Use Of Umbilical Cord Blood Research Articles

Using autologous umbilical cord blood and placental cells for hypoxic-ischemic encephalopathy: an exploratory safety and feasibility study.

Introduction. Hypoxic-ischemic encephalopathy (HIE) caused by lack of oxygen and perfusion to the brain can lead to acute neurological damage in newborns. Therapeutic hypothermia (TH) is the most effective and safest treatment. However, mortality remains high with numerous long-term sequelae. Cellular therapies, particularly umbilical cord blood (UCB), are being studied as alternative therapies. The aim of this study is to assess the feasibility and safety of combining autologous cord blood cell infusion with moderate hypothermia. Population and methods. Twelve infants of 36 weeks gestational age or older, diagnosed with moderate or severe HIE and with umbilical cord blood (UCB) collected were included. UCB was volume-reduced, and up to four doses were obtained. These doses were infused within the first 72 postnatal hours. Time to the first infusion and possible adverse reactions to the infusion were evaluated. Results. Between 2014 and 2019, 12 infants were included in the protocol (TH + UCB), 9 with a diagnosis of moderate HIE and 3 with severe HIE. In all cases, at least one dose of UCB was obtained for infusion. In all cases, the first dose was infused within 24 hours in every case, and no adverse reactions attributable to the infusion were observed. Conclusions. The collection, processing, and infusion of fresh autologous umbilical cord blood for use in newborns with HIE are feasible and safe under our conditions.

Extensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cells

BackgroundEx vivo haematopoietic stem/progenitor cell (HSPCs) expansion constitutes an important area of research, and has the potential to improve access to umbilical cord blood (UCB) as a source of stem cells for haematopoietic stem cell transplantation (HSCT). The ability to improve stem cell dose and thereby reduce delayed engraftment times, which has plagued the use of UCB as a stem cell source since inception, is a recognised advantage. The extent to which cluster of differentiation (CD)34 sub-populations are affected by expansion with StemRegenin1 (SR1), and whether a particular subtype may account for better engraftment than others, is currently unknown. The purpose of this study was to determine the impact of SR1-induced HSPC expansion on CD34+ immunophenotypic subsets and gene expression profiles.MethodsUCB-derived CD34+ HSPCs were characterised before (D0) and after expansion (D7) with SR1 using an extensive immunophenotypic panel. In addition, gene expression was assessed and differentially expressed genes were categorised into biological processes.ResultsA dose-dependent increase in the number of CD34+ HSPCs was observed with SR1 treatment, and unbiased and extensive HSPC immunophenotyping proved to be a powerful tool in identifying unique sub-populations within the HSPC repertoire. In this regard, we found that SR1 promotes the emergence of HSPC subsets which may aid engraftment post expansion. In addition, we observed that SR1 has a minimal effect on the transcriptome of 7-day expanded CD34+ HSPCs when compared to cells expanded without SR1, with only two genes being downregulated in the former.ConclusionThis study revealed that SR1 selects for potentially novel immunophenotypic HSPC subsets post expansion and has a minimal effect on the transcriptome of 7-day expanded HSPCs when compared to vehicle controls. Whether these distinct immunophenotypic sub-populations possess greater engraftment capacity remains to be tested in animal models.

Cinética de la liberación del factor de crecimiento derivado de plaquetas (PDGF-BB) derivado del plasma rico en plaquetas de cordón umbilical humano

