Umbilical Cord Blood In Patients Research Articles

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

A novel peptide promotes human trophoblast proliferation and migration through PI3K/Akt/mTOR signaling pathway.

BackgroundPreeclampsia (PE) is a complex pregnancy-related disease that endangers the safety of maternal and fetal. The purpose of this study is to reveal the pathogenesis of preeclampsia and discover new predictors from the perspective of peptidomics. The umbilical cord blood of PE and control group was analyzed by peptidomics. A peptide named Regulation of Proliferation Process in Preeclampsia (ROPPIP) was screened out to explore its role in the proliferation, migration and apoptosis of trophoblast cells in preeclampsia.MethodsWe compared and analyzed the umbilical cord blood of patients with PE and normal pregnant women using liquid chromatography-tandem mass spectrometry (LC-MS). hTR-8/Svneo cells cultured in vitro were divided into ROPPIP group and a disordered peptide group as control. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to the expression of Matrix metalloproteinase-2 (MMP2), nuclear associated antigen Ki67, B-cell lymphoma-2 (Bcl2), Caspase 3, and β-actin protein.ResultsWe identified 133 differential peptides. Of these, 51 were up-regulated while 82 were down-regulated. the polypeptide SFGVRMATASPTDGNV with low differential expression in the serum of PE patients was selected for the study, we named the polypeptide as Regulation of Proliferation Process in PE (ROPPIP). The experiment shows that ROPPIP can up-regulate the expression levels of MMP2, Ki67, and Bcl2 in HTR-8/Svneo cells, down-regulate the expression of caspase-3, promote the proliferation and migration of HTR-8/Svneo cells and inhibit the apoptosis induced by cisplatin, the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway may be associated with the function of ROPPIP.ConclusionsROPPIP promotes HTR-8/Svneo cells migration and proliferation, and inhibits apoptosis, by regulating the activation of the PI3K/AKT/mTOR signaling pathway.

Exosomal circular RNA circ_0074673 regulates the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells via the microRNA-1200/MEOX2 axis

ABSTRACT Circular RNAs (circRNAs) are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to investigate the roles and molecular mechanism underlying the effects of circ_0074673 in GDM. Exosomal morphology was visualized by transmission electron microscopy (TEM), while exosomal size and concentration were determined by nanoparticle tracking analysis (NTA). The expression of CD9 and CD63 was measured by western blotting. The levels of circ_0074673, miR-1200 and mesenchyme homeobox 2 (MEOX2) were determined by quantitative real-time polymerase chain reaction (qPCR). Cellular proliferation, migration, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), transwell, and tube formation assays, respectively. The binding relationship between circ_0074673 or MEOX2 and miR-1200 was evaluated by luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull-down assay. The results showed that exosomal size and concentration were greater in the umbilical cord blood of patients with GDM than in that of the healthy controls. The expression of circ_0074673 was upregulated in exosomes from GDM and in human umbilical vein endothelial cells (HUVECs) co-cultured with exosomes. High glucose (HG) treatment suppressed cellular proliferation, migration, and angiogenesis. Circ_0074673 knockdown enhanced the proliferation, migration, and angiogenesis of HG treated HUVECs (HG-HUVECs). As circ_0074673 and MEOX2 directly bind to miR-1200, circ_0074673 silencing promoted the biological functions of HG-HUVECs by sponging miR-1200 and further targeting MEOX2. Altogether, the loss of exosomal circ_0074673 facilitated the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200/MEOX2 axis, suggesting that circ_0074673 is a potential therapeutic target for GDM.

Maternal Noninfectious Fever Enhances Cell Proliferation and Microglial Activation in the Neonatal Rat Dentate Gyrus

(Anesth Analg. 2019;128(6):1190–1198) Maternal fever during labor is a complication that poses many risks for the infant being delivered, and is frequently associated with epidural analgesia. Elevated levels of a proinflammatory cytokine called interleukin-6 (IL-6) are found in the maternal serum and umbilical cord blood of patients with fevers who received an epidural. These investigators have demonstrated through previous studies that higher IL-6 levels can cause temperature increases in rats, and are also connected with microglial activation and subventricular inflammation. In addition, the authors have conducted prior research that connected a higher IL-6 measurement to maternal systemic and fetal brain inflammation. This current study aimed to examine the effect of maternally administered IL-6 on neonatal brain development.

Correlation of lipid peroxidation and ATP enzyme on erythrocyte membrane with fetal distress in the uterus in patients with intrahepatic cholestasis of pregnancy.

This paper aims to investigate the correlation of lipid peroxide in erythrocytes and ATP (Adenosine Triphosphate) enzyme activity of erythrocyte membrane with fetal distress in patients with intrahepatic cholestasis of pregnancy (ICP). Forty-three patients with ICP treated at Jining No. 1 People's Hospital were enrolled as a study group, and another forty healthy parturient women in the same period were enrolled as a control group, to extract their elbow venous blood and fetal umbilical cord blood. Thiobarbituric acid (TBA) was used to detect superoxide dismutase (SOD) activity of erythrocytes, malondialdehyde (MDA) activity in plasma, Na+-K+-ATP enzyme activity and Ca2+-Mg2+-ATP enzyme activity of erythrocytes, which were compared between the study and control groups. The correlation of MDA, Na+-K+-ATP enzyme and Ca2+-Mg2+-ATP enzyme activities with fetal distress in the study group was analyzed, and the correlation of MDA with Na+-K+-ATP enzyme activity was investigated. SOD and MDA activities of erythrocytes in maternal blood of the study group were significantly higher than those in the control group (p<0.05, p<0.001, respectively), but MDA activity in umbilical cord blood of the study group was markedly higher than that in the control group (p<0.001). Na+-K+-ATP enzyme and Ca2+-Mg2+-ATP enzyme activities of maternal and fetal erythrocytes of the study group were remarkably lower than those of the control group (p<0.001). MDA in the fetal distress group was significantly higher than that in the no fetal distress group in the study group (p<0.001). Na+-K+-ATP enzyme activity was negatively correlated with MDA concentration in maternal and fetal erythrocytes of patients with ICP (both p<0.001). Lipid peroxidation in patients with ICP will affect ATP enzyme activity of erythrocyte membrane, and the down-regulation of ATP enzyme activity in umbilical cord blood of patients with ICP may cause fetal distress in the uterus.

High-dose sitagliptin for systemic inhibition of dipeptidylpeptidase-4 to enhance engraftment of single cord umbilical cord blood transplantation.

Delayed engraftment remains a limitation of umbilical cord blood (UCB) transplantation. We previously showed that inhibition of dipeptidylpeptidase (DPP)-4 using sitagliptin 600 mg daily was safe with encouraging results on engraftment, but inhibition was not sustained. We evaluated the efficacy and feasibility of higher doses of sitagliptin to enhance engraftment of UCB in patients with hematological cancers. Fifteen patients, median age 41 (range, 18-59) years, received single UCB grafts matched at 4 (n=11) or 5 (n=4) of 6 HLA loci with median nucleated cell dose of 3.5 (range, 2.57-4.57) x107/kg. Sitagliptin 600 mg every 12 hours was administered days -1 to +2. All patients engrafted by day 30, with 12 (80%) engrafting by day 21. The median time to neutrophil engraftment was 19 (range, 12-30) days. Plasma DPP-4 activity was better inhibited with a mean residual trough DPP-4 activity of 70%±19%. Compared to patients previously treated with 600 mg/day, sitagliptin 600 mg every 12 hours appeared to improve engraftment, supporting the hypothesis that more sustained DPP-4 inhibition is required. In-vivo inhibition of DPP-4 using high-dose sitagliptin compares favorably with other approaches to enhance UCB engraftment with greater simplicity, and may show synergy in combination with other strategies.

Markers of oxidative stress in umbilical cord blood from G6PD deficient African newborns.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that affects as many as 400 million people worldwide, making it the most common enzymatic defect. Subjects with G6PD deficiency are more likely to develop neonatal hyperbilirubinemia potentially leading to kernicterus and are at increased risk for acute hemolytic anemia when exposed to pro-oxidant compounds such as anti-malarial drugs. We collected umbilical cord blood from 300 males born in Uganda to assess for novel markers of systemic oxidative stress. We determined that 10.7% of the samples collected were G6PD A- deficient (G202A/A376G) and when these were compared with unaffected controls, there was significantly higher 8-hydroxy-2’-deoxyguanosine (8-OHdG) concentration, elevated ferritin, increased leukocyte count and higher small molecule antioxidant capacity. These data suggest increased baseline oxidative stress and an elevated antioxidant response in umbilical cord blood of patients with G6PD deficiency.

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke (CoBIS): Clinical Outcomes from a Phase 1 Safety Study

Background: Over 750,000 patients/year in the US experience a debilitating stroke. Approximately 88% of adult strokes are ischemic in etiology, and occur when cerebral blood flow is blocked by a clot or mechanical event. To date, there are no effective therapies. The initial neuroinflammatory response following stroke results in the release of inflammatory mediators which may exacerbate the development of cerebral edema and secondary tissue injury. Preclinical data suggest that cell-based therapy may favorably alter the natural history of these processes through paracrine signaling that reduces inflammation, promotes angiogenesis, neurogenesis and recruitment of endogenous cell repair mechanisms. We hypothesize that intravenous infusion of banked non-HLA matched allogeneic umbilical cord blood (UCB) is safe and will, through tropic effects, improve functional outcome in patients with acute ischemic stroke.Methods: The CoBIS study (NCT02397018) is a prospective, open-label, multi-center, Phase 1 safety study of a single intravenous infusion of allogeneic UCB in patients with ischemic stroke. Adult patients experiencing a recent, acute cortical ischemic stroke in the middle cerebral artery (MCA) with a National Institutes of Health Stroke Scale (NIHSS) score of 8-15(right hemisphere) or 8-18 (left hemisphere) were eligible for enrollment. Cord blood units were selected to match for ABO/Rh and race but not for HLA. Subjects were not pre-treated with immunosuppressive drugs and infused with cell product 3-9 days post stroke. The primary endpoint was safety as assessed by the frequency and severity of adverse events occurring within 24 hours of cord blood infusion within a 12-month period post-infusion. Secondary outcome measures to assess physical and neurological function included modified Rankin Scale (mRS), NIHSS, and Barthel Index (BI).Results: Ten male patients with a mean age of 61.5 years (range 45-79) were enrolled between July 2015 and February 2016 at Duke University and Houston Methodist Hospital. All subjects were independent prior to the stroke; 9 subjects had an historic mRS of 0 and one subject had an historic mRS of 1 due to bilateral below the knee amputation. Study participants received an intravenous infusion of 0.83-3.34 X 10e7 TNC/kg administered between 3-9 days post stroke. At time of infusion (baseline), the mean mRS was 4.4±0.5 (range 4-5). At 3 months, the mean mRS was 2.8±0.9 (range 2-4) and 50% of subjects exhibited a 1 grade increase (improvement) in mRS, 40% had improved by 2 grades and one subject by 3 grades. According to studies examining change in mRS over time, 58% of patients disabled by stroke (mRS 3-5) will improve by at least one grade by 3 months (Kelly-Hayes et al, J. Neurol Rehab 1989). The mean NIHSS at the time of enrollment was 13.6±0.8 (range 12-15), at infusion (baseline) 11.2 ±1.6 (range 9-14), and at 3 months 5.3±2.2 (range 3-9) with a shift down (improvement) by at least 4 points (mean 6.1±1.7; range 4-9) relative to baseline. Similarly, all patients showed improvement in basic activities of daily living at 3 months relative to infusion (baseline), as measured by the BI (mean 52.0±24.7; range 10-80). As of June, 2016, four serious AEs were observed in one study subject but were unrelated to study therapy and not reportable.Conclusions: Six month safety data suggests intravenous infusion of unmatched, allogeneic, UCB cells is feasible and well tolerated in adult patients with acute ischemic stroke. Furthermore, all patients exhibited improved functional outcomes at 3 months relative to baseline as measured by mRS, NIHSS and BI. These results should be further investigated in a controlled and randomized Phase 2 study using human UCB and placebo in patients with ischemic stroke which is planned to begin Q4 2016. DisclosuresNo relevant conflicts of interest to declare.

