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Les greffes de cellules souches hématopoïétiques sont effectuées depuis plusieurs dizaines d'années au sein des Cliniques Universitaires Saint-Luc. La qualité des soins prodigués a permis l'octroi d'une accréditation JAClE (Joint Accreditation committee - ISCT& EBMT) en 2009 et en 2013. Suite à cette accréd itation, une analyse des indicateurs qualité proposés par les Cliniques s'est avérée intéressante afin de permettre une évaluation des soins administrés aux patients.Le programme d'accréditation JACIE est un système de contrôle qualité qui vise à conférer aux patients candidats à une greffe de cellules souches hématopoïétiques une qualité de soins optimale en ce qui concerne la prise en charge du patient ainsi qu'au niveau de la préparation et de la prise en charge du greffon. Ce travail en amont de la greffe consiste en la collecte et la préparation des cellules souches avant la transplantation au patient, dans le respect des critères de qualité prédéfinis. Ces différents aspects nécessitent une grande collaboration des différentes parties.Suite à cette accréditation, une étude rétrospective des indicateurs qualité utilisés afin d'évaluer le processus de greffe a été imaginée, et ce afin de faire le point sur différents aspects cliniques et biologiques liés à une greffe de cellules souches hématopoïétiques.Cette étude comparera les données de Saint-Luc avec les données publiées par l'EBMT (European Group for Blood and Marrow Transplantation) ainsi que d'autres publications de la littérature et permettra, d 'une certaine manière, d'évaluer la qualité des soins prodigués aux patients. De plus, les résultats obtenus permettront d'éventuellement définir de nouveaux indicateurs qualité qui pourront être pris en considération dans l'avenir, toujours dans le but d'améliorer la qualité de soin des patients. Hematopoietic stem cell transplantations are since several years currently performed in Saint-Luc hospital. The quality of care allowed the hospital to get a JACIE (Joint Accreditation committee - ISCT & EBMT) accreditation in 2009 and 2013. Thank to this accreditation, a review of the quality indicators established by the hospital seemed to be interesting in regard to evaluate the care which are given to the patients.JACIE accreditation program is a quality control system which aim is to offer the best quality of care to the patient candidate to a hematopoietic stem cell transplantation. This quality concems the patient but also the preparation of the graft. This upstream work consist in collection and preparation of stem cells before transplanting them to the patient , in regard of the respect of predeterminated quality criteria. These differents aspects require a huge collaboration between the differents parts.In regard to this accreditation, a retrospective study conceming quality indicators evaluating the graft process were thought, to evaluate different clinicat and biological aspects linked to hematopoietic stem cell transplantation .This study will compare data coming for Saint-Luc hospital with data published by the EBMT (European Group for Blood and Marrow Transplantation), but also with other publications and will allowed to evaluate the quality of care given to the patients. Moreover, the results obtained will allow to define new quality indicators which could possibly be taken into account in the future, always with the aim of improving the quality of care given to the patients.
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Hematopoietic stem cell transplantation --- methods --- Hematopoietic stem cell transplantation --- methods
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Hematopoietic stem cell transplantation --- economics --- Hematopoietic stem cell transplantation --- economics
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Busulfan is an alkylating agent that blocks the cell cycle. It was synthesized in 1950, it has been used for more than thirty years in association with cyclophosphamide or melphalan as an alternative to total body irradiation as conditioning treatment for hematopoietic stem cell transplantation. Oral busulfan (Myleran®) has a large inter- and intra-individual variability. This variability leads either to an under-exposure resulting in a lower efficacy or to an over exposure resulting in a more important toxicity. The major side effects of busulfan are gastro-intestinal disorders, pulmonary toxicity or hepatic veno-occlusive disease. Moreover, the tablet low dosage is not favourable to a good compliance. The launching of a intravenous form of busulfan partly solves these issues; the poor aqueous solubility and instability of busulfan has actually delayed the development of this i.v. drug now available as Bulsilvex®. Advantages are a lesser pharmacokinetic variability and the limitations of side effects. The manufacturing costs of the intravenous form are high but partly compensated by the fact that contrary to the oral form, a therapeutic monitoring is not required Le busulfan est un agent alkylant bloquant le cycle cellulaire. Synthétisé en 1950, il est utilisé, depuis plus d’une trentaine d’années, en association avec le cyclophosphamide ou la melphalan dans le conditionnement des greffes de cellules souches hématopoïétiques comme alternative à l’irradiation corporelle totale. Le busulfan administré par voie orale (Myleran®) présente une forte variabilité inter- en intra-individuelle provoquant soit un sous-dosage résultant en une diminution de l’efficacité, soit à) un surdosage ayant pour conséquence une toxicité plus importante. La toxicité du busulfan se manifeste, par exemple, par des troubles gastro-intestinaux, une toxicité pulmonaire ou encore une maladie veino-occlusive hépatique. Le conditionnement complique également la compliance. Une forme intraveineuse du busulfan est une solution à ces différents problèmes. Sa faible solubilité et son instabilité dans l’eau justifient l’avènement tardif du busulfan sous forme intraveineuse, commercialisée sous le nom de Busilvex®. Les avantages sont une moindre variabilité pharmacocinétique et la limitation de certains effets indésirables. Cette forme plus onéreuse que la forme orale ne nécessite pas de monitoring thérapeutique, permettant ainsi une certaine compensation des coûts engendrés pour sa production
Busulfan --- Hematopoietic Stem Cell Transplantation --- Drug Toxicity
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In clinical practice, the use of platelet transfusion has increases progressively. A common complication is platelet alloimmunization, a major cause for refractoriness to repeated platelet transfusions. Therefore several attempts mere made to produce autologous platelets in-vitro to prevent this complication.
In this study, we were able to produce platelets in-vitro from cultured human peripheral blood stem cells (DC34+) in liquid culture medium that promotes megakaryocytopoiesis and thrombocytopoiesis.
Cells in culture did show a high proliferative capacity throughout the culture days, with megakaryocytic proliferation and differenciation, in the presence of growth factors that stimulate megakaryocytopoiesis and thrombocytopoiesis (rh-TPO, rh-IL-3, rh-IL-6, and rh-IL-11).
The megakaryocytic cells were identified by flow cytometry as CD61+ cells with scatter properties of nucleated cells, by morphology, by immunocytochemistry. MKs were first observed in culture medium from 7 days, many of them releasing proplatelets. They reached a peak on day 14. Thereafter cells disappeared from the culture medium. Most of the MKs did not show a ploidy of more than 4N by our measurement methodology and only a very few proportion of them reached 8N.
Culture-derived were detected as CD41+ events and shared the same scatter properties of normal blood platelets in flow cytometry. Although they are successfully produced in culture, they seem to be somewhat activated since expression of P-selectin (GMP 140; CD62+) detected by flow cytometry, a finding that makes their clinical use still questionable. They appeared from day 7 and reached a peak on day 14.
In summary, we settled a technology for producing platelets in in-vitro culture. These platelets show characteristics of normal platelets; however, more experiments are required in order to improve their rate of production and to obtain a normal function
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Hematology --- Lymphoma --- Hematopoietic Stem Cell Transplantation
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