Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women

Background.

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women.

Materials and methods.

This study was conducted at the “Sapienza” University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women.

Results.

Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use.

Discussion.

The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.     

Viral metagenomics in blood donations with post-donation illness reports from Brazil

BackgroundPost-donation illness can be described as appearance of clinical symptoms in blood donors after donation. The consequent call back of the donor to report these symptoms to the blood collection institution is considered a post-donation illness report (PDIR). The most suitable way to examine whether PDIR is related to infection is to apply next-generation sequencing (NGS) and viral metagenomics. Investigation into a PDIR can reveal its importance for transfusion safety and help elaborate strategies for donor education in order to prevent the transfusion transmission of infections which are not routinely tested by the blood collection services.Materials and methodsWe applied NGS and viral metagenomics on blood donations which were deferred due to a PDIR. Thirty-three PDIR donations obtained in the Blood Center of Ribeirão Preto, Southeast Brazil, were evaluated. Sequencing was performed using Illumina NextSeq 550 (Illumina Inc, San Diego, CA, USA) equipment and the reads obtained for each sample were analysed by specific bioinformatic pipeline for the classification and discovery of emerging viruses. The identified viral agents by metagenomics were directly confirmed by molecular methods.ResultsIn all PDIR donations, we found abundant reads of commensal viruses belonging to the Anelloviridae family as well as human pegivirus-1. However, we were also able to identify blood donations positive for clinically important viruses like dengue serotype-2 (DENV-2) of the Asian-American genotype and parvovirus B19 (B19V). Both viruses were also confirmed by real-time polymerase chain reaction, detecting DENV-2 RNA in a significant number of cases (7 samples, 21.2%), compared to B19V which was confirmed in 1 case (3.0%).DiscussionOur study applies for the first time viral metagenomics to evaluate the significance of PDIRs. We confirm the crucial importance of the donor providing a timely PDIR for the prevention of transfusion transmission of viral infections which are not routinely tested in the blood banks worldwide.     

Trends in cord blood banking

Background

Umbilical cord blood (UCB) is a source of hematopoietic precursor cells for transplantation. The creation of UCB banks in 1992 led to the possibility of storing units of UCB for unrelated transplants. The distribution of cell contents in historical inventories is not homogenous and many units are not, therefore, suitable for adults. The aim of this study was to analyse our UCB bank inventory, evaluate the units released for transplantation and calculate the cost of the current process per unit of UCB stored.

Methods

Three study periods were defined. In the first period, from January 1996 to January 2006, the total nucleated cell (TNC) count acceptable for processing was 4–6×10⁸ and a manual processing system was used. In the second period, from October 2006 to July 2010, processing was automated and the acceptable TNC count varied from 8–10×10⁸. In the third period, from January 2009 to June 2010, an automated Sepax-BioArchive procedure was used and the accepted initial TNC count was >10×10⁸. Within each period the units were categorised according to various ranges of cryopreserved TNC counts in the units: A, >16.2×10⁸; B1, from 12.5–16.1×10⁸; B2, from 5.2–12.4×10⁸; and C, <5.1×10⁸.

Results

The third period is best representative of current practices, with homogenous TNC acceptance criteria and automated processing. In this period 15.7% of the units were category A and 25.5% were category B. Overall, the mean TNC count of units released for transplantation was 14×10⁸ (range, 4.6×10⁸ to 36.5×10⁸). The cost of the processed UCB in 2009 was 720.41 euros per unit.

Conclusion

An UCB bank should store units of high-quality, in terms of the TNC count of units issued for transplantation, have a training programme to optimise the selection of donors prior to delivery, use similar volume reduction systems and homogenous recovery indices, express its indicators in the same units, use validated analytical techniques, and bear in mind ethnic minorities.     

Eliciting repeat blood donations: tell early career donors why their blood type is special and more will give again

BACKGROUND AND OBJECTIVES: This study was designed to investigate whether sending a personalized and informative letter to early career donors would increase the number returning to donate again, as the literature suggests that it is at around the third donation that people become career donors. MATERIALS AND METHODS: Experimental participants were sent a recruitment letter that included information about their own blood type and the percentage of the general population with the same blood type who donated. Control participants received a recruitment letter with some general information. The aim of the study was to determine whether more participants in the experimental group, compared with the control group, would donate blood within a 4-week period after receiving their personalized recruitment letter. RESULTS: Donors in the experimental group were 43% more likely to return to donate than those in the control group [chi(2) (1) = 5.79, P < 0.016]. CONCLUSIONS: Sending out personalized, informative letters appears to be a potentially powerful donor-retention tool.     

