Public Cord Blood Banks Research Articles

Hybrid cord blood banks may be advantageous for scientific as well as economic reasons

Background & Aim BACKGROUND AND AIM: Public cord blood banks have thresholds for accepting cord blood unit (CBU) collections for processing based on economic models developed using surrogate markers of suitability, i.e. volume and total nucleated cell count (TNCC). Only after processing has it been possible to look at CD34+ cell numbers and colony forming units (CFU). Since as few as 0.52 × 105 CD34+ cells can be expanded in vitro and used successfully for transplant, it is important to understand what is in the smaller collections that public bank guidelines currently prevent from being processed. Hybrid public/private cord blood banks permit economic support from the private bank to help support the public bank. They also offer an opportunity to evaluate products outside public banking thresholds because all collections are processed. AIM To present data from the first 72 private cord blood unit (CBU) collections processed for the Cord Blood Bank of Arkansas, showing the relationship between collection volume, TNCC and CD34+ cell numbers. Methods, Results & Conclusion METHODS: The CBBA is a hybrid bank, providing cord blood banking for public, private and research use. Parents are informed of the different options for banking available, document their informed consent, and then receive a collection kit to bring to the delivering obstetrician. Cord blood is collected with the placenta in utero using Pall model # 791-08 collection kits. Collections are processed within 72 h of collection at a central site with plasma and red cells removed. Pre-processing TNCC are performed with a Beckman Coulter Ac.T Diff2 cell counter and TNCC determined as follows: actual cord blood weight x WBC 103/100=TNCC. Flow cytometry is performed using the ISHAGE technique with a Beckman Coulter CytoFLOW. RESULTS Mean maternal age for CBU was 34y (range 26-45). Of 72 CBU donated (37 male, 35 female), delivery route was spontaneous vaginal for 50 (69.45%) and caesarian section for 22 (30.55%). Mean birth weight was 3341.5 g (median 3355; range 2296-4337). Mean gestational age was 38.92 weeks (median 39; range 36-41.14). CONCLUSION Data on hematopoietic potential of low volume/low TNCC products are currently available only from a hybrid or private bank. Here we show that CBU below threshold TNCC and volume for public banks can have a significant number of CD34+ cells available for expansion and use in transplant.

Successful scale up expansion of Wharton's jelly mesenchymal stromal cells in different commercial xeno-free and serum-free media

Background & Aim Cell-based therapies are becoming widely accepted in regenerative medicine and their demand and potential is increasing. Human multipotent Mesenchymal Stromal Cells (MSC) derived from the Wharton's jelly (WJ) of the umbilical cords can be obtained from samples typically discarded from public cord blood banking programmes. However, current cell culture bioprocesses for the derivation, scale up expansion, and GMP-compliant product manufacturing for early phase clinical trials use serum and xenogeneic proteins in medium formulation. Therefore, the use of xeno-free and serum-free media (XSFM) formulations is required to ensure more homogenous cell populations. The aim of this study was to compare four commercially available XSFM as an alternative to human serum-containing media in WJ-MSC culture. Methods, Results & Conclusion Cryopreserved MSC derived from WJ in serum-conditions were cultured in four commercial XSFM, namely PRIME-XV MSC Expansion XSFM, MSC Nutristem® XF, MesenCult™-ACF Plus Medium, and MSC-Brew GMP Medium and were further compared with conventional expansion medium Dulbecco's modified Eagle's medium (DMEM) containing 2 mM glutamine and supplemented with 10% of human serum B (hSerB). Cells were successfully expanded in culture in all XSFM conditions. Cumulative population doublings and harvest cell densities were higher in early passages for 3 out of 4 XSFM than serum-containing expansion medium. WJ-MSC proliferation was higher than 1 × 105 cells/cm2 in early culture (passage 2) while it decreased under 1 × 105 cells/cm2 in late culture (passage 8) in XSFM conditions. Spindle shaped morphology was kept upon passages in XSFM conditions. In all cases, cells were highly positive for CD73, CD90 and CD105 and negative for CD31, CD45 and HLA-DR expression in passage 1 and 6 and multilineage capacity to osteogenic, adipogenic and chondrogenic lineages was confirmed after in vitro induction. These data demonstrate that WJ-MSC can be successfully cultured and expanded in commercially available xeno-free and serum-free media and retain all necessary characteristics attributed to MSC for potential therapeutic use.

Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile

Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Cord blood-derived platelet concentrates as starting material for new therapeutic blood components prepared in a public cord blood bank: from product development to clinical application.

There are many advantages to using cord blood (CB) as a source of therapeutic platelet and plasma derivatives for regenerative medicine. These include availability, universal use, young donor source, and virally safe biological material, rich in tissue regenerative factors. We aimed to validate a bioprocess design for the production of cord blood-derived platelet concentrates (CBPC) in a public Cord Blood Bank (CBB). CBPC was defined as a product of 10±5 mL, 1,000±200×109/L total platelets, free of erythrocytes and leukocytes. A total of 300 CB units were centrifuged in two steps to enrich for platelets, in compliance with Good Manufacturing Practice. The samples were tested for the degree of platelet activation present, and the levels of growth factor were analysed to evaluate their potential function. CBPC were then activated after thawing with 10% calcium gluconate to generate platelet gels (CBPG) to treat patients with diabetic foot ulcers. After processing, 84% of the products fulfilled the acceptance criteria. Final products contained 1,017±149×106 platelets/mL in 10±3mL of plasma. Platelet recovery was 50±9%. The methods described here ensure depletion of white and red blood cells down to a residual concentration of 0.2±0.1×106/mL and 0.03±0.02×106/mL, respectively. Platelets showed low levels of activation during processing, but were significantly activated after thawing, as indicated by an increase in CD62p expression. The growth factors EGF, VEGF, bFGF, PDGF AB/BB and TGF-β1 were at concentrations of 1,706±123 pg/mL; 1,602±227 pg/mL; 314±26 pg/mL; 30±1.5 ng/mL; 24±2 ng/mL (mean±standard error of mean), respectively. For clinical evaluation, a total of 21 CBPG were applied in 3 patients, with no reported adverse events and improvement of ulcers in all of them. We designed and validated a highly reproducible, closed system method to manufacture high quality CBPC suitable for clinical applications using CB units not suitable for transplantation in a public CBB.

The Binns Program for Cord Blood Research: A Novel Program for Cord Blood Procurement in an Academic Setting for Biomedical Research

<h3>Introduction</h3> Umbilical cord blood (UCB) is a vital source of hematopoietic stem and progenitor cells (HSPCs). Since 1991, UCB has been collected and stored in public cord blood banks to be primarily used as a source for allogeneic hematopoietic stem cell transplantation (HSCT). Since the seminal UCB transplant reported in 1988 by Gluckman et al., UCB has contributed to advances in HSCT and clinical trials. However, UCB-derived cells remain costly and difficult to procure for pre-clinical research. Here we present a protocol for a multidisciplinary, self-sustaining cord blood program dedicated to biomedical research: The Binns Program for Cord Blood Research, piloted at the Stanford University School of Medicine. <h3>Objectives</h3> The primary objective of this study was to educate others on the benefits of implementing a self-sustaining cord blood program that increases biomedical research throughout the medical community. <h3>Methods</h3> Eligible donors are identified using IRB-approved inclusion criteria. UCB samples are then collected in utero, with informed consent, by obstetric providers at the time of delivery. Within 24-48 hours of isolation, deidentified samples are processed into three fractions: (1) plasma, (2) hematopoietic stem and progenitor cells (HSPCs) by immunomagnetic separation, and (3) non-HSPC cellular flow-through. UCB-derived fractions are then distributed to researchers upon request. <h3>Results</h3> Between November 2015 and April 2019, 1,385 women gave informed consent to donate their cord blood following delivery. Of those participants, 1,147 (83%) samples were collected and 927 (81%) distributed for research purposes. The median post-enrichment cell count per cord following positive selection for CD34+ HSPCs was 1.25 × 10⁶ (Figure 1). Corresponding median post-enrichment sample purity was 90% following single-step purification. By October 2016, a protocol had been developed and optimized for the Binns Program to begin providing UCB-derived products to six laboratories. Now, the program supports 47 laboratories across Stanford. The research being supported spans a broad array of topics including normal and abnormal hematopoiesis, genetic engineering, and novel approaches to HCST. <h3>Conclusions</h3> After initial start-up funding, the Binns Program became self-sustaining, representing a feasible model for cord blood banking to support the advancement of research by providing fresh or cryopreserved UCB-derived cells to the research community. We hope this model may be useful for other institutions and centers where the need to support research is high and the traditional model for public cord blood banking may not be a suitable option.

Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.

“Cut the Cord but don't throw it away”-Umbilical Cord Blood Banking

Umbilical cord blood stem cell transplantation has been used to cure many malignant disorders, hematological conditions, immune deficiency disorders and inherited metabolic disorders. Cord Blood Collection procedure is safe for mother as well as baby in an otherwise uncomplicated delivery. According to Indian academy of pediatrics public cord blood banking should be promoted over private banking. Private cord blood banking is highly recommended when an already existing family member is suffering from diseases managed by stem cell transplantation. Otherwise, private cord blood banking is not a ‘biological insurance’, and should not be encouraged. At present, autologous cord stem cells cannot be used for treating diseases of genetic origin, metabolic disorders and hematological cancers. Advertisements for private umbilical cord blood banking are often misleading.

Values in tension. Clinical quality and civic participation in umbilical cord blood banking in Italy.

In the dominant narrative of bioethics and biomedical discourse on public Umbilical Cord Blood (UCB) banking, the ethical value of donating UCB is unproblematically associated with the clinical quality of collected UCB. This article shows that this view is analytically untenable as it overlooks tensions and conflicts between the social values of donation and the clinical value of banked UCB in concrete arrangements regarding the logistics of UCB donation and collection. Adopting the notion of registers of valuing (Heuts and Mol 2013: Valuation Studies, 1, 2, 125-46) and analysing the case of the Italian network of public UCB banks and collection sites, this article shows how conflicting registers of valuing concerning UCB can shape different organisational models of UCB donation and collection, in which social values and clinical value are not unproblematically conflated. The article aims to demonstrate that the functioning of biobanking arrangements is dependent on how different values are accomplished and aligned in concrete practices of tissue donation and collection.

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

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. 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. 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.

‘It’s a family affair’: The discursive entanglement of social formations in public and private cord blood banking in Italy

The dominant narrative in bioethical and biomedical literature criticises private/family cord blood banking as selling a biomedical service that challenges the system of public banks that is based on voluntary donations and distributing umbilical cord blood for medical needs. While the public system is described as embedded in the social relations of reciprocity, solidarity and obligation to the collectivity, private/family banking is accused of being a for-profit commercial market that exploits the emotional vulnerabilities of parents with exaggerated and misleading claims about the clinical uses of umbilical cord blood. This article challenges this view by showing that both banking systems are embedded in social relations. It analyses the discourses produced by Italian public and private umbilical cord blood banks and by healthcare institutions to show how these discourses constitute different social formations and attach diverging meanings of umbilical cord blood banking and clinical use to the set of responsibilities, values and obligations characterising these formations.

What will Become of the Taxpayer Investment in Public Cord Blood Stem Cell Banking?

Cord Blood (CB) is a unique and readily available source of hematopoietic stem cells for transplantation. CB also contains other types of stem cells, including endothelial stem cells and mesenchymal stem cells, that may prove useful in non-traditional clinical uses. Genetic and molecular analyses have demonstrated that CB stem cells lie somewhere between mature stem cells like those found in Bone Marrow (BM), and fetal stem cells. After 25 years of clinical experience, CB is now used in the same fashion as BM for all typical malignant and genetic diseases treated by bone marrow transplant. Due to the establishment of CB banks in the US and abroad, more than 35,000 CB transplants have been performed over the past 25 years. An average of 700-800 CB transplants are performed annually. In addition, CB is now used more frequently for regenerative medicine and tissue engineering applications. At first glance, it seems that everything could not be better with the public cord blood banks and the use of their samples in the clinic. However, a recent report by the Rand Corp. reviewed the US national cord blood stem cell banking program and detailed many ongoing problems. However, some details were omitted from the report that would shed some light on the causes of many of the problems. This paper will summarize the status of the public cord blood stem cell banking program in the US, detail the problems associated with the program that could jeopardize its existence and suggest possible solutions to resolve these issues.

Establishing the ethical and regulatory frame work for a clinically compliant ipsc cell line bank; from qa to donor reconsent.

Background & Aim A global network of iPSC banks would create a strong future basis for new cellular therapies, providing GMP quality clinically complaint cell lines to produce differentiated cells to facilitate research studies through to clinical trials. Cryopreserved Cord Blood (CB) is an excellent starting material for iPSC production, however setting up these banks requires clear and transparent reconsent of donors along with a strong QA and QC framework. We aim to provide a clear ethical pathway towards the creation of such a resource, along with a dynamic follow up and reconsent process of donors from the public BMDI Cord Blood Bank. Methods, Results & Conclusion Review of the literature and a round-table workshop with Ethics and Legal experts have identified the key issues to be resolved in order to obtain consent to make iPSC lines from CB donors. Regulatory challenges that would affect global acceptance of any cell lines, along with the Quality framework and the standards required to operate as part of a global network, are being met by working in collaboration with bodies such as the Global Alliance for iPSC Therapies (GAiT) and participating in an iPSC Quality Assessment Round. Developing the mechanism for reconsenting donors and increasing their understanding to allow fully informed consent, in addition to establishing ethical guidelines for confidentiality, have presented challenges. CB donor letters and information sheets have been developed and Ethics approvals have been sought and processed by an Institutional HREC, prior to submission for government approval. New issues of whole genome sequencing and the relevant donor safeguards and protections have been considered with input from clinical genetics services, including the rights and information flow to donors about what happens to the cells after banking and commercialization aspects. Freedom to operate and GMP manufacture and oversight is currently under investigation. This work is continuing and the ongoing success of many of these processes has confirmed feasibility and utility of using banked CB to produce clinical–grade iPSC lines for potential cellular therapies. By facilitating clinical research, we can improve Australia's position in the clinical trials space, providing a standardised and characterised resource that could lead to eventual new cell therapies that will be available to Australian and international communities.

Repurposing the public cord blood bank inventory in Korea to enhance cord blood use

To enhance public cord blood (CB) use, we examined the current status of CB banking and tried to suggest revision of the banking standard. We retrospectively analyzed the use of stored public CB units between 2011 and 2016 using data from the CB information center in Korea. A total of 19,871 CB units were registered, and 363 units were selected for transplantation. The transplanted CB units contained significantly higher numbers of CD34+ cells than the average numbers in the stored CB units (5.5 × 10^6 vs. 3.2 × 10^6, p < 0.01). They also contained more total nucleated cells (TNCs) than the average of the stored CB units (13.7 × 10^8 vs. 10.7 × 10^8, p < 0.01). Only 49% of the stored CB units contained>10 × 10^8 TNCs, while 81% of the units transplanted contained >10 × 10^8 TNCs. The average length of cryopreservation of the transplanted CB units was 4.58 years and 95% of them had been stored for less than 10 years. During the study period, 18,763 CB units were requested for research, but only 5,888 were released. This discrepancy was mostly due to errors in regulatory and/or networking elements of the CB supply system. The data suggest that preserving CB units for less than 10 years and increasing the required minimum TNC count to 10 × 10^8 would produce an inventory containing units that were more useful for CBT. CB units that did not meet the requisite quality standards could be used for research, and systems for their fair distribution to researchers are needed.

Cord Blood Banking: Antenatal Care Provider's Roles and Responsibilities.

Background Umbilical Cord Blood (UCB) banking done either for private storage or for donation to public cord blood banks involves active participation of obstetricians. Counseling the expectant parents, providing them with unbiased and balanced information, and collecting the UCB with diligence confer a lot of social as well as moral responsibility upon obstetricians. This makes it even more important that the obstetricians in current practice stay well-informed and updated with UCB collection and its storage guidelines. The present study was conducted to assess the current status of obstetricians about UCB banking in terms of their awareness, attitude, and expectations from it. Materials and Methods A cross-sectional study was conducted across three hospitals. A self-administered 22-item questionnaire was given to obstetricians to assess their awareness, attitude, and expectations about UCB banking. Finally, 154 completed questionnaires were analyzed using SPSS software (version 15.0). The awareness, attitude, and expectations were assessed and reported as primary endpoints and the self-rated knowledge levels, and sources of information were reported as secondary endpoints. Results Overall, the awareness was poor, but the attitude was favorable for UCB banking amongst obstetricians. Around 74% felt that obstetricians must be well-informed about UCB banking-related counseling and collection protocols. However, 55% felt it to be an additional burden for the obstetrician, and 57% believed that financial compensation must be given to obstetricians involved with cord blood collection procedures. The majority remained unclear about their expectations from UCB banking. The self-rated knowledge was poor and very poor for 75% obstetricians. 89.6% derived their information from representatives of private cord blood companies. Conclusion Although poor in awareness levels, obstetricians possessed a favorable attitude towards UCB banking. Continuing medical education needs to focus more on such current issues of public importance to keep professionals updated. This is one way to minimise percolation of wrong facts and figures by the industries with conflicting interest to the healthcare providers.

ACOG Committee Opinion No. 771: Umbilical Cord Blood Banking.

Since the first successful umbilical cord blood transplant in 1988, it has been estimated that more than 35,000 transplants have been performed in children and adults for the correction of inborn errors of metabolism, hematopoietic malignancies, and genetic disorders of the blood and immune system. Two types of banks have emerged for the collection and storage of umbilical cord blood: 1) public banks and 2) private banks. The benefits and limitations of public versus private umbilical cord blood banking should be reviewed with the patient because they serve different purposes. This patient discussion also should include the concept of autologous and allogeneic use of umbilical cord blood. Umbilical cord blood collected from a neonate cannot be used to treat a genetic disease or malignancy in that same individual (autologous transplant) because stored cord blood contains the same genetic variant or premalignant cells that led to the condition being treated. There is no current evidence to support the use of an autologous umbilical cord blood sample in regenerative medicine. Patients should be made aware of the quality control and regulatory organizations that provide oversight for the process of umbilical cord collection and storage. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice of delayed umbilical cord clamping with the rare exception of medical indications for directed donation. Therefore, it is important to inform patients that the medical condition of the woman or neonate may prevent adequate umbilical cord blood collection. This document is updated with a statement that the routine use of private cord blood banking is not supported by available evidence and that public banking is the recommended method of obtaining cord blood. In addition, the importance of contribution from all ethnicities and races to public banks is highlighted.

ACOG Committee Opinion No. 771 Summary: Umbilical Cord Blood Banking

Since the first successful umbilical cord blood transplant in 1988, it has been estimated that more than 35,000 transplants have been performed in children and adults for the correction of inborn errors of metabolism, hematopoietic malignancies, and genetic disorders of the blood and immune system. Two types of banks have emerged for the collection and storage of umbilical cord blood: 1) public banks and 2) private banks. The benefits and limitations of public versus private umbilical cord blood banking should be reviewed with the patient because they serve different purposes. This patient discussion also should include the concept of autologous and allogeneic use of umbilical cord blood. Umbilical cord blood collected from a neonate cannot be used to treat a genetic disease or malignancy in that same individual (autologous transplant) because stored cord blood contains the same genetic variant or premalignant cells that led to the condition being treated. There is no current evidence to support the use of an autologous umbilical cord blood sample in regenerative medicine. Patients should be made aware of the quality control and regulatory organizations that provide oversight for the process of umbilical cord collection and storage. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice of delayed umbilical cord clamping with the rare exception of medical indications for directed donation. Therefore, it is important to inform patients that the medical condition of the woman or neonate may prevent adequate umbilical cord blood collection. This document is updated with a statement that the routine use of private cord blood banking is not supported by available evidence and that public banking is the recommended method of obtaining cord blood. In addition, the importance of contribution from all ethnicities and races to public banks is highlighted.

Contextual factors influencing donor recruitment and cord blood collection: perspectives of frontline staff of the Canadian Blood Services' Cord Blood Bank.

Umbilical cord blood (CB) is an important source of hematopoietic stem cells that are used to treat blood- and immune-system disorders. Public CB banks aim to build inventories with high-quality CB units to meet healthcare needs. While research has noted the influence of broader contextual factors on donor recruitment and CB collection processes, to date, no published study has identified the specific contextual factors and challenges to donor recruitment and CB collection. This paper addresses this gap in the literature. A qualitative case study focusing on donor recruitment and CB collection processes was conducted to identify the contextual factors influencing these processes. This paper reports the findings from in-depth, semi-structured interviews conducted with 15 frontline staff of the Canadian Blood Services' Cord Blood Bank. Interview data were analyzed using inductive interpretive methods to identify the contextual conditions and factors that influence recruitment and collection. Frontline staff described various social factors that influenced and challenged the processes of donor recruitment and CB collection. These were categorized into four overlapping contexts: birthing context, hospital context, CB bank organizational context, and sociocultural context. Consideration of social context is necessary in order to effectively address the factors and challenges that influence the successful development of high-quality CB inventories, and to guide resource allocation. Further examination of contextually-rooted factors and their interactions is necessary to optimize donor recruitment and CB collection processes.

Nucleated red blood cells as a novel indicator of CD34+ cell content in umbilical cord blood

Umbilical cord blood (UCB) has become an important source of transplantable CD34+ hematopoietic progenitor cells. Cord blood banks (CBBs) can increase their efficiency by minimizing the processing of UCB units with low CD34+ content, which have a lower likelihood of transplant utilization. We sought to identify a readily available preprocessing metric that would correlate with CD34+ cell counts, without the cost of additional analysis. Data were compiled for 131 UCB units processed at the regional CBB. Preprocessing hematologic metrics, including complete blood count and differential, were compared to postprocessing CD34+ cell quantities. The data were divided into six groups of varying preprocessing metrics, then compared for significant differences in postprocessing CD34+ cell quantities to develop a screening guidance. UCB units with nucleated RBC (nRBC) content of 15% or greater were found to have a significant increase in CD34+ cell percentage (p < 0.00001) and total CD34+ cell content (p < 0.0001). Units with preprocessing total nucleated cell count (TNC) of ≥ 1.50 × 109 with nRBC content of 15% or greater, and for TNC ≥ of 2.00 × 109 with nRBC content less than15%, had a significant increase in CD34+ content (p < 0.05 and p < 0.001, respectively). Applied as a screening guideline, these units had an increase in mean CD34+ content from 6.24 × 106 to 9.27 × 106 . Units originally in the bottom and top quartiles of CD34+ content constitute 5% and 53% of processed units meeting these TNC/nRBC criteria, respectively. These screening criteria utilizing nRBC provides a guideline that public CBBs may use to increase their efficiency by minimizing the processing of UCB units with lower CD34+ cell content.

Evaluation of Cord Blood (CB) Unit TNC & CD34+ Cell Content & Donor-Recipient High-Resolution 8 HLA-Allele Match By Patient Ancestry: An Evaluation of 513 CB Units in a Racially & Ethnically Diverse Population of Adults with Hematologic Malignancies

