Recruiting unrelated donors for the National Marrow Donor Program

Medical advances have made bone marrow transplantation the treatment of choice for certain hematologic diseases. For those patients eligible for a marrow transplant only about 30 percent find an HLA-compatible match within their families. Studies indicate that unrelated volunteers are willing to donate their marrow. The National Marrow Donor Program was formed in 1986 as a result of a federal contract. This group is a network of donor centers, transplant centers, and collection centers. The Connecticut Red Cross Blood Services is one of approximately 70 donor centers. Recruitment methods vary with each donor center, depending on the resources available. The Connecticut Red Cross Blood Services has recruited more than 1,000 volunteers for entry into the National Marrow Donor Program.     

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks

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.     

High quality cord blood banking is feasible with delayed clamping practices. The eight-year experience and current status of the national Swedish Cord Blood Bank

The National Swedish Cord Blood Bank (NS-CBB) is altruistic and publicly funded. Herein we describe the status of the bank and the impact of delayed versus early clamping on cell number and volume. Cord Blood Units (CBUs) were collected at two University Hospitals in Sweden. Collected volume and nucleated cell content (TNC) were investigated in 146 consecutive Cord Blood (CB) collections sampled during the first quarter of 2012 and in 162 consecutive CB collections done in the first quarter of 2013, before and after clamping practices were changed from immediate to late (60 s) clamping. NS-CBB now holds close to 5000 units whereof 30 % are from non-Caucasian or mixed origins. Delayed clamping had no major effect on collection efficiency. The volume collected was slightly reduced (mean difference, 8.1 ml; 95 % CI, 1.3–15.0 ml; p = 0.02), while cell recovery was not (p = 0.1). The proportion of CBUs that met initial total TNC banking criteria was 60 % using a TNC threshold of 12.5 × 10⁸, and 47 % using a threshold of 15 × 10⁸ for the early clamping group and 52 and 37 % in the late clamping group. Following implementation of delayed clamping practices at NS-CBB; close to 40 % of the collections in the late clamping group still met the high TNC banking threshold and were eligible for banking, implicating that that cord blood banking is feasible with delayed clamping practices.     

Histocompatibility and immunogenetics in cord blood transplantation

This review of the immunogenetics of cord blood transplantation attempts to highlight the connections between classical studies and conclusions of the tissue transplantation field as a scholarly endeavor, exemplified by the work of Professor Hoecker, with the motivations and some recent and key results of clinical cord blood transplantation. The authors review the evolution of understanding of transplantation biology and find that the results of the application of cord blood stem cells to Transplantation Medicine are consistent with the careful experiments of the pioneers in the field, from the results of tumor and normal tissue transplants, histocompatibility immunogenetics, to cell and molecular biology. Recent results of the National Cord Blood Program of the New York Blood Center describe the functioning in cord blood transplantation of factors, well known in transplantation immunogenetics, like the Fl anti-parent effect and the tolerance-like status of donors produced by non-inherited maternal HLA antigens. Consideration of these factors in donor selection strategies can improve the prognosis of transplantation by characterizing "permissibility" in HLA-incompatible transplantation thereby increasing the probability of survival and reducing the likelihood of leukemic relapse.     

Equity, Utility, and the Marketplace: Emerging Ethical Issues of Umbilical Cord Blood Banking in Australia

Over the past decade, umbilical cord blood (UCB) has routinely been used as a source of haematopoietic stem cells for allogeneic stem cell transplants in the treatment of a range of malignant and non-malignant conditions affecting children and adults. UCB banks are a necessary part of the UCB transplant program, but their establishment has raised a number of important scientific, ethical and political issues. This paper examines the scientific and clinical evidence that has provided the basis for the establishment of UCB banks. We also discuss the major ethical issues that UCB banks raise, including ownership of cord blood, processes for obtaining consent for its collection and storage, and confidentiality. Finally, we review other concerns about commercial non-altruistic banking, including concerns about social justice, equity of access and equity of care.     

脐带血移植的应用进展及脐带血库建设

脐带血(umbilical cord blood)作为公认的造血干细胞重要来源之一,已经被广泛地用于治疗儿童和成人的良恶性血液系统疾病以及中枢神经系统疾病、实体瘤、缺血性下肢血管病和组织再生等。相对于骨髓移植和外周血来源的造血干细胞移植,脐带血移植(UCBT)在细胞收集使用、干细胞增殖能力以及移植物抗宿主反应等方面都具有明显的优势。目前的数据显示,因为HLA配型等原因而无法进行骨髓移植的患者应该尽早进行UCBT。此外,UCBT的增多促进了脐带血库的快速建设。本文针对UCBT和脐带血库的最新进展进行了综述。     

“Good Mothering” or “Good Citizenship”? Conflicting Values in Choosing Whether to Donate or Store Umbilical Cord Blood

Umbilical cord blood banking is one of many biomedical innovations that confront pregnant women with new choices about what they should do to secure their own and their child’s best interests. Many mothers can now choose to donate their baby’s umbilical cord blood (UCB) to a public cord blood bank or pay to store it in a private cord blood bank. Donation to a public bank is widely regarded as an altruistic act of civic responsibility. Paying to store UCB may be regarded as a “unique opportunity” to provide “insurance” for the child’s future. This paper reports findings from a survey of Australian women that investigated the decision to either donate or store UCB. We conclude that mothers are faced with competing discourses that force them to choose between being a “good mother” and fulfilling their role as a “good citizen.” We discuss this finding with reference to the concept of value pluralism.     

