No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Industrial Economics of Cord Blood Banks
Abstract
Cord blood banks represent a major step in the advent of tissue economies in the twenty-first century. Cord blood units (CBUs) are becoming biological assets imported and exported worldwide, and valued according to a pricing logic based on their level of quality and compatibility. The controversy over public and private banking is based on a confusion between access to storage and access to a graft. In this chapter, we analyze the financial difficulties that allogeneic banks face and their dependency on the limited public funding available, which results in hindered growth. The economic analysis of commercial banks remains unexplored in the literature because of a lack of available data on their management practices and their financial performance. In 2013, out of 310 commercial banks identified in 86 countries, six banks were listed on European, Asian, and American stock exchanges. We found from their annual reports that, over the 2009–2012 period, their compound annual revenue growth rate was 9.18% despite a global economic crisis. Their average gross profit margin was 67.3% with only 1.1% of their revenue invested in R&D. In terms of cost–utility, in other words, the medical service provided for the price paid, we found that the total inventory of four leading commercial banks was 1.58 times larger than that of the combined inventories of all 137 public banks worldwide, yet their number of released CBUs—i.e., their therapeutic usefulness for patients—was 269 times lower. Given this medico-economic impasse, commercial banks probably need to rethink their business model, move away from therapeutic storage and develop into scientific banking.
... In 2014, France decided to shut down half of its operating public banks just two years after launching a national development plan to support public banking. Without new banking strategies, many more public banks are likely to close in the coming years [6].The economic vulnerability of public banks requires that selective criteria be established to help decide which CBUs are eligible for cryopreservation. Composite scoring systems have been proposed to measure the biological quality of collected units before storage and after thawing to help transplant physicians obtain the best possible grafts for their patients [7]. ...
Background:
Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies.
Methods:
Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit.
Results:
When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that using a pre-freezing level of 18 x 108 TNC would be the most cost-effective strategy for a public bank.
Conclusion:
Our study shows that a swift transition from strategy A to C can play a vital role in preventing public cord blood banks worldwide from collapsing.
Over the last 2 decades, cord blood (CB) has become an important source of blood stem cells. Clinical experience has shown that CB is a viable source for blood stem cells in the field of unrelated hematopoietic blood stem cell transplantation.
Studies of CB units (CBUs) stored and ordered from the US (National Marrow Donor Program (NMDP) and Swiss (Swiss Blood Stem Cells (SBSQ)) CB registries were conducted to assess whether these CBUs met the needs of transplantation patients, as evidenced by units being selected for transplantation. These data were compared to international banking and selection data (Bone Marrow Donors Worldwide (BMDW), World Marrow Donor Association (WMDA)). Further analysis was conducted on whether current CB banking practices were economically viable given the units being selected from the registries for transplant. It should be mentioned that our analysis focused on usage, deliberately omitting any information about clinical outcomes of CB transplantation.
A disproportionate number of units with high total nucleated cell (TNC) counts are selected, compared to the distribution of units by TNC available. Therefore, the decision to use a low threshold for banking purposes cannot be supported by economic analysis and may limit the economic viability of future public CB banking.
We suggest significantly raising the TNC level used to determine a bankable unit. A level of 125 × 10(7) TNCs, maybe even 150 × 10(7) TNCs, might be a viable banking threshold. This would improve the return on inventory investments while meeting transplantation needs based on current selection criteria.
Umbilical cord blood banking efforts have increased dramatically in the past two decades in response to increasing demand for alternative sources of blood stem cells to support patients requiring hematopoietic stem cell transplantation. Transplant centres have accumulated increasing expertise in their understanding of umbilical cord blood characteristics that are associated with improved outcome following transplantation. These characteristics and factors can assist transplant centres in selecting cord blood units from the worldwide inventory of banked units. Umbilical cord blood banks, therefore, need to remain agile in adjusting the inventory of the banks to address shifts or changes in the needs of transplant centres. Public umbilical cord blood banks face the challenge of building inventory while managing limited resources and are faced with decisions regarding which units can be stored and which units that have been collected should be discarded or used for other endeavours such as research. To this end, we sought to review parameters influencing the decision to bank a collected cord blood unit. In this paper, we will address parameters associated with graft potency and address other factors that guide the decision to bank collected units.
Collection and banking of umbilical cord blood can provide a virtually unlimited source of ethnically diverse stem cell donors. It can be used in place of bone marrow or peripheral blood stem cells for hematologic transplants as well as in a variety of regenerative medicine applications. In this study, we review the latest developments in cord blood banking. We have banked over 300,000 collections at our facility, which were processed by either Ficoll or AXP methodologies. An average 95-99% processing efficiency was obtained. Processed samples can be frozen in either cryovials or bags and banked in the vapor phase of a liquid nitrogen dewar for prolonged periods of time. In conclusion, it is possible to simply and reproducibly harvest, process, and bank cord blood samples using currently available technology.
Umbilical cord blood is a source of haematopoietic progenitor cells, which are used to treat a range of malignant, genetic, metabolic and immune disorders. Until recently, cord blood was either collected through donations to publicly funded cord blood banks for use in allogeneic transplantation, or stored in commercial cord blood banks for use in autologous transplantation. The line between public and private cord blood banking is being blurred by the emergence of "hybrid" models that combine aspects of both the public and private systems. The authors describe these hybrid models and argue that their emergence is explained by both market forces and public sector policy They propose that the future of the sector will depend heavily on several key developments that will differentially affect public, private and hybrid banking models.
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.
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 4-6×10(8) 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 8-10×10(8). In the third period, from January 2009 to June 2010, an automated Sepax-BioArchive procedure was used and the accepted initial TNC count was >10×10(8). Within each period the units were categorised according to various ranges of cryopreserved TNC counts in the units: A, >16.2×10(8); B1, from 12.5-16.1×10(8); B2, from 5.2-12.4×10(8); and C, <5.1×10(8).
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 14×10(8) (range, 4.6×10(8) to 36.5×10(8)). The cost of the processed UCB in 2009 was 720.41 euros per unit.
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.
Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.
Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.
Umbilical cord blood is a potential vast source of primitive hematopoietic stem and progenitor cells available for clinical application to reconstitute the hematopoietic system and/or restore immunological function in affected individuals requiring treatment. Cord blood can be used as an alternative source for bone marrow transplantation and its use is developing into a new field of treatment for pediatric and adult patients presenting with hematological disorders, immunological defects and specific genetic diseases.
More than 25,000 allogeneic cord blood transplantations have been performed worldwide since the first cord blood transplantation in 1988. There are two banking options for storing umbilical cord blood [private (family) and public]. Cord blood stored in private banks are used for either autologous or allogeneic transplants for the infant donor or related family members but private cord blood banks are not searchable or available to the public. More than 780,000 cord blood units are stored in over 130 private cord blood banks, worldwide, and over 400,000 units in more than 100 quality controlled public cord blood banks.
Researchers continue to evaluate the usefulness of cord blood cells in treating human diseases or disorders for purposes other than hematological disorders including heart disease, strokes, brain or spinal cord injuries and cancer. This review summarizes the status of umbilical cord blood banking, its history and current and potential use in the treatment of human disease.
A new biobanking method is proposed, wherein samples and associated data would be deposited anonymously and labelled using a PIN code that is produced on the basis of personal biological characteristics, such as single nucleotide polymorphisms. The code would be the 'Bio-PIN' to uniquely distinguish the sample depositors, plus their samples and data. This method could help to diminish several long-discussed ethical, legal and societal problems in biobanking regarding privacy, informed consent, autonomy, data security and public trust.
Allogeneic transplant access can be severely limited for patients of racial and ethnic minorities without suitable sibling donors. Whether cord blood (CB) transplantation can extend transplant access because of the reduced stringency of required HLA-match is not proven. We prospectively evaluated availability of unrelated donors (URD) and CB according to patient ancestry in 553 patients without suitable sibling donors. URDs had priority if adequate donors were available. Otherwise ≥4/6 HLA-matched CB grafts were chosen utilizing double units to augment graft dose. Patients had highly diverse ancestries including 35% non-Europeans. In 525 patients undergoing combined searches, 10/10 HLA-matched URDs were identified in 53% of those with European ancestry, but only 21% of patients with non-European origins (P < .001). However, the majority of both groups had 5-6/6 CB units. The 269 URD transplant recipients were predominantly European, with non-European patients accounting for only 23%. By contrast, 56% of CB transplant recipients had non-European ancestries (P < .001). Of 26 patients without any suitable stem cell source, 73% had non-European ancestries (P < .001). Their median weight was significantly higher than CB transplant recipients (P <.001), partially accounting for their lack of a CB graft. Availability of CB significantly extends allo-transplant access, especially in non-European patients, and has the greatest potential to provide a suitable stem cell source regardless of race or ethnicity. Minority patients in need of allografts, but without suitable matched sibling donors, should be referred for combined URD and CB searches to optimize transplant access.
The success of solid organ transplantation in the treatment of end-stage organ failure has fuelled a growing demand for transplantable organs worldwide that has far outstripped the supply from brain dead heart-beating donors. In Singapore, this has resulted in long waiting lists of patients for transplantable organs, especially kidneys. The Human Organ Transplant Act, introduced in 1987, is an opt-out scheme that presumes consent to removal of certain organs for transplantation upon death. Despite this legislation, the number of deceased organ donors in Singapore, at 7 to 9 per million population per year, remains low compared to many other developed countries. In this paper, we reviewed the clinical challenges and ethical dilemmas encountered in managing and identifying potential donors in the neurological intensive care unit (ICU) of a major general hospital in Singapore. The large variance in donor actualisation rates among local restructured hospitals, at 0% to 56.6% (median 8.8%), suggests that considerable room still exists for improvement. To address this, local hospitals need to review their processes and adopt changes and best practices that will ensure earlier identification of potential donors, avoid undue delays in diagnosing brain death, and provide optimal care of multi-organ donors to reduce donor loss from medical failures.
Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking.
We e-mailed a cross-sectional survey to pediatric hematopoietic cell transplantation physicians in the United States and Canada; 93 of 152 potentially eligible physicians (93 of 130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed by using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking.
Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36 of 40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with 1 healthy sibling when both parents were of northern European descent; 11% would recommend banking when parents were of different minority ethnicities.
Few transplants have been performed by using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric hematopoietic cell transplantation physicians endorse private cord blood banking in the absence of an identified recipient, even for mixed-ethnicity children for whom finding a suitably matched unrelated donor may be difficult.
When people have access to information sources such as newspaper weather forecasts, drug-package inserts, and mutual-fund brochures, all of which provide convenient descriptions of risky prospects, they can make decisions from description. When people must decide whether to back up their computer's hard drive, cross a busy street, or go out on a date, however, they typically do not have any summary description of the possible outcomes or their likelihoods. For such decisions, people can call only on their own encounters with such prospects, making decisions from experience. Decisions from experience and decisions from description can lead to dramatically different choice behavior. In the case of decisions from description, people make choices as if they overweight the probability of rare events, as described by prospect theory. We found that in the case of decisions from experience, in contrast, people make choices as if they underweight the probability of rare events, and we explored the impact of two possible causes of this underweighting--reliance on relatively small samples of information and overweighting of recently sampled information. We conclude with a call for two different theories of risky choice.
New strategies are emerging in cord blood banking where focusing on birth clinics caring for a high number of mothers belonging to ethnic minorities could offer new possibilities for allotransplantation both for patients of European origin and for patients from ethnic minorities or mixed ancestries.
Marseilles Cord Blood Bank works with one university birth clinic caring for a culturally and sociologically diverse population. Stringent French legal restrictions apply to recording the geographic origin of parents. To circumvent this limitation and evaluate the contribution of newly banked cord blood units (CBUs) to increasing HLA diversity, we applied an algorithm that allows for the determination of parents' putative haplotypes and thus grossly deduce information on their ancestry. Generic resolution HLA-A, HLA-B, and allelic resolution HLA-DRB1 genotyping for 328 CBUs and 2691 unrelated donors (UDs) between January 2009 and May 2012 were performed. Enrichment from international CBU registry with nonreferenced generic HLA-A, HLA-B, and allelic HLA-DRB1 phenotypes was compared between CBUs identified with one or two non-European haplotypes and CBUs identified with two European haplotypes.
Marseilles CBUs display an increased proportion of HLA antigens frequently expressed in African populations compared to UDs. Whereas 93% of 199 CBUs identified with one or two non-European haplotypes enrich international CBU registry, this result is reduced to 42% for the 129 CBUs identified with two European haplotypes.
This study supports a new method to assess HLA diversity. However, such an increased of HLA diversity raises questions about frequencies of CBUs released and clinical relevance from their uses.
Despite the well-known therapeutic utility of cells derived from umbilical cord, the public health code still qualifies it as a simple operating waste what requires the adoption of an adapted legal status. This situation enabled the appearance of private commercial banks storing the blood of umbilical cord for autologous or intra-family purposes in spite of the absence of any authorization. This raises numerous questions of legal, ethical and social order. According to the French general principles in public health, only banks storing transplants for non-commercial allogeneic purposes are currently authorized in France. However, a bill would come to modify this situation by possibly allowing commercial banks. The Council of State, the Senate and the Government consider however that ethical requirements and public utility have to prevail in this domain. Recently, these principles have been resumed by a second bill. The next revision of the Bioethical law should revive the debate.
As new medical technologies are developed, more and more human tissues—such as skin, bones, heart valves, embryos, and stem cell lines—are stored and distributed for therapeutic and research purposes. The accelerating circulation of human tissue fragments raises profound social and ethical concerns related to who donates or sells bodily tissue, who receives it, and who profits—or does not—from the transaction. Catherine Waldby and Robert Mitchell survey the rapidly expanding economies of exchange in human tissue, explaining the complex questions raised and suggesting likely developments. Comparing contemporary tissue economies in the United Kingdom and United States, they explore and complicate the distinction that has dominated practice and policy for several decades: the distinction between tissue as a gift to be exchanged in a transaction separate from the commercial market and tissue as a commodity to be traded for profit.
Waldby and Mitchell pull together a prodigious amount of research—involving policy reports and scientific papers, operating manuals, legal decisions, interviews, journalism, and Congressional testimony—to offer a series of case studies based on particular forms of tissue exchange. They examine the effect of threats of contamination—from HIV and other pathogens—on blood banks’ understandings of the gift/commodity relationship; the growth of autologous economies, in which individuals bank their tissues for their own use; the creation of the United Kingdom’s Stem Cell bank, which facilitates the donation of embryos for stem cell development; and the legal and financial repercussions of designating some tissues “hospital waste.” They also consider the impact of different models of biotechnology patents on tissue economies and the relationship between experimental therapies to regenerate damaged or degenerated tissues and calls for a legal, for-profit market in organs. Ultimately, Waldby and Mitchell conclude that scientific technologies, the globalization of tissue exchange, and recent anthropological, sociological, and legal thinking have blurred any strict line separating donations from the incursion of market values into tissue economies
Cord blood units are now routinely used as an alternative source of haematopoietic stem cells from unrelated donors for allogeneic transplantation. In France, cord blood units are collected in a network of more than 70 maternity hospitals in relationship with 11 public cord blood banks part of the Réseau Français de Sang Placentaire. Unrelated cord blood unit donation is an altruistic act, anonymous and free. Donors are selected on medical criteria. Then, only cord blood unit containing more than 100×10(7) total nucleated cells and more than 1.8×10(6) CD34+ cells are cryopreserved according to Réseau Français de Sang Placentaire recommendations. Cord blood units qualification will be completed by viral and functional testings and the clinical outcome of the newborn child 6weeks after the collection. Since the last 5years, cord blood banking growing in France in order to enhance the French registry of volunteer donors by increasing both the number and diversity of the donors listed and make available cord blood banking for transplantation.
Cord blood is increasingly used as a hematopoietic progenitor cell source for bone marrow transplantation.
Development of cord blood banks for altruistic use was essential to open the possibility of opting for cord blood therapy for patients lacking a conventional donor.
Cord blood has major advantages as a resource for donor provision. First, it universalizes the access to the therapy since it allows transplantation of partially matched HLA grafts, benefiting ethnicities less represented in the adult volunteer list. Second, it is an off-the-shelf, ready-to-use source that avoids donor risk and attrition. Third, potentially it has better long term sustainability if a defined optimal size of the inventory is achieved; currently, more than 80% of patients, regardless ethnicity, can find a reliable cord blood donor with the current worldwide inventory.
In order that this approach may definitely solve the problem of an equitable access to the therapy, two aspects need to be improved: the quality of CB inventories (driven by a higher stringency of regulatory requirements), and clinical outcomes, particularly understanding the appropriate donor selection and focusing research on accelerating the speed of engraftment and immune reconstitution.
Background:
This study explores pregnant women's awareness of cord blood stem cells and their attitude regarding banking options in France, Germany, Italy, Spain, and the UK.
Study design and methods:
Questionnaires were distributed in six maternities. This anonymous and self-completed questionnaire included 29 multiple-choice questions based on: 1) sociodemographic factors, 2) awareness and access to information about cord blood banking, 3) banking option preferences, and 4) donating cord blood units (CBUs) to research.
Results:
A total of 79% of pregnant women had little awareness of cord blood banking (n = 1620). A total of 58% of women had heard of the therapeutic benefits of cord blood, of which 21% received information from midwives and obstetricians. A total of 89% of respondents would opt to store CBUs. Among them, 76% would choose to donate CBUs to a public bank to benefit any patient in need of a cord blood transplant. Twelve percent would choose a mixed bank, and 12%, a private bank. A total of 92% would donate their child's CBU to research when it is not suitable for transplantation.
Conclusion:
The study reveals a strong preference for public banking in all five countries, based on converging values such as solidarity. Attitudes of pregnant women are not an obstacle to the rapid expansion of allogeneic banking in these EU countries. Banking choices do not appear to be correlated with household income. The extent of commercial marketing of cord blood banks in mass media highlights the importance for obstetric providers to play a central role in raising women's awareness early during their pregnancy with evidence-based medical information about banking options.
The increasing momentum of stem cell research continues, with the better characterization of induced pluripotent stem (iPS) cells, the conversion of differentiated cells into different cell types and the use of pluripotent stem cells to generate whole tissues, among other advances. Here, six experts in the field of stem cell research compare different stem cell models and highlight the importance of pursuing complementary experimental approaches for a better understanding of pluripotency and differentiation and an informed approach to medical applications.
Umbilical cord blood (UCB) has become the second most common source of stem cells for cell therapy. The recent boom in stem cell research and public fascination with promises of stem cell-based therapies, fueled by the media, have led researchers to explore the potential of UCB stem cells in therapy for non-hematological disorders.
ClinicalTrials.gov database searched with key words 'cord blood stem cells' on December 28, 2011.
As a rich source of the most primitive hematopoietic stem cells, UCB has a strong regenerative potential in stem cell-based-therapy for hematological disorders.
Potential of UCB stem cells in therapy for non-hematological disorders.
Increasing number of clinical trials with UCB stem cell-based therapy for a variety of diseases.
A need for standardization of criteria for selection of UCB units for stem cell-based therapy, outcome measures and long-term follow-up.
Hematopoietic cell transplantation (HCT) has become a standard practice to treat a number of malignant and nonmalignant hematologic diseases. Bone marrow, mobilized peripheral blood, and umbilical cord blood can all serve as primary sources of cells for HCT. The number of cord blood units currently stored is large, although it represents only a fraction of potential collections. With much of the collection being sequestered in private banks for possible autologous use, there is a reason to expect that public banks may not be able to provide for the demand in coming years as use of cord blood for treatment of patients with diseases such as leukemia and lymphoma continues to increase. We suggest that a possible solution to encourage private banks to share their valuable units is to apply recent methodologies to generate induced pluripotent stem cells from cord cells and to optimize techniques to generate hematopoietic lineages from them. This strategy would allow us to take advantage of the units already collected under appropriate regulatory guidelines, to access a pristine cell that can be converted to a pluripotent cell at a much higher efficiency and in a shorter time period than other cells. The ability to potentially replenish a used cord unit with new cells, as well as extend the potential utility of cord blood for additional therapeutic applications, should allow banks to develop an appropriate business model for both private and public cord blood banks to flourish.
Engraftment failure and delays, likely due to diminished cord blood unit (CBU) potency, remain major barriers to the overall success of unrelated umbilical cord blood transplantation (UCBT). To address this problem, we developed and retrospectively validated a novel scoring system, the Cord Blood Apgar (CBA), which is predictive of engraftment after UCBT.
In a single-center retrospective study, utilizing a database of 435 consecutive single cord myeloablative UCBTs performed between January 1, 2000, to December 31, 2008, precryopreservation and postthaw graft variables (total nucleated cell, CD34+, colony-forming units, mononuclear cell content, and volume) were initially correlated with neutrophil engraftment. Subsequently, based on the magnitude of hazard ratios (HRs) in univariate analysis, a weighted scoring system to predict CBU potency was developed using a randomly selected training data set and internally validated on the remaining data set.
The CBA assigns transplanted CBUs three scores: a precryopreservation score (PCS), a postthaw score (PTS), and a composite score (CS), which incorporates the PCS and PTS values. CBA-PCS scores, which could be used for initial unit selection, were predictive of neutrophil (CBA-PCS ≥ 7.75 vs. <7.75, HR 3.5; p < 0.0001) engraftment. Likewise, CBA-PTS and CS scores were strongly predictive of Day 42 neutrophil engraftment (CBA-PTS ≥ 9.5 vs. <9.5, HR 3.16, p < 0.0001; CBA-CS ≥ 17.75 vs. <17.75, HR 4.01, p < 0.0001).
The CBA is strongly predictive of engraftment after UCBT and shows promise for optimizing screening of CBU donors for transplantation. In the future, a segment could be assayed for the PTS score providing data to apply the CS for final CBU selection.
Nature - the world's best science and medicine on your desktop
Genomic biobanks—repositories of human DNA and/or associated data, collected and maintained for biomedical research—present
ethical challenges different from those traditionally associated with medical research. Historically, when researchers obtained
and used tissue samples, it was for defined purposes and the nature of the research was disclosed to contributors, who were
asked to consent to the specific research project. With genomic biobanks, in contrast, the entity holding the samples may
not be involved in the research, and future uses of the samples may be unknown. Although traditional research promised confidentiality
and/or anonymity to participants, advances in DNA technology may render these safeguards meaningless (1–3). As a consequence, many ethicists argue that traditional informed consent may be illusory if not impossible (1, 4) and that different approaches to the ethics of genetic sample collections are needed (5, 6).
On 31 May 2010, 14 072 567 bone marrow/apheresis donors registered in 44 countries and 426 501 cord blood units banked in 26 countries for public use were available to treat candidates to haemopoietic stem cell transplant lacking a family related compatible donor. Despite these impressive numbers, additional efforts are required to ensure that all patients, including those from ethnic minorities, can promptly find a suitable donor. Governments, clinicians, scientists, patients and stakeholders should share the responsibility to develop haemopoietic stem cell donation and cord blood banking models able to fully match all patient needs. In this regard, current scientific evidence and prevalent opinions among expert clinicians support solidaristic cord blood donation for public use against the alternative option of commercial autologous cord blood storage.
This paper examines an emerging bioeconomy centred on the international banking and trade in cord blood. Since the late 1980s cord blood has been used in an expanding range of treatments and as an alternative to the use of bone marrow stem cells. This is particularly the case in treating ethnic minority populations who have historically been under-represented in bone marrow registries. The paper explores the mobilisation and commercialisation of an increasingly important bioeconomic resource with cord blood units trading internationally at high prices. This is a market mediated through a sophisticated global network of immunologically typed and matched bodily matter in which immunity has become a form of 'corporeal currency'. Based on recent international figures we reflect upon the balance of trade between imports and exports across the world's cord blood bioeconomy. Theoretically, this case is, we suggest, an extension of what Roberto Esposito (2008) has termed an 'immunitary paradigm' in which immunity has become the basis for new forms of bioeconomic flow, circulation and exchange. Esposito (2008). Bios: Biopolitics and Philosophy. Minnesota, MN: University of Minnesota Press.
The controversy surrounding private banking of umbilical cord blood units (CBU), as a safeguard against future malignancy or other life-threatening conditions, raises many questions in pediatric clinical practice. Recent favorable experiences with autologous transplantation for severe aplastic anemia using privately stored CBU, suggested a possible utility. While private banking is difficult to justify statistically or empirically, there may exist rare cases where autologous transplant of stored umbilical CBU could be beneficial. The reality of privately banked CBU and the possibility for future discovery of additional indications for autologous cord blood transplant, motivated us to re-examine our attitudes towards private cord blood banking.
Once considered biological waste, umbilical cord blood (UCB) has become an accepted source of haematopoietic stem cells (HSCs). With initial success in the pediatric setting, UCB transplantation continues to gain favor in the adult patient population. Novel approaches to UCB transplantation include use of two units and a variety of graft manipulations. Additional uses for UCB are currently being explored and include applications in regenerative medicine and immunotherapy. © 2010 The Author(s). Vox Sanguinis
SUMMARY: BACKGROUND AND METHODS: As a source of hematopoietic stem cells, cord blood (CB) is an alternative to bone marrow or peripheral blood stem cells (PBSC). The Mannheim Cord Blood Bank has currently stored about 1,750 allogeneic CB units. Here we report our experiences and discuss future perspectives of CB banking. We analyzed CB units for nucleated cell (NC), mononucleated cell (MNC) and CD34+ cell count, volume, colony-forming units (CFU-GM) as well as ethnic background of the donor. Transplanted CB units were analyzed for patient and transplant characteristics and compared to stored CB units. RESULTS: Only 25% of all collected CB units met storage criteria. Main reasons for exclusion were: i) insufficient volume (57.7%), ii) delayed arrival at the processing site (19.2%) and iii) little cell count (7.2%). Up to now 36 CB units have been released for transplantation mainly to children (62%). Transplant indications were hematological diseases, immune deficiencies and metabolic diseases. Transplanted CB units showed significantly higher cell counts compared to stored units (NC: 12.5 vs. 7.2 x 10(8), MNC: 4.7 vs. 2.9 x 10(8), CD34+ cells: 3.3 vs. 1.8 x 10(6), mean; p < 0.001 each) and were found more often in ethnic minority groups (36 vs. 20%; p = 0.04). CONCLUSIONS: Even though cell count and volume are key parameters for the eligibility of CB units, our data indicate that the ethnic background of the donor also plays a major role. Collection and processing of CB should be optimized in order to gain maximum volume and cell counts.
