BackgroundHematopoietic stem cells (HSCs) are primitive cells that often appear in peripheral blood (PB) following mobilization events from bone marrow due to stress, injury, exercise, or pharmaceutical agents like filgrastim and pegfilgrastim. These cells can be concentrated into platelet-rich plasma (PRP), widely used in orthopedics. Filgrastim requires consecutive daily doses, while pegfilgrastim requires a single dose. Hypothesis/PurposeThis crossover study aimed to compare the safety profiles of filgrastim and pegfilgrastim administration and quantify the cellular content of PRP derived from peripheral blood following drug administration. We hypothesized comparable rates and severity of adverse events among participants, along with similar cellular content in the PRP products. Study DesignProspective, single center, cross over and controlled laboratory study MethodsHealthy participants aged 19-39 years and weighing 50-100 kilograms were screened and enrolled. They underwent a crossover design with two interventions separated by a washout period: four days of 10mcg/kg filgrastim or a single 6mcg/kg pegfilgrastim injection. Peripheral blood samples were collected before and after each intervention to produce PRP samples for cellular comparison in vitro. Adverse events (AEs) were monitored for severity and frequency throughout the study. Results10 healthy male participants were included in this study. The mean ± (SD) age of the participants was 28.30 ± 6.48 years, with a mean ± (SD) BMI of 25.29 ± 3.80. The most common adverse events for filgrastim included fatigue (36%) myalgia (36%) and back pain (9.1%), and the most common adverse events for pegfilgrastim included myalgia (31%), fatigue (23%), and back pain (23%). There were no significant differences in safety data between filgrastim and pegfilgrastim in terms of adverse event occurrence (P=0.49) nor relationship to study drug (P>0.99). The baseline PRP samples had an average TNC count of mean ± (SD) 3,844.77 ± 1,326.71, the filgrastim PRP samples had 6,939.20 ± 6,252.24, and the pegfilgrastim PRP samples had 8,923.20 ± 3,258.09. The baseline PRP samples had an average TNC concentration of mean ± (SD) 1.33×107±4.60×106 cells/mL, the filgrastim PRP samples had 1.83×107±1.81×107 cells/mL, and the pegfilgrastim samples had 3.09×107±1.13×107cells/mL. Significant differences were found in both TNC count (P=0.010) and TNC concentration (P=0.004). Specifically, there were significantly higher average TNC counts in the pegfilgrastim PRP samples compared to control (P=0.0082), but there were no differences between the filgrastim and pegfilgrastim PRP samples (P=0.1515). There was also a significantly higher average TNC concentration in the pegfilgrastim PRP samples compared to control PRP (P=0.0082) and compared to filgrastim PRP (P=0.0197). White blood cells, basophils, and immature granulocytes were significantly higher in the pegfilgrastim PRP compared to control (P=0.0082, P=0.0002, and P=0.0272). Neutrophils were significantly higher in both the filgrastim PRP (P=0.0357) and pegfilgrastim PRP (P=0.0024) compared to control. There were no differences detected for these measures among the filgrastim and pegfilgrastim PRP groups. None of the cultured PRP samples produced CFU-Fs, however cellular growth was qualitatively observed after overnight incubation. All PRP products expressed high levels (>88%) of HPC/HSC-specific CD45+, CD34+, CD45dim+, and HPC/HSC+ markers. There were no statistically significant differences in cell-surface antigens between the PRP products. ConclusionsThis prospective, single center, cross over and controlled laboratory study demonstrated that filgrastim and pegfilgrastim administration appears safe and pegfilgrastim is equivalent to filgrastim for the mobilization of white blood cells and cells expressing hematopoietic cell-surface markers into the peripheral blood and consequently, into the derived platelet rich plasma product. Clinical RelevanceThis study presents pegfilgrastim as a single-injection alternative to filgrastim for the mobilization of HSCs into the PB and subsequent PB-derived PRP, which is more convenient and less invasive for patients.