The HSCT procedure (I): Mobilization, collection, manipulation, and cryopreservation of a HSC graft.

Most hematopoietic stem cell transplants performed for an autoimmune disease of the nervous system, use the patient's hematopoietic stem cells (HSCs). Obtaining an HSC graft is the first step of the process. This typically involves mobilization of bone marrow HSCs into the circulation using high-dose cyclophosphamide followed by filgrastim, a drug based on granulocyte colony-stimulating factor. Toxicity from these agents is usually manageable and adverse events are less severe and less frequent than those experienced during the hematopoietic stem cell transplant. Following mobilization, HSCs are collected from the circulation by leukapheresis. Some centers deplete the graft of lymphocytes using an ex vivo immunomagnetic selection procedure. HSC grafts are cryopreserved until required for the stem cell transplant. Quality testing of the graft ensures sterility and it contains sufficient HSCs and hematopoietic progenitors. The clinical and laboratory aspects of HSC graft mobilization, collection, and storage must meet standards set by national regulatory bodies and accredited by international professional standards organizations. Experienced stem cell transplant teams are important for minimizing procedural toxicity and enhancing successful collection.

Cord blood vitamin E and lipids in infants born small for gestational age.

Vitamin E is associated with the regulation of lipid metabolism. Our previous study revealed an inverse relationship between birth weight and cord blood vitamin E levels, suggesting a potential link between vitamin E and fetal growth. The aim of this study was to determine the association between vitamin E with fetal growth and lipids. In this investigation, a study involving 146 mother-infant pairs was performed. Cord plasma concentrations of vitamin E and lipids were measured. Our findings showed that cord plasma vitamin E levels were elevated in small for gestational age (SGA) infants, and higher vitamin E levels were associated with an increased risk of SGA (OR = 2.239, 95% CI 1.208, 4.742). Additionally, among lipid levels, higher cord plasma triglyceride (TG) levels were associated with increased risks of SGA (OR = 97.020, 95% CI 5.137, 1832.305), whereas after adjusting for confounding factors, the risk became no longer statistically significant. We also found a positive correlation between cord blood vitamin E concentrations and lipid levels. CONCLUSION:  elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and are positively correlated with lipid levels, suggesting a potential role for vitamin E in fetal lipid metabolism. WHAT IS KNOWN: • Vitamin E is associated with the regulation of lipid metabolism. • Vitamin E is inversely related to birth weight. WHAT IS NEW: • Elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and positively correlated with lipid levels.

The clinical influence of complete remission with incomplete count recovery (CRi) on single-unit umbilical cord blood transplantation in patients with acute leukemia.

BACKGROUND: Recent evidence has indicated that measurable residual disease (MRD) markedly affects the prognosis of patients with acute leukemia post-transplantation. However, the prognostic relevance of complete remission with incomplete count recovery (CRi) before transplantation has not been extensively explored. METHODS: In this single-center, longitudinal study, we assessed the outcomes of 466 MRD-negative acute leukemia patients who underwent single-unit unrelated cord blood transplantation (sUCBT), including 117 patients with CRi. RESULTS: We observed that acute myeloid leukemia (AML) patients with CRi had a significantly lower cumulative incidence of both neutrophil (90.8% vs. 96.5%) and platelet engraftment (67.2% vs. 85.3%) and experienced increased transplant-related mortality (TRM) (100-day TRM: 14.2% vs. 5.3%; 1-year TRM: 20.6% vs. 11.3%; P = 0.024 and 0.063, respectively), mainly due to infection-related deaths, compared to those in complete remission (CR). Multivariate analysis revealed that CRi was an independent adverse predictor of both neutrophil and platelet engraftment and increased 100-day TRM in AML patients. However, CRi status did not affect relapse or reduce 5-year overall survival (OS), leukemia-free survival (LFS), or GVHD-free relapse-free survival (GRFS) in the AML cohort. Conversely, for patients with acute lymphoblastic leukemia (ALL), CRi did not impact engraftment, TRM, relapse or survival after sUCBT. CONCLUSIONS: Our findings underscore that CRi status before sUCBT portends poorer engraftment outcomes and a greater TRM in AML patients, although it does not significantly affect the prognosis of ALL patients.

Posttransplantation cyclophosphamide mediates effective reconstitution of memory B cells after allogeneic hematopoietic cell transplantation.

OBJECTIVES: Impaired B-cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT) contributes to the pathogenesis of chronic graft-versus-host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long-term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo-HCT and prevent subsequent GVHD. METHODS: We comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo-HCT. RESULTS: The absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood. CONCLUSIONS: PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.

Recipient IL-17A polymorphism rs2275913 is associated with acute graft-versus-host disease after single-unit cord blood transplantation.

BACKGROUND: Interleukin-17 (IL-17) is elevated in human inflammatory and autoimmune diseases. The polymorphism in the promoter region of the IL-17 A gene is associated with susceptibility to several inflammatory diseases, including acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation from adult donors. However, the impacts of IL-17 A polymorphism on cord blood transplantation (CBT) outcomes remain unclear. OBJECTIVE: The objective of this study was to assess the impact of IL-17 A polymorphism rs2275913 on GVHD, survival, relapse, non-relapse mortality (NRM), and hematopoietic recovery after CBT. STUDY DESIGN: We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from January 2005 to March 2023 for whose recipient or donor DNA samples were available. IL-17 A genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2275913. RESULTS: A total of 158 recipients and 136 donors were evaluated in this study. Multivariate analysis showed that rs2275913 GA or AA recipients were associated with increased risk of grades II to IV acute GVHD compared to GG recipients (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00-2.13; P = 0.047). Serum IL-17 A levels at eight weeks were significantly higher in rs2275913 GA or AA recipients compared to GG. The rs2275913 polymorphism did not affect survival, relapse, NRM, or hematopoietic recovery after single-unit CBT. CONCLUSION: Our data showed recipient IL-17 A polymorphism rs2275913 was associated with the risk of grade II to IV acute GVHD in adults undergoing single-unit CBT. However, the rs2275913 polymorphism in recipients and donors did not affect survival or relapse. Thus, the polymorphism of IL-17 A rs2275913 in recipients might predict the risk of acute GVHD after single-unit CBT.

Umbilical cord blood as a substitute for neonatal blood in measuring serum albumin and immunoglobulin G levels.

OBJECTIVES: In this study, we investigated the clinical feasibility of using umbilical cord blood as an alternative to neonatal blood for measuring serum albumin and immunoglobulin G (IgG) levels in newborns, including preterm newborns. METHODS: Serum levels of albumin and IgG were measured in cord and neonatal blood from singleton newborns. We analyzed correlations and systematic errors between cord and neonatal blood measurements, stratifying the results for very preterm newborns (VPNs) born at a gestational age of less than 32 weeks and non-VPNs born at a gestational age of 32 weeks or later. RESULTS: Among all 494 newborns (78 VPNs and 416 non-VPNs), serum albumin and IgG levels were determined for 95.7% and 88.7% of them, respectively. Strong correlations between cord and neonatal blood were observed for the serum albumin and IgG levels (rs = 0.864 and 0.966, respectively). Moreover, the measurement errors between cord and neonatal blood were small for all newborns (0.2 g/dL and 65 mg/dL, respectively). These findings were consistent with both VPNs and non-VPNs. CONCLUSIONS: Umbilical cord blood is a suitable substitute for neonatal blood in measuring serum albumin and IgG levels in newborns, even in premature newborns.

Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population.

BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade all mammalian cells. It is well established that natural killer (NK) cells have critical protective roles in innate immunity during infections by intracellular pathogens. In the current study, we conducted an in vitro experiment to evaluate NK cell differentiation and activation from human umbilical cord blood mononuclear cells (UCB-MNCs) after infection with T. gondii tachyzoites. METHODS: UCB-MNCs were infected by fresh tachyzoites of type I (RH) or type II (PTG) strains of T. gondii pre-expanded in mesenchymal stem cells for 2 weeks in a medium enriched with stem cell factor, Flt3, IL-2, and IL-15. Flow cytometry analysis and western blot analysis were performed to measure the CD57+, CD56+, and Granzyme A (GZMA). RESULTS: Data revealed that incubation of UCB-MNCs with NK cell differentiation medium increased the CD57+, CD56+, and GZMA. UCB-MNCs cocultured with PTG tachyzoites showed a significant reduction of CD56+ and GZMA, but nonsignificant changes, in the levels of CD56+ compared to the control UCB-MNCs (p > .05). Noteworthy, 2-week culture of UCB-MNCs with type I (RH) tachyzoites significantly suppressed CD57+, CD56+, and GZMA, showing reduction of NK cell differentiation from cord blood cells. CONCLUSION: Our findings suggest that virulent T. gondii tachyzoites with cytopathic effects inhibit NK cell activation and eliminate innate immune responses during infection, and consequently enable the parasite to continue its survival in the host body.

An Assessment of the Relationships Between Umbilical Cord Blood Gas Analysis, APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) Scores, and Neonatal Outcomes.

Introduction Intrapartum hypoxic-ischemic injury is a condition that significantly affects neonatal health and, therefore, needs to be attended to urgently. Umbilical cord blood gas analysis (BGA) results and APGAR (appearance, pulse, grimace, activity, and respiration) scores are commonly used to assess birth asphyxia and the severity of neonatal acidemia. In this context, this study was conducted to investigate the correlations of BGA results and APGAR scores with neonatal outcomes to determine the combined value of BGA results and APGAR scores in neonatal health assessment. Methods The sample of this retrospective cohort study consisted of 593 consecutive-term newborns delivered in a tertiary referral center in Turkey between January 2020 and December 2022. All newborns' maternal, delivery, and neonatal characteristics, BGA results, and APGAR scores were analyzed to determine correlations with composite adverse neonatal outcomes. The study's primary outcome was defined as the rate of the composite adverse neonatal outcomes, whereas the secondary outcomes were determined as the impact of maternal and neonatal characteristics on composite neonatal morbidity and the correlation between the one- and five-minute APGAR scores and umbilical cord BGA parameters. Results Of the 593 infants included in the study, 191 (32.2%) infants experienced composite adverse neonatal outcomes, primarily mechanical ventilation (47.7%), followed by respiratory distress/syndrome (35.6%). Significant correlations were detected between composite adverse neonatal outcomes and advanced maternal age (p = 0.025), cesarean section history (p < 0.001), preterm delivery (p < 0.001), lower one- and five-minute APGAR scores (p < 0.001 for both cases), and acidemia severity (p = 0.007). However, the correlations between BGA parameters and APGAR scores were weak (r < 0.2). Conclusion This study investigated the correlations between neonatal mortality and morbidity and maternal factors, delivery characteristics, and fetal features, including one- and five-minute APGAR scores and BGA parameters. Nevertheless, weak correlations between BGA parameters and APGAR scores warrant further comprehensive prospective studies.

The Cytokine Levels of Cord Blood- and Wharton's Jelly-Derived Mesenchymal Stem Cells from Early to Late Passages.

Mesenchymal stem cells (MSCs) are promising for clinical studies owing to their self-renewal, multipotency, trophic, and immunomodulatory properties. This study aimed to investigate the cytokine levels of human umbilical cord blood (CB) and Wharton's Jelly-(WJ) derived MSCs relevant to immune modulation on different passage levels in vitro. Umbilical CB MSCs were isolated using the ficoll-paque gradient method, and WJ-MSCs were isolated by the explant method. After isolation, the MSCs were characterized using flow cytometry. The supernatant cytokine levels (interferon-gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 (IL-17)) of MSCs at each passage were evaluated using the ELISA assay. MSCs exhibited different cytokine levels with each passage number. In WJ-MSC culture supernatants, IL-17 levels significantly increased at P4 and P5 compared to the first passage (p < 0.005), while the other passages showed a decrease. IFN-γ levels increased at passage P1 and P4 and decreased at other passages (p < 0.005). IL-4 levels significantly increased only at passage P3 (p < 0.005). In CB-MSC culture supernatants, IL-17 and IL-4 cytokines decreased compared to P0, while IFN-γ cytokine increased from P0 (p < 0.005). The changing ratio of cytokine levelsfor both CB-MSCs and WJ-MSCs were similarly maintained from early to late passages. More research is needed to understand the immunomodulatory functions of MSCs.

Maternal APOE ε2 as a possible risk factor for elevated prenatal Pb levels.

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.

Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells.

Background: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. Method: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. Results: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. Conclusion: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. Supplementary Information: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.

[The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation].

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Evolution of the Umbilical Cord Blood Proteome Across Gestational Development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 24 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. Furthermore, these data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions.

Umbilical Cord Blood Hematopoietic Cells: From Biology to Hematopoietic Transplants and Cellular Therapies.

Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells that are biologically superior to their adult counterparts. UCB cells can be stored for several years without compromising their numbers or function. Today, public and private UCB banks have been established in several countries around the world. After 35 years since the first UCB transplant (UCBT), more than 50,000 UCBTs have been performed worldwide. In pediatric patients, UCBT is comparable to or superior to bone marrow transplantation. In adult patients, UCB can be an alternative source of hematopoietic cells when an HLA-matched unrelated adult donor is not available and when a transplant is urgently needed. Delayed engraftment (due to reduced absolute numbers of hematopoietic cells) and higher costs have led many medical institutions not to consider UCB as a first-line cell source for hematopoietic transplants. As a result, the use of UCB as a source of hematopoietic stem and progenitor cells for transplantation has declined over the past decade. Several approaches are being investigated to make UCBTs more efficient, including improving the homing capabilities of primitive UCB cells and increasing the number of hematopoietic cells to be infused. Several of these approaches have already been applied in the clinic with promising results. UCB also contains immune effector cells, including monocytes and various lymphocyte subsets, which, together with stem and progenitor cells, are excellent candidates for the development of cellular therapies for hematological and non-hematological diseases.

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion.

BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.

Impact of Race and Ethnicity on Outcomes After Umbilical Cord Blood Transplantation.

BACKGROUND: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. OBJECTIVE: To compare outcomes by social determinants of health. STUDY DESIGN: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N = 1752) or reduced intensity conditioning (N = 759) for acute myeloid leukemia, acute lymphoid leukemia, or myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). RESULTS: For 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6 to 45.3) for Whites, 36.1% (99% CI, 28.2 to 44.5) for Latinx, 45.8% (99% CI, 36.7 to 55.1) for Blacks, and 44.5% (99% CI, 33.6 to 55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p = .0005, HR 1.45, 99% CI 1.18 to 1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7 to 72.2) for Whites, 57.1% (99%CI, 49 to 64.9) for Latinx, 46.8% (99%CI, 35.3 to 58.4) for Blacks, and 53.8% (99%CI, 32.7 to 74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = .051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p = .0016, HR 2.25, 99% CI 1.36 to 3.74) and Latinx (p = .0016, HR 2.17, 99% CI 1.43 to 3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults. Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p = .03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p = .02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p = .02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. CONCLUSIONS: OS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

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.

Hemostatic Status of Neonates with Perinatal Hypoxia, Studied via NATEM in Cord Blood Samples.

BACKGROUND: Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. METHODS: 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. RESULTS: Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92-96) Vs 93 (91-95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. CONCLUSION: Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates.

Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights in Sanliurfa, Turkey.

BACKGROUND: Controversy surrounds the impact of persistent organic pollutants (POPs) on fetal development. This study aimed to investigate levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in umbilical cord blood from Sanliurfa mothers in Turkey, exploring associations with gestational age and birth weight. METHODS: Participants included voluntary mothers pregnant with a single fetus, providing details on maternal factors. Cord blood samples were collected immediately after delivery. Samples were extracted with a modified QuEChERS method, and OCPs (17 pesticides) and PCBs (11 congeners) compound levels were analyzed with a gas chromatograph/mass spectrometry. Detection frequencies and levels of POPs by single pollutant type and pollutant groups were calculated and compared according to gestational duration and birth weight. We used partial least squares discriminant analysis to identify the key chemicals and distinguish their respective statuses. RESULTS: Among 120 infants, 35 were preterm but appropriate for gestational age, 35 were term but small for gestational age (SGA), and 50 were term and appropriate for gestational age (AGA). Beta HCH, Oxy-Chlordan, and PCB 28, were not detected in cord blood samples. Half of the samples contained at least 4 types of OCPs, with a median OCP level of 38.44 ng/g. Among the DDT, 2,4'-DDE was found at the highest concentration in cord plasma samples. The PCB congeners with a frequency exceeding 50% were ranked in the following order: 151, 149, 138, 146. The median level of ∑PCBs was 5.93 ng/g. Male infants born at term with SGA status exhibited lower levels of ∑DDTs, ∑OCPs compared to male infants born preterm or at term with AGA status. Di-ortho-substituted PCBs and hexachlorinated PCBs were higher in male infants born at term with SGA status than male infants born preterm with AGA status. CONCLUSION: Overall, exposure to DDT and PCBs demonstrates varying effects depending on gestational duration and birth weight, with exposure levels also differing by gender. This underscores the necessity for studies across diverse populations that investigate the combined effects of multiple pollutant exposures on gestational age, birth weight, and gender simultaneously.