Automated closed volume reduction process for apheresis stem cell grafts: From development to clinical implementation.

BACKGROUND: Collection of HPC by apheresis (HPC-A) can sometimes result in higher collection volumes, increasing the dimethyl sulfoxide (DMSO) volume infused into patients and the space requirements in liquid nitrogen freezers. Volume reduction prior to the addition of cryoprotectant is an efficient means to reduce the DMSO load infused into patients and to optimize freezer storage space. STUDY DESIGN AND METHODS: To implement a closed semi-automated volume reduction process, a method was developed to produce leukocyte-rich mock apheresis products using buffy coats derived from whole blood collections. The mock HPC products were then used to measure the efficiency and reliability of the semi-automated process over a range of volumes and cell concentrations. The resulting data was used to support the implementation of the process with concurrent monitoring. RESULTS: A closed, semi-automated volume reduction process resulted in recoveries of over 93% and 91% of white blood cells and CD34+ cells with no significant loss of product viability or potency. Mean doses of CD34+ and CFU infused per kilogram recipient body weight were 4.0 ± 1.1 × 106 /kg and 4.2 ± 1.7 × 105 /kg, resulting in no delays in median time to neutrophil and platelet engraftment, significant increase in adverse reaction or nonconformances. DISCUSSION: The effectiveness outcomes of the first Canadian experience in the implementation of a closed semi-automated volume reduction system in the processing of HPC-A products for autologous transplant have met the predetermined acceptance criteria, supporting its use in a stem cell manufacturing laboratory compliant with good manufacturing practice regulations.

MSC-Derived Extracellular Vesicles in Preclinical Animal Models of Bone Injury: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising treatment for bone injuries, although studies remain preclinical. A systematic review and meta-analysis can assess the efficacy of MSC-EVs and identify treatment aspects associated with enhanced bone repair. METHODS: English language, preclinical, controlled, in vivo studies identified in our systematic search (up to May 8, 2020) examining the use of MSC-EVs in bone healing were included. Risk of bias (ROB) was assessed using the SYRCLE tool. Aggregate Data Meta-Analysis was performed to determine the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) and New Bone Formation (NBF). RESULTS: Thirteen studies were included. Twelve reported either BV/TV or NBF and were included in meta-analysis. ROB was unclear in all studies. Overall, MSC-EVs displayed benefit in terms of bone healing for both BV/TV (22.2% mean difference (MD); 95% CI: 15.8-28.5%, p < 0.001) and NBF (26.1% MD; 10.3-41.8%, p = 0.001) versus controls. Substantial heterogeneity, however, was observed between studies. MSC-EVs were reported to activate multiple signaling pathways including mTOR/AKT, AMPK and BMP2. Subgroup analysis indicated no significant difference in the improvement of BV/TV when using modified EVs isolated after gene transfection, preconditioning (p = 0.61), or using EVs in combination with a tissue scaffold and/or hydrogel versus other delivery methods (p = 0.20). CONCLUSION: Use of MSC-EVs to promote healing of bone injury appears promising, however, heterogeneity between studies and the potential for reporting bias limits confidence in the extent of benefit. Reducing bias between studies and addressing aspects of potential reporting bias should augment confidence in future meta-analyses and propel the field towards clinical studies. Forest Plot analysis assessing the percentage change in bone volume (BV) / total volume (TV) in the presence (experimental) or absence (control) of MSC-EVs.

Multimedia resources to support the recruitment of committed hematopoietic stem cell donors: Perspectives of the most-needed donors.

BACKGROUND: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment. STUDY DESIGN AND METHODS: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia. RESULTS: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning. CONCLUSIONS: Several considerations were generated to inform the development of future multimedia for donor education/recruitment and are relevant to donor recruitment organizations worldwide.

Factors associated with registrant availability for unrelated adult donor hematopoietic stem cell donation: Analysis of the stem cell registry at Canadian Blood Services.

BACKGROUND: Greater use of unrelated donors to support hematopoietic cell transplantation can be hampered by unavailability of registrants when identified as potential candidates for donation. METHODS: Multivariate analysis was performed to identify donor factors associated with availability for verification of human leukocyte antigen typing (VT) needed before donor activation. All VT requests for registrants on the Canadian Blood Services Stem Cell Registry between 1 January and 31 December 2018 were reviewed (n = 1358). RESULTS: Potential donors identified by transplant centers were categorized as available at the time of VT but ineligible for medical or other reasons (n = 130 and excluded from further analysis), available (n = 622) or unavailable (n = 566) due to scheduling, loss of interest, and/or inability to contact. With multivariate analysis, registrants who previously donated blood, those recruited online or from blood donation clinics, and a shorter interval between registration and VT request were significantly correlated with increased donor availability. Donor sex and geographic location, however, displayed no correlation. CONCLUSION: Online registration and recruitment at whole blood donation centers should be enhanced to increase the availability of registrants at VT. More insight is needed to maintain registrant availability following community in-person recruitment events, especially if the interval between registration and activation is prolonged. Recruitment of male registrants who are well informed should not negatively impact availability.

