Comparison of Graft Acquisition and Early Direct Charges of Haploidentical Related Donor Transplantation versus Umbilical Cord Blood Transplantation.

Alternative donor allogeneic hematopoietic cell transplants (HCTs), such as double umbilical cord blood transplants (dUCBT) and haploidentical related donor transplants (haplo-HCT), have been shown to be safe and effective in adult patients who do not have an HLA-identical sibling or unrelated donor available. Most transplant centers have committed to 1 of the 2 alternative donor sources, even with a lack of published randomized data directly comparing outcomes and comparative data on the cost-effectiveness of dUCBT versus haplo-HCT. We conducted a retrospective study to evaluate and compare the early costs and charges of haplo-HCT and dUCBT in the first 100 days at 2 US transplant centers. Forty-nine recipients of haplo-HCT (at 1 center) and 37 with dUCBT (at another center) were included in the analysis. We compared graft acquisition, inpatient/outpatient, and total charges in the first 100 days. The results of the analysis showed a significantly lower cost of graft acquisition and lower total charges (for 100-day HCT survivors) in favor of haplo-HCT. Importantly, to control for the obvious shortcomings of comparing costs at 2 different transplant centers, adjustments were made based on the current (2018) local wage index and inflation rate. In the absence of further guidance from a prospective study, the cost analysis in this study suggests that haplo-HCT may result in early cost savings over dUCBT and may be preferred by transplant centers and for patients with more limited resources.

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.

Cord Blood Banking for Potential Future Transplantation.

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking.

From waste to (fool's) gold: promissory and profit values of cord blood.

According to biomedical discourse, cord blood has been transformed from 'waste' to 'clinical gold' because of its potential for use in treatments. Private cord blood banks deploy clinical discourse to market their services to prospective parents, encouraging them to pay to bank cord blood as a form of 'biological insurance' to ensure their child's future health. Social scientists have examined new forms of (bio)value produced in biological materials emergent with contemporary biotechnologies. This paper contributes to this literature by examining the social and technical production of value in cord blood units collected for private banking. Value, in this paper is defined as a socio-cultural concept in which an object is made meaningful, or valuable, through its relations with social actors and within specific regimes of value. I draw on in-depth interviews with women who banked cord blood and key informants in private banks in Canada, to analyze how social actors produced cord blood as a valuable biological object. I show that a cord blood unit holds promissory value for women who bank and profit value for private banks and that these values are folded into each other and the biological material itself. Analyzing how specific cord blood units are made valuable provides insight into the multiple and possibly competing values of biological materials and the tensions that may arise between social actors and forms of knowledge during the valuing process.

Is there a best graft source of transplantation in acute myeloid leukemia?

Only 30% of patients in the US who require an allogeneic hematopoietic cell transplant will have a fully HLA matched sibling donor. The National Marrow Donor Program/Be the Match has grown to over 25 million unrelated donors. However, a fully matched unrelated donor may not be available for many patients, particularly for patients of diverse racial and ethnic backgrounds. Over the last 10 years, considerable progress has been made in alternative donor transplant with improvements in outcomes for umbilical cord blood (UCB), haploidentical (haplo) related donor, and mismatched unrelated donor (MMUD) for patients with acute myeloid leukemia. Retrospective studies indicate comparable survival for these three graft sources. In this chapter, we review the latest results for patients receiving alternative donor transplants, and discuss strategies for choosing the optimal donor for each individual patient.

Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer.

BACKGROUND: BMT CTN 1101 is a Phase III randomized controlled trial evaluating the comparative effectiveness of double unrelated umbilical cord blood (dUCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) donor cell sources for blood or bone marrow transplantation (BMT) in patients with hematologic malignancies. Herein, we present the rationale, design and methods of the first cost-effectiveness analysis to be conducted alongside a BMT trial. METHODS: Consenting patients will provide health insurance information to allow calculation of direct medical costs from reimbursement records, and will provide out-of-pocket costs, time costs and health-related quality of life measures through an online survey. These outcomes will inform a cost-effectiveness analysis comparing dUCB and haplo-BM donor cell sources from patient, payer and societal perspectives. CONCLUSION: Novel approaches may significantly change the cost, outcomes or availability of BMT. The results of this analysis will be the first to provide a comprehensive evaluation of the comparative effectiveness of these approaches from multiple perspectives.

Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France.

Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years.

Background and future considerations for human cord blood hematopoietic cell transplantation, including economic concerns.

Cord blood (CB) has been used since 1988 as a source of hematopoietic stem cells (HSCs) and progenitor cells for hematopoietic cell transplantation (HCT) to treat patients with malignant and nonmalignant disorders. CB has both advantages and disadvantages when compared with other tissue sources of HSCs such as bone marrow and mobilized peripheral blood, which are also being used in the setting of HCT. This short review focuses on some historical information, as well as current efforts that are being assessed to enhance the efficacy of CB HCT. Also of importance are the costs of CB, and the feasibility and economics of using such to be identified, and newly confirmed improvements worldwide for the greatest number of patients. In this context, simple methods that would not necessarily entail the need for selected cell-processing facilities to ex vivo expand or improve the CB graft's functional activity may be of interest, with one such possibility being the use of an orally active inhibitor of the enzyme dipeptidylpeptidase 4, alone or in combination with other new and innovative approaches for improving HSC engraftment and in vivo repopulating capability of CB.

Contradictions of value: between use and exchange in cord blood bioeconomy.

Umbilical cord blood (CB) has become established as an increasingly viable clinical alternative to bone marrow in the treatment of leukaemia leading to the construction of a global network of CB banks promoted through a moral ethos of gift. Additionally, some banks offer the opportunity to retain stem cells privately. CB is discursively presented as clinical 'waste', a 'by-product' of birthing. In this way CB units are made available to a global exchange-based bioeconomy. Crucially, CB collection has developed in parallel with several necessary obstetric practices, especially the immediate clamping of the cord following delivery, essential to high volume collection. However, this article strongly suggests the promotional basis of CB banking (such as by gift, waste or donation) is in tension with the growing preference of new parents to delay cord clamping. Based on focus groups with expectant parents, the promotion of CB banking can in fact be seen to feed into critical reflection on the value of CB for newborn infants, potentially reinvigorating a tradition of delayed umbilical cord clamping. Theoretically, these contradictory systems of valuing are conceptualised through recent literature on bioeconomy and Marx's writings on the contrasting tensions between use and exchange value.

Umbilical cord blood banks. Ethical aspects. Public versus private banks.

The creation of umbilical cord blood (UCB) banks raises interesting medical, social, economic and ethical issues. This paper reviews the ethical problems specifically. In this respect, it evaluates: a) whether there are advantages to the use of UCB compared to bone marrow, b) whether or not it is ethical to create UCB banks, c) whether their creation is ethically acceptable in terms of their clinical usefulness or d) the use made of them for therapeutic purposes, and finally e) whether their creation is ethically justified from a cost/profitability point of view. We focus primarily on evaluating the ethical controversy between public and private banks, particularly on whether it is ethical to bank autologous blood in private UCB banks, on the basis of its limited possibilities for use by the cord blood donor. We can conclude that, from an ethical point of view, autologous blood banks have limited acceptance among specialised researchers, scientific societies and other public institutions. Therefore, we believe that it is ethically more acceptable to support the creation of public UCB banks for medical and social reasons and, above all, based on the principle of justice and human solidarity. Nevertheless, there is no definitive ethical argument why a couple, according to their autonomy and freedom, cannot bank their child's UCB in a private bank. An equally acceptable solution could be the creation of mixed banks, such as that proposed by the Virgin Health Bank or like the Spanish system where autologous samples can be stored in public banks but with the proviso that if at any time the stored sample is required by any person other than the donor, it would have to be given to them.

Real-world costs of autologous and allogeneic stem cell transplantations for haematological diseases: a multicentre study.

Haematopoietic stem cell transplantation (SCT) is an expensive lifesaving procedure, which is increasingly performed in patients with haematological diseases. Developments in the protocol for SCT have resulted in cost estimates that require updating. We aimed to calculate actual costs for SCT and to identify major cost drivers by means of a daily practice cost study. We randomly selected 191 patients, treated at three university hospitals, who underwent an autologous (auto) SCT or allogeneic (allo) SCT in 2007, 2008 or 2009. Allo-SCT included sibling donors, matched unrelated donors (MUD) and umbilical cord blood (UCB). Resource use was collected from the hospital registration systems and medical files. The total costs included selection and harvesting of stem cells, transplantation and 1-year follow-up. The average costs per patient were 45,670 € for auto-SCT and 101,919 € for sibling allo-SCT. The costs of transplantations from unrelated donors were much higher: 171,478 € for allo-SCT-MUD and 254,689 € for allo-SCT-UCB. Hospital inpatient days together with laboratory and other activities were the main cost drivers across all types of SCT. Besides, donor search costs were a large cost component in allo-SCT-sib (18 %) and allo-SCT-MUD (12 %). Real-world costs were above routine reimbursement and appropriate financing is necessary to guarantee the continuation of SCT. The costs calculated in this study provide reliable up-to-date input for cost-effectiveness studies and budget revision.

Cord blood banking activities at a university hospital in northeast Mexico: an 8-year experience.

BACKGROUND: Umbilical cord blood (UCB) represents an alternative source of stem cells for transplantation for the treatment of hematologic malignancies and genetic disorders. There is scarce information detailing cord blood bank (CBB) collection and transplantation activities from developing countries. We documented our experience at a public university hospital in northeast Mexico. STUDY DESIGN AND METHODS: We carried out a retrospective and descriptive analysis of our CBB activity during an 8-year period from May 2002 to September 2010. Collection, processing, and cryopreservation of CB were carried out following standard operating procedures. The minimum volume and total nucleated cell (TNC) content for cryopreservation were 80 mL and 8.0 × 10(8) , respectively. RESULTS: A total of 1256 UCB units were collected; 428 (34%) were banked and 828 (66%) were discarded. The main reason for exclusion was biologic: low volume and/or low number of TNC accounted for 84% of the total discarded units. Cryopreserved cord blood units (CBUs) had a median volume of 113.8 mL (range, 80-213.2 mL) and 13.0 × 10(8) (range, 8 × 10(8) -36.6 × 10(8) ) TNCs. Cell viability was 99.3% (88-100%). The median CD34+ cell content was 4.0 × 10(6) (0.46 × 10(6) -19.38 × 10(6) ). Sixteen units have been released for transplantation, leading to a utilization rate of 3.7%. CONCLUSION: CBB demands considerable human and financial resources; it is then essential for centers at developing countries to share their experience, results, and databases to increase the probability of finding matching units for their patients. Efforts to create and maintain CBBs allow to offer this therapeutic option at an affordable cost.

Costs and cost-effectiveness of hematopoietic cell transplantation.

Interest is growing in economic and comparative effectiveness analyses, with increasing emphasis on optimizing healthcare resources and costs. Limited information is available on the economic aspects of hematopoietic cell transplantation (HCT). We review contemporary literature on the costs and cost-effectiveness of HCT in the United States and worldwide. Published studies confirm the high costs associated with HCT, although the reported costs are highly variable, related to the differing methodologies used across studies. We examine the challenges in reviewing costs and cost-effectiveness across studies specific to HCT and highlight factors identified as associated with higher costs of HCT. We also discuss opportunities for future research in this area.

Family-directed umbilical cord blood banking.

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.

Stem cell biobanks.

Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.