The Experts below are selected from a list of 72138 Experts worldwide ranked by ideXlab platform
Hal E Broxmeyer - One of the best experts on this subject based on the ideXlab platform.
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umbilical Cord Blood transplantation the first 25 years and beyond
Blood, 2013Co-Authors: Karen K. Ballen, Eliane Gluckman, Hal E BroxmeyerAbstract:Umbilical Cord Blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical Cord Blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated Cord Blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical Cord Blood transplantation have improved, with greater emphasis on Cord Blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical Cord Blood units and improved supportive care techniques. Cord Blood expansion trials have recently shown improvement in time to engraftment. Umbilical Cord Blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
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alloantigen priming induces a state of unresponsiveness in human umbilical Cord Blood t cells
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Grant Risdon, Jay Gaddy, Masato Horie, Hal E BroxmeyerAbstract:Abstract Induction of alloreactivity in human adult and umbilical Cord Blood T cells was evaluated in mixed leukocyte culture by exposure to an allogeneic lymphoblastoid line that expresses known costimulatory molecules. Initial exposure to alloantigen-presenting cells (allo-APC) induced strong proliferative responses in both adult and Cord Blood T cells. However, in contrast to adult T cells, Cord Blood T cells exhibited little proliferation after restimulation with donor APC. Primed Cord Blood T cells could respond to interleukin 2 (IL-2), but unresponsiveness to alloantigen was not overcome by addition of exogenous IL-2. Unresponsiveness was long-lasting and appeared to be maintained by a combination of induction of anergy and activity of CD8+ suppressor cells. This information may contribute to use of human Cord Blood as an allogeneic source of transplantable stem cells.
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Cord Blood banking for hematopoietic stem cell transplantation an international Cord Blood transplant registry
Bone Marrow Transplantation, 1993Co-Authors: E Gluckman, John E. Wagner, J Hows, N Kernan, B Bradley, Hal E BroxmeyerAbstract:Human umbilical Cord Blood contains enough hematopoietic stem cells for transplantation instead of marrow cells to cure children and adults with leukemia and other potentially fatal marrow disorders. An international Cord Blood transplantation registry is currently collecting information about the results of these transplants. As a result of relative immune deficiency at birth, it is likely that partially matched unrelated transplants can be successful; for this purpose an international Cord Blood banking project is described.
Louis Yiksi Chan - One of the best experts on this subject based on the ideXlab platform.
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Cord Blood thyroid stimulating hormone level in high risk pregnancies
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2003Co-Authors: Louis Yiksi Chan, Pui Yu ChiuAbstract:OBJECTIVE: To evaluate the effect of various antepartum conditions on Cord Blood thyroid-stimulating hormone (TSH) level. STUDY DESIGN: The study group consisted of 24,892 consecutive singleton deliveries over a period of 4 years. The effect of preeclampsia, glucose intolerance, maternal medical diseases, and antepartum hemorrhage of unknown origin (APHUO) on Cord Blood TSH level were assessed by univariate analysis and linear regression. RESULTS: After controlling for potential confounders, there was a significant independent association between Cord Blood TSH level and preeclampsia (P=0.043), glucose intolerance (P=0.015), and maternal medical diseases (P=0.022). Antepartum hemorrhage of unknown origin was not associated with a higher Cord Blood TSH level. CONCLUSION: Cord Blood TSH level was significantly elevated in various adverse antepartum conditions. This may be related to the placental insufficiency and fetal hypoxia commonly found in these high-risk pregnancies.
