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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.
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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5.
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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6.
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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7.
Factors associated with opting-out of donation among registered, young, unrelated hematopoietic stem cell donors
Hamed, A. B., Bruce, J. G., Kuniyil, V., Mattila, D., Williams, E. P., Dew, M. A., Myaskovsky, L., Confer, D. L., Switzer, G. E.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Young adults enrolled in hematopoietic stem cell (HSC) donation registries, including the Be The Match® registry in the US, often opt out of the registry when a potential recipient is identified. This results in a limited supply, from the most desirable allogeneic source, of HSCs that are used to treat serious health conditions. The differences in demographic, psychosocial, registry-related, and donation-related characteristics between those who continue to donation and those who opt out may elucidate the modifiable risk factors for attrition, but these characteristics have not been extensively studied in young donors up to age 30. OBJECTIVE Our goal was to study demographic, psychosocial, registry-related, and donation-related characteristics in a young group of HSC donor registry members who had recently been contacted about a potential recipient, to determine the key characteristics that differ between those who continued toward donation and those who opted out, and the extent of these differences. STUDY DESIGN AND METHODS We conducted a cross-sectional survey in a random sample of young (age 18-30) current and former registry members, stratified by race/ethnicity and sex. Demographic, psychosocial (e.g., life goals, HSC allocation mistrust), registry-related (e.g. context and motive for joining the registry), and donation-related characteristics (e.g., ambivalence, religious objections to donation, knowledge about donation) were assessed. Chi-squared and two-sample t-tests were used to examine differences between those who continued (CT-C) and those who opted out (CT-NI). Hierarchical logistic regression was used to estimate adjusted covariate effects on the odds of opting out. RESULTS 935 participants were surveyed. Donation-related knowledge was higher in the CT-C group than in the CT-NI group. HSC allocation mistrust, religious objections, and concerns regarding donation were higher in the CT-NI group. After adjusting for covariates in a logistic regression model, we found that having more intrinsic life goals, more ambivalence, and talking with registry staff only once/twice were significantly associated with opting out of the registry. Ambivalence had the strongest association with opting out. In contrast, remembering joining the registry, believing that parents would support donation, and having medical concerns were significantly associated with continuing toward donation. This effect of medical concerns on donation was discovered only after adjusting for the related but distinct Ambivalence variable, with the remaining effect of medical concerns relating to engagement with the donation process and information-seeking. The model had strong discriminative ability (AUC=0.92) and classification accuracy (86.6%). CONCLUSION Among young adult members of a national HSC donor registry, ambivalence and limited contact with registry staff were more strongly associated with opting out of the registry. Medical concerns were associated with continuing toward donation. Further studies are needed to confirm a causal link between medical concerns and continuing toward donation among young donors. Our study suggests these concerns may not be directly related to attrition, whereas other factors (e.g. ambivalence, low donation-related knowledge) are associated with attrition and thus should be targeted for attrition reduction strategies.
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8.
Racial and Ethnic Differences in Attitudes, Perceptions, and Knowledge about Unrelated Hematopoietic Stem Cell Donation: A Study of Younger Newly Recruited Potential Donors
Hamed, A. B., Bruce, J. G., Kuniyil, V., Mattila, D., Williams, E. P., Dew, M. A., Myaskovsky, L., Confer, D. L., Switzer, G. E.
Transplantation and Cellular Therapy. 2022;28(6):340.e1-340.e16
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Abstract
Attrition of young adult registry members is a significant issue impacting hematopoietic stem cell (HSC) donation registries, including the Be The Match registry in the US. The resulting limited supply of allogeneic HSCs, used to treat serious health conditions, has a stronger impact on racial/ethnic minority groups in the US. Compared with young white adults, young adults identifying with these minority groups are more likely to drop out of the donor registry when called to donate. However, the underlying psychosocial factors that differ between white and nonwhite registrants have not been fully investigated. The central goal of this study was to examine demographic, registry-related, and donation-related characteristics in a young, newly registered group of potential donors and to determine whether these characteristics differed by, or were distributed differently among, racial/ethnic groups. We conducted a cross-sectional survey in a random sample of young (age 18 to 30 years) newly registered members, stratified by racial/ethnic group and sex. Demographic, registry-related (eg, context and motive for joining the registry), and donation-related (eg, ambivalence, religious objections to donation, knowledge about donation) characteristics were assessed. The chi-square test and analysis of variance were used to examine differences among racial/ethnic groups. Discriminant function analysis was used to assess whether patterns of the 3 classes of characteristics were associated with membership in particular racial/ethnic groups. A total of 524 participants were surveyed. Joining online was most common among white individuals, whereas joining at college was most common among black and Hispanic individuals. Ambivalence toward donation was higher among Asian/Pacific Islanders compared with white or multiracial/multiethnic individuals. Discriminant function analysis revealed 4 psychosocial/attitudinal functions predicting membership in certain racial/ethnic groups. The function accounting for the most variance in responses included mistrust of HSC allocation, religious objections to donation, low parental support, and low knowledge level. This function discriminated significantly between the white and nonwhite groups. Another function also identified ambivalence as a discriminating factor, which was most strongly associated with Asian/Pacific Islanders. Among young adult members of an HSC donor registry, such factors as ambivalence, family concerns about donation, mistrust of HSC allocation, religious objections, and less knowledge about donation were more strongly associated with membership in the nonwhite groups compared with the white group. These factors are known to be associated with a higher risk of opting out after having been preliminarily matched with a patient. The finding that these characteristics are associated with racial/ethnic minority group membership provides targets for recruitment strategies aimed at improving retention of young registry members.
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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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Psychosocial outcomes of parents in pediatric haploidentical transplant: parental hematopoietic cell donation as a double-edged sword
Aguilera, V., Schaefer, M. R., Parris, K., Long, A., Triplett, B., Phipps, S.
Bone marrow transplantation. 2022
Abstract
Parents are increasingly used as donors for their child's haploidentical hematopoietic cell transplant, creating a dual role for parents that may increase the stress of caring for their ill child. Empiric research on the psychological adjustment of parental donors is lacking. We conducted a retrospective survey of parents (n = 136) whose child underwent transplant with a parental donor or a matched-unrelated donor, including both donor and nondonors, and both parents of survivors and bereaved. All parents completed standardized measures of quality of life, depression, anxiety, post-traumatic stress, and life satisfaction. Bereaved parents also completed measures of their grief response, while parents of survivors completed measures of the parent-child relationship. The overall sample reported psychological functioning near normative levels, but bereaved parents demonstrated significantly poorer outcomes across all measures. The effect of donor status differed by transplant outcome: for parents of survivors, donors reported better mental health than nondonors, but amongst bereaved parents, donors fared more poorly than nondonors. Bereaved donors reported greater difficulties with grief than nondonors. Results suggest that serving as donor can be a double-edged sword, acting as a protective factor when there is a successful outcome but a significant risk factor when the child does not survive.