Cord Blood Units Research Articles

Sterility of cord blood units: Evaluation of the collection, preparation and conservation process with a view to establishing a bank of stem cells from cord blood at the Biological Resources Center of the Institut Pasteur de Côte d’Ivoire (2024)

Introduction: Cord blood stem cells are used as an alternative to bone marrow and peripheral blood cell transplantation. For this purpose, cord blood banks have been established worldwide for the collection and cryopreservation of cord blood units. These banks must implement rigorous protocols to ensure the microbiological safety of grafts. The aim of this study is to evaluate the process of selecting mothers and collecting and processing these samples developed for this purpose. Methodology: Pregnant women were enrolled in the study on the basis of selection criteria. Maternal blood and cord blood samples were collected by the in utero method. Serological analyses of maternal blood for the detection of vertically transmitted infections and microbiological examinations of cord blood units were carried out. Results: 31 women out of 46 (68.4%) were enrolled. All had negative serology for the targeted pathogens. Similarly, microbiology revealed no microbial contamination of the cord blood units. Conclusion: This work demonstrates that the procedures for selecting mothers and processing implementations are effective in ensuring the microbiological safety of cord blood units and could be suggested in the context of banking cord blood stem cells at the Institut Pasteur de Côte d’Ivoire.

Development of a quantitative prediction algorithm for human cord blood-derived CD34+ hematopoietic stem-progenitor cells using parametric and non-parametric machine learning models

The transplantation of CD34+ hematopoietic stem-progenitor cells (HSPCs) derived from cord blood serves as the standard treatment for selected hematological, oncological, metabolic, and immunodeficiency disorders, of which the dose is pivotal to the clinical outcome. Based on numerous maternal and neonatal parameters, we evaluated the predictive power of mathematical pipelines to the proportion of CD34+ cells in the final cryopreserved cord blood product adopting both parametric and non-parametric algorithms. Twenty-four predictor variables associated with the cord blood processing of 802 processed cord blood units randomly sampled in 2020–2022 were retrieved and analyzed. Prediction models were developed by adopting the parametric (multivariate linear regression) and non-parametric (random forest and back propagation neural network) statistical models to investigate the data patterns for determining the single outcome (i.e., the proportion of CD34+ cells). The multivariate linear regression model produced the lowest root-mean-square deviation (0.0982). However, the model created by the back propagation neural network produced the highest median absolute deviation (0.0689) and predictive power (56.99%) in comparison to the random forest and multivariate linear regression. The predictive model depending on a combination of continuous and discrete maternal with neonatal parameters associated with cord blood processing can predict the CD34+ dose in the final product for clinical utilization. The back propagation neural network algorithm produces a model with the highest predictive power which can be widely applied to assisting cell banks for optimal cord blood unit selection to ensure the highest chance of transplantation success.

A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients

Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics. To date, the only curative treatment is allogeneic (allo) hematopoietic cell transplantation (HCT), but high incidences of graft versus host disease (GVHD), non-relapse mortality (NRM) and disease progression remain important obstacles. Cord blood (CB) transplantation has been associated with low rates of relapse and chronic (c) GVHD, but its use has declined because of high incidences of infections, severe acute GVHD and high NRM. In other hematologic malignancies, UM171-expanded CB transplants have led to improved outcomes, allowing for the selection of smaller, better HLA-matched units. We aimed to investigate the safety and feasibility of single UM171-expanded single CB unit transplantation in frontline tandem auto/allo HCT for HR/ultra-HR MM patients. Newly diagnosed MM patients ≤ 65 years with an ISS stage II/III and del17p, t4,14, t14,16, t14,20, del1p or +1q, R-ISS 3, ≥ 2 cytogenetic abnormalities, or plasma cell leukemia without a sibling donor and availability of a 5-7/8 matched CB graft with ≥ 0.5 x 105 CD34+/kg and ≥ 1.5 x 107 TNCs/kg were eligible to this phase I/II prospective study (ClinicalTrials.gov NCT03441958). After induction and autologous HCT, patients received a reduced intensity conditioning regimen and were infused with 7-day UM171-expanded CD34+ cells, along with the lymphocytes contained in the CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety, kinetics of engraftment, incidences and maximum grades of acute and cGVHD at 1 and 2 years, assessment of measurable residual disease (MRD) and quality of life (QoL). Between 05/2018 and 11/2021, 20 patients were enrolled. One patient had an unsuccessful CB expansion with UM171, leaving 19 patients with a median age of 56 years. Median CD34+ cell dose infused after expansion was 4.62 x 106/kg (range: 0.79-5.76). Median times to achieve absolute neutrophil counts of 0.1 and 0.5 x 109/L were D+6 and D+10.5; median time to reach ≥ 20 x 109/L platelets was D+36. Full donor chimerism was achieved in all cell lineages by D+120 in recipients of reduced intensity conditioning. Cumulative incidences of grade II-IV, grade III-IV acute GVHD and moderate/severe cGVHD at 12 months were 68.4% (95% CI: 46-90), 5.3% (95% CI: 0-16%), and 10.5% (95% CI: 0-25%), respectively. With a median follow-up of 2.9 years (range: 0.46-5.3), cumulative incidences of relapse, PFS, OS and NRM at 3 years were 36.8% (95% CI: 14-59), 47.4% (95% CI: 29-76), 68.4% (95% CI: 50-93) and 15.8% (95%CI: 0-33), respectively. Median time to complete immunosuppression discontinuation was D+238. No unexpected adverse events were observed. Only one of 7 patients alive at 2 years with negative MRD at transplant has relapsed. Non-relapsing patients had a QoL after transplant similar to the general population. UM171-expanded CB transplant in HR/ultra-HR myeloma patients is feasible and allows the use of single CB units with a low risk of cGVHD. Patients with negative pre-transplant MRD might benefit most from a UM171-expanded CB transplant.

Insights into the Structural Modification of Selenium-Doped Derivatives with Narrowband Emissions: A Theory Study.

The research on boron/nitrogen (B/N)-based multiresonance thermally activated delayed fluorescence (MR-TADF) emitters has been a prominent topic due to their narrowband emission and high luminous efficiency. However, devices derived from the common types of narrowband TADF materials often experience an efficiency roll-off, which could be ascribed to their relatively slow triplet-singlet exciton interconversion. Since inserting the heavy Se atom into the B/N scheme has been a proven strategy to address the abovementioned issues, herein, extensive density functional theory (DFT) and time-dependent DFT (TD-DFT) simulations have been employed to explore the effects of the structural modification on a series of structurally modified selenium-doped derivatives. Furthermore, the two-layered ONIOM (QM/MM) model has been employed to study the pressure effects on the crystal structure and photophysical properties of the pristine CzBSe. The theoretical results found that the introduced tert-butyl units in Cz-BSeN could result in a shorter charge transfer distance and smaller reorganization energy than the parent CzBSe. In contrast to directly incorporating the o-carborane (Cb) unit to CzBSe, incorporating the bridged phenyl units is important in order to achieve narrowband emissions and high luminous efficiency. The lowest three triplet excited states of CzBSe, Cz-BSeN and PhCb-BSeN all contribute to their triplet-singlet exciton conversions, resulting in a high utilization of triplet excitons. The pressure has an evident influence on the photophysical properties of the aggregated CzBSe and is favored for obtaining narrowband emissions. Our work is promised to provide a feasible strategy for designing selenium-doped derivatives with narrowband emissions and rapid triplet-singlet exciton interconversions.