Successful Engraftment of Donor Umbilical Cord Blood (UCB) Cells after Co-Transplantation of Nicord® (Ex Vivo Expanded UCB Progenitor Cells with Nicotinamide) and a Second Unmanipulated Cord Blood Unit after Myeloablative Chemotherapy in Pediatric Patients with Severe Sickle Cell Disease

Background: Patients with severe sickle cell disease (SCD) experience organ damage, poor quality of life, and are at high risk of premature mortality. To date, allogeneic hematopoietic stem cell transplant remains the only available curative therapy for SCD. However, patients with SCD have difficulties finding matched related or unrelated donors for transplantation. UCB could be an alternative graft option for most of the SCD patients but, to date, results with unrelated UCB have not been satisfactory for these hard to engraft patients. NiCord is an ex vivo expanded product manufactured from an entire UCB unit which has been shown to produce rapid and sustained engraftment in combination with a second unmanipulated CB unit or as a standalone graft in adult patients with high-risk hematologic malignancies. We hypothesized that the combination of NiCord with an unmanipulated UCB unit might overcome the engraftment barriers which have limited the success of UCBT in patients with SCD. This strategy is currently evaluated for safety and efficacy in a phase I/II multi-center study in pediatric patients with SCD undergoing myeloablative conditioning therapy. Here we report the results of the first 8 patients in the study.Methods: Patients with SCD and high risk features were eligible if they were between 2 and 45 years of age and if they had adequate performance status and organ function, 2 suitable unrelated UCB units that minimally matched the patient at 4/6 HLA alleles, and if they did not have a fully HLA matched related or unrelated adult donor. The NiCord graft, manufactured by the study sponsor, consisted of a CD133+ expanded cell fraction and an uncultured CD133- T-cell containing fraction. All patients received hydroxyurea beginning on day -35. Patients were subsequently prepared for transplantation with myeloablative chemotherapy: Busulfan/Cyclophosphamide and Anti Thymocyte Globulin (ATG). After the first 3 patients an adverse effect of ATG on the expanded graft was suspected and ATG was replaced by Fludarabine for the subsequent 5 patients. On day 0, the unmanipulated CB unit and NiCord graft were infused. Engraftment, GVHD incidence, treatment related mortality and survival were assessed by conventional parameters.Results: Eight patients, at a median age of 12 years (range 3-16 years) and a median weight of 41 kg (range 17-67 kg) were transplanted. HLA matching between patients and NiCord units was 4/6 (n=7) and 5/6 (n=1); and that between patients and unmanipulated units was 4/6 (n=5) and 5/6 (n=3). Median CD34+ cell dose infused in the NiCord graft was 107 x 105/kg. All 8 transplanted patients initially engrafted neutrophils at a median of 7 days (range 6-20 days) with the NiCord graft. One patient experienced secondary graft failure and died after a second transplant. Ultimately, long term engraftment was derived from NiCord in 2 patients, from the unmanipulated unit in 4 patients and mixed donor chimerism is still sustained in one patient. Patients were hospitalized for initial transplant for a median of 55 days (range 43-100 days). The 7 patients with sustained full donor cell engraftment are currently alive at a median follow-up of 33 months (range 3-45 months), transfusion free and without sickle cell related symptoms. Engraftment and clinical outcomes of the 8 patients are shown in Table 1.Conclusions: NiCord appears to overcome the engraftment barriers of UCB in patients with SCD. Remarkably, sustained donor cell engraftment was obtained in 7/8 patients, despite 4/6 matched UCB units and 5 patients without ATG. NiCord has the potential to increase access to transplantation for patients with SCD by enabling the successful use of unrelated UCB donors. Further optimization of this approach with strategies to further decrease GVHD is warranted. [Display omitted] DisclosuresMartin:Novartis: Other: Support of clinical trials; Jazz Pharmaceuticals: Other: One time discussion panel. Galamidi:Gamida Cell Ltd.: Employment. Peleg:Gamida Cell Ltd.: Employment. Goshen:Gamida Cell Ltd.: Employment. Schwarzbach:Gamida Cell Ltd.: Employment. Snyder:Gamida Cell Ltd.: Employment. Peled:Gamida Cell Ltd.: Employment.

Unrelated donor stem cell transplantation for transfusion-dependent thalassemia.

Thalassemia major is characterized by severe anemia dependent on red cell transfusions from infancy. Conservative management requires a safe source of compatible blood throughout life, strategies to combat iron overload, monitoring and treatment of transfusion-related complications, and management of cardiac and/or hepatic dysfunction from iron accumulation. Complications can result in premature morbidity and mortality. Stem cell transplantation is curative, but outcomes depend on the availability of a histocompatible donor, recipient age, and disease-related complications. Successful transplantation requires stable donor engraftment and donor-derived erythropoiesis and a low incidence of graft-versus-host disease, organ toxicities, and mortality. This translates to a cure with good quality of life and life span. Since recipients are at a high risk for graft rejection (prior transfusions, immunocompetency), myeloablative transplants have been the norm. Recent modifications to standard preparative regimens have significantly reduced transplant toxicities, resulting in >80% disease-free survival in children. Aiming to further reduce regimen-related toxicities, such as veno-occlusive liver disease and sterility, a recent trial explored reduced-intensity conditioning in unrelated donor (URD) transplants utilizing marrow or umbilical cord blood in patients without suitable familial donors. This report summarizes advances in URD transplantation for thalassemia, focusing on conditioning regimen nuances.

In vitro cardiomyocyte differentiation of umbilical cord blood cells: crucial role for c-kit+ cells

Background aimsAlthough bone marrow c-kit+ progenitor cells support myocardial regeneration, the cardiomyocyte differentiation potential of umbilical cord blood (UCB) c-kit+ cells is unknown. MethodsUCB mononuclear cells (MNCs) and c-kit+ cells purified by use of immunomagnetic beads were used. Cardiomyocyte differentiation was induced with (i) α-minimum essential medium (MEM) with cyclosporine A, (ii) α-MEM with bone morphogenic protein 4 (BMP-4) and transforming growth factor-β (TGF-β) or (iii) MEM with dexamethasone. The expression of cardiac markers (GATA4, GATA6, β-myosin heavy chain, α-sarcomeric actin and cardiac Troponin T) was investigated, and whole-cell current and voltage-clamp recordings were performed. ResultsAlthough c-kit+ cells revealed an immature gene profile, with high expression of CD34, CD133, aldehyde dehydrogenase-A1 and c-myc RNAs, purified c-kit+ cells did not succeed in differentiating into cardiomyocyte-like cells in culture. In contrast, MNCs (either in α-MEM plus cyclosporine A or in α-MEM plus BMP-4 and TGF-β) produced large, adherent cells expressing several cardiac genes and exhibiting an excitable phenotype. Cardiomyocyte-like cell formation was prevented by removing the c-kit+ cell fraction from MNCs. Furthermore, after co-culturing carboxyfluorescein diacetate succynimidyl ester (CFSE)-tracked c-kit+ cells together with c-kit– cells, we found that cardiac Troponin T–expressing cells were also CFSE+. ConclusionsWe show that UCB contains progenitors endowed with differentiation potential into cardiomyocytes: these cells reside in the c-kit+ fraction and require the presence of abundant accessory cells to accomplish the differentiation. These preliminary observations provide the basis for consider the storage of autologous UCB in patients with prenatal diagnosis of congenital heart diseases potentially amenable by myocardial regenerative approaches.

Similar Outcome Between Siblings, Unrelated Donors and Cord Blood After Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients Older Than 50 Years with Acute Myeloid Leukemia in Complete Remission

AbstractAbstract 1985 Introduction:For older patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) provides the best chance of long-term survival. Because older patients less often have available healthy sibling donors, alternative donors may be more important. We compared the outcomes of reduced intensity conditioning (RIC) HCT for AML patients over 50 years in complete remission (CR) using matched sibling (SIB), unrelated (URD) or umbilical cord blood (UCB) donors. Patients, methods and HCT characteristics:From January 2000 to December 2010, 197 consecutive patients (median age 59, range 50–74) received RIC and allogeneic HCT in 3 independent centers, either from SIB (n=82), HLA 8/8 allele-matched URD (n=35) or UCB (n=80; 10 single unit). One patient received an HLA 7/8 allele-mismatched URD. SIB and URD all received peripheral blood as source of stem cells. Conditioning was fludarabine-based in the majority (86%) and most received Graft versus Host Disease (GvHD) prophylaxis using cyclosporine plus MMF (79%). 68% were in CR1; 6% of patients had good risk cytogenetics and 29% had poor risk (MRC classification). Results:Patient characteristics were similar between the 3 groups for age, gender, CR# and the median time interval from diagnosis to HCT. UCB recipients had more frequent high risk features including: KPS<90% (19% versus 10% and 3% for SIB and URD, respectively, p=0.04); female donor: male recipient (44% versus 20% SIB and 17% URD, p=0.04); and somewhat more high risk cytogenetics (UCB 34%, SIB 22%, URD 17%, p=0.06). Conditioning regimens using Fludarabine and low dose TBI were more frequent in UCB: 100% vs. 24% for SIB and 11% for URD, p<0.0001); Fludarabine and Busulfan (more in URD: 71% vs. 43% for SIB and 0 for UCB, p<0.0001); and Cyclophosphamide plus low dose TBI (more in SIB: 28% vs. 3% for URD and 0 for UCB, p<0.0001) also differed between the 3 groups. Moreover, more ATG was used in URD (86% vs. 29% for SIB and 29% for UCB, p<0.0001). After a median follow-up of 39 months (range 2 to 104, 42 months for SIB, 25 months for URD and 51 months for UCB), 103 patients survive. The 3-year cumulative incidence function (CIf) of transplant related (non-relapse) mortality (TRM) was 18%, 14% and 24% with SIB, URD and UCB, respectively (p=0.22). The 3-year CIf of relapse was 33%, 29% and 43% with SIB, URD and UCB, respectively (p=0.04). Consequently, the 3-year CIf of leukemia free survival (LFS) was 48%, 57% and 33% with SIB, URD and UCB, respectively (p=0.009). In multivariate analysis, poor cytogenetic risk was associated with a higher rate of relapse (HR 1.7 [95% CI 1.0–3.0], p=0.04), worse LFS (HR 1.6 [1.0–2.5], p=0.03) and a trend for worse OS (HR 1.6 [1.0–2.4], p=0.06), but survival using each donor sources was similar (UCB HR 1.2 [0.7–2.1], p=0.45; URD 1.2 [0.5–2.7], p=0.73 as compared to SIB). Adjusted, 3-year OS was 55% with SIB, 45% with URD and 43% with UCB (p=0.26) (Figure 1). The use of TBI-containing regimen was associated with a non-significant, but worse OS in recipients of MRD and URD grafts (HR 1.8 [0.9–3.8], p=0.11). Outcome was similar between the 3 centers. Conclusion:These data suggest equivalence of outcome using SIB, URD or UCB in patients >50 years with AML in CR. Poor cytogenetic risk was the dominant prognostic factor, influencing relapse and LFS with a trend for worse OS. Until prospective studies are completed, this study supports the recommendation to consider SIB, URD or UCB for HCT for patients with older AML in CR. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Effects of combined spinal-epidural analgesia and patient controlled epidural labor analgesia in latent and active phase

Objective To compare the effects,stress reaction and concentration of ropivacaine in umbilical cord blood of patients who accepted combined spinal epidural analgesia or patient controlled epidural labor analgesia in latent and active phase.Methods After approved by the ethics committee and informed consents from 80 nulliparous parturients who were admitted to Beijing Friendship Hospital,Capital University of Medical Sciences between January to June 2009,and who were term,single,cephalic presentation delivery and ASA Ⅰ-Ⅱ,were divided into two groups randomly:latent phase group (Group L,cervical dilation 0.5-2.5 cm,n=40) and active phase group (Group A,cervical dilation ≥3.0 cm,n =40).Ropivacaine 2 mg and fentanyl 10 μg was administered in subarachnoid space of all patients.Then,patient controlled epidural infusion of 0.1 ％ ropivacaine plus fentanyl 2 μg/ml were administered.Pain scores (visual analogue score,VAS),lower extremity muscle strength,duration of labor,delivery mode,total dosage used,maternal satisfaction,Apgar score (1 min and 5 min) were evaluated; concentration of ropivacaine (high performance liquid chromategraphy) in cord blood,and concentration of cortisol (radioimmunoassay) in maternal venous blood and cord blood were detected.Forty nulliparous parturients without labor analgesia were taken as control group (Group C).Chi-square test and one way analysis of variance was applied for statistical analysis.Results (1) VAS in Group L and Group A were lower than that of Group C when cervix dilated at 7.0-8.0 cm (2.9± 1.4,2.6± 1.5 vs 9.2±0.7,F=201.50,P＜0.01) and fully dilated (4.7±2.2,3.6±2.0 vs 9.1±0.7,F =-62.07,P＜0.01,respectively).(2) Tbe concentration of cortisol in maternal venous blood right after delivery was higher than that before analgesia in all groups,and the change in group C was significantly greater than that in group L and group A [(902±172) μg/L vs (761±125) μg/L and (731±184) μg/L,t =-3.491 and-3.483,all P＜0.01],moreover there was no significant difference between group L and group A (P＞0.05).There were no difference in cortisol concentration of umbilical blood among the three groups [(168±46) μg/L,(159±49) μg/L and (170±86) μg/L,F=0.23,P＞0.05].(3) There was no difference between ropivacaine concentration in umbilical blood of group L and group A [(0.21±0.10) mg/L vs (0.20±0.03) mg/L,t=0.557,P＞0.05].(4) No significant differences was shown among the three groups in the duration of first and second stage of labor,rate of augmentation,neonatal birth weight,Apgar score at 1 min and 5 min (all P＞0.05).Compared with group C,group L and group A had higher rate of vaginal delivery (52.5％ vs 75.0％ and 85.0％,P＜0.05) and lower rate of cesarean section (45.0％ vs 20.0％ and 15.0％,P＜0.05).The duration of analgesia in group L was longer than that in group A [(215±143) min vs (118±50) min,t =3.722,P＜0.01] and the dosage of fentanyl was also higher [(28± 11) μg vs (17±6) μg,t =5.084,P＜0.01].Conclusions Labor analgesia with combined spinal epidural could decrease cesarean section rate and maternal stress reaction without prolonging the duration of labor and inhibiting neonatal stress reaction.Labor analgesia start from latent phase would not increase the concentration of ropivacaine in cord blood. Key words: Lobor, obstetric; Analgesia, obstetrical; Analgesia, patient-controlled; Anesthesia, epidural; Anesthesia, spinal

Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia.

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.