Introduction: Optimal CB unit selection guidelines recommend consideration of CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is not known.Methods: We analyzed the infused graft & back-up unit cryopreserved total nucleated cell (TNC) x 107 & CD34+ x 105 cell content, the cell dose (incorporating pt weight), & 4-6/6 & 8-allele HLA-match by pt ancestry in CB transplant (CBT) recipients transplanted 1/2014-6/2018. Units were chosen based on banking practices (e.g. RBC depleted, standard cryo volumes), TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match with dose usually taking priority over match given pt size at our center. The analysis included transplanted units (considered the best choice) & the next best high resolution typed back-up units (reserved but not shipped). Pt racial/ ethnic origins were prospectively obtained by detailed family history & grouped as previously described (Barker J. et al. BBMT 2010).Results: The characteristics of 513 units chosen for 136 CBT recipients by pt ancestry are shown (Table 1). Pts had highly diverse origins including 70 (51%) non-Europeans. The 513 units included 270 units infused as the graft (134 doubles & 2 singles) & 243 back-up units (109 pts had 2 back-ups, 25 pts had one & 2 had none). Thus, 4 best units were analyzed in 109 pts (all double unit recipients), 3 best in 25 pts (all doubles), & 1 unit in 2 pts (both singles). The median weight of the 136 pts was 81 kg. Asian pts (median 68 kg) had a lower weight than other groups. The median TNC content of units for the 66 European pts was higher than that for the 70 Non-Europeans (218 vs 196, p = 0.004). Units chosen for Northwestern (NW) Europeans had the highest median TNC content (235) with lower TNC content in units for Southern Europeans (202), Asian (193), African (191) & White Hispanic (189) pts. Units chosen for European pts also had a higher median CD34+ cell content (162) than Non-Europeans (138), p = 0.004. NW Europeans had units with a higher median CD34+ content (198) & the lowest CD34+ content were those for African (124) & Middle Eastern pts (124). When patient weight was considered, median TNC/kg dose per unit was similar in European and Non-European pts (2.7 vs 2.6, p = NS). Units for NW Europeans had the highest median TNC dose (3.0) whereas those for African pts had the lowest TNC dose (2.4). Units for Europeans had a higher median CD34+ dose (2.0) than Non-Europeans (1.7) although this difference was not significant (p = 0.15). Additionally, similar to TNC dose, median CD34+ dose was highest in units for NW European pts (2.2) & lowest in units chosen for African pts (1.5). 89% of chosen units were 4/6 HLA-matched with no differences between Europeans & non-Europeans. Furthermore, the median 8 allele HLA-match was 5/8 (range 2-8/8) with no overall differences between units for Europeans and Non-Europeans (p = NS).When only transplanted units were analyzed (Table 2), the median TNC & CD34+ contents were significantly lower in non-Europeans than Europeans (238 vs 216, p = 0.01 & 184 vs 160, p = 0.016). Overall, however, units received by Europeans vs non-European pts had similar TNC & CD34+ doses (p = NS). However, differences in the CD34+ content combined with differences in pt weights resulted in disparities in CD34+ doses by ancestry sub-group. NW Europeans (high weight, high CD34+ content) received the best CD34+ doses; lower CD34+ content in Asian pts was compensated for by their lower weight. African pts (high weight, low CD34+ content) received the lowest CD34+ doses. The median 8 allele HLA-match for all was 5/8 (range 3-8/8) with the exception of African pts [median 4/8 (range 3-7/8)]. Moreover, while 108 (40%) of transplanted units were 3-4/8 HLA-matched overall, there were marked differences between pt sub-groups with only 23% of units for NW Europeans being 3-4/8 vs 42% for southern Europeans, 46% for white Hispanics & 53% for Africans.Conclusions: While CB significantly extends transplant access to racial & ethnic minorities, differences in cellular content translates to many minority pts receiving lower dosed units. There are also marked racial/ ethnic differences in HLA-match grade with African pts the most likely to receive highly mismatched units. This data supports ongoing funding of public CB banks to further increase the inventory of high dosed & better matched units for all but especially racial & ethnic minority pts. [Display omitted] DisclosuresShah:Janssen: Research Funding; Amgen: Research Funding. Kernan:National Cancer Institute: Research Funding.

New HLA-C alleles identified in two donors from the Colombian public umbilical cord blood bank.

Two novel HLA-class I alleles discovered: HLA-C*08:162 and HLA-C*03:296:02.