70,756 research outputs found

    Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

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    Thalassemia major and sickle cell disease are the two most widely disseminated hereditary hemoglobinopathies in the world. The outlook for affected individuals has improved in recent years due to advances in medical management in the prevention and treatment of complications. However, hematopoietic stem cell transplantation is still the only available curative option. The use of hematopoietic stem cell transplantation has been increasing, and outcomes today have substantially improved compared with the past three decades. Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%. However, only a few controlled trials have been reported, and decisions on patient selection for hematopoietic stem cell transplantation and transplant management remain principally dependent on data from retrospective analyses and on the clinical experience of the transplant centers. This consensus document from the European Blood and Marrow Transplantation Inborn Error Working Party and the Paediatric Diseases Working Party aims to report new data and provide consensus-based recommendations on indications for hematopoietic stem cell transplantation and transplant management

    Further development and refinement of hematopoietic cell transplantation in zebrafish

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    Hematopoietic stem cells are a rare but crucial population of cells that are responsible for maintaining hematopoiesis throughout vertebrate life. Clinically, hematopoietic stem cells have been utilised for treatment of hematological disease, autoimmune disorders and cancer through the application of hematopoietic cell transplants. A detailed understanding of the behaviour of hematopoietic stem cells and their post-transplant interaction with the niche can lead to improved transplant outcomes. However, there are many challenges in studying hematopoietic stem cell transplantation in mammalian systems owing to the difficulty of observing transplanted cells in vivo. This thesis aims to refine hematopoietic cell transplantation protocols described in adult zebrafish (Danio rerio). To this end, fluorescent hematopoietic stem and precursor populations were further characterised in transgenic donor fish using a combination of flow cytometry and microscopy techniques. Furthermore, Runx:mCherry positive populations were assessed for stem cell functionality through transplantation. The utility of bloodless cmybt25127 mutant fish to investigate hematopoietic cell transplantation by longitudinal imaging was evaluated. In addition, the stimulatory effects of viral mimetics were assessed in transgenic and cmybt25127 mutant fish. Finally, the effect of antibiotic treatment was investigated in transgenic fish. These experiments revealed two fluorescent cell populations in Tg(Runx:mCherry) transgenic zebrafish kidney marrow. Hematopoietic cell transplant studies and transcript analysis indicated that the Runx:mCherry low population could be enriched for hematopoietic stem cells. Furthermore, experiments revealed that homozygous cmybt25127 mutant fish are capable of regenerating their tail fin following amputation and of initiating a partial anti-viral response to resiquimod stimulation. Finally, a post-transplant scoring system was devised in homozygous cmybt25127 mutant fish and used to assess functional differences between Runx:mCherryhigh and low populations. Overall, this thesis has further developed hematopoietic cell transplantation in zebrafish and demonstrated that in vivo imaging can be used to track the transplant outcome and behaviour of transplanted cells.Open Acces

    Innovations in hematopoietic stem-cell mobilization: A review of the novel CXCR4 inhibitor motixafortide

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    Hematopoietic stem-cell transplantation (HCT) and stem-cell-based gene therapies rely on the ability to collect sufficient CD34+ hematopoietic stem and progenitor cells (HSPCs), typicall

    Hematopoietic Stem Cell Source and Storage

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    Hematopoietic stem cell transplantation(HSCT), has been accepted as a feasible treatment option that prolongs survival in hematological malignancies. Stem cell choice during hematopoietic stem cell transplantation can differ according to the experience of physicians, mostly treated hematological diseases in the centers or ongoing clinical trials. In this chapter we will discuss the advantages and disadvantages of three stem cell sources peripheral blood, bone marrow and umbilical cord blood

    Haploidentical Hematopoietic Stem-Cell Transplantation in Adults

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    Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies

    Impact of COVID-19 and Future Emerging Viruses on Hematopoietic Cell Transplantation and Other Cellular Therapies

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    COVID-19, where Co stands for corona, VI stands for virus, and D denotes disease, in the recent past referred to as 2019 novel coronavirus or 2019-nCoV, has impacted numerous lives and businesses, and has led to a surreal emergency state within world communities. COVID-19 and the future emergence of dangerous viruses will have strong and as yet possibly unanticipated consequences and impact on the present and future use of cellular therapies. In this commentary, we offer a dispassionate assessment of where we believe COVID-19, as well as future emerging viruses, might compromise successful cell transplantation (Fig. 1). These therapies include hematopoietic cell transplantation (HCT) using umbilical cord blood (CB), bone marrow (BM), and mobilized peripheral blood, which contain hematopoietic stem (HSC) and progenitor (HPC) cells, as well as various cellular populations involved in the emerging fields of reparative and regenerative medicine. Such cell populations include HSC, HPC, mesenchymal stem/stromal cells (MSC), and immune cells such as lymphocytes used in chimeric antigen receptor (CAR) T-cell therapies, as well as pluripotent stem cell–based therapies

    Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors.

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    Transforming growth factor beta-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/ p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year nonrelapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/ p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor beta-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor beta-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms

    Transfusion in Transplantation

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    Hematopoietic stem cell transplantation is increasingly performed in several diseases; majority of them are hematologic malignancies. Hematopoietic stem cell transplantation is not an instant procedure; contrarily, its unique clinical and laboratorial consequences may take life‐long time. Blood product transfusion is an inevitable and critical component for the management. Hematopoietic stem cell transplant patients have different requirements regarding blood products transfusion because of their immune status, long‐term cytopenias and especially HLA and ABO incompatibilities. Health‐care staff who take a part in the management of those patients should be aware of specific and specialized transfusion requirements

    Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization

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    Hematopoietic stem cell transplantation is the only curative option for a number of malignant and non-malignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which lead to the widespread use of peripheral blood stem cells for transplantation, with a look towards future enhancements to mobilization strategies
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