Banking and transplantation of umbilical cord blood in Guangzhou, China

BACKGROUND: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSC) for transplantation of patients with hematologic malignancies or hereditary diseases. METHODS: We developed a provincial UCB bank in Guangzhou, China, using good manufacturing practices and standard operating procedures to address donor eligibility, collection, characterization, processing, storage and release from quarantine. The banking activities were analyzed. RESULTS: From June 1998 to May 2005, 8623 UCB units of Han ethnic origin were collected; 4147 (48.1%) were stored, while 4476 (51.9%) were discarded as a result of pre-determined exclusion criteria. A median volume of 95.5 mL (range 60-227.7) and 1.2 x 10(9) (0.8-9.3) nucleated cells were collected. The cell viability was 97.8% (90-100%). The CD34+ cell count of 3691 (89.0%) UCB units was 5.2 x 10(6) (0.3-131.6) and clonogenic assays of 4036 (97.3%) UCB units demonstrated 9.8 x 10(5) (0.04-135.8) CFU-GM, 0.3 x 10(5) (0.0-18.6) CFU-GEMM and 8.8 x 10(5) (0.0-74.2) BFU-E. A total of 0.4% (15/3863) UCB derived from babies known to have health problems at age 6 months was discarded. Up to May 2005, 151 units were issued for transplantation to 127 patients [90 (70.9%) children and 37 (29.1%) adults]. The infused nucleated cells in unrelated single-unit recipients were 3.4 x 10(7)/kg (1.7-14.9) for adults (n=19) and 5.7 x 10(7)/kg (2.0-20.5) for children (n=71), respectively. The numbers of days for the engraftment of neutrophils among 65 children and 22 adults were 17 (7-41) and 20 (10-42), respectively. DISCUSSION: Data of this study show that stringent procedures and comprehensive policies are requisite for pursuing the banking and release of quality UCB for successful transplantation.     

Results of unrelated umbilical cord blood hematopoietic stem cell transplantation

The number of umbilical cord blood transplants is increasing worldwide. The purpose of Eurocord is to evaluate the results and to compare the outcome of umbilical cord blood transplants with allogeneic bone marrow transplants. Data have been reported to Eurocord by multiple transplant centers. Close links have been established with the cord blood banks through Netcord. Bone marrow transplant data have been provided by transplant centers and also through the European Group for Blood and Marrow Transplantation (EBMT) and International Bone Marrow Transplant Registries (IBMTR). Eurocord has analyzed the outcome of unrelated umbilical cord blood transplants from 121 transplant centers and 29 countries. The results showed that survival with unrelated mismatched umbilical cord blood transplants was comparable to that with unrelated bone marrow transplants. Engraftment with cord blood was delayed, resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-vs.-host disease was reduced with cord blood grafts even in human leukocyte antigen (HLA)-mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to the rate of relapse after bone marrow transplant. The overall event-free survival with umbilical cord blood transplantation was not statistically different when compared to bone marrow transplants. This large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.     

Insights into the biology of cord blood stem/progenitor cells

OBJECTIVES: To review information on cord blood banking and transplantation with respect to the author's studies, and in context of this field of investigation. RESULTS: Cord blood transplantation has been successfully used to treat a number of malignant and non-malignant disorders. However, this technique is still associated with limited numbers of cells for transplantation, and with delayed engraftment of neutrophils and platelets. The field of cord blood transplantation will benefit from enhanced and mechanistically based information on haematopoietic stem cell function and potential means to enhance its effectiveness are reviewed. This includes notions concerning possibility of retrieving more cells from the placenta and cord blood, to expand haematopoietic stem cells ex vivo and to increase efficiency of homing and engraftment of these cells. Also discussed are cryopreservation and long-term storage of cord blood haematopoietic and progenitor cells, and new laboratory findings and animal studies for non-haematopoietic uses of cord blood.     

Analysis and cryopreservation of hematopoietic stem and progenitor cells from umbilical cord blood

BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic stem and progenitor cells (HSC/HPC) for the reconstitution of the hematopoietic system after clinical transplantation. Cryopreservation of these cells is critical for UCB banking and transplantation as well as for research applications by providing readily available specimens. The objective of this study was to optimize cryopreservation conditions for CD34+ HSC/HPC from UCB. METHODS: Cryopreservation of CD34+ HSC/HPC from UCB after mononuclear cell (MNC) preparation was tested in a research-scale setup. Experimental variations were concentration of the cryoprotectant, the protein additive and cell concentration. In addition, protocols involving slow, serial addition and removal of DMSO were compared with standard protocols (fast addition and removal of DMSO) in order to avoid osmotic stress for the cryopreserved cells. Viability and recoveries of MNC, CD34+ cells and total colony-forming units (CFU) were calculated as read-outs. In addition, sterility testing of the collected UCB units before further processing was performed. RESULTS: The optimal conditions for cryopreservation of CD34+ HPC in MNC preparations were 10% DMSO and 2% human albumin at high cell concentrations (5 x 10(7) MNC/mL) with fast addition and removal of DMSO. After cryopreservation using a computer-controlled freezer, high viabilities (89%) and recoveries for CD34+ cells (89%) as well as for CFU (88%) were observed. Microbial contamination of the collected UCB samples was reduced to a rate of 6.4%. DISCUSSION: Optimized cryopreservation conditions were developed for UCB MNC in respect of the composition of the cryosolution. In addition, our results showed that fast addition of DMSO is essential for improved cryopreservation and post-thaw quality assessment results, whereas the speed of DMSO removal after thawing has little influence on the recoveries of CD34+ cells and CFU.     

Banking strategies for improving the hematopoietic stem cell content of umbilical cord blood units for transplantation

Umbilical cord blood (UCB) has become an alternative source of hematopoietic progenitors (HSC) for transplantation. Although most CB transplants have been performed in children, unrelated donor-cord blood transplants in adults have been growing steadily in recent years. HSC content of CB units influence significantly the transplantation outcome, as shown by many clinical studies. UCB banks are fundamental to support this increasing clinical activity and one of their main goals must be to store good quality units. Strategies for increasing HSC content of UCB units are reviewed and also its influence on transplantation outcome. Our bank selected the UCB units for cryopreservation on the basis of their total nucleated cells (TNC) and CD34(+) cells content. We also reviewed the results of our UCB bank program.     

Whole blood and component use in resource poor settings

Data on blood collection, testing and component preparation has improved worldwide; however, there is limited information on blood utilization from the developing countries. Blood requirement in the Southeast Asia region is 15 million units against a collection of 9.3 million. There is huge diversity in the management of blood transfusion services, the voluntary blood collection (range 40–100%) and proportion of blood separated into components (10–95%). The major indications for transfusion are for emergency obstetric care, surgery, pediatric and trauma patients. The prevalence of thalassemia in this region is high and in India alone 2 million units of packed red cells are required for transfusion to these patients. The Blood Safety Program in India has developed as a component of the National Aids Control Program and has lead to infrastructure development, blood component separation facilities and formulation of a National Blood Policy. In order to facilitate emergency obstetric care nearer home, blood storage centers are being established at primary health care centers. Emerging infectious threats like dengue hemorrhagic fever necessitate platelet transfusion therapy. A few centers in India issue NAT screened blood. It is envisaged to establish a nationally co-ordinated transfusion service for cost-effective quality blood/components for appropriate clinical use.     

脐带血干细胞移植治疗非恶性血液病进展

异基因造血干细胞移植（allo-HSCT）是治愈多种非恶性病的有效方法。脐带血干细胞（UCB）具有免疫原性低、人类白细胞抗原不合耐受性好、移植物抗宿主反应发生率低以及获取相对快捷等特点,可作为非恶性血液疾病患者allo-HSCT的来源。本文简要综述脐血干细胞移植在原发性免疫缺陷病、遗传性骨髓衰竭、遗传代谢病以及自身免疫性疾病等非恶性血液疾病的治疗效果。     

Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation

BackgroundUmbilical cord blood (UCB) is an alternative graft source for hematopoietic stem cell transplantation and has been shown to give results comparable to transplantation with other stem cell sources. Donor lymphocyte infusion (DLI) is an effective treatment for relapsed malignancies after hematopoietic stem cell transplantation. However, DLI is not available after UCB transplantation.MethodsIn this study, in vitro–cultured T cells from the UCB graft were explored as an alternative to conventional DLI. The main aim was to study the safety of the cultured UCB T cells used as DLI because such cell preparations have not been used in this context previously. We also assessed potential benefits of the treatment.ResultsThe cultured UCB T cells (UCB DLI) were given to 4 patients with mixed chimerism (n = 2), minimal residual disease (n = 1) and graft failure (n = 1). No adverse reactions were seen at transfusion. Three of the patients did not show any signs of graft-versus-host disease (GVHD) after UCB DLI, but GVHD could not be excluded in the last patient. In the patient with minimal residual disease treated with UCB DLI, the malignant cell clone was detectable shortly before infusion but undetectable at treatment and for 3 months after infusion. In 1 patient with mixed chimerism, the percentage of recipient cells decreased in temporal association with UCB DLI treatment.ConclusionsWe saw no certain adverse effects of treatment with UCB DLI. Events that could indicate possible benefits were seen but with no certain causal association with the treatment.     

Hybrid UCB banks in China – public storage as ethical biocapital

In China, under the heading of “private-for-public” banking, hybrid UCB banking has been politically supported by the government and is based on regulation developed since the 1990s. Although hybrid UCB banking was regarded as an “ethical” alternative to private UCB banking due to its accessibility to “the people”, this study, based on archival research and interviews with bankers, medical professionals, scientists and pregnant women contends that the practice of this ideal needs to be closely scrutinized. Analysing UCB bank networks in China in terms of “public biovalue” and “ethical biocapital”, we illustrate, first, how the synergy of public and private storage of UCB in hybrid models benefit private storage, and how transparency and oversight may increase donation and the uptake of UCB. Second, we describe the problems associated with this hybrid model. Finally, we show how the biovalue of public storage is used as ethical biocapital to buttress UCB networks.     

The US Navy Tissue Bank: 50 Years on the Cutting Edge

The US Navy Tissue Bank was established in 1949 by Dr. George Hyatt, an orthopaedic surgeon at the Naval Medical Center in Bethesda, Maryland. The Navy program was the first of its kind in the world and established many of the standards that are followed today. During the 1950s, the identification of appropriate donor criteria for tissue donation, the development of procurement and processing methods, the establishment of a graph registry and documentation and the clinical evaluation of a variety of tissues were pioneered at this facility. Cryopreservation, freeze-drying, irradiation sterilization of tissue, as well as immunological principles of tissue transplantation, were developed during the 50 years of research and development by Navy scientists. Organ preservation, cadaveric bone marrow recovery and immunosuppressive protocols were also developed at the Navy Tissue Bank. The Navy was also instrumental in the establishment of the National Marrow Donor Program and the American Association of Tissue Banks in the US.Although the Navy Tissue Bank has ceased activity after 50 years of excellence, it should be recognized as the first standard setter for the world community of tissue banks.     

脐带血IGF-1浓度和DNA甲基化与巨大儿发生的相关性研究

为探究脐带血中胰岛素样生长因子Ⅰ（insulin like growth factor 1, IGF-1）的浓度和基因甲基化变化与巨大儿发生的关系,选择152名正常妊娠足月分娩的产妇和新生儿为对象,其中68名巨大儿,84名正常出生体重儿.收集产妇及新生儿的基本信息和脐带血样品. 采用双抗体夹心ABC ELISA法测定脐带血IGF-1蛋白浓度,基质辅助激光解吸附电离飞行时间质谱分析技术（MALDI-TOF）测定脐带血IGF-1基因启动子区CpG位点的甲基化水平. 结果显示,脐带血IGF-1启动子区CpG位点均呈低甲基化状态. 以所有研究对象出生体重的上四分位数（4 260 g）为拐点,出生体重＜4 260g组的脐带血IGF 1浓度显著高于出生体重≥4 260 g组（P=0.015）,且与出生体重呈正相关关系（r=0.242,P=0.011）. 表明在出生体重＜4 260 g范围内,脐带血IGF-1浓度的增加贡献于出生体重的增长. 但当胎儿过大时,存在负反馈调节机制,使脐带血IGF-1浓度降低,以限制胎儿过度增长. 这些结果提示,脐带血IGF-1浓度与出生体重呈双向性关联,两者均与处于低甲基化状态的脐带血IGF-1的甲基化程度无关.     

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

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

Potential for access to embryonic-like cells from human umbilical cord blood

Abstract.  All too often media attention clouds the reality that there are many types of stem cell. The embryos, bone marrow and umbilical cord blood (UCB) are the three most used sources. However, despite what it would appear, embryonic stem cells have not been the first to yield life-saving cures at present. Faster routes to clinical intervention have been using adult stem cells that can be sourced from bone marrow and from cord blood, and that are readily accessible and are more ethically acceptable to the general public. Both these non-embryonic sources have been able to provide sufficient numbers of cells to allow development of clinical translational protocols. Bone marrow-derived cells have been used successfully in myocardial infarct therapy where relining by endothelial tissue has allowed limited reperfusion to damaged cardiac tissue. UCB have also demonstrated significant success for around 20 years in haematotransplantation. With a global human population in excess of 6 billion, births thus UCB, remain the largest untouched source of stem cells available every year. UCB also provide a distinct advantage over other adult stem cells due to the length of the telomere and also due protected immunological status of the developing neonatal environment. The total mutation load in the UCB populations is clearly likely to be significant less than in adult tissues.