Highly effective strategy for isolation of mononuclear cells from frozen cord blood

Background aimsCord blood mononuclear cells (CBMCs) comprise a variety of single-nucleated cells found in the cord blood, mainly consisting of monocytes and lymphocytes. They also include a smaller proportion of other cell types, such as hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). CBMCs are vital for acquiring HSPCs, MSCs, and other immune cells, like natural killer cells. These cells are essential for supporting subsequent research and clinical applications. Although automated equipment for CBMC enrichment has shown promise, the high cost of these machines and the expense of disposable consumables limit their routine use. Furthermore, limited information is available on manual strategies for isolating CBMCs from cryopreserved cord blood. Therefore, we aimed to optimize the dilution buffer and refine the isolation procedure for CBMCs. MethodsWe enhanced the CBMC recovery rate from cryopreserved cord blood using an optimized dilution buffer and a modified isolation procedure. ResultsWe achieved average recovery rates of 42.4 % and 54.3 % for CBMCs and CD34+ cells, respectively. Notably, all reagents used in the isolation procedure were of GMP-grade or pharmaceutical preparations, underscoring the potential clinical benefits of our strategy. DiscussionWe devised an optimized protocol suitable for routine research and clinical applications for enhanced recovery of CBMCs from cryopreserved cord blood units using an optimized dilution buffer and a modified isolation procedure.

Abstract 9: No Evidence of Mycoplasma or Ureaplasma Contamination of Cord Blood Units Collected from at Term Mothers

Abstract 9: No Evidence of Mycoplasma or Ureaplasma Contamination of Cord Blood Units Collected from at Term Mothers

Abstract 7: Influence of Long-term Storage of Cryopreserved Automated Volume-Reduced Cord Blood Units Until 20 Years: Analysis From Barcelona Cord Blood Bank, Spain.

Abstract 7: Influence of Long-term Storage of Cryopreserved Automated Volume-Reduced Cord Blood Units Until 20 Years: Analysis From Barcelona Cord Blood Bank, Spain.

Efficiency assessment of cord blood banking and compatibility with delayed cord clamping.

There is debate whether delayed umbilical cord clamping following delivery, the current gold standard, affects the proportion of cord blood units (CBU) suitable for public cord blood banking. This study was designed to assess the impact of delayed cord clamping on the number of CBU suitable for therapeutic uses. To minimize variability, data from the four most active collection centers within the Programa Concordia (Spain) were included. Data on CBU collected in utero from mothers following normal vaginal deliveries from July 2018 to December 2021 were analyzed. The weight of the collection bags (as a surrogate of volume) and total nucleated cell (TNC) count were analyzed according to three defined clamping times: 30 s, 60 s and ≥120 s. The CBU were stratified as suitable for stem cell transplantation (≥110 g and ≥1,500×106 TNC/unit) or other clinical applications (≥100 g but TNC count below the threshold). - There were 131 (18%), 548 (76%), and 40 (5%) CBU collected at 30 s, 60 s and ≥120 s, respectively. The median weight of the CBU decreased gradually with time, with a significant difference between units collected when the cord was clamped at 30 s or 60 s (p=0.036), so significantly fewer CBU met the minimal weight criterion (100 g) at 60 s than at 30 s (p=0.002). However, this was not reflected by the TNC available, resulting in non-statistical differences in CBU eligible for banking between these times. The major predictor of collection success was the neonate's birth-weight. -Despite decreases in the volume of cord blood collected when cord clamping at 30 s or 60 s, TNC count is maintained resulting in similar numbers of CBU eligible for banking. The different clamping delays investigated in this study are, therefore, compatible with public cord blood banking needs.

Mitigation of supply chain challenges in cell therapy manufacturing: perspectives from the cord blood alliance.

Cellular therapies rely on highly specialized supply chains that often depend on single source providers. Public cord blood banks (CBB) manufacturing the first cell therapy to be highly regulated by the FDA and related international agencies are a prime example of being subject to this phenomenon. In addition to banking unrelated donor cord blood units for transplantation, CBBs also source and characterize starting materials for supply to allogeneic cell therapy developers that often employ customized technologies offered by just a small number of manufacturers. As such, these supply chains are especially sensitive to even minor changes which often result in potential major impacts. Regulations can shape supply chain efficiencies, both directly via the definition of restricted technology and process requirements and indirectly by steering strategic business decisions of critical supply or service providers. We present 3 current supply chain issues with different root causes that are swaying efficiencies in cord blood banking and beyond. Specifically, the shortage of Hespan, a common supplement used in cord blood processing, the decision by the provider to stop supporting medical device marking of the Sepax system broadly used in cord blood banking, and a new European ruling on phasing out plasticizers that are critical for providing flexibility to cord blood collection bags, are all threatening downstream supply chain issues for the biologics field. We discuss overcoming these hurdles through the prism of unified mitigation strategies, defined, and implemented by multi-factorial teams and stakeholders, to negotiate resolutions with providers and regulators alike.

Donor selection in allogeneic stem cell transplantation.

Recent progress in human leukocyte antigen (HLA) characterization, increased accrual of unrelated donors and cord blood units, and a new platform for haploidentical transplantation have resulted in the widespread availability of donors for allogeneic hematopoietic stem cell transplantation. Advances in HLA typing have identified an increasing number of loci and alleles that are crucial for successful transplantation. Newer HLA A, B, C, DRB1, and DQB1 alleles, DPB1 mismatches, and HLA B leader sequence matching are incorporated into donor selection algorithms. Donor selection is highly relevant because of recently published conflicting studies using different donor types. These studies are largely retrospective and compare patients with different diseases and stages, conditioning regimens, graft versus host disease (GVHD) prophylaxis, and time periods. A broad consensus indicates that the best donor is an available matched sibling, followed by a matched unrelated donor, and then alternative donors such as haploidentical, mismatched unrelated, and cord blood units. This consensus is being challenged by other factors, such as donor age, patient condition, urgency of transplantation, and costs involved. In this review, we will analyze the unique characteristics of each donor type, the HLA and non HLA factors that affect donor choices, and the outstanding comparative outcome studies of different donor usage in hematologic malignancies.

Optimisation of global stem cell donor recruitment based on analysis of unsuccessful donor searches.

Despite over 41 million registered potential volunteer stem cell donors worldwide, many patients in need of a transplant do not find an HLA-matched unrelated donor or cord blood units, with the respective odds differing significantly between various populations. In this study, we analysed data of 2205 unsuccessful real-life donor searches sent to the DKMS Registry to identify populations in which further donor recruitment would be associated with particularly large patient benefits. For that purpose, we estimated haplotype frequencies of 67 donor populations at various sample sizes and entered them into two different mathematical models. These models assessed patient benefits from population-specific donor recruitment, operationalised by the number of originally unsuccessful searches that may become successful due to new donors. Consistently, across the different mathematical models and sample sizes, we obtained several countries from East and Southeast Asia (Thailand, Vietnam, China, and the Philippines) and the population of Asians in the USA as countries/populations where donor recruitment activities would be particularly beneficial for patients. We also identified various countries in Southeast and Central Europe as possible target regions for donor recruitment with above-average patient benefits. The results presented are registry-specific in the sense that they were obtained by optimising unsuccessful searches that had been sent to the DKMS Registry. Therefore, it would be desirable to apply the presented methods to a global data set that includes all unsuccessful stem cell donor searches worldwide and uses population-specific haplotype frequencies based on all donors available in the WMDA Search & Match Service.

Bacterial species in cord blood and their significance in the context of clinical use

Approximately 90 % of infants born before 28 full weeks(extremely-preterm-infants) receive erythrocyte transfusions in early life. Umbilical cord blood(UCB) has been investigated as an alternative source for erythrocyte transfusions to preterm neonates. This retrospective study aimed to compile/evaluate spectrum of bacteria groups/species intermittently detected in processed UCB at National-Swedish-Cord blood bank, (NS-CBB) during the years 2008–2020.Consecutive data from the years 2008–2020 were investigated. UCB from healthy newborns born after 37 full weeks of gestation was collected following clamping of cord (1 min) through cannulation of umbilical vein(vaginal-and C-section-deliveries). In total, 5194 cord blood units (UCBUs) that met NS-CBB-guidelines for total nucleated-cell-content(TNC) were manufactured from 8875 collections. Of 5194 UCBUs,77,6 % were from vaginal-and 22,4 % from C-section deliveries.Samples(10 mL) were collected from surplus eryhtrocyte fraction post-processing(n = 5194), transferred into BACT/ALERT® aerobic/anaerobic culture flasks and monitored 10 days using BACT/ALERT®−3D-Microbial-Detection-Systems. Positive samples were subcultured and typed for bacterial groups and/or species.Out of 5194 processed sampled UCB units,186 (3,6 %) were discarded due to positive sterility tests, 92 % were detected in samples from vaginal-deliveries and 8 % from C-section-deliveries. In all,16 different groups of bacteria and 27 species were identified. Common bacterial/groups and species were anaerobe gram-negative rods(n = 28),coagulase-negative-staphylococci(n = 21),gram-positive rods(n = 21),anaerobe-gram-positive cocci(n = 20) and viridans-streptococci(n = 13). Extracted from these results,in positive samples(n = 13) from C-section deliveries, bacteria were found:viridans-streptococci(n = 7),Aerococcus-urinae(n = 1), Staphylococcus lugdunensis(n = 1),other coagulase-negative staphylococci(n = 1) or a mix of aerobic/anaerobic bacteria(n = 3).Our results are in alignment with previously published contamination rates in processed UCBUs. Still, results point towards importance of strict microbial monitoring when manufacturing UCBUs to achieve patient-safe- products for stem-cell transplantation/transfusion.