Development and evaluation of stem cell collection procedure diagrams to support the education and recruitment of committed stem cell donors.

BACKGROUND: Diagrams which allow potential unrelated stem cell donors to visualize the stem cell collection process were hypothesized to support the recruitment and education of committed stem cell donors. STUDY DESIGN AND METHODS: A series of bone marrow and peripheral blood stem cell collection procedure diagrams were developed, featuring young adult male donors of varied ethnic backgrounds. Post-implementation, surveys were conducted to evaluate stakeholder perspective on the diagrams' utility. A quality improvement project was conducted at five stem cell drives from 2017 to 2018 at which recruiters did or did not show the diagrams to potential donors. Following the drives, registrants were invited to complete a survey exploring their experience, knowledge and attitude towards donation. RESULTS: The diagrams were implemented in Canada in 07/2016. Of 293 participating registrants (24·7% non-Caucasian males) recruited at five drives between 2017 and 2018, 76% (n = 197) were shown the diagrams. Participants who were shown the diagrams were significantly more likely to report that the recruiters appeared very knowledgeable (89% vs. 76%, P = 0·019) and to report improved self-reported knowledge of stem cell donation (P = 0·010) compared to participants not shown the diagram. Data are also shown demonstrating that stakeholders in donor recruitment used and valued the diagrams and that use of the diagrams was associated with improved donor recruitment outcomes in Canada. CONCLUSION: This report is the first evaluation of stem cell collection diagrams in the literature. The diagrams are relevant to donor registries, recruitment organizations and transplant centres worldwide, and their use may support efforts to educate and recruit committed, ethnically diverse donors.

Development and Evaluation of a Whiteboard Video Series to Support the Education and Recruitment of Committed Unrelated Donors for Hematopoietic Stem Cell Transplantation.

Whiteboard videos are a popular video format, allowing viewers to see drawings of concepts alongside explanatory text and speech. We hypothesized that whiteboard videos could support the education and recruitment of unrelated stem cell donors in Canada. A series of 5 sharable whiteboard videos about stem cell donation was produced and posted online in September 2018, including 1 full-length video (https://youtu.be/V4fVBtxnWfM) and 4 shorter videos titled "What Is Stem Cell Transplantation?" "How Does the Matching Process Work?" "How Are Stem Cells Donated?" and "How Can I Register as a Stem Cell Donor?" In the videos, metaphorical interpretations of stem cells as factories and genetic markers as barcode labels are employed to communicate complex concepts. The particular need for young, male, and ethnically diverse donors is reflected in the characters portrayed. Surveys demonstrated the videos (1) were used and valued by stakeholders in donor recruitment and (2) significantly improved objective and self-reported knowledge about stem cell donation and reduced donation-related ambivalence among viewers from the most-needed donor demographics. Use of the whiteboard videos was also associated with improved donor recruitment outcomes in Canada. Our work is relevant to donor registries and recruitment organizations worldwide that seek to improve their recruitment efforts.

Transient warming affects potency of cryopreserved cord blood units.

BACKGROUND AIMS: Cryopreserved cord blood units (CBUs) can be exposed to transient warming events (TWEs) during routine banking operations, which may affect their potency. NetCord-FACT guidelines recommend removal of these CBUs from inventory. The objective of this work was to evaluate warming kinetics of frozen CBUs in different settings to determine the optimal working environment and define the impact of different TWE scenarios on CB post-thaw quality and potency. METHODS: The warming kinetics of frozen CBUs was influenced by both working surfaces and ambient working temperature, with cold plates providing better protection than vinyl or metal surfaces. Measurement of time for required operational activities revealed that CBUs are probably exposed to core temperatures greater than -150°C even when cold plates are used to reduce warming rates. RESULTS: On the basis of the warming kinetics and observed operational activities, three TWE causing scenarios (control, typical, worst case) were investigated using a pool-and-split design and cell viability, recovery and potency (colony-forming unit [CFU]) assays were performed. TWEs were found to have little impact on the recovery of total nucleated cells or on the viability of CD34+ cells. In contrast, the viability and recovery of CD45+ cells in the smaller CBU compartments were reduced by TWEs. Moreover, the worst-case TWE reduced CFU recovery from CBUs, whereas the typical-scenario TWE had little effect. CONCLUSIONS: Our results demonstrate that the distal segment underestimates the viability and potency of CBUs and that TWEs can affect the post-thaw viability and potency of CBUs. Although TWEs are almost inevitable during cord-blood banking operations, their effects must be diminished by reducing exposure time, using cold plates and strict operational protocols, to prevent worst-case TWEs.

