Hematopoietic stem cell transplantation in patients with myelodysplastic syndrome

Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). However, the morbidity and mortality associated with conventional HSCT have traditionally prevented many patients from undergoing such treatment. Recent advances, including better prognostic algorithms, the introduction of reduced intensity conditioning regimens, and experience with alternative donors, have made HSCT a realistic option for an increasing number of patients with MDS

Demystifying the Meaning of Active Learning in Postsecondary Biology Education

Active learning is frequently used to describe teaching practices, but the term is not well-defined in the context of undergraduate biology education. To clarify this term, we explored how active learning is defined in the biology education literature ( = 148 articles) and community by surveying a national sample of biology education researchers and instructors ( = 105 individuals). Our objectives were to increase transparency and reproducibility of teaching practices and research findings in biology education. Findings showed the majority of the literature concerning active learning never defined the term, but the authors often provided examples of specific active-learning strategies. We categorized the available active-learning definitions and strategies obtained from the articles and survey responses to highlight central themes. Based on data from the BER literature and community, we provide a working definition of active learning and an Active-Learning Strategy Guide that defines 300+ active-learning strategies. These tools can help the community define, elaborate, and provide specificity when using the term active learning to characterize teaching practices.</p

The third way of umbilical cord blood banking

This paper analyses the current problems of public and private banks, and gives two hybrid models which facilitate the cell exchange and allocate resource more efficiently. One is the 'public and private combination' model, and the other is the 'donatable family banking' model. It analyzes these models in terms of cell exchange, quality and financial consideration. This paper provides an alternative perspective on how the cord blood industry can cooperate with stem cell science

Survival Improvements in Adolescents and Young Adults after Myeloablative Allogeneic Transplantation for Acute Lymphoblastic Leukemia

AbstractAdolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children

Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT

The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Relationship of Race/Ethnicity and Survival after Single Umbilical Cord Blood Transplantation for Adults and Children with Leukemia and Myelodysplastic Syndromes

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 107/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used

Correction: The European Society for Blood and Marrow Transplantation (EBMT) consensus guidelines for the detection and treatment of donor-specific anti-HLA antibodies (DSA) in haploidentical hematopoietic cell transplantation

The original version of this Article contained a typographical error in the spelling of the author Marcelo Fernandez-Vina, which was incorrectly given as Marcelo Fernadez-Vina. This has now been corrected in the PDF and HTML versions of the Article

Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients

We have previously identified sole +9, 13q- or 20q-, as ‘favorable' and sole +8 or complex karyotype as ‘unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (−7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), −5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-year survival rates were 8 and 51% (hazard ratio (HR): 3.1, 95% confidence interval (CI): 2.2–4.3; P<0.0001). Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of cytogenetic-risk categorization and also identified thrombocytopenia (platelets <100 × 109/l) as another independent predictor of inferior survival (P<0.0001). A similar multivariable analysis showed that karyotype (P=0.001) and platelet count (P=0.04), but not IPSS (P=0.27), predicted leukemia-free survival; the 5-year leukemic transformation rates for unfavorable versus favorable karyotype were 46 and 7% (HR: 5.5, 95% CI: 2.5–12.0; P<0.0001). This study provides the rationale and necessary details for incorporating cytogenetic findings and platelet count in future prognostic models for PMF

Ethical issues relating to the banking of umbilical cord blood in Mexico

<p>Abstract</p> <p>Background</p> <p>Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico.</p> <p>Discussion</p> <p>A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord.</p> <p>Summary</p> <p>Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance.</p