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Cord Blood thyroid stimulating hormone level in twin pregnancy
Acta Obstetricia et Gynecologica Scandinavica, 2003Co-Authors: Louis Yiksi Chan, Pui Yu ChiuAbstract:Cord Blood thyroid-stimulating hormone level is elevated among neonates who undergo more perinatal stress. The aim of this study was to investigate the effect of twin pregnancy on the Cord Blood thyroid-stimulating hormone level. The study group consisted of 24 910 singleton and 543 twin neonates over a 4-year period. The effect of twin pregnancy on the Cord Blood thyroid-stimulating level was evaluated. Linear regression analysis was used to control for the effect of mode of delivery birth weight and infant sex. The median Cord Blood thyroid-stimulating hormone levels (interquartile range) in the singletons and in the twins were 5.8mIU/l (4.2–8.6) and 5.6mIU/l (4.3–7.5) respectively. Linear regression analysis revealed no significant difference between singleton and twin Cord Blood thyroid-stimulating hormone levels (p = 0.23). Cord thyroid-stimulating hormone levels tended to be higher in second-born twins (p = 0.08) and monochorionic twins (p = 0.097) compared with singleton neonates. Twins with more than 20% weight disCordance were associated with a significantly higher Cord Blood thyroid-stimulating hormone level (p = 0.035). Cord Blood thyroid-stimulating hormone level is elevated in some subgroups of twins who are at higher risk of adverse perinatal outcomes. However the overall effect of multiple pregnancy on the Cord Blood thyroid-stimulating hormone level is small. Cord Blood thyroid-stimulating hormone screening for congenital hypothyroidism is also valid in twin pregnancies. (authors)
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influences of perinatal factors on Cord Blood thyroid stimulating hormone level
Acta Obstetricia et Gynecologica Scandinavica, 2001Co-Authors: Louis Yiksi Chan, Tse Ngong LeungAbstract:Background. Cord Blood thyroid-stimulating hormone level is affected by various perinatal factors. The aim of this study is to investigate the relative impact of these factors on the Cord Blood thyroid-stimulating hormone results in singleton pregnancies. Methods. The study group consisted of 20,086 consecutive singleton deliveries over a 3 year period. The effect of mode of delivery, infant sex, gestation at birth, birth weight, and duration of labor on the incidence of false elevation of Cord Blood thyroid-stimulating hormone was assessed by univariate analysis and logistic regression. Results. There was an independent positive association between false elevation of Cord Blood thyroid-stimulating hormone (≥15.0 mIU/L) and birth weight ( p =0.005), male infant sex ( p <0.001), and instrumental delivery ( p <0.001). Both elective and emergency cesarean section were negatively associated with elevated Cord thyroid-stimulating hormone level ( p <0.001). When the cutoff level was raised to 40.0 mIU/L, none o...
Karen K. Ballen - One of the best experts on this subject based on the ideXlab platform.
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Cord Blood transplant for acute myeloid leukaemia
British Journal of Haematology, 2016Co-Authors: Karen K. Ballen, Hillard M LazarusAbstract:Umbilical Cord Blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first Cord Blood transplants were done in children, there are currently more Cord Blood transplants performed in adults. In this review, we explore the history of umbilical Cord Blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical Cord Blood transplantation cures approximately 30-40% of adults and 60-70% of children with AML. Controversial issues, including the use of double versus single Cord Blood units for transplantation, optimal Cord Blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed.
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atg for Cord Blood transplant yes or no
Blood, 2014Co-Authors: Karen K. BallenAbstract:In this issue of Blood , Lindemans et al report on the impact of thymoglobulin (antithymocyte globulin [ATG]) during the preparative regimen for pediatric unrelated umbilical Cord Blood transplantation (UCBT). Survival and chronic graft-versus-host disease (GVHD) were similar whether or not patients
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umbilical Cord Blood transplantation the first 25 years and beyond
Blood, 2013Co-Authors: Karen K. Ballen, Eliane Gluckman, Hal E BroxmeyerAbstract:Umbilical Cord Blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical Cord Blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated Cord Blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical Cord Blood transplantation have improved, with greater emphasis on Cord Blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical Cord Blood units and improved supportive care techniques. Cord Blood expansion trials have recently shown improvement in time to engraftment. Umbilical Cord Blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
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pre infusion characteristics of the predominant Cord Blood unit correlate with hematopoietic engraftment in the setting of non myeloablative double Cord Blood transplant dcbt