Improved access to better HLA-matched hematopoietic cells for allogeneic transplant: analysis of donors and cord blood units selected for Canadian patients in 2018.

BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) often require use of an unrelated donor or cord blood unit (CBU). An understanding of evolving practices in graft selection is needed for optimization of donor recruitment and cord blood collection. STUDY DESIGN AND METHODS: Each donor workup (WU) requested in 2018 involving a Canadian (CDN) patient and unique donor product or CBU was reviewed (n = 598). Degree of HLA match; product origin (domestic or international [INT]); and non-HLA factors including donor age, sex, cytomegalovirus (CMV), and ABO compatibility were analyzed for WUs that proceeded to transplant (n = 414). We also analyzed changes compared to a similar analysis performed in 2013. RESULTS: The majority of transplants used matched unrelated donors (MUDs; n = 323; 78%) and were most often young (≤35 years), male, INT donors (n = 136). The proportion of transplants involving MUDs, as opposed to mismatched unrelated donors or CBUs, increased by 12.4% compared with 2013. When young, male, CDN MUDs were identified in patient search reports but not selected, CMV mismatching and ABO incompatibility were most likely to have influenced the decision to use an INT MUD. Consistent with global trends, CBU transplants decreased compared to 2013; however, the degree of HLA matching improved significantly, and 27% of transplanted CBUs were procured from the Canadian Blood Services Cord Blood Bank. CONCLUSIONS: Access to MUDs and better HLA-matched CBUs by CDN patients has increased since 2013. Ongoing recruitment of young registrants and cord blood donors with diverse HLA haplotypes will support selection of donors with optimal non-HLA characteristics.

Willingness of volunteers from Canadian Blood Service's Stem Cell Registry to donate blood, marrow, and other tissues for regenerative therapy.

BACKGROUND: As research surrounding cell-based regenerative therapy advances toward human trials, greater demand for cell products sourced from healthy donors will arise. The extent to which volunteers in Canadian Blood Services Stem Cell Registry would be willing to donate cells to support regenerative therapy is not known and warrants exploration. METHODS: We conducted a Web-based survey to assess factors that would influence donor willingness to donate various tissues (blood, skin, fat, and bone marrow) for regenerative therapy. The survey was provided to 15,000 randomly selected donors who registered between 2013 and 2018. Data from the 1118 respondents were analyzed. RESULTS: Despite a mixed degree of familiarity with regenerative medicine, potential donors were very supportive of donating for direct patient care and for research, and increasing their familiarity by reading a brief paragraph of information on regenerative medicine increased willingness to donate. Canadian Blood Services' stem cell registrants greatly preferred supporting nonprofit groups in research and development in comparison to entities that represent profit-seeking industry involvement. The most important factors influencing donor willingness to donate were having an impact on patients, safety of donation, advancing knowledge in regenerative medicine, a manageable time commitment, and tolerable pain that could be managed. Donors were most willing to donate blood and had mixed responses to donating other tissue types. CONCLUSIONS: Adult volunteers from a national stem cell registry are willing to support donation of biospecimens for regenerative therapy.

Multi-laboratory assay for harmonization of enumeration of viable CD34+ and CD45+ cells in frozen cord blood units.

BACKGROUND AIMS: In 2016, specifications for both pre-cryopreserved and post-thawed cord blood were defined in the sixth edition of NetCord Foundation for the Accreditation of Cellular Therapy (FACT) Standards for Cord Blood Banks. However, for several experts, harmonization regarding flow cytometry analysis performed on post-thawed samples is still a concern. A multicenter study led by Héma-Québec aimed to provide scientific data to support the cord blood accreditation bodies such as NetCord FACT in the revision of standards. METHODS: Twelve cord blood units were processed for plasma and red cell reduction following standard operating procedures. Cord blood unit aliquots were shipped to eight participating centers under cryogenic conditions for analysis before and after standardization of protocol. Repeatability of stem cell count, measured pre- and post-intervention with the centers, was estimated using multilevel linear regression models with a heterogeneous compound symmetry correlation structure among repeated measures. RESULTS: Excellent inter-center repeatability was reported by each participant regarding the viable CD34+ cells concentration, and a successful improvement effect of protocol standardization was also observed. However, we observed that better control over the critical parameters of the protocol did not have a significant effect on improving homogeneity in the enumeration of CD45+ cells. CONCLUSIONS: The current practice in cord blood selection should now also consider relying on post-thaw CD34+ concentration, providing that all cord blood banks or outsourcing laboratories in charge of the analysis of post-thaw CB samples take into account the consensual recommendations provided in this work and adhere to a good-quality management system.

