that can be applied across multiple product categories may help to facilitate a more efficient biosimilar development program. We previously validated an ELISA-based method and observed significant variability even in samples prepared with known drug concentrations. We decided that a cell-based assay (CBA) might offer greater translatability to other PEGylated products. CBAs rely on cells with receptors for the drug product being tested, and the choice of cell line would vary depending on the specific drug product. In this study, we utilized pegfilgrastim, a PEGylated granulocyte-colony stimulating factor (G-CSF) product, for PK determination using the CBA method. This proof-of-concept study demonstrates that while the sensitivity of the CBA is lower than that of the validated ELISA, its ability to capture receptor-accessible drug provides an important advantage for pharmacokinetic assessment. Moreover, it exhibits good reproducibility and can be read using a 96-well platform. This CBA approach may be a viable option for the rapid development of PK assays for other PEGylated drug products.

Granulocyte-colony stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells (PBSCs) for hematopoietic cell transplantation (HCT). G-CSF is generally well-tolerated but can cause life-threatening complications such as splenic rupture in rare cases. Long-acting pegfilgrastim (Peg-G) is increasingly used for PBSC mobilization, but its risk for splenic rupture is less well characterized. Here, we report a case of splenic rupture secondary to Peg-G administered for PBSC mobilization in a healthy 25-year-old male haploidentical donor. He presented with left upper quadrant abdominal pain shortly after PBSC harvest 5 days following administration of Peg-G. Computed tomography (CT) revealed splenomegaly with rupture, and small bloody peri-splenic and pelvic ascites. He was managed conservatively, but the next evening his symptoms temporarily worsened, prompting a repeat CT scan, which showed no change. Thereafter, the pain did not recur, and the patient was discharged on day 8. One month later, a follow-up CT demonstrated complete resolution. To our knowledge, this is the first case of splenic rupture secondary to Peg-G for PBSC mobilization in a healthy allogeneic donor and highlights the importance of vigilance for this rare complication when G-CSF or Peg-G is used for mobilization.

Feline panleukopenia (FPL) is a serious viral disease caused by Feline panleukopenia virus (FPV) that causes leukopenia, lymphopenia, and neutropenia, particularly in young or unvaccinated cats. There is no specific antiviral treatment available for FPL, and treatment protocols generally consist of fluid therapy and supportive care. This study evaluated the clinical and hematological efficacy of filgrastim, a granulocyte colony-stimulating factor (G-CSF) that has shown successful results in treating FPL in various studies, and the paraimmune activator-inactivated Parapoxvirus ovis (iPPVO) in 49 cats naturally infected with FPV. Cats were randomly assigned to four groups: low-dose filgrastim (5 µg/kg, n = 13), high-dose filgrastim (20 µg/kg, n = 14), iPPVO (n = 12), and standard supportive treatment (n = 10). Clinical signs and complete blood counts were assessed on days 0 and 7. By day 7, high-dose filgrastim showed greater increases in white blood cell, lymphocyte, monocyte, and neutrophil counts compared with the other groups (p < 0.05), whereas moderate improvements were observed in the iPPVO group. Leukopenia and lymphopenia resolved faster in the high-dose filgrastim group than in the low-dose filgrastim and standard treatment groups. Clinical recovery, including reduction in vomiting and lethargy, was more pronounced in the high-dose filgrastim and iPPVO groups. Survival rates did not differ significantly among groups (p = 0.615), although the high-dose filgrastim group showed the lowest mortality (42.9%). These findings suggest that high-dose filgrastim may contribute to cytopenias and promote hematological recovery in FPL, while iPPVO may serve as a supportive immunomodulatory therapy. However, it should be noted that the efficacy of filgrastim and/or iPPVO treatments has not been definitively confirmed, likely due to the small sample size and the lack of well-controlled randomized studies.

Mobilized hematopoietic stem and progenitor cells (HSPCs) are essential for transplantationbased therapies, including curative gene therapies for sickle cell disease (SCD). While granulocyte colony-stimulating factor (G-CSF, filgrastim) remains the standard mobilization agent, many patients respond inadequately, and it can trigger life-threatening vaso-occlusive crises in SCD. The CXCR4 antagonist AMD3100 (plerixafor) is routinely combined with G-CSF for non- SCD settings but is ineffective as a single agent in SCD, underscoring the urgent need for alternative strategies. We previously identified 27-hydroxycholesterol (27HC) as a physiological inducer of HSPC mobilization during pregnancy. Here, we show that exogenous 27HC enhances AMD3100-induced HSPC mobilization in mice, either alone or with G-CSF. Because 27HC is metabolized by the enzyme Cyp7b1, we tested whether pharmacological Cyp7b1 inhibition could mimic this effect. Treatment with clotrimazole, an antifungal and Cyp7b1 inhibitor, significantly enhanced AMD3100-induced HSPC mobilization in wild-type, SCD, and humanized mice. Importantly, intravenous administration of voriconazole, a clinically approved systemic antifungal with Cyp7b1-binding activity, similarly augmented AMD3100-induced HSPC mobilization in wildtype and SCD mice without altering steady-state hematopoiesis. These findings establish Cyp7b1-inhibiting azoles as novel and clinically relevant enhancers of HSPC mobilization, particularly for SCD patients who cannot safely receive G-CSF but require robust HSPC yields for gene therapy.

BackgroundDuring the COVID-19 pandemic, guidance broadened indications for primary G-CSF prophylaxis to reduce chemotherapy-related neutropenia while minimizing clinic visits. Evidence on the optimal duration of daily G-CSF in biweekly FOLFOX remains limited, particularly in gastrointestinal malignancies.MethodsWe conducted a retrospective study of COVID-negative adults with gastrointestinal cancers receiving FOLFOX during the pandemic. Patients were categorized by G-CSF strategy: no prophylaxis, 3-day filgrastim, or 5-day filgrastim. Primary outcomes were overall neutropenia and grade 3-4 neutropenia. Secondary outcomes included treatment modifications and adverse events. Multivariable logistic regression assessed independent associations.ResultsNeutropenia was higher without G-CSF versus 3-day and 5-day (64.4% vs 37.1% vs 39.6; p < 0.001); grade 3-4 neutropenia likewise (30.1% vs 7.9% vs 11.9; p < 0.001). 3-day vs 5-day showed no significant difference (neutropenia p = 0.67; grade 3-4 p = 0.29). G-CSF use independently lowered neutropenia risk; female sex independently increased risk.ConclusionIn patients receiving biweekly FOLFOX for gastrointestinal cancers, primary G-CSF prophylaxis was associated with lower rates of neutropenia. No statistically significant difference was observed between the 3-day and 5-day daily G-CSF schedules in this cohort. However, given the retrospective design and the absence of a predefined non-inferiority framework, these findings do not establish equivalence and should be interpreted with caution. Prospective multicenter studies specifically designed to compare 3- and 5-day regimens are warranted.