Introduction: The use of umbilical cord blood (UC) has many advantages in regenerative medicine. Platelet-rich plasma (PRP) is a source of growth factors where its dynamics over time has been evaluated in peripheral blood, however, its evaluation in UC blood has not been studied. Objective: To evaluate the kinetics of PDGF-BB release from PRP obtained from UC blood. Materials and methods: An in vitro experimental study was conducted. UC blood samples were collected from 6 term deliveries of healthy pregnant women between 18 and 36 years of age who attended the Cayetano Heredia Hospital in Lima-Peru. The samples obtained were centrifuged at 900 g for 10 minutes to prepare the PRP. Activation was performed with 10% calcium gluconate (GLu.Ca) and divided into 4 aliquots: (i) without activator; (ii) 1 hour; (iii) 24 hours; (iv) 48 hours. PDGF-BB quantification was evaluated by the ELISA method. Results: The mean (standard deviation) of PDGF-BB concentration measured at 1 hour, 24 hours, and 48 hours were 6127.9 ± 101.6 pg/mL, 6197.5 ± 34 pg/mL, and 6176.8 ± 63.3 pg/mL, respectively. The kinetics of PDGF-BB released by PRP showed constant values during the 48 hours. Conclusions: PDGF-BB release from PRP obtained from UC blood was rapidly induced and remained constant and sustained during the first 48 hours after activation.

The use of umbilical cord blood as an alternative to venous blood for newborns

The use of umbilical cord blood as an alternative to venous blood for newborns

Umbilical blood as a trophic-growth supplement for cultural work

This review analyzes the results of modern high-tech research on the use of umbilical cord blood serum/plasma as an additive to culture media for cell culture growth. Since culture media are a key factor in cell culture, the review addresses the composition and properties of the major culture media used in cell biology and regenerative medicine. The authors pay special attention to growth factors; they describe the functional properties of the main families of these polypeptides (fibroblast growth factors, epidermal growth factors, transforming growth factors, differentiation growth factors, epidermal growth factors, endothelial cell growth factors, hematopoietic growth factors, etc.). It was found that one of the most promising sources of growth factors is cord blood serum/plasma. In this publication, the main technologies for cord blood collection and systematic studies on the content of growth factors, cytokines, exosomes and mRNA in cord blood are presented. Experimental data on the use of umbilical cord blood serum/plasma as an additive to culture media for the growth of various cell cultures of animal origin are described. Human umbilical cord blood serum/plasma is an affordable, safe product with a high content of biologically active molecules compared to animal sources. In order for umbilical cord blood serum/plasma to be widely used as an adjunct to culture media, standards for the manufacture and testing of this product must be developed.

Perspectives for the Use of Umbilical Cord Blood in Transplantation and Beyond: Initiatives for an Advanced and Sustainable Public Banking Program in Greece.

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.

Mesenchymal Stromal Cells from Perinatal Tissues as an Alternative for Ex Vivo Expansion of Hematopoietic Progenitor and Stem Cells from Umbilical Cord Blood.

Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.

Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies.

Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence.

298 - The Use of Umbilical Cord Blood in Hematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia and Acute Myeloid Leukaemia

298 - The Use of Umbilical Cord Blood in Hematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia and Acute Myeloid Leukaemia

A new beginning: can omidubicel emerge as the next, viable alternative donor source?

Umbilical cord blood (UCB) transplantation (CBT) has been an important alternative donor option for patients lacking matched related donor (MRD) or unrelated donor (URD) grafts. Only 30% of patients with high-risk hematologic malignancies have a human leukocyte antigen (HLA)-identical sibling; subjects without a MRD option are referred for HLA-matched URD selection, or utilize alternative donor sources such as HLA-mismatched URD, UCB, or haploidentical donor grafts. While CBT demonstrates an excellent graft-versus-leukemia (GVL) effect, use of UCB as a graft source is limited due to a lower cell dose that can result in delayed engraftment and an immature immune system with increased infectious risk as a consequence. Together, increased transplant related mortality (TRM) has been associated with UCB allografts. Omidubicel is an ex vivo expanded single cord blood product that has demonstrated rapid engraftment, improved immune reconstitution, and reduced infectious complications in clinical trials. Omidubicel has now been granted U.S. Food & Drug Administration approval to enhance neutrophil recovery and decrease infectious risk. This review will focus on CBT, benefits and barriers to using this alternative donor source, and finally the potential advancements with incorporation of omidubicel in the transplant setting for malignant and non-malignant diseases.

Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells

Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34+ stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34+ HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2–5 × 105 CD34+ HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34+ HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34+ HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival.

Does Race/Ethnicity Impact Umbilical Cord Blood Transplant Outcomes in a Contemporary Era?

Background: Studying the impact of race/ethnicity on stem cell transplant outcomes helps us improve health care disparities and access to transplant. The use of umbilical cord blood (UCBT) was designed to allow mismatched UCB units and improve access to transplant for patients lacking a fully matched donor. Previous CIBMTR studies (Ballen et al, BBMT, 2012) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT; however, outcomes were similar when UCB units of comparable cell dose and HLA match were used. The current study draws on a larger, more modern cohort and compares outcomes among non-Hispanic White (White), non-Hispanic Black (Black), Hispanic/Latinx (Latinx) and Asian patients. Methods: CIBMTR data from 2007 to 2017 were used. Patients were between ages 1 and 80; 983 received single and 1259 double UCBT, following either a myeloablative (N=1752) or reduced intensity conditioning (N=759). The primary outcome was OS at 2 years, which was estimated using the Kaplan-Meier method with the log-rank test used for univariate comparisons. 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). Multivariate analysis was performed to determine factors associated with outcomes and whether race/ethnicity influences these outcomes. Results: A total of 1705 adults and 807 children were included. For adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6-45.3) for Whites, 36.1% (99% CI, 28.2-44.5) for Latinx, 45.8% (99% CI, 36.7-55.1) for Blacks, and 44.5% (99% CI, 33.6-55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to other racial/ethnic groups (p=0.005) (Figure 1). OS improved over time across all racial/ethnic groups (p=0.009; 2016-2017 vs. 2007-2009 HR 0.68, 99% CI 0.51-0.91). Relapse and TRM rates were higher in Latinx compared to other groups but did not reach statistical significance. GVHD rates were comparable among the different racial/ethnic groups. There was no survival advantage to receiving a UCB unit from a donor of similar race/ethnicity, for any racial/ethnic groups In children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7-72.2) for Whites, 57.1% (99%CI, 49-64.9) for Latinx, 46.8% (99%CI, 35.3-58.4) for Blacks, and 53.8% (99%CI, 32.7-74.2) for Asians. In multivariate analysis of children, no difference in OS was observed among racial/ethnic groups (p = 0.05) (Figure 2). Similarly, there was no difference in relapse (p=0.40) and TRM rates (p=0.14). Grade 3-4 Acute GVHD was higher in Blacks compared with Whites (p= 0.0016, HR 2.25, 99% CI 1.36-3.74). There was no survival advantage to receiving a UCB unit from a donor of similar race/ethnicity, for any racial/ethnic groups. Conclusion: 1. UCBT provides a donor for diverse patients. 2. In adults, OS has improved over time for all racial/ethnic groups. 3. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. 4. In children, OS is comparable among Whites, Blacks, Latinx, and Asians. 5. In children, Grade 3 and 4 acute GVHD was higher in Black patients. 6.There was no survival benefit to matching UCB unit and patient by race/ethnicity for adults and children, although the numbers were small in the non-White cohorts. As our study reveals race/ethnicity matching has minimal to no impact on outcomes post UCB transplant it may be advantageous for UCB banks to target collection of larger units over race/ethnicity quotas. Future studies will study biologic or socioeconomic explanations for the lower OS in adult Latinx patients and the higher acute GVHD in pediatric black patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications.

The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions. When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or 'haplo-cord' transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics. The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.

The Novel Use of Umbilical Cord Blood to Obtain Complete Blood Counts for Critical Neonatal Assessment.

