12 research outputs found
The Interaction between Surfactants and Montmorillonite and its Influence on the Properties of Organo-Montmorillonite in Oil-Based Drilling Fluids
International audienceThe increasing demands for oil and gas and associated difficult drilling operations require oil-based drilling fluids that possess excellent rheological properties and thermal stability. The objective of the present work was to investigate the rheological properties and thermal stability of organo-montmorillonite (OMnt) modified with various surfactants and under various loading levels in oil-based drilling fluids, as revealed by the interaction between organic surfactants and montmorillonite. The influence of the structural arrangement of surfactants on the thermal stability of organo-montmorillonite (OMnt) in oil-based drilling fluids was also addressed. OMnt samples were prepared in aqueous solution using surfactants possessing either a single long alkyl chain two long alkyl chains. OMnt samples were characterized by X-ray diffraction, high-resolution transmission electron microscopy, thermal analysis, and X-ray photoelectron spectroscopy. Organic surfactants interacted with montmorillonite by electrostatic attraction. The arrangements of organic surfactants depended on the number of long alkyl chains and the geometrical shape of organic cations. In addition to the thermal stability of surfactants, intermolecular interaction also improved the thermal stability of OMnt/oil fluids. A tight paraffin-type bilayer arrangement contributed to the excellent rheological properties and thermal stability of OMnt/oil fluids. The deterioration of rheological properties of OMnt/oil fluids at temperatures up to 200°C was due mainly to the release of interlayer surfactants into the oil
A standardized medical report template for car t-cell therapy patients: guidelines of the francophone society of bone marrow transplantation and cellular therapy (sfgm-tc)
International audienceTisagenlecleucel (Kymriahâą) and axicabtagene ciloleucel (Yescartaâą) are the first representatives of a new class of gene therapies produced by ex-vivo genetic modification of human autologous T lymphocytes, now using viral vectors. In 2020, there are three independent CAR-T cell databases in France: DESCAR-T (database supported by LYSARC, GRAALL and the IFM), ProMISe (EBMT database) and ATIH (database of the Agence Technique de l'Information sur l'Hospitalisation). Only the EBMT database is common to France and the French-speaking countries that are members of the SFGM-TC. In 2019, a workshop was held to draft a manual for entering data specific to CAR-T cells in the EBMT ProMISe database. As a follow-up to this article, we present a medical report template containing all the data required to enter the data of patients treated with CAR-T in the EBMT registry, in the CRF of the DESCAR-T registry and in the ATIH registry. This document aims to improve the completeness and quality of the data while optimizing data entry time.Tisagenlecleucel (Kymriahâą) et axicabtagene ciloleucel (Yescartaâą) sont les premiers reprĂ©sentants dâune nouvelle classe de thĂ©rapies gĂ©niques produites aujourdâhui par modification gĂ©nĂ©tique ex-vivo de lymphocytes T autologues humains, Ă lâaide de vecteurs viraux. En 2020, il existe trois bases indĂ©pendantes de recueil de donnĂ©es CAR-T cells en France : DESCAR-T (base de donnĂ©es portĂ©e par LYSARC, GRAALL et lâIFM), ProMISe (base de donnĂ©es de lâEBMT) et lâATIH (base de donnĂ©es de lâAgence Technique de lâInformation sur lâHospitalisation). Seule la base EBMT est commune Ă la France et aux pays francophones adhĂ©rents Ă la SFGM-TC. En 2019, un atelier avait rĂ©digĂ© un manuel de saisie des donnĂ©es spĂ©cifiques aux CAR-T cells dans la base ProMISe de lâEBMT (1). Pour faire suite Ă cet article, nous prĂ©sentons cette annĂ©e un modĂšle de compte-rendu mĂ©dical comportant toutes les donnĂ©es nĂ©cessaires Ă la saisie des donnĂ©es des patients traitĂ©s par CAR-T dans le registre de lâEBMT, dans le CRF du registre DESCAR-T et dans lâoutil de saisie de lâATIH. Ce document vise Ă amĂ©liorer lâexhaustivitĂ© et la qualitĂ© des donnĂ©es tout en optimisant le temps de saisie
Acute Functional Iron Deficiency in Obese Subjects During a Very-Low-Energy All-Protein Diet
We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone
Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells.
BACKGROUND: A study of CD34+ cell selection and transplantation was carried out with particular emphasis on characteristics of short- and long-term hematopoietic recovery. STUDY DESIGN AND METHODS: Peripheral blood stem and progenitor cells (PBPCs) were collected from 32 patients, and 17 CD34+ cell-selection procedures were carried out in 15 of the 32. One patient in whom two procedures failed to provide 1 x 10(6) CD34+ cells per kg was excluded from further analysis. After conditioning, patients received CD34+ cells (n = 10, CD34 group) or unmanipulated (n = 17, PBPC group) PBPCs containing equivalent amounts of CD34+ cells or progenitors. RESULTS: The yield of CD34+ cells was 53 percent (18-100) with a purity of 63 percent (49-82). The CD34+ fraction contained 66 percent of colony-forming units--granulocyte-macrophage (CFU-GM) and 58 percent of CFU of mixed lineages, but only 33 percent of burst-forming units-erythroid (BFU-E) (p < 0.05). Early recovery of neutrophils and reticulocytes was identical in the two groups, although a slight delay in platelet recovery may be seen with CD34+ cell selection. Late hematopoietic reconstitution, up to 1.5 years after transplant, was also similar. The two groups were thus combined for analyses of dose effects. A dose of 40 x 10(4) CFU-GM per kg ensured recovery of neutrophils to a level of 1 x 10(9) per L within 11 days, 15 x 10(4) CFU of mixed lineages per kg was associated with platelet independence within 11 days, and 100 x 10(4) BFU-E per kg predicted red cell independence within 13 days. However, a continuous effect of cell dose well beyond these thresholds was apparent, at least for neutrophil recovery. CONCLUSION: CD34+ cell selection, despite lower efficiency in collecting BFU-E, provides a suitable graft with hematopoietic capacity comparable to that of unmanipulated PBPCs. In both groups, all patients will eventually show hematopoietic recovery of all three lineages with 1 x 10(6) CD34+ cells per kg or 5 x 10(4) CFU-GM per kg, but a dose of 5 x 10(6) CD34+ cells or 40 x 10(4) CFU-GM per kg is critical to ensure rapid recovery
Administration of erythopoietin and granulocyte colony-stimulating factor in donor/recipient pairs to collect peripheral blood progenitor cells (PBPC) and red blood cell units for use in the recipient after allogeneic PBPC transplantation.
BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more peripheral blood progenitor cells (PBPC) with a combination of granulocyte colony-stimulating factor (G-CSF) + recombinant human erythropoietin (rHuEpo) and by administering rHuEpo post-transplantation. DESIGN AND METHODS: Eight ABO-compatible donors were treated with rHuEpo and intravenous iron to collect 12 RBC units for use in their recipients. PBPC were collected after mobilization with rHuEpo and G-CSF in the same donors. The recipients received G-CSF and rHuEpo post-transplantation. A control group of 10 donor/recipient pairs received G-CSF alone for PBPC mobilization and after the transplantation. RESULTS: Eighty-six out of 91 planned RBC units were collected in the donors without significant decrease in hematocrit because of a 4-fold increase in RBC production despite functional iron deficiency. After 2 leukaphereses, the cumulative yields of NC and CFU-GM were lower in the study group while those of BFU-E, CFU-Mix and CD34+ cells were similar. However, erythroid recovery was significantly accelerated in the study group. INTERPRETATION AND CONCLUSIONS: Collection of 12 RBC units within 6 weeks is feasible with rHuEpo and intravenous iron; this strategy allows a dramatic reduction in recipient exposure to homologous blood; rHuEpo has no synergistic effect with G-CSF for mobilization of PBPC in normal donors and may even be deleterious; and rHuEpo in the recipient may enhance erythroid engraftment
Le dĂ©veloppement des cellules CAR-T et autre thĂ©rapie gĂ©nique : tout nâest pas si simple
International audienc
Reporting data of patients receiving car t cell therapy into the ebmt registry: guidelines of the francophone society of bone marrow transplantation and cellular therapy (sfgm-tc)
International audienceTisagenlecleucel (Kymriahâą) and axicabtagene ciloleucel (Yescartaâą) are the first two approved drug products that belong to of a new class of therapies manufactured through an industrial process that includes the ex vivo genetic modification of human autologous T lymphocytes with viral vectors. Since CAR-T Cells qualify as gene therapy medicinal products, there is a requirement for long-term (15 years) follow-up of treated patients. As part of a global initiative aiming at a better use of continental registries to study the outcome of homogeneous groups of patients, EMA issued a positive opinion on the use of the EBMT registry to capture LTFU of patients treated with CAR-T Cell in EU Member states. The use of a European registry will provide a global view of this new field across EU countries and across diverse indications, and bears advantages over the use of registries dedicated to specific categories of diseases, or national registries. This is an important asset to fully measure the medical value of these innovative therapies in real-life conditions, and assess whether pricing is fully justified. To fulfill EMA requirements, as well as requirements from Pharma companies, EBMT has designed a new Cellular Therapy Med-A form that allows to capture the essential information on the administered drug product, disease and patient. Registering patients and capturing follow-up data is already possible in Promise, and will be made easier when the full migration of the EBMT database from Promise to MACRO is completed in the forthcoming weeks. Negotiations are ongoing with all interested parties including patients to define in which conditions data will be accessed and analyzed; the underlying principle is to favor rather than restrict the use of data, with a view to build cooperative projects involving relevant cooperative groups and professional associations. Here, we present practical recommendations issued by SFGM-TC to help data managers capture information related to patients treated with CAR-T Cells.Tisagenlecleucel (Kymriahâą) et axicabtagene ciloleucel (Yescartaâą) sont les premiers reprĂ©sentants dâune nouvelle classe de thĂ©rapies cellulaires produites par modification gĂ©nĂ©tique ex vivo de lymphocytes T autologues humains, aujourdâhui Ă lâaide de vecteurs viraux. Dans le cadre dâune dĂ©marche globale visant Ă identifier des registres transnationaux sur des groupes de malades homogĂšnes en termes de diagnostic ou dâapproches thĂ©rapeutiques, lâAgence EuropĂ©enne du MĂ©dicament (EMA) a Ă©mis une opinion favorable Ă lâendroit du registre existant de lâEBMT, comme outil susceptible dâĂȘtre utilisĂ© pour collecter de façon prospective les donnĂ©es dâefficacitĂ© et de toxicitĂ© Ă court et long terme survenant chez les patients traitĂ©s en Europe avec des « CAR-T Cells » ; en raison de leur statut de « thĂ©rapies gĂ©niques », le suivi clinique des « CAR-T Cells » doit ĂȘtre organisĂ© au cours des 15 prochaines annĂ©es. Lâutilisation dâun registre europĂ©en a lâavantage de permettre de disposer dâune vision globale, transnationale et « transpathologies » et Ă©vitera la multiplication des registres de donnĂ©es. Pour rĂ©pondre aux exigences de lâEMA, des laboratoires pharmaceutiques dĂ©veloppant des « CAR-T cells » et autres thĂ©rapies cellulaires ou gĂ©niques, et des autres parties intĂ©ressĂ©es, lâEBMT a crĂ©Ă© un nouveau formulaire en ligne permettant de saisir les informations essentielles sur le mĂ©dicament de thĂ©rapie innovante administrĂ©, sur la pathologie traitĂ©e et sur le devenir du patient. Dans cet article, nous prĂ©sentons les recommandations de la SFGM-TC pour aider les data manageurs Ă mieux saisir les donnĂ©es des patients traitĂ©s par cellules CAR-T dans le registre de lâEBMT
Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF.
BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials