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1.
Incidence of cardiovascular disease in healthy Swedish peripheral blood stem cell donors - a nationwide study
Pahnke, S., Hägglund, H., Larfors, G.
Bone marrow transplantation. 2024
Abstract
Granulocyte colony-stimulating factor (G-CSF) is used in a majority of healthy donors to obtain peripheral blood stem cells for allogeneic stem cell transplantation. Since high levels of G-CSF activates endothelial cells and can induce a pro-coagulatory state, and fuelled by case reports of cardiovascular events in donors, some concerns have been raised about a potential for an increased risk of cardiovascular events for the donors after donation. We studied the incidence of cardiovascular disease following stem cell donation in a Swedish national register based cohort of 1098 peripheral blood stem cell donors between 1998 and 2016. The primary objective was to evaluate if the incidence of cardiovascular disease was increased for donors treated with G-CSF. The incidence of any new cardiovascular disease was 6.0 cases per 1000 person years, with a median follow up of 9.8 years. The incidence did not exceed that of age- sex- and residency-matched population controls (hazard ratio 0.90, 95% confidence interval (CI) 0.76-1.07, p-value 0.23), bone marrow donors, or non-donating siblings. Long-term cardiovascular disease incidence was not increased in this national register based study of peripheral blood stem cell donors treated with G-CSF.
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2.
The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study
Çakmaklı, H. F., Gökçe, H., Söylemez, E., Topçuoğlu, P., Kayaaltı, Z., İleri, D. T.
The Turkish journal of pediatrics. 2023;65(5):809-821
Abstract
BACKGROUND Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge. METHODS Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed. RESULTS MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004). CONCLUSIONS Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.
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3.
Worries and Psychological Well-Being in Potential Hematopoietic Stem Cell Donors Before Donation-A Swedish National Study
Winterling, J., Pahnke, S., Lagnebjörk, J., Hägglund, H., Larfors, G., Lenhoff, S., Kisch, A. M.
Transplantation proceedings. 2023;55(1):242-248
Abstract
BACKGROUND The physical risks involved in donating hematopoietic stem cells have been thoroughly studied, but little is known about the psychological risks potential donors might face before donation. The aim of this study was to describe potential the pre-donation worries and psychological well-being of hematopoietic stem cell donors and investigate possible associations between donor characteristics and psychological well-being. METHODS In a cross-sectional, national cohort study, we describe pre-donation worries and psychological well-being and investigate possible associations between donor characteristics and psychological well-being. A questionnaire was sent to prospective adult hematopoietic stem cells donors. RESULTS The study included 210 participants, 47% of whom were related and 53% unrelated to the recipient. Of the participants, 39% reported great worry about the recipient and 12% great worry about themselves as potential donors. Symptoms of anxiety were expressed by 21%, whereas symptoms of depression were uncommon and perceived general mental health was slightly lower than in the Swedish population. Great worry about oneself, lower age, and female sex were related to increased anxiety and lower mental health. CONCLUSION This study highlighted that some potential donors report high levels of pre-donation worry and that greater worry about oneself, lower age, and female sex are associated with lower psychological well-being. Although further studies are needed to investigate this psychological risk over time, it is clear that some potential donors are particularly vulnerable.
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4.
Ethylene oxide-type hypersensitivity reactions in G-CSF mobilized, peripheral blood hematopoietic progenitor cell donors and review
Cooling, L., Sherbeck, J.
Journal of clinical apheresis. 2023
Abstract
BACKGROUND Ethylene oxide (EtO) is a volatile, ringed toxic ether used to sterilize heat-labile plastics including apheresis sets. In the 1980s, EtO-associated severe hypersensitivity reactions during hemodialysis led to widespread adoption of alternative sterilization for dialysis kits but not apheresis tubing sets. We now report several cases of EtO-type hypersensitivity reactions in autologous donors undergoing hematopoietic progenitor cell collection (HPCC). MATERIALS AND METHODS A 10-year retrospective review of allergic EtO-type reactions in adults undergoing HPCC on the COBE Spectra and SPECTRA Optia was performed. Donor medical history and absolute eosinophil counts were compared between cases and 34 HPCC controls. Published EtO reactions during extracorporeal procedures were reviewed with statistical analysis. Graphics and statistics were performed using commercial software. RESULTS Three autologous HPCC donors experienced EtO-type reactions within 15 min of initiating HPCC, for a 10-year incident rate of 0.08% per procedure and 0.18% per donor. All three reactions occurred using the Spectra Optia and IDL tubing set, for an Optia/IDL specific rate of 0.2% per procedure and 0.5% per donor. There was no correlation between EtO reactions, eosinophil counts, or saline prime dwell times. No patient had classic predisposing risk factors for EtO hypersensitivity. Two patients required medical intervention whereas the third responded by pausing the procedure and slowing the inlet rate. CONCLUSION EtO-type hypersensitivity reactions can be observed during HPCC, especially with the Optia IDL tubing set. EtO reactions may be missed due to their rarity and staff unfamiliarity with this clinical entity.
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5.
Assessing the cognition, attitudes and intentions of volunteers regarding unrelated peripheral blood stem cell donation: The UPBSC-DQ instrument in Chinese
Ding, N., Ye, Z., Jin, X., Zhang, G., Yu, Q., Liu, Y.
Heliyon. 2023;9(11):e20663
Abstract
OBJECTIVES This study aimed to develop and validate the Unrelated Peripheral Blood Stem Cell Donation Questionnaire (UPBSC-DQ) (an instrument in Chinese) to assess the degree of cognition, attitude and intention of enrolled volunteers towards UPBSC donation. METHODS The development process of the UPBSC-DQ was performed in a stepwise approach that included extensive literature retrieval, expert revision, and pretesting with 442 students. We conducted an online cross-sectional survey using the final version of the UPBSC-DQ among 336 participants. The reliability of the questionnaire was assessed by Cronbach's α and corrected item-total correlation (CITC), and the validity was evaluated by a correlation coefficient matrix, confirmatory factor analysis (CFA), and t-test. RESULTS The UPBSC-DQ consists of four domains: basic information, cognitive, attitude, and intention. The Cronbach's α values were 0.88 and 0.86 for the attitude and intention scales, respectively, indicating strong internal consistency and good reliability. Correlation analysis and CFA showed good structure and content validity. Interitem correlations indicated that each item had only a weak correlation with the other scales. CONCLUSIONS The UPBSC-DQ is a reliable and valid assessment questionnaire for individuals' attitudes and intentions towards UPBSC donation. The questionnaire showed good to high reliability, content and construct validity.
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6.
Pediatric Hematopoietic Cell Transplantation: A Longitudinal Assessment of Health-Related Quality of Life of Pediatric Donors
Hou, S. H. J., Stokoe, M., Zwicker, H., Young-Speirs, M., Pelletier, W., Guilcher, G. M. T., Khu, M., Schulte, F. S. M.
Journal of clinical psychology in medical settings. 2023
Abstract
Pediatric donors may be at increased risk of psychological and social challenges following hematopoietic cell transplantation (HCT). Through a retrospective chart review, we evaluated the health-related quality of life (HRQL) of pediatric donors over time and examined facilitators and barriers to implementing a longitudinal psychosocial assessment. Fifty-one pediatric donors (M = 10.7 years, SD = 3.7) completed an HRQL questionnaire across six time points (T1 to T6) from prior to donation to 2 years after. Change in mean scores was assessed using a linear mixed-effect model for repeated measures design. Facilitators and barriers to implementation were examined. HRQL of pediatric donors improved between T1 and T6 with significant change in physical, emotional, and overall functioning. Facilitators to retention included the support of a clinical coordinator. Barriers to implementation included the absence of infrastructure to maintain contact with pediatric and their families. HRQL of pediatric donors of HCT improved steadily over time. Pattern of results suggests a need to further explore factors that contribute to change across time. Development of a longitudinal standardized assessment protocol that can be prospectively and feasibly implemented is integral to supporting the well-being of this group.
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7.
Superior physical and mental health of healthy volunteers before and five years after mobilized stem cell donation
Heyn, J., Bräuninger, S., Dimova-Dobreva, M., Mathieson, N., Koptelova, N., Kolpakova, A., Seidl, C., Reinhardt, P., Tsamadou, C., Schrezenmeier, H., et al
Journal of translational medicine. 2022;20(1):121
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.
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8.