Background: Neonates undergoing clinical evaluations are often subjected to potentially painful phlebotomy for laboratory tests. The use of cord blood laboratory values for admission has been suggested as a means to decrease the risk of painful venipuncture and anemia.Methods: Peripheral and umbilical cord blood complete blood count (CBC) results were obtained from infants who required a CBC. Results were compared using the Sysmex XN heme analyzer (Sysmex, Kobe, Japan).Results: White blood cell (WBC) and hemoglobin (HgB) values were significantly higher in peripheral samples than in cord samples. The mean cord WBC count was 14.1 × 103/mm3 versus 15.6 × 103/mm3 peripherally (p < 0.001). The mean cord HgB was 15.8 g/dL versus 16.8 g/dL peripherally (p < 0.001). Cord platelet (Plt) counts were, conversely, lower in peripheral samples than in cord samples (264.8 × 103/mm3 versus 242.3 × 103/mm3, respectively; p < 0.001). Although statistically different, the mean CBC values from both samples were within the reference ranges. Delayed cord clamping (DCC) increased peripheral versus cord HgB difference nearly threefold (0.6-1.7 g/dL; p = 0.01).Conclusions: Cord blood is an acceptable source for CBC blood sampling in newborn infants and can be used for clinical decisions. CBC laboratory values for cord blood remained within the peripheral blood reference range, with slight variability between the two samples.

Knowledge, Awareness, and Attitudes toward Umbilical Cord Blood Biobanking

BACKGROUND: Umbilical Cord Blood (UCB) stem cells are a non-invasive, effective alternative source of hematopoietic stem cells for the treatment of a variety of diseases. AIM: The aim of the study was to research knowledge, awareness, and attitudes of the general public and health professionals regarding the UCB storage. MATERIALS AND METHODS: A cross-sectional study was conducted with an online survey (n = 408) using the snowball method. RESULTS: A majority of respondents declared that they were not aware of UCB banking; however, people with an academic background in healthcare have a greater awareness of UCB banking. A subjective assessment found that their knowledge of UCB banking is better than that of non-professionals, however, they exhibited better knowledge and understanding of UCB use and banking in only a few aspects. People with an academic background in healthcare have a more polarized attitude toward cord blood banking and a higher percentage are unwilling to pay for UCB banking services. However, their preferences regarding public/private UCB banking do not differ significantly from those of non-professionals. CONCLUSION: Here, we show that there is not much difference between the laic and professional categories in terms of knowledge about the specific purpose and characteristics of UCB storage.

Prospective Comparison Of Five Viral Infections (HHV6, CMV, EBV, ADV, BKv) After Umbilical Cord Blood (UCB) Vs PBSC Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (allo-SCT) In Adults

Viral infections are well-known complications after allo-SCT and are responsible for morbidity and mortality in patients. Previous retrospective studies have reported a strong association between HHV6 infection and the use of umbilical cord blood (UCB) as stem cell source for allo-SCT. To better define the characteristics and consequences of HHV6 infection after UCB allo-SCT, we conducted the first prospective study comparing the frequencies of HHV6 infections and of 4 other viral reactivations (cytomegalovirus (CMV), Epstein Barr virus (EBV), adenovirus (ADV) and BK virus (BKv)) in 65 adults receiving either UCB allo-SCT (n=31) or unrelated PBSC allo-SCT (n= 34) after a reduced intensity conditioning regimen. Except graft source, characteristics of patients were similar between UCB vs PBSC groups in terms of sex, age at transplant, type of disease and disease status at transplant.Viral loads were measured in whole blood (608 samples) before the graft and at least once a month up to six months post-graft. Data were analysed for correlation with various clinical/biological events occurring after the graft (engraftment, hematopoietic and immune reconstitutions, GVHD, deaths or the five considered viral infections).Frequency of HHV-6 infections was significantly higher in the UCB group (83.9% vs 21.2%; p<0.0001). In this context, HHV-6 reactivations were observed mainly during the first month post-transplant occurring earlier (p<0.0001) and with a longer duration (median: 148 days vs 31 days) in the UCB group. However, there was no difference regarding viral loads between both groups. Neutrophils and platelets recoveries were significantly delayed in HHV-6 positive patients (median: 20 days vs 15 days, p=0.002; and 40 days vs 12 days; p=0.0001, respectively), especially when HHV-6 reactivations occurred before the end of aplasia (median: 28 days vs 17 days; p=0.0054 and 56 days vs 15 days; p=0.0006). The delayed recoveries was accordingly associated with a higher need for units of red blood cells and platelet packs in infected patients (median number of transfused units per patient: 8 vs 2; p=0.006 and 11 vs 1; p<0.0001, respectively). Moreover, HHV-6 infection was not associated with higher incidence of acute GHVD, CMV reactivations, relapses or death.Regarding the four other viral infections, we observed a significant higher frequency of EBV reactivations in PBSC allo-SCT recipients (70.6% vs 25.8%; p=0.0003) but similar incidence of CMV infections between both groups. ADV infections were observed only in 4 UCB allo-SCT cases. Finally, BKv reactivations studied up to 2 months post-graft were significantly more frequent in the UCB group (51.6% vs 23.5%; p=0.019).In conclusion, we prospectively confirm here a specific relationship between HHV6 and BKv infections and UCB allo-SCT. The pattern of immune reconstitution and the multivariate analyses are on-going and will be presented at the meeting. Disclosures:Moreau:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