Blood, 2005Co-Authors: Richard L Haspel, Jerome Ritz, Grace Kao, Beow Y Yeap, Thomas R Spitzer, Joseph H Antin, Karen K. BallenAbstract:It is well established that delayed engraftment following transplant of single Cord Blood unit is mainly due to low CD34 cell dose. Protocols utilizing sequential infusion of two Cord Blood units increase the total dose of CD34 cells and lead to more rapid hematopoietic engraftment. One of the two Cord Bloods usually predominates. We assessed the effect of the pre-infusion variables of each Cord Blood unit on engraftment. Twenty-one patients with hematologic malignancies underwent non-myeloablative conditioning with fludarabine, mephalan and antithymocyte globulin. Two Cord Bloods, each a minimum 4/6 HLA match with the recipient and each other, were then infused sequentially 1 to 6 hours apart. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Chimerism analysis of peripheral Blood leukocytes was performed by PCR amplification of short tandem repeat loci. Four patients with less than 4 weeks of chimerism data due to death or failed engraftment were excluded. The logrank test, using median values as the cutoff, was used to determine the relationship between pre-infusion variables and time to engraftment. All exact p-values are based on two-sided tests. In all patients, a single Cord Blood predominated by 3 months post-infusion. In 13 out of 17 transplants (76%), the first Cord Blood infused predominated (p=.05). The median times for engraftment were 41 days (range: 21–55 days) for platelets >20000 (P20), 65 days (range: 34–91 days) for platelets > 100000 (P100) and 18 days (range: 15–34 days) for ANC>500. Total (Cord1 + Cord2) CD34 cells/kg (median: 1.9 x 10 5 ; range: 6.3 x 10 4 to 1.0 x 10 6 ) and total nucleated cells/kg (median: 4.02 x 10 7 ; range 2.98 x 10 7 to 5.27 x 10 7 ) infused did not affect engraftment. However, patients receiving greater than 1.1x 10 5 CD34/kg in the predominant unit (median: 1.1 x 10 5 ; range: 3.0x10 4 to 8.7x10 5 ) but not losing unit (median: 6.92 x 10 4 ; range: 8.3.0x10 3 to 7.4x10 5 ) had faster P100 (p=.042 versus p=0.54). The median storage time of the Cord Blood units infused was 1374 days (range: 272–3047 days). Faster P100 was observed when the predominant unit had a shorter storage time relative to the losing unit (median difference between units: 392 days, p=.03). Our study demonstrated that in the setting of non-myeloablative sequential DCBT, the majority of predominant units engrafted is the first one infused. The CD34 dose and storage time of the predominant unit are factors that can affect engraftment. Although only a small number of patients were studied, these results suggest that the capacity of stem cell niche may be limited and the quality of the Cord Blood unit occupying this niche can affect the speed of hematopoietic engraftment.
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New trends in umbilical Cord Blood transplantation
Blood, 2005Co-Authors: Karen K. BallenAbstract:Since the first report of a successful umbilical Cord Blood transplantation in 1988, there has been great interest in the use of Cord Blood as an alternative stem cell source to treat cancer and genetic diseases. More than 4000 Cord Blood transplantations have been performed worldwide. In this review, the scientific rationale for this therapy, as well as related preclinical studies, Cord Blood banking issues, and ethical concerns, will be addressed. Results of studies in both pediatric and adult transplantation will be discussed. Finally, new indications for Cord Blood use and emerging technologies will be addressed.
Liesbeth Duijts - One of the best experts on this subject based on the ideXlab platform.
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Cord Blood DNA methylation reflects Cord Blood C-reactive protein levels but not maternal levels: a longitudinal study and meta-analysis
Clinical Epigenetics, 2020Co-Authors: Edwina H. Yeung, Weihua Guan, Xuehuo Zeng, Lucas A. Salas, Sunni L. Mumford, Paula Prado Bert, Evelien R. Meel, Anni Malmberg, Jordi Sunyer, Liesbeth DuijtsAbstract:Background Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in Blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in Cord Blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in Cord Blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Results Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size ( n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in Cord Blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Conclusions Maternal CRP levels measured during each trimester were not associated with Cord Blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in Cord Blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways. Trial registration Clinicaltrials.gov, NCT00467363 , Registered April 30, 2007, http://www.clinicaltrials.gov/ct2/show/NCT00467363
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Cord Blood dna methylation reflects Cord Blood c reactive protein levels but not maternal levels a longitudinal study and meta analysis
Clinical Epigenetics, 2020Co-Authors: Edwina H. Yeung, Weihua Guan, Xuehuo Zeng, Lucas A. Salas, Sunni L. Mumford, Paula Prado Bert, Anni Malmberg, Jordi Sunyer, Evelien R Van Meel, Liesbeth DuijtsAbstract:Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in Blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in Cord Blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in Cord Blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in Cord Blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Maternal CRP levels measured during each trimester were not associated with Cord Blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in Cord Blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways. Clinicaltrials.gov, NCT00467363, Registered April 30, 2007, http://www.clinicaltrials.gov/ct2/show/NCT00467363
Eliane Gluckman - One of the best experts on this subject based on the ideXlab platform.
