Browsing by Subject "Blood Banks"
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Item Open Access A History of Cord Blood Banking and Transplantation.(Stem cells translational medicine, 2017-05) Kurtzberg, JoanneItem Open Access Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.(PloS one, 2015-01) Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, GregoryBackground
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 10(8) 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.Item Open Access CD34+ cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.(Blood advances, 2019-04) Barker, Juliet N; Kempenich, Jane; Kurtzberg, Joanne; Brunstein, Claudio G; Delaney, Colleen; Milano, Filippo; Politikos, Ioannis; Shpall, Elizabeth J; Scaradavou, Andromachi; Dehn, JasonCD34+ cell dose is critical for cord blood (CB) engraftment. However, the CD34+ content of the CB inventory in the United States is unknown. We examined the CD34+ cell content of 126 341 red blood cell-depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 107 and a cryovolume of 24-55 mL. Median pre-cryopreservation TNC content was 127 × 107 (interquartile range [IQR], 108-156 × 107); CD34+ cell content was 44 × 105 (IQR, 29 to 67 × 105). The median CD34+:TNC ratio was 0.34%. TNC and CD34+ cell content correlation was weak (r = 0.24). Of 7125 units with TNCs of ≥210 × 107, only 47% had CD34+ content of ≥100 × 105 However, some units had high CD34+ content for a given TNC count. Only 4% of CB units were acceptable as single-unit grafts (TNCs, ≥2.5 × 107/kg; CD34+ cells, ≥1.5 × 105/kg) for 70-kg patients; 22% of units were adequate for 70-kg patients using lower dose criteria (TNCs, ≥1.5 × 107/kg; CD34+ cells, ≥1.0 × 105/kg) suitable for a double-unit graft. These findings highlight that units with the highest TNC dose may not have the highest CD34+ dose, units with unexpectedly high CD34+ content (a ratio of >1.0%) should be verified, and the US CB inventory of adequately sized single units for larger patients is small. They also support the ongoing use of double-unit grafts, a focus on banking high-dose units, and development of expansion technologies.Item Open Access Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States.(Emerging infectious diseases, 2016-08) Edwards, James M; Gilner, Jennifer B; Hernandez, Jose; Kurtzberg, Joanne; Heine, R PhillipsTo assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007-2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease.Item Open Access Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders.(Transfusion, 2010-09) Sun, Jessica; Allison, June; McLaughlin, Colleen; Sledge, Linda; Waters-Pick, Barbara; Wease, Stephen; Kurtzberg, JoanneBackground
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.Study design and methods
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.Results
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.Conclusion
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.Item Open Access Eighth Annual International Umbilical Cord Blood Transplantation Symposium, San Francisco, California, June 3-5, 2010.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2011-02) Laughlin, Mary; Kurtzberg, Joanne; McMannis, John; Petz, LawrenceItem Open Access Family-directed umbilical cord blood banking.(Haematologica, 2011-11) Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M; Eurocord, Netcord, World Marrow Donor Association and National Marrow Donor ProgramUmbilical 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.Item Open Access Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.(Cytotherapy, 2017-06) Scotland, Paula; Buntz, Susan; Noeldner, Pamela; Saha, Arjun; Gentry, Tracy; Kurtzberg, Joanne; Balber, Andrew EBackground aims
DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14+ monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14+ monocytes.Methods
Cell cultures were initiated with MNC or with immunoselected CD14+ monocytes isolated from the same CB unit. Cell products present in these cultures after 2 and 3 weeks were compared by three methods. First, quantitative polymerase chain reaction was used to compare expression of 77 transcripts previously shown to be differentially expressed by freshly isolated, uncultured CB CD14+ monocytes and DUOC-01. Second, accumulation of 16 soluble proteins in the culture medium was measured by Bioplex methods. Third, whole transcriptomes of the cell products were compared by microarray analysis.Results
Key transcripts in multiple pathways that promote remyelination were up-regulated in DUOC-01, and substantial secretion of proteins corresponding to many of these transcripts was detected. Cell products manufactured from MNC or from CD14+ monocytes were similar with regard to all metrics. Upregulation of gene products characteristic of DUOC-01 was largely completed within 14 days of culture.Conclusion
We demonstrate that expression of multiple gene products that promote remyelination is up-regulated during the first 2 weeks of manufacturing of DUOC-01. Measuring these mechanistically important transcripts and proteins will be useful in monitoring manufacturing, evaluating manufacturing changes, and developing mechanism-based product potency assays.Item Open Access Guidelines for the development and validation of new potency assays for the evaluation of umbilical cord blood.(Cytotherapy, 2011-08) Spellman, Stephen; Hurley, Carolyn K; Brady, Colleen; Phillips-Johnson, Lisa; Chow, Robert; Laughlin, Mary; McMannis, John; Reems, Jo-Anna; Regan, Donna; Rubinstein, Pablo; Kurtzberg, Joanne; National Marrow Donor Program Cord Blood Advisory GroupThe following commentary was developed by the National Marrow Donor Program Cord Blood Advisory Group and is intended to provide an overview of umbilical cord blood (UCB) processing, summarize the current state of potency assays used to characterize UCB, and define limitations of the assays and future needs of the cord blood banking and transplant community. The UCB banking industry is eager to participate in the development of standardized assays to uniformly characterize cellular therapy products that are manufactured in a variety of ways. This paper describes the desired qualities of these assays and how the industry proposes to co-operate with developers to bring relevant assays to market. To that end, the National Marrow Donor Program (NMDP) Cord Blood Bank Network is available to serve as a resource for UCB testing material, research and development consulting, and product/assay testing in an accredited UCB manufacturing environment.Item Open Access Hematopoietic cell transplantation with cord blood for cure of HIV infections.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2013-03) Petz, Lawrence D; Redei, Istvan; Bryson, Yvonne; Regan, Donna; Kurtzberg, Joanne; Shpall, Elizabeth; Gutman, Jonathan; Querol, Sergio; Clark, Pamela; Tonai, Richard; Santos, Sarah; Bravo, Aide; Spellman, Stephen; Gragert, Loren; Rossi, John; Li, Shirley; Li, Haitang; Senitzer, David; Zaia, John; Rosenthal, Joseph; Forman, Stephen; Chow, RobertHematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 10(7) total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 10(7) TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection.Item Open Access How transplant centers deal with the dextran shortage: recommendations for comparing alternatives.(Transfusion, 2016-11) Brady, Colleen; Armitage, Sue; Freed, Brian; Duffy, Merry; Gass, Anne; Spellman, Stephen; Kurtzberg, Joanne; Regan, DonnaBackground
In the United States, dextran 40 in 0.9% NaCl is the preferred reagent for the thawing and preparation of cord blood units for hematopoietic stem cell transplantation. The recurring nationwide shortage of this reagent could have implications that extend to the avoidance of cord blood for transplantation.Study design and methods
To address the shortage, the National Marrow Donor Program and its Cord Blood Advisory Group sought to identify available alternative reagents or manufacturers. A sample of transplant centers (TCs) were surveyed to determine their process to compare these alternatives. The TCs were then asked to share their comparability protocols for review.Results
The 12 TCs that responded to the survey studied various types of alternative reagents and manufacturers of the standard dextran 40 in 0.9% NaCl. Four TCs submitted their protocols from which a model comparability protocol was created for centers who need assistance.Conclusion
Whether comparing dextran 40 in 0.9% NaCl to that of a different manufacturer or a different reagent, the results of the comparability studies submitted by the TCs indicated equivalency. During a shortage, the model comparability study protocol can be used as a reference to establish an alternative to dextran 40 in 0.9% NaCl.Item Open Access In reply.(Transfusion, 2014-02) Page, KM; Kurtzberg, JItem Open Access Noninvasive white blood cell quantification in umbilical cord blood collection bags with quantitative oblique back-illumination microscopy.(Transfusion, 2020-03) Casteleiro Costa, Paloma; Ledwig, Patrick; Bergquist, Austin; Kurtzberg, Joanne; Robles, Francisco EBACKGROUND:Umbilical cord blood has become an important source of hematopoietic stem and progenitor cells for therapeutic applications. However, cord blood banking (CBB) grapples with issues related to economic viability, partially due to high discard rates of cord blood units (CBUs) that lack sufficient total nucleated cells for storage or therapeutic use. Currently, there are no methods available to assess the likelihood of CBUs meeting storage criteria noninvasively at the collection site, which would improve CBB efficiency and economic viability. MATERIALS AND METHODS:To overcome this limitation, we apply a novel label-free optical imaging method, called quantitative oblique back-illumination microscopy (qOBM), which yields tomographic phase and absorption contrast to image blood inside collection bags. An automated segmentation algorithm was developed to count white blood cells and red blood cells (RBCs) and assess hematocrit. Fifteen CBUs were measured. RESULTS:qOBM clearly differentiates between RBCs and nucleated cells. The cell-counting analysis shows an average error of 13% compared to hematology analysis, with a near-perfect, one-to-one relationship (slope = 0.94) and strong correlation coefficient (r = 0.86). Preliminary results to assess hematocrit also show excellent agreement with expected values. Acquisition times to image a statistically significant number of cells per CBU were approximately 1 minute. CONCLUSION:qOBM exhibits robust performance for quantifying blood inside collection bags. Because the approach is automated and fast, it can potentially quantify CBUs within minutes of collection, without breaching the CBUs' sterile environment. qOBM can reduce costs in CBB by avoiding processing expenses of CBUs that ultimately do not meet storage criteria.Item Open Access Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality.(Transfusion, 2014-02) Page, Kristin M; Mendizabal, Adam; Betz-Stablein, Brigid; Wease, Stephen; Shoulars, Kevin; Gentry, Tracy; Prasad, Vinod K; Sun, Jessica; Carter, Shelly; Balber, Andrew E; Kurtzberg, JoanneBackground
Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs.Study design and methods
Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics.Results
High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 10(9)) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL).Conclusions
We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory.Item Open Access The Cord Blood Apgar: a novel scoring system to optimize selection of banked cord blood grafts for transplantation (CME).(Transfusion, 2012-02) Page, Kristin M; Zhang, Lijun; Mendizabal, Adam; Wease, Stephen; Carter, Shelly; Shoulars, Kevin; Gentry, Tracy; Balber, Andrew E; Kurtzberg, JoanneBackground
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.Study design and methods
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.Results
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).Conclusion
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.Item Open Access Umbilical cord blood donation: public or private?(Bone marrow transplantation, 2015-10) Ballen, KK; Verter, F; Kurtzberg, JUmbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ~35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ~4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ~30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.Item Open Access Umbilical cord blood: a guide for primary care physicians.(American family physician, 2011-09) Martin, Paul L; Kurtzberg, Joanne; Hesse, BrettUmbilical cord blood stem cell transplants are used to treat a variety of oncologic, genetic, hematologic, and immunodeficiency disorders. Physicians have an important role in educating, counseling, and offering umbilical cord blood donation and storage options to patients. Parents may donate their infant's cord blood to a public bank, pay to store it in a private bank, or have it discarded. The federal government and many state governments have passed laws and issued regulations regarding umbilical cord blood, and some states require physicians to discuss cord blood options with pregnant women. Five prominent medical organizations have published recommendations about cord blood donation and storage. Current guidelines recommend donation of umbilical cord blood to public banks when possible, or storage through the Related Donor Cord Blood Program when a sibling has a disease that may require a stem cell transplant. Experts do not currently recommend private banking for unidentified possible future use. Step-by-step guidance and electronic resources are available to physicians whose patients are considering saving or donating their infant's umbilical cord blood.