HHV-6 Prophylaxis with Foscanet Improves Hematopoietic Engraftment after Umbilical Cord Blood Transplantation

Delayed hematopoietic recovery is a major obstacle for successful use of umbilical cord blood (UCB) transplantation. In our recent report of patients receiving non-myeloablative (NMA) UCB transplantation with sirolimus/MMF as GVHD prophylaxis, we observed an association between early post-transplant HHV6 viral reactivation and delayed hematopoietic recovery. Therefore, in order to improve hematopoietic recovery, we added foscarnet (45 mg/kg twice daily) as antiviral prophylaxis for at least 10 days starting at day +7 until neutrophil engraftment. Here we report results in 19 consecutive patients treated with foscarnet and compared results in those treated with acyclovir (n=60, historical control) after NMA UCB transplant with sirolimus/MMF GVHD prophylaxis. The median age for the entire cohort was 63 years (range, 16-73 years). Acute leukemia was the principal indication for transplantation (45%). At the time of transplantation, 25% of the patients had many comorbidities (HCT-CI≥3), 21% had Karnofsky performance status (KPS) ≤80% and nearly 60% were CMV seropositive with 7 patients (9%) having had a prior allogeneic transplant (alloHCT). All patients received the same NMA conditioning regimen consisting of fludarabine (150 mg/m2), cytoxan (50mg/kg) and TBI (200 cGy) with 46% also receiving ATG if there was no recent chemotherapy. Median infused total nucleated cell dose for the entire cohort was 4.1 x107/kg (range, 2.7-9.6 x107/kg). Groups were similar except for prior alloHCT (21% vs. 5%, p=0.03) and lower KPS ≤80% (58% vs. 10%, p <0.01) in recipients of foscarnet as compared to the acyclovir cohort. Cumulative incidence of neutrophil engraftment by day 42 was 100% in the foscarnet group vs. 75% (64-85%) in those treated with acyclovir (p= 0.08). Cumulative incidence of platelet engraftment by 6 months was 95% (69-100%) for foscarnet group vs. 75% (60-90%) for acyclovir group (p=0.02). In multiple regression analysis (Table), after adjusting for CMV serostatus, neutrophil engraftment was 2-fold increased in recipients of prophylactic foscarnet as compared to acyclovir (HR=2.0, CI 95% 1.1-3.6; p= 0.02). Similarly, after adjusting for age and CMV serostatus platelet engraftment was 2.4-fold increased in recipients of foscarnet as compared to acyclovir (HR=2.4, 95% CI 1.3-4.0; p <0.01). In addition, positive recipient CMV serostatus was associated with poor hematopoietic engraftment. These data support the use of prophylactic foscarnet for prevention of HHV-6 reactivation which may delay or prevent successful engraftment after NMA UCB transplantation with sirolimus/MMF as GVHD prophylaxis. [Display omitted] DisclosuresBrunstein:Magenta Therapeutics: Research Funding; Novartis: Research Funding.

Characterisation of Naive Immunological Profile of Umbilical Cord Blood: The Role of Mucosal-Associated Invariant T Cells and Functional Defects of T Cells and Natural Killer Cells

Patients undergoing allogeneic haematopoietic stem cell (HSC) transplantation are susceptible to infection and reactivation of viruses, such as cytomegalovirus, due to impairment of the T cell compartment following intensive immunosuppressive therapy. There is a growing interest in evaluating cell-mediated immunity to improve the management of these infections. Over the last two decades, umbilical cord blood (UCB) has emerged as an alternative source of cellular products for the treatment of a range of haematological disorders. UCB HSCs have a number of distinguishing characteristics which differentiate them from adult HSCs, including increased proliferation and increased in vitro colony forming capacity. The use of UCB as HSC grafts for allogeneic stem cell transplant has a number of advantages, including immediate availability and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the limited number of HSCs present in a single UCB collection and incomplete immune reconstitution because of delayed HSC engraftment has restricted the use of cord blood in stem cell transplantation. In addition, UCB transplantation is associated with lack of transferred adoptive immunity, resulting in transplant related morbidity and mortality due to infectious complications. While the human neonatal immune system is considered to be immature compared with its adult counterpart, the role of the innate immune cells in the immunological naïvety is not fully understood.Here, we describe the collection and characterisation of UCB units collected from a series of Irish mothers who delivered term infants by elective caesarean at a major Irish maternity hospital. Pre analytical variables included maternal factors such as gestation at delivery, blood group, age, medical history and BMI, and neonatal factors such as birth weight and gender. Mononuclear cells (MNC) were isolated and the immunological profile was analyzed by flow cytometry for the surface markers CD3, CD4, CD5, CD8, CD19, CD34, CD45, CD56, CD161 and the Vα24Jα17, Vα7.2, Vδ1, Vδ2 and Vδ3 T cell receptors. Progenitor cell colony forming ability was assessed by CFU-GM and BFU-E assays. Stimulation of T cells, by cross-linking of CD3 and CD28 using tetrameric antibodies, and Natural Killer (NK) cells, with IL12/IL18 and target cells, was assessed by measurement of surface expression of CD107a and intracellular production of IFNγ, IL4 and IL17a.We showed no difference in the overall numbers of B cells, T cells (CD4+ and CD8+) and γδ T cells between UCB (n=23) and adult blood (n=4); however, NK cells (p<0.001) and mucosal-associated invariant T (MAIT) cells (p<0.0001) were significantly depleted in UCB. Stimulated UCB T cells and NK cells (n=17) showed significantly reduced IFNγ production compared to adult blood counterparts (n=4) (p<0.01) Following thaw of cryopreserved UCB MNC, we observed no significant change in CFU-GM, CD34+ cell concentration or immunological profile/function compared to fresh MNC (n=7).Our study suggests that reduced numbers of circulating innate immune cell populations, as well as reduced cytokine responses following stimulation, may contribute to the naïve immunological phenotype and hyporesponsiveness of UCB. Further investigation and manipulation of these innate immune cell populations could improve UCB transferred adoptive immunity potential and assist in the management of post allogeneic stem cell transplant viral infections. DisclosuresNo relevant conflicts of interest to declare.

Umbilical Cord Blood Use For Admission Blood Tests of VLBW Preterm Neonates: A Randomized Clinical Trial

Umbilical Cord Blood Use For Admission Blood Tests of VLBW Preterm Neonates: A Randomized Clinical Trial

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological "layer" of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid cells, myeloid cells, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity-with a substantial degree of inter-individual variation at the time of birth-rather than via a transition between discrete waves. These findings have important implications for the design of strategies for prophylaxis against infection in the newborn and for the use of umbilical cord blood (UCB) in the setting of transplantation.