Obstetrical and neonatal factors associated with optimal public banking of umbilical cord blood in the context of delayed cord clamping.

PURPOSE: To assess the association of specific newborn and maternal factors with indicators of increased blood-forming capacity in umbilical cord blood to inform strategic collection strategies that could augment the quality of units in public cord blood banks. METHODS: Data regarding 268 consecutive cord blood units (CBUs) banked by Canadian Blood Services were analyzed. Multivariate analysis was performed to identify factors associated with markers of hematopoietic potency and likelihood of utilization. RESULTS: Delayed clamping of the cord beyond 60 s was associated with reduced volume collected. Any delay in clamping of the cord was associated with reduced total nucleated cell counts. Newborn weight >4,000 g was also associated with greater blood volume in the collection but not with other measures of hematopoietic potency. Cord blood acidosis at birth (pH.

Reducing ethnic disparity in access to high-quality HLA-matched cord blood units for transplantation: analysis of the Canadian Blood Services' Cord Blood Bank inventory.

BACKGROUND: Launched in 2013, Canadian Blood Services' Cord Blood Bank (CBS' CBB) has built a high-quality, ethnically diverse cord blood repository that aims to reduce ethnic disparity in accessing suitable units for transplantation. METHODS AND RESULTS: As of December 2016, 2000 units have been banked. The self-reported maternal ethnicity was 58% non-Caucasian. Overall, 26% of units were classified as multi-ethnicity with Caucasian (84%) most frequently observed in combination with Asian, First Nations (predominant indigenous peoples in Canada south of the Arctic Circle), or African ethnicity. Utilization scores that incorporate total nucleated and CD34+ cell counts in the CBS' CBB were associated with greater likelihood of utilization compared with the international inventory of units (p < 0.05). The distribution of utilization scores was similar for Caucasians compared with non-Caucasians (p < 0.05). Using HLA genotypes of cord blood units and their mothers, we determined probable ethnic assignments for each haplotype using HaploStats (National Marrow Donor Program). Significant increases in HLA-match likelihoods are predicted for all ethnicities as the inventory grows to its target of 10,000 units and the gap in HLA-match likelihoods for Caucasian and non-Caucasian patients progressively declines. CONCLUSIONS: The CBS' CBB inventory is predicted to have high HLA-matching likelihoods across a broad spectrum of ethnic groups, improving access to high-quality stem cell products for all patients.

Assessing opportunities and challenges for establishing a national program to distribute cord blood for research.

BACKGROUND: Research is needed to enhance cord blood (CB) transplantation outcomes and to develop new clinical applications. Based on quality criteria for transplantation, CB collected by public CB banks (CBBs) is often unsuitable for banking, but may still be valuable for research. Canadian researchers have described a need for a centralized program providing ethically sourced CB for research projects. To meet this need, Canadian Blood Services (CBS), in partnership with The Ottawa Hospital, launched the Cord Blood for Research Program (CBRP) in 2014. STUDY DESIGN AND METHODS: The CBRP developed processes for donor research consent and research project approval with oversight from CBS's CBB and appropriate research ethics boards. The CBRP distributes deidentified CB products to research projects across Canada. RESULTS: Since its inception, the CBRP has distributed more than 525 CB units to researchers, supporting 11 research projects. Of the mothers who donate their baby's CB, 77% have chosen to consent to its use for research if it is not bankable. The number of CB units currently available for research via the CBRP exceeds the requests from researchers. CONCLUSION: The CBRP reliably distributes quality CB products that do not qualify for banking to investigators across Canada in an ethical, legal, and transparent manner. This provides an opportunity for the public to directly support research, helps meet the need expressed by Canada's research community, and maximizes the donor's gift. More research is needed to clarify the factors influencing donor and researcher participation in the CBRP.

Development of a proof of principle for universal neutralization of antibiotics in cord blood by-products used for sterility testing.