Characterization of cord blood immune and stem cells from Vietnamese infants

Cord blood has emerged as a valuable and versatile resource, holding within its grasp a myriad of immune and stem cell types with immense therapeutic potential. Moreover, immune profiling in cord blood, a burgeoning field of research, offers profound insight into the early immune development of newborns, paving the way for understanding immune health, disease susceptibility, and therapeutic interventions. Therefore, in this research, we aimed to characterize the diverse immune and stem cell types present in the cord blood of Vietnamese infants. In this study, a total of 59 cord blood samples were examined for immune cell populations. Cell populations were identified using flow cytometry based on the expression of specific markers on the cell surface. The results showed that the CD3+/CD4+ population accounted for the greatest proportion of lymphocytes (46.71 ± 8.99%), followed by the CD3+/CD8+ population (22.58 ± 6.73%). The mature B-cell population (CD3-/CD19+) accounted for 9.52 ± 3.28%, while CD3+/CD19+ cells accounted for an average of 8.59 ± 5.77%. Moreover, the NK population (CD3-/CD56+ cells) accounted for 6.44 ± 4.9%, T lymphocytes carrying both CD4 and CD8 markers (CD3+/CD4+/CD8+) accounted for 0.63 ± 0.41%, and NKT cells (CD3+/CD56+) accounted for only 0.30 ± 0.53%. Moreover, the number of hematopoietic stem cells (HSCs) tends to increase in umbilical cord blood units with a high volume and number of TNCs and MNCs. In contrast, the number of HSCs was negatively correlated with the ratio of B lymphocytes. The TCD4 ratio was positively correlated with the number of HSCs but negatively correlated with the NK ratio (p = 0.01). The study initially characterized the diversity of some stem and immune cell types present in the umbilical cord blood of Vietnamese infants. These findings laid the groundwork for developing novel immune profiles and expanding the potential applications of umbilical cord blood in cellular therapy.

Criteria for storage of cord blood units at Japan's largest cord blood bank.

In Japan, cord blood transplantations exceed those done with adult-sourced unrelated stem cells. This study analyses cord blood (CB) storage criteria to maintain high-quality CB units. The Kanto-Koshinetsu Cord Blood Bank received 29,795 units from 2014 to 2021, mostly >60 mL, and 5486 (18.4%) were stored as transplantable units. We investigated the mother's gestational period, CB volume, total nucleated cells (TNCs), CD34+ cells, total colony-forming units (CFUs), time from collection to reception and cryopreservation, cell viability, and the reasons for not storing a unit. The average time from collection to reception of 29,795 units was 18.0 h. The most common reason for not storing a CB unit was low cell numbers (pre-processing TNC count <1.2 billion), accounting for 67.9% of the units received. There was no correlation between the CB volume and the CD34+ cell count. The shorter the gestational period, the lower the TNC count, but the higher the CD34+ cell count. There was no correlation between the time from collection to cryopreservation, within a 36-h time limit, and the CD34+ cell recovery rate. We could accept units with a TNC count <1.2 billion and a CB volume <60 mL from a gestational period of 38 weeks or less if we did a pre-processing CD34+ cell count. This would secure more units rich in CD34+ cells.

Hybrid cord blood banking in a private-public-partnership: Women's perspectives.

The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft. The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions. We performed a prospective survey study in postpartum women, using a validated questionnaire. A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage. Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB.

Single vs double umbilical cord blood transplantation in acute leukemia: Systematic review and meta-analysis

Background and aimsUmbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation. Both single (sUCBT) and double cord blood units (dUCBT) demonstrate potential benefits, but studies comparing their effectiveness have shown mixed results. This meta-analysis aimed to determine the comparative safety and efficacy of sUCBT versus dUCBT in acute leukemia patients. MethodsElectronic databases were systematically examined to identify relevant studies comparing single vs double UCBT published until November 2023. Nine studies involving 3864 acute leukemia patients undergoing UCBT were included. Outcomes analyzed were acute graft-versus-host disease (GVHD), chronic GVHD, relapse, non-relapse mortality, leukemia-free survival and overall survival. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. ResultsThe risk of Grade II-IV acute GVHD (RR 1.55, 95% CI 1.19–2.03) and Grade III-IV acute GVHD (RR 1.25, 95% CI 1.07–1.46) were significantly higher with dUCBT. Relapse risk was lower with dUCBT (RR 0.57, 95% CI 0.38–0.88) while overall survival favored sUCBT (RR 1.25, 95% CI 1.06–1.46). No significant differences were observed for chronic GVHD, non-relapse mortality or leukemia-free survival. ConclusionBoth single and double UCBT have potential as effective treatments for acute leukemia. The choice of treatment should consider various factors, including the risk of GVHD, relapse, and mortality. More research, especially randomized trials, is needed to provide definitive guidance on the optimal use of single and double unit UCBT in patients with acute leukemia.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial

sCoinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18–60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75–46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7–87.9 vs. 67.8% 95% CI 60.0–76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6–78.8 vs. 57.6%, 95% CI 49.6–67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0–12.2 vs. 30.3%, 95% CI 30.1–30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3–4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

Effect of fetal distress on viability and yield of umbilical cord blood stem cells–a prospective comparative study

IntroductionDifferent factors affect the quality and viability of cord blood stem cells, and therefore the efficacy of umbilical cord stem cell transplantation. Fetal distress is one factor affecting the quantity of CD34+ cells in cord blood. This study was designed to compare the viability and yield of the umbilical cord blood stem cells of women who have undergone emergency lower segment caesarean section for fetal distress or for other causes. Materials and methodsThis cross-sectional analytical study was performed at a tertiary care hospital facility with a total sample size of 68: 34 participants had undergone emergency C-section for fetal distress, and 34 had undergone emergency C-section for other causes. Umbilical cord blood was collected ex-utero in a 350 mL bag with citrate-phosphate-dextrose solution with adenine. Three milliliter of blood were transferred to an ethylenediaminetetraacetic acid (EDTA) tube for cell counts and flow cytometry testing for CD34+. The chi-square test was used to compare the total mononuclear cell, CD34+, and viability between the groups. ResultsThe CD34+ count [mean 4.9 versus 1.1 (× 106 cells/unit)] and total nucleated cell count [mean 14.2 versus 7.5 (× 108/unit)] were significantly higher in cord blood units collected from women who delivered by C-section for fetal distress (p-value <0.05). However, the volume of umbilical cord stem cells and viability of stem cells did not vary significantly based on the presence or absence of fetal distress (p-value >0.05). ConclusionThe current study shows that umbilical cord blood collected during fetal distress has a significantly higher content of stem cells and total nucleated cells than the non-fetal distress group

Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients With Anti-HLA Antibodies Other Than Against HLA-A, -B, -C, and -DRB1

Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibody-negative patients, while those of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be a useful strategy to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.

Impact of FDA's HCT/P ZIKV Recommendations on Cord Blood Unit Eligibility and Utilization in a Large Public Cord Blood Bank.

Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.