Milestones in umbilical cord blood transplantation

Much has been learned about umbilical cord blood (UCB) since the first human cord blood transplant was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation and distribution of UCB for allogeneic haematopoietic stem cell transplantation. UCB has now become one of the most commonly used sources of haematopoietic stem cells for allogeneic transplantation. Today, a global network of cord blood banks and transplant centres has been established with a large common inventory, allowing for more than 20000 transplants worldwide in children and adults with severe haematological diseases. Several studies have been published on UCB transplant, assessing risk factors such as cell dose and human leucocyte antigen mismatch. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality and include the use of reduced-intensity conditioning regimen, intra-bone injection of cord blood cells, double cord blood transplants or ex vivo expansion of cord blood cells. The absence of ethical concern and the unlimited supply of cells explain the increasing interest of using UCB for developing regenerative medicine.     

Allogeneic cord blood red blood cells: assessing cord blood unit fractionation and validation

BackgroundFor neonates and preterm infants, in whom a transfusion dose is low, the use of red blood cells (RBC) from cord blood appears to be feasible. Standardisation of fractionation and identification and assessment of quality control parameters for such RBC are still lacking.Materials and methodsWe describe the process used to obtain RBC from cord blood for transfusion purposes, including quality controls to evaluate fractionation performance and the effects of storage. The cord RBC, to which SAG-M was added, were sampled on the day of fractionation, and 7 and 14 days (end of storage) later in order to measure the complete blood count, biochemical parameters and residual white blood cells. We also assessed microbial contamination.ResultsData relative to 279 cord blood units were evaluated. The median gestational age at collection was 40 weeks (interquartile range [IQR] 39.1–40.7) and the median volume was 90 mL (IQR 81–103). Units were subjected to automated fractionation with Compomat, and packed RBC were suspended in SAG-M solution. The median volume of the SAG-M-suspended units was 31 mL (IQR 24.0–38.1) and the median haematocrit was 54.2% (IQR 49.4–59.5). The median volume after leukoreduction was 22 mL (IQR 17–28), with the volume decrease being similar in units leukoreduced before (n=75) or after (n=204) storage. The haematocrit of leukoreduced units was higher than that of buffy coat-depleted units. Storage at 2–6 °C for 14 days was accompanied by an increase of potassium levels and percentage of haemolysis. Microbial cultures were positive for 2.9% of the collected units.DiscussionFractionation of whole cord blood can provide RBC concentrates with similar baseline characteristics as units from adults. The transfusion dose and quality of the units appear safe and suitable for clinical use in neonates, with a satisfactory haematocrit and residual white blood cell content, despite a very variable collection volume.     

Recruiting and retaining young people as voluntary blood donors

OBJECTIVES: Reasons for predonation deferral of young potential donors and prospects of recruiting and retaining young people (age 18-29) as voluntary blood donors were studied. STUDY DESIGN AND METHODS: Three different sources of data were analysed: (i) the subsequent donation history of 2057 donors who started their donation career at the Blood Bank of Oslo (BBO) in 1999, age and gender of all new donors accepted for donation at BBO in 2004 was retrieved from electronic data files; (ii) data on reasons for predonation deferral, age and gender of all deferred prospect donors at BBO in 2004 was obtained from original screening questionnaires; and (iii) results from a national telephone survey of the general population's attitudes regarding blood donation, conducted in 2005. RESULTS: Twenty-five per cent of the first-time donors recruited in 1999 remained active in 2005, but the percentage was higher among older than younger donors. Change of residency was the most frequent reason for termination of donation among young donors. Young prospect donors were more frequently than older ones deferred for lifestyle-related reasons. Prospect donors older than 30 years were more frequently deferred for health-related reasons. A large proportion (57.7%) of young adults reported a favourable attitude towards becoming blood donors. Lack of a personal request (not being asked) was the most frequently reported reason for not giving blood among young people with no donation record. Only a minor proportion of young non-donors considered themselves disqualified from donating blood due to health status. CONCLUSIONS: Lifestyle-related eligibility criteria and changes of residency pose problems for recruitment and retention of young donors. However, a large proportion of young adults state that they are able and willing to donate blood; therefore, the prospects of recruiting young people as voluntary blood donors seem generally positive.     

Milestones in umbilical cord blood transplantation

Since the first human cord blood transplant, performed in 1988, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. Umbilical cord blood (UCB) has now become one of the most commonly used source of hematopoietic stem cells for allogeneic transplantation. Today a global network of cord blood banks and transplant centers has been established for a common inventory with an estimated 600,000 UCB have been banked and more than 20,000 UCB units distributed worldwide for adults and children with severe hematological diseases. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. The absence of ethical concern, and the unlimited supply of cells explain the increasing interest of using cord blood for developing regenerative medicine.     