A pilot study was conducted to determine the safety and feasibility of intravenous administration of autologous umbilical cord blood (CB) in young children with acquired neurologic disorders. Most CB units (CBUs) were electively stored in private CB banks. Unlike public banks, which utilize specific criteria and thresholds for banking, private banks generally store all collected CBUs.
CBUs of eligible patients containing more than 1 × 10⁷ cells/kg were shipped to Duke from the banks of origin after confirming identity by HLA typing. On the day of infusion, CBUs were thawed and washed in dextran-albumin and infused intravenously. Patients were medicated with acetaminophen, diphenhydramine, and methylprednisolone before transfusion. Data regarding patients, infusions, and CBUs were collected retrospectively. Characteristics of CBUs were compared to existing data from CBUs publicly banked at the Carolinas Cord Blood Bank.
From March 2004 to December 2009, 184 children received 198 CB infusions. Three patients had infusion reactions, all responsive to medical therapy and stopping the infusion. Median precryopreservation volume (60 mL vs. 89 mL, p < 0.0001), total nucleated cell count (4.7 × 10⁸ vs. 10.8 × 10⁸, p < 0.0001), and CD34 count (1.8 × 10⁶ vs. 3.0 × 10⁶, p < 0.0001) were significantly lower than publicly stored CBUs. Postthaw sterility cultures were positive in 7.6% of infused CBUs.
IV infusion of autologous CB is safe and feasible in young children with neurologic injuries. Quality parameters of privately banked CBUs are inferior to those stored in public banks. If efficacy of autologous CB is established clinically, the quality of autologous units should be held to the same standards as those stored in public banks.
Paradoxically, France is one of the leading exporters of cord blood units worldwide, but ranks only 17th in terms of cord blood units per inhabitant, and imports 64% of cord blood grafts to meet national transplantation demands. With three operational banks in 2008, the French allogeneic cord blood network is now entering an important phase of development with the creation of seven new banks collecting from local clusters of maternities. Although the French network of public banks is demonstrating a strong commitment to reorganise and scale up its activities, the revision of France's bioethics law in 2010 has sparked a debate concerning the legalisation of commercial autologous banking. The paper discusses key elements for a comprehensive national plan that would strengthen the allogeneic banking network through which France could meet its national medical needs and guarantee equal access to healthcare.
To investigate the cost-effectiveness of private umbilical cord blood banking.
A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood.
Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective.
Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member.
III.
Document S1. Supplemental Experimental Procedures and 11 FiguresxDownload (.88 MB ) Document S1. Supplemental Experimental Procedures and 11 FiguresMovie S1. Rhythmically Beating Cardiomyocytes from CBiPS2F-1Specific in vitro differentiation of CBiPS2F-1 into beating cardiomyocytes.xDownload (.75 MB ) Movie S1. Rhythmically Beating Cardiomyocytes from CBiPS2F-1Specific in vitro differentiation of CBiPS2F-1 into beating cardiomyocytes.
Using processed consensus investment research, AVOS Life Sciences has analysed the performance of the top 14 pharmaceutical companies as a group for the period 2008–2013E (Supplementary information S1 (box)). The analysis focuses on the major Rx drug portfolio (MRDP; the collection of branded drugs, each of which is predicted to achieve at least US$500 million in annual sales) of each company as a measure of its overall performance.
To determine risk factors of umbilical cord blood transplantation (UCBT) for patients with lymphoid malignancies.
We evaluated 104 adult patients (median age, 41 years) who underwent unrelated donor UCBT for lymphoid malignancies. UCB grafts were two-antigen human leukocyte antigen-mismatched in 68%, and were composed of one (n = 78) or two (n = 26) units. Diagnoses were non-Hodgkin's lymphoma (NHL, n = 61), Hodgkin's lymphoma (HL, n = 29), and chronic lymphocytic leukemia (CLL, n = 14), with 87% having advanced disease and 60% having experienced failure with a prior autologous transplant. Sixty-four percent of patients received a reduced-intensity conditioning regimen and 46% low-dose total-body irradiation (TBI). Median follow-up was 18 months.