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umbilical Cord Blood transplantation the first 25 years and beyond
Blood, 2013Co-Authors: Karen K. Ballen, Eliane Gluckman, Hal E BroxmeyerAbstract:Umbilical Cord Blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical Cord Blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated Cord Blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical Cord Blood transplantation have improved, with greater emphasis on Cord Blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical Cord Blood units and improved supportive care techniques. Cord Blood expansion trials have recently shown improvement in time to engraftment. Umbilical Cord Blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
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donor selection for unrelated Cord Blood transplants
Current Opinion in Immunology, 2006Co-Authors: Eliane Gluckman, Vanderson RochaAbstract:The number of unrelated Cord Blood transplants is increasing, with more than 8000 patients reported worldwide. Criteria of donor choice have been identified. Cell dose measured by number of nucleated cells is the most important factor, thus increases in cell dose can partially overcome the presence of HLA incompatibilities. Overall, increasing the number of HLA incompatibilities is associated with non-engraftment, but it also decreases the risk of relapse in patients with malignant disease, resulting in an absence of effect of HLA incompatibilities on event-free survival (survival without relapse or complications related to the transplant). However, in patients with non-malignant disorders, increasing the number of HLA incompatibilities decreases the overall survival. These results show that criteria of donor choice based on number of infused cells, number of HLA incompatibilities and diagnosis improve outcomes of unrelated Cord Blood transplants. Currently, owing to the possibility of using a non HLA identical donor, most patients can find a donor, increasing the need for the development of the inventory of Cord Blood banks. Methods of improving engraftment are currently under investigation.
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results of unrelated umbilical Cord Blood hematopoietic stem cell transplant
Transfusion Clinique Et Biologique, 2001Co-Authors: Eliane Gluckman, V Rocha, S ChevretAbstract:The number of umbilical Cord Blood transplants (UCBT) is increasing worldwide, and the purpose of EuroCord is to evaluate the results and compare the outcome of UCBT with allogeneic bone marrow transplants (BMT). Data have been reported to EuroCord by many transplant centers. Close links have been established with Cord Blood banks through NetCord. BMT data have been provided by transplant centers and also by the European Blood and Marrow Transplant (EBMT) and International Bone Marrow Transplant Registries (IBMTR). EuroCord has analyzed the outcome of unrelated UCBT from 121 transplant centers and 29 countries. The results have shown that survival with unrelated mismatched UCBT was comparable to that with unrelated BMT. Engraftment with Cord Blood was delayed, resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-versus-host-disease (GVHD) was reduced with Cord Blood grafts even in HLA mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to that after BMT. The overall event-free survival with UCBT was not statistically different when compared to BMT. In conclusion, this large registry study confirms the potential benefit of using umbilical Cord Blood hematopoietic stem cells for allogeneic transplants.
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current status of umbilical Cord Blood hematopoietic stem cell transplantation
Experimental Hematology, 2000Co-Authors: Eliane GluckmanAbstract:Abstract Objective The number of umbilical Cord Blood transplants is increasing worldwide. At this time, it is important to evaluate their results and to compare the outcome of umbilical Cord Blood transplants with allogeneic bone marrow transplants. Data Sources Data have been reported to the EuroCord Registry by multiple transplant centers. Close links have been established with the Cord Blood banks through NetCord. Bone marrow transplant data have been provided by transplant centers and through the European Blood and Marrow Transplant (EBMT) and International Bone Marrow Transplant Registries (IBMTR). Results EuroCord has analyzed the outcomes of 527 umbilical Cord Blood transplants from 121 transplant centers and 29 countries. The donor was related in 138 cases and unrelated in 399 cases. The results showed that survival with umbilical Cord Blood transplants was comparable to that with related or unrelated bone marrow transplants. Engraftment with Cord Blood was delayed resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-vs-host disease was reduced with Cord Blood grafts even in HLA-mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to the rate of relapse after bone marrow transplant. The overall event-free survival with umbilical Cord Blood transplantation was not statistically different compared to bone marrow transplants. Conclusions This large registry study confirms the potential benefit of using umbilical Cord Blood hematopoietic stem cells for allogeneic transplants.