The acceptability to women in Mombasa, Kenya, of the donation and transfusion of umbilical cord blood for severe anaemia in young children

BACKGROUND AND OBJECTIVES: Severe anaemia, for which a blood transfusion can be life saving, is common in hospitalized children in sub-Saharan Africa but blood for transfusion is often in short supply. Umbilical cord blood is usually thrown away but could be a useful source of red cells for small volume transfusions in young children in this setting. The objective of this study was to evaluate the attitudes of women using the maternity services of the provincial hospital in Mombasa, Kenya, towards cord blood donation and transfusion, and essential aspects of this process including informed consent and the acceptability of screening for human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: A structured questionnaire was developed based on data provided by focus group discussions with women attending the hospital's maternity unit and administered to women who had recently delivered at the hospital. RESULTS: Of the 180 women who completed a questionnaire, the donation and transfusion of cord blood were acceptable to 81% and 78%, respectively. Ninety per cent of women who supported cord blood donation were willing to undergo further HIV testing at the time of delivery. Seventy-seven per cent of women wanted informed consent to be sought for cord blood donation and 66% of these felt they could make this decision alone. CONCLUSION: The donation of umbilical cord blood and its transfusion are acceptable to the majority of women delivering at Coast Provincial General Hospital, Mombasa. Findings from the study will benefit the planned cord blood donation programme at this facility.     

Improving cord blood transplantation in children

Umbilical cord blood transplantation (UCBT) is widely used to treat children affected by many disorders. In comparison to bone marrow transplantation, the advantages of UCBT are represented by lower incidence and severity of graft- versus -host disease, easier procurement and prompter availability of cord blood cells, and by the possibility of using donors showing human leucocyte antigen disparities with the recipient. Despite these advantages, the large experience gained over the last decade has clearly demonstrated that UCBT patients may be exposed to an increased risk of early fatal complications, due to the lower engraftment rate of donor haematopoiesis, delayed kinetics of neutrophil recovery and lack of adoptive transfer of pathogen-specific memory T-cells. An inverse correlation between the number of nucleated cord blood cells infused per kilogramme recipient body weight and the risk of dying from transplantation-related causes exists. Thus, it is not surprising that strategies aimed at increasing the number of cord blood progenitors, favouring stem cell homing, and transferring pathogen-specific lymphocytes, have been recently investigated. In particular, selection of the richest cord blood units, infusion of 2 units in the same recipient, intrabone injection of cord blood cells, and transplantation of ex-vivo expanded progenitors can contribute to improve the results of UCBT.     

Detection of HTLV-I and -II in Scottish blood donor samples and archive donations

BACKGROUND AND OBJECTIVES: Positive samples identified during routine serological screening for HCV (hepatitis C virus), HBV (hepatitis B virus) and HIV (human immunodeficiency virus) are confirmed by nucleic acid testing in the SNBTS (Scottish National Blood Transfusion Service) PCR Reference laboratory. Serological screening for HTLV-I (human T-cell lymphotropic virus type I) and -II was implemented in Scotland in November 2002, at which time a PCR assay was not available for confirmation. Our aim was to develop a real-time PCR assay that could be used for the confirmation of samples showing HTLV-I serological positive or indeterminate reactivity and to investigate whether a serologically silent carrier status exists ('Tax' only) in the Scottish donor population. MATERIALS AND METHODS: A real-time HTLV PCR was devised using a lymphoblastoid cell line which has HTLV-I sequence integrated in the genome (C8166 cells). These were spiked into peripheral blood mononuclear cells. The assay was evaluated on archived serologically confirmed HTLV-positive samples and new positives identified since implementation of screening. RESULTS: HTLV-I and -II were detected in cells and plasma from stored donations and a serological positive donation identified in routine screening. HTLV DNA can also be amplified from the plasma obtained from plasma preparation tubes. There was no evidence of a carrier status ('Tax' only) in 100 serologically negative blood donors tested. The PCR assay developed is reliable and sensitive, capable of identifying one copy of HTLV-I. CONCLUSIONS: The HTLV PCR is a useful addition for HTLV confirmation, especially in serologically indeterminate samples and for look-back studies. HTLV PCR confirmation will provide additional useful information for donor medical staff for counselling donors.     

Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation

A 'cytokine storm' consisting of IL-1, IL-2, IL-12, IFNgamma and TNFalpha is considered important in the development of graft-versus-host disease (GvHD). These cytokines activate effector cells or damage host tissues. Cord blood transplantation has been associated with a low incidence of GvHD. We hypothesized that the low incidence of GvHD relates to the cord mononuclear cells being poor producers of pro-inflammatory cytokines. The cytokine profile (IL-1alpha/beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFNgamma and TNFalpha) of cord blood cells induced by immune stimuli was determined in heparinized whole blood. Compared to adult, cord blood CD3+ and NK cells produced less IFNgamma, less cord blood CD3+ cells and monocytes produced TNFalpha and less monocytes produced IL-1alpha/beta. Although more cord T cells produced IL-2 compared to adult T cells at 4 h, adult T cells produced more at 24 h. Cord blood had similar proportions of monocytes to adult producing IL-6, IL-10 and IL-12. Both adult and cord mononuclear cells constitutively expressed receptors for IFNgamma and TNFalpha but not IL-12. In contrast to the adult cells, cord CD3+ and NK cells did not express IL-12 receptor but did up-regulate IL-10 receptor after mitogenic stimulation. The findings of this study indicate that the cord blood cytokine-receptor network is biased towards anti-inflammatory activity compared to adult and helps to explain the decreased incidence of GVHD in cord blood transplantation.     

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

During pregnancy women can develop B- and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly onco-fetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC). We hypothesized that maternal anti-IPA immune elements cross the placenta and might confer a potent graft-versus-leukemia effect when cord blood (CB) is used in unrelated HSC transplantation. In a retrospective study of single-unit CB recipients with all grafts provided by the New York Blood Center, we show that patients with acute myeloid or lymphoblastic leukemia (n = 845) who shared one or more HLA-A, -B, or -DRB1 antigens with their CB donor's IPAs had a significant decrease in leukemic relapse posttransplantation [hazard ratio (HR) = 0.38, P < 0.001] compared with those that did not. Remarkably, relapse reduction in patients receiving CB with one HLA mismatch (HR = 0.15, P < 0.001) was not associated with an increased risk of severe acute graft-versus-host disease (HR = 1.43, P = 0.730). Our findings may explain the unexpected low relapse rate after CB transplantation, open new avenues in the study of leukemic relapse after HSC transplantation (possibly of malignancies in general), and have practical implications for CB unit selection.     

Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation

Cord blood has been used successfully for stem cell transplantation in several haematological conditions: Fanconi's anaemia, leukaemia and Wiskott-Aldrich syndrome. On account of the low incidence of GVHD observed following cord blood transplantation, it has been suggested that cord blood be used for HLA-matched, or perhaps one or two antigens mismatched, and unrelated stem cell transplantation. Based on an extensive immunophenotype-functional correlation, we determined that cord blood contains mainly immature unprimed T lymphocytes that are predominantly suppressor cells. Recent findings suggest that dysregulated production of cytokines (IL-1, IL-2, TNFα) plays a role in GVHD. We showed that T cells in cord blood express receptors for IL-2, TNFα, but no receptors for IL-1. Similarly, NK cells, one of the effector cells of GVHD, express receptors for TNFα and γIFN but do not express receptors for IL-1, nor IL-2R α-chain (CD25) although IL-2R β-chain is expressed. The potential for activation of T lymphocytes and NK cells therefore exists in the context of bone marrow transplantation. However, the high number of suppressor cells in cord blood most likely modulate the activation of lymphocytes and NK cells thereby minimizing GVHD.     

An international survey of unrelated umbilical cord blood banking

OBJECTIVES: To investigate operational and technical practices within the field of cord blood banking. MATERIALS AND METHODS: Cord blood banks world-wide were invited to participate in a survey of collection, processing and testing. The survey covered a 12-month period up to August 1998. RESULTS: Replies were received from 18 cord blood banks. Analysis of the survey responses demonstrated wide variations in many aspects of cord blood banking. CONCLUSION: There is a need for standardization to ensure adoption of best practice.     

The use of cord blood for transfusion purposes: current status

Although the use of umbilical cord blood (UCB) for transfusion purposes has been proposed decades ago, the employ is still limited. In this article we review studies evaluating UCB collection efficiency and sterility, examine processing and storage of UCB-derived red blood cells (RBC) and discuss clinical studies in which UCB was used for transfusion purposes.
Efforts to provide preterm newborns with autologous RBC derived from UCB have not been very successful. UCB collected after full-term deliveries can however easily be processed into RBC products and could be used autologous in case surgery of the neonate is indicated early after birth, or for allogeneic small volume paediatric transfusions. To harvest enough UCB volume, immediate clamping of the umbilical cord is commonly used as standard practice. Although delayed cord clamping has shown to improve the iron status in full-term infants; for small-for-gestational-age infants this has not been demonstrated. In addition, an increased need for phototherapy after delayed clamping exists. Altogether, we could find no disencouraging evidence to collect UCB, which could be processed into an easily available RBC product for paediatric transfusion in resource-restricted countries.