Systematic scoping review of studies reporting unexpected donor-derived abnormalities from recipients of allogeneic hematopoietic cell transplantation: a proposed framework for donor disclosure: donor-derived abnormalities in allogeneic HCT
J, C., Am, K., R, S., Morris, G., P, B., Md, S., Ds, A.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Allogeneic hematopoietic cell transplantation (HCT) is used increasingly to treat blood and immune-based disorders. Post-transplant testing of HCT recipients can lead to unexpected molecular, cytogenetic and other information in donor-derived cells, evoking questions regarding the potential impact on donor health. OBJECTIVE To identify the breadth of donor-derived abnormalities identified by testing HCT recipients and the extent to which disclosure and donor follow up are described. METHODS A systematic search and scoping review were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews in OVID MEDLINE and EMBASE (1947 to May 24, 2021). RESULTS We identified 38 studies (63 donor-recipient pairs) addressing non-leukemic abnormalities, to complement existing literature describing donor cell leukemia and donor-derived myelodysplasia. Donors were unrelated adults (n=20), related family members (n=28), cord blood donors (n=6) or were not reported (n=9). Acquired cytogenetic, molecular, and morphologic abnormalities were reported. Donor origin was confirmed by cytogenetic analysis via karyotyping, FISH, STR-PCR, and other techniques. A disease in donor-derived cells was described in 35 recipients (56.5%). Despite the relevance for testing and disclosure to donors, only 22 cases (32%) mentioned donor follow-up, and 5 cases confirmed that the donor developed a disease associated with the identified abnormality. Unrelated donor disclosure was mentioned in 3 of 26 cases (12%), where the findings were reported back to the registry. CONCLUSION Incidental abnormalities identified in transplanted donor cells may contribute to post-transplant risk of illness in the recipient and may be relevant to donor health. A framework for donor disclosure is proposed that incorporates consideration of analytic validity of the testing, potential significance of the finding, and the extent to which the abnormality is actionable. Adoption of effective processes to safeguard both donor and recipient health outcomes related to this issue is needed. [295].
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9.
Development and evaluation of checklists to support the recruitment of committed hematopoietic stem cell donors
Fingrut, W. B., Chen, A. C., Green, M., Weiss, J. T., Mercer, D., Allan, D.
Transfusion. 2022
Abstract
BACKGROUND Checklists are memory recall tools used across healthcare to improve outcomes. Here, we describe the development and evaluation of checklists to support recruitment of committed allogeneic hematopoietic stem cell donors. STUDY DESIGN AND METHODS Checklists were developed with the following objectives: (1) improve best-practice adherence; (2) reduce errors; and (3) support standardization at stem cell drives. Topics included: recruiting needed donors; securing informed consent; maintaining good-documentation practices; and supervising registration and tissue sample collection. Checklists were iteratively revised with input from stakeholders. We evaluated the checklists by examining recruitment outcomes and errors (i.e., preventing registrants from being listed as donors) pre- (11/2011-8/2016) and post- (9/2016-11/2019) implementation by the Canadian donor recruitment organization Stem Cell Club. Quantitative and qualitative methods were employed to analyze recruiters' perspectives on the checklists. RESULTS The checklists supported recruitment of donors from needed demographic groups as Stem Cell Club expanded its recruitment effort from 4118 registrants (60% male, 58% non-European) pre-implementation to 10,621 (52% male, 56% non-European) post-implementation. Checklist implementation was associated with a marked reduction in errors (from 13.2% to 1.9%) and a three-fold increase in the match rate of recruited donors (from 0.024% to 0.075%). Qualitative and quantitative analysis of recruiter feedback supported that the checklists' objectives were realized from the recruiter perspective. DISCUSSION We developed checklists to support donor recruitment and showed that their implementation was valued by recruiters and associated with both reduced errors and improved donor recruitment outcomes. The checklists are relevant to donor recruitment organizations worldwide.
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10.
Severe short-term adverse events in related bone marrow or peripheral blood stem cell donors
Yanagisawa, R., Hirakawa, T., Doki, N., Ikegame, K., Matsuoka, K. I., Fukuda, T., Nakamae, H., Ota, S., Hiramoto, N., Ishikawa, J., et al
International journal of hematology. 2022
Abstract
The incidence of severe adverse events (SAEs) and associated risk factors in hematopoietic cell transplantation donors needs to be clarified for related donors (relatives of the transplant recipient), whose criteria for donation are more lenient than for unrelated donors. Data from related donors registered in the Japanese national data registry database between 2005 and 2021 were evaluated to determine the association of short-term SAE incidence with donor characteristics at registration.Fourteen of 4339 bone marrow (BM) donors (0.32%) and 54 of 10,684 peripheral blood stem cell (PBSC) donors (0.51%) experienced confirmed SAEs during the short donation period. No deaths were observed. Past medical history was a common risk factor for SAEs in both BM and PBSC donors. Age of 60 years or older and female sex were identified as risk factors for SAEs in PBSC donors. Female sex was also a risk factor for poor mobilization, which resulted in discontinuation of PBSC collection.Although donors should be selected carefully, a certain level of safety is ensured for related donors in Japan. Donor safety should be further increased by improving the selection method for related donors and extending the follow-up period.