Superior physical and mental health of healthy volunteers before and five years after mobilized stem cell donation

Abstract

Background: Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being "warm glow", hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally.

Methods: We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire.

Results: Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time.

Conclusions: HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk-benefit assessment of volunteer HSPC donation. Trial registration National Clinical Trial NCT01766934.

Keywords: Filgrastim; Healthy stem cell donors; Physical and mental health; SF-12.

Conflict of interest statement

JH, MDD, NM, NK, AK and RN are employees of Sandoz-Hexal, sponsor of the trial and manufacturer of filgrastim “Zarzio”. HB has received research funding and served on the speaker’s board of Sandoz-Hexal. The other authors have no declarations.

© 2022. The Author(s).

Figures

Fig. 1

Well-being over time as assessed with the SF-12 self-guided questionnaire. A Physical and mental well-being (Y-axis) over the phases of screening, apheresis and follow-up (X-axis) are displayed (mean, SD; for legibility, SD is drawn in only one direction). A dramatic transient dip in physical well-being is observed after mobilization with G-CSF, assessed just prior to the first apheresis, as well as a slow but steady decline of both physical and mental health scores is seen over time. B, C Age- (left) and sex-(right) adjusted physical and mental well-being of donors compared to a healthy cohort of German non-donors (published by Kuehne et al. [22]) at the time of donor screening (B) and at the five-year follow-up time point (C). D, E Age-adjusted physical and mental well-being of donors compared to a healthy cohort of German non-donors (published by Gandek et al.[23]) at the time of donor screening (D) and at the five-year follow-up time point (E). For both comparisons, donors were assigned to the respective age group based on their age at this specific time-point (i.e. at the time of donation, of 5-year follow-up). Of note, the Gandek cohort contains equal numbers of women and men, whereas our cohort is significantly skewed towards men who generally score higher on the SF-12 for both physical and mental health status. The data in panels B–E show a markedly better than expected health status of HSPC donors compared to healthy non-donors of all age groups and for both sexes; the advantage is largely maintained over time. Throughout, physical and mental well-being are depicted as blue diamonds and red circles, respectively. Values for donors from our cohort are displayed as full symbols, those for the published reference groups as empty symbols. Asterisks indicate statistical significance at the ≤ 0.0001 (***), ≤ 0.001 (**), ≤ 0.01 (*) level, values between 0.01 and 0.05 are shown, n.s. (not significant) indicates a p > 0.05