BACKGROUND: Bacterial contamination of cord blood (CB) represents a safety risk for transplantation patients. CB sterility testing at Canadian Blood Services' Cord Blood Bank is performed using a 1:1 mix of CB-derived plasma and red blood cells (RBCs). Culture bottles of an automated culture system, which lack antimicrobial neutralization properties, are used for bacterial screening of CB. This process is unsuitable for CB-containing antibiotics, potentially resulting in false-negative results. This study was aimed at developing a protocol for antibiotic neutralization in CB used for sterility testing. STUDY DESIGN AND METHODS: Phase 1: four neutralizers-penicillinase, ion exchange resins L and A, lecithin + Tween80, and activated charcoal (AC)-were individually tested to neutralize penicillin or gentamicin in cultures of Staphylococcus epidermidis or Klebsiella pneumoniae, respectively, adjusted to 100 colony forming units/mL, in Müller-Hinton broth (MHB). Phase 2: combinations of penicillinase plus resin L or penicillinase plus AC were assayed for the simultaneous neutralization of both antibiotics in MHB. Phase 3: penicillinase plus resin L was used to neutralize both antibiotics in CB sterility testing samples (plasma + RBCs). RESULTS: Phase 1: penicillin was neutralized by penicillinase and resin A, while gentamicin was neutralized by resin L and AC. Phase 2: the antibiotics were simultaneously neutralized by the two neutralizer combinations tested. Phase 3: neutralization of both antibiotics in CB was achieved with penicillinase and resin L. CONCLUSION: A protocol for antibiotic neutralization in CB sterility testing samples has been successfully developed at Canadian Blood Services' Cord Blood bank. This in-house assay applies to any culture-based CB bacterial screening method.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended.

Development and testing of a stepwise thaw and dilute protocol for cryopreserved umbilical cord blood units.

BACKGROUND: It is clinically important to maintain high viability and potency of umbilical cord blood units (CBUs) for transplantation during thawing. In the absence of a standard thawing protocol, this study was designed to develop one based on the consensus practice of transplant centers and address the shortage of dextran 40 thawing solution. STUDY DESIGN AND METHODS: Frozen CBU aliquots were thawed using dextran 40 thawing solution while manipulating temperature and volume of diluent and mode of dilution. The effects of these on CD45+ and CD34+ cell viability were measured through annexin V and SYTOX green staining. The developed protocol was then used to compare dextran 40 and PLASMA-LYTE A thawing solutions and finally tested on whole CBUs. RESULTS: Step-by-step investigations resulted in the development of a protocol that thaws and dilutes CBUs with room temperature diluent to five times the original volume using two sequential dilutions separated by equilibration times. PLASMA-LYTE A diluent provided superior viability of CD45+ and CD34+ cells than dextran 40 and recovered more colony-forming units. However, both diluents were equally effective in maintaining stability of the thawed CBU for 4 hours. Moreover, the stem cell-enriched CD34+CD38- subpopulations appeared more resistant to cryoinjuries than their CD34+CD38+ counterpart. CONCLUSION: The developed thawing protocol recovers viable CD45+ and CD34+ cells above the standard thresholds and maintains CBU potency. PLASMA-LYTE A for thawing solution proved to be an efficient alternative to dextran 40. Finally, greater dilution should be avoided to maintain the viability of CD45+ cells and maximize graft cell dose.

Safety of Living Donation of Hematopoietic Stem Cells.

More than 12 000 volunteer unrelated hematopoietic stem cell donations are undertaken annually, and the World Marrow Donor Association established an expert committee to examine all reports of adverse events affecting donors globally, eventually making such reporting a necessary part of World Marrow Donor Association accreditation. The committee evaluates and responds to reported events in a nonpunitive confidential process designed to alert the community of rare events which might be missed by local follow-up. Each report is evaluated by the committee for imputability (causal link between the donation and the adverse event) and compared with that submitted by the reporting registry. In 2014, there were 50 reports received from 16 different registries in 15 countries. There were 16 reports of malignancies arising in donors including 3 hematologic malignancies. All but 2 of the 16 occurred more than a year after donation. There were 4 reports of autoimmune phenomena in donors all occurring more than a year postdonation. Of the 30 remaining events, 6 were allergic, 4 cardiac, 3 gastrointestinal, 2 infections, 2 pulmonary, and 13 miscellaneous. Causation was assessed differently to the reporting registry in 17 events with 6 thought to be less likely causally linked to the donation and 10 more likely with 1 requiring more information. Volunteer unrelated hematopoietic stem cell donation is a safe and effective altruistic contribution to the treatment of patients with life-threatening hematologic disorders. A decade of detailed examination of adverse donor events has contributed to the safety of these donations.