Cumulative incidence of neutrophil engraftment was 84% by day 60, with greater engraftment in recipients of higher CD34(+) kg/cell dose (P = .0004). CI of non-relapse-related mortality (NRM) was 28% at 1 year, with a lower risk in patients treated with low-dose total-body irradiation (TBI; P = .03). Cumulative incidence of relapse or progression was 31% at 1 year, with a lower risk in recipients of double-unit UCBT (P = .03). The probability of progression-free survival (PFS) was 40% at 1 year, with improved survival in those with chemosensitive disease (49% v 34%; P = .03), who received conditioning regimens containing low-dose TBI (60% v 23%; P = .001), and higher nucleated cell dose (49% v 21%; P = .009).
UCBT is a viable treatment for adults with advanced lymphoid malignancies. Chemosensitive disease, use of low-dose TBI, and higher cell dose were factors associated with significantly better outcome.
The recent Perspective by Sullivan (Sullivan, M. J. Banking on cord blood stem cells. Nature Rev. Cancer 8, 555–563 (2008)
To develop consensus-based recommendations guiding the conduct of cost-effectiveness analysis (CEA) to improve the comparability and quality of studies. The recommendations apply to analyses intended to inform the allocation of health care resources across a broad range of conditions and interventions. This article, first in a 3-part series, discusses how this goal affects the conduct and use of analyses. The remaining articles will outline methodological and reporting recommendations, respectively.
The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS).
The panel reviewed the theoretical foundations of CEA, current practices, and alternative procedures for measuring and assigning values to resource use and health outcomes.
The panel met 11 times during 2 1/2 years with PHS staff and methodologists from federal agencies. Working groups brought issues and preliminary recommendations to the full panel for discussion. Draft recommendations were circulated to outside experts and the federal agencies prior to finalization.
The panel's recommendations define a "reference case" cost-effectiveness analysis, a standard set of methods to serve as a point of comparison across studies. The reference case analysis is conducted from the societal perspective and accounts for benefits, harms, and costs to all parties. Although CEA does not reflect every element of importance in health care decisions, the information it provides is critical to informing decisions about the allocation of health care resources.
A large number of institutions have started programs banking umbilical cord blood (UCB) for allogeneic unrelated-donor and related-donor transplantation. However, limited information is available on the financial issues surrounding these activities.
The aim of this study was to determine the fee per UCB unit released for transplantation that would allow cost recovery after 10 years. Three organizational models were considered suitable to provide units for five UCB transplants per 1 million population per year, a figure that would translate into an annual need for 280 units in Italy. Models A, B, and C included, respectively, seven networked banks, each with an inventory of 1,500 units; two networked banks, each with an inventory of 5,000 units; and one bank with an inventory of 10,000 units. It was estimated that it would take 3 years to develop the cryopreserved inventory and that approximately 3 percent of the inventory could be released and replaced each year during the 7-year interval between the fourth and tenth years of activity. The data on the costs of labor, reagents and diagnostics, disposables, depreciation and maintenance, laboratory tests, and overhead, as well as the operational data used in the analysis were collected at the Milano Cord Blood Bank in 1996.
Fees of US $15,061, $12,666, and $11,602 per unit released during the fourth through the tenth years of activity allow full cost recovery (principle and interest) under Models A, B, and C, respectively.
Although UCB procurement costs compare favorably with those of other hematopoietic cell sources, these results and the current fee of US $15,300 used in some institutions show that UCB is an expensive resource. Therefore, judicious planning of banking programs with high quality standards is necessary to prevent economic losses. The advantages of lower fees associated with the centralized banking approach of Model C should be balanced with the more flexible collection offered by Model A.
Pregnant patients have the option of storing their infant's cord blood with a private/commercial company for possible future use by the child or other family members. Some patients also have the option to donate the cord blood to a public bank for anyone to use. We evaluated patient understanding about cord blood banking in a cohort of patients with access to both options.
Anonymous questionnaires were collected from 325 pregnant patients seen in our Antepartum Testing Unit.
Compared to those donating to a public bank, women planning on storing with a private/commercial company were less likely to believe that a suitable donor could be found from a public cord blood bank. Women had a strikingly poor understanding regarding the current uses for cord blood therapy. When asked whether cord blood has been used successfully to treat Alzheimer's disease, Parkinson's disease, and spinal cord injury only 28%, 24%, and 24%, respectively, correctly knew that it had not.
Obstetricians should assume that pregnant women are poorly informed about cord blood banking. The decision making process should be conducted with the goal of ensuring every pregnant woman the opportunity to make a well informed decision about cord blood banking.