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1. Pooled Fecal Allogenic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Early Access Program in France

Author

Florent Malard, Michael Loschi, Thomas Cluzeau, Faezeh Legrand, Jean-Baptiste Mear, Faustine Lhomme, Sarah Guenounou, Anne Huynh, Cecile Borel, Deborah Desmier, Niels Moya, Amandine Charbonnier, Delphine Lebon, Hélène Labussière-Wallet, Corentin Orvain, Sylvain Chantepie, Claude-Eric Bulabois, Vincent Camus, Marie-Anne Couturier, Jérôme Cornillon, Patrice Chevallier, Clémence Mediavilla, Patrice Ceballos, David Beauvais, Marion Bruelle, Emilie Plantamura, Mohamad Mohty, DESSAIVRE, Louise, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, Université Grenoble Alpes (UGA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, MaaT Pharma [Lyon], CEREST-TC [CHU Saint-Antoine], and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP]

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Introduction Acute graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Standard 1st line therapy for the treatment of aGvHD involves corticosteroids (CS). However, more than 50% of patients are refractory to CS (SR-aGvHD) and the associated mortality rate is of up to 80%. Recently, Ruxolitinib has been approved as 2nd line treatment for SR-aGvHD. However, patients with severe gastrointestinal (GI) aGvHD seem less likely to respond to Ruxolitinib and have poor outcomes with limited therapeutic options.In this context, fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory GI-aGvHD. Here we report clinical outcomes from 81 patients diagnosed with SR or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in France.Methods 81 patients with SR/SD GI-aGvHD (Classical n=62, late onset n=12, overlap syndrome n=7) were treated with MaaT013 as part of an EAP in France. These patients had failed 1 to 6 prior systemic GvHD treatment lines (median 2; 66/81 received Ruxolitinib). Most patients had grade III-IV aGvHD (11% grade II, 51% grade III, 38% grade IV).For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days. Each dose comprised 30g of feces in 150 mL of diluent, from 4 to 8 healthy donors, administered by enema (except for 1 patient by nasogastric tube).Treatment response was calculated among all treated patients based on aGvHD staging and grading at day 28 (D28) at the time of the EAP request.Results At D28, the GI-overall response rate (ORR) was 56%: 30 complete response (CR, 37%), 11 very good response rate (VGPR, 14%), 4 partial response (PR, 5%). The GI-ORR was higher in patients with lower grade aGvHD (89% in grade II, 66% in grade III, 32% in grade IV) and higher in SD versus SR patients (92% versus 49%). Including skin and liver symptoms (n=78), response rate was 49%, including 24 CR, 11 VGPR and 3 PR and inversely correlated with aGvHD initial grade (88% in grade II, 55% in grade III, 30% in grade IV).Overall survival (OS) was 51% at 6 months (M6) and 39% at M12. The median follow-up among surviving patients was 355 days (range, 53-731). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=45) compared to patients in treatment failure (Non-responder, NR; n=35): 69% versus 28% at M6, 59% versus 14% at M12, respectively. Median survival duration in R was 451 days versus 32 days in NR.Interestingly, aGvHD response was improved in the subgroup of 31 patients previously treated with Ruxolitinib as 2nd line and MaaT013 as 3rd line (65% D28 GI-ORR, OS M6 55% and 49% M12 and 74% versus 15% at M6 and 74% versus 0% at M12 for R and NR respectively).MaaT013 displayed a good overall safety profile in the EAP population: 20 pharmacovigilance cases were reported in 18 patients: sepsis in 11 patients, C. difficile colitis in 2, E. coli osteoarthritis in 1, G. silvicola in stools from 1, P. aeruginosa sinusitis in 1, appearance of air bubbles in the mesorectum in 1, respiratory distress in 1. No pathogen transmission was reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013 batch. Causality could not be formally excluded in these cases.The overall incidence of bacteremia (14%) remains low, compared to an incidence of 31% to 74% in bloodstream infections reported in patients with GI-aGvHD. This suggests that fecal microbiotherapy may have a protective effect on bacterial translocation, but this needs to be confirmed in further clinical trials.47 deaths have been reported; the cause of which was GvHD in 21 patients, severe infection in 13, relapse of underlying malignancy in 6, COVID-19 in 3, hemorrhage during surgery in 1, neurological complications post allo-HCT in 1, and cardiac arrest in 2 patients. No causality link with MaaT013 administration has been identified.Conclusion Overall, EAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, GI-response to aGvHD correlates with increased OS, suggesting a strong favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895).

Published
2022
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2. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Author

null Olivier Tournilhac, null Magali Le Garff-Tavernier, null Stéphanie Nguyen Quoc, null Edouard Forcade, null Patrice Chevallier, null Faezeh Legrand-Izadifar, null Gandhi Laurent Damaj, null David Michonneau, null Cécile Tomowiak, null Cécile Borel, null Corentin Orvain, null Pascal Turlure, null Rabah Redjou, null Gaëlle Guillerm, null Laure Vincent, null Celestine Simand, null Richard Lemal, null Claire Quiney, null Patricia Combes, null Bruno Pereira, null Laure Calvet, null Aurélie Cabrespine, null Jacques-Olivier Bay, null Véronique Leblond, null Nathalie Dhédin, French Innovative Leukemia Organization (FILO), Société Francophone de Greffe De Moelle et de Thérapie Cellulaire (SFGM-TC), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)

Subjects
Oncology, medicine.medical_specialty, Neoplasm, Residual, Transplantation Conditioning, Chronic lymphocytic leukemia, medicine.medical_treatment, Phases of clinical research, Graft vs Host Disease, Hematopoietic stem cell transplantation, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Cumulative incidence, Prospective Studies, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Donor Lymphocytes, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Regimen, Graft-versus-host disease, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing chronic lymphocytic leukemia (CLL). Minimal residual disease (MRD) assessment at 12 months (M12) post-HSCT is predictive of relapse. This phase II study aimed to achieve M12 MRD negativity (MRDneg) using an MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed in case of failure by donor lymphocytes infusions. Patients had high-risk CLL according to the 2006 European Society for Blood and Marrow Transplantation consensus, in complete or partial response with lymphadenopathy

Published
2021
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3. Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation

Author

Christian Chabannon, Reda Bouabdallah, Sabine Furst, Thomas Pagliardini, Raynier Devillier, Boris Calmels, Samia Harbi, Didier Blaise, Charlotte Nykolyszyn, Pierre-Jean Weiller, Norbert Vey, Luca Castagna, Faezeh Legrand, Claude Lemarie, Angela Granata, Valerio Maisano, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
medicine.medical_specialty, Globulin, Cyclophosphamide, medicine.medical_treatment, Hematopoietic stem cell transplantation, Single Center, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Cumulative incidence, ComputingMilieux_MISCELLANEOUS, Transplantation, biology, business.industry, Mismatched Unrelated Donor, Hematology, 3. Good health, 030220 oncology & carcinogenesis, biology.protein, Chronic gvhd, Gvhd prophylaxis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology, medicine.drug
Abstract

Posttransplant cyclophosphamide (PT-Cy) is an efficient GVHD prophylaxis but has not been extensively evaluated in mismatched unrelated donor (MMUD) allo-HSCT, for which antithymocyte globulin (ATG) is still considered as a standard. Thus, we evaluated the outcome of MMUD allo-HSCT with PT-Cy (n = 22) and performed a historical comparison with a control group receiving ATG (n = 40) in a single center experience. Compared with the ATG group, the risk of grade 2–4 acute GVHD was significantly lower in the PT-Cy group (HR = 0.12, 95% CI = [0.03–0.48], p = 0.002). No difference was observed in the cumulative incidence of chronic GVHD. The risk of both NRM and relapse was significantly lower in the PT-Cy group (NRM: HR = 0.05, 95% CI = [0.00–0.63], p = 0.021; relapse: HR = 0.31; 95% CI = [0.09–1.10], p = 0.07). Thus, we observed significantly better PFS (HR = 0.22, 95% CI = (0.07–0.65); p = 0.006), OS (HR = 0.24, 95% CI = (0.07–0.84); p = 0.026), and GRFS (HR = 0.37, 95% CI = (0.17–0.80); p = 0.011) in the PT-Cy group. We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT, resulting in a better outcome compared with standard prophylaxis using ATG. This suggests that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approach those observed after HLA matched allo-HSCT.

Published
2020
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4. HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison

Author

Sabine Furst, Catherine Faucher, Boris Calmels, Samia Harbi, Colombe Saillard, Thomas Pagliardini, Bilal Mohty, Angela Granata, Christian Chabannon, Evelyne D'Incan, Aude Charbonnier, Raynier Devillier, Jerome Rey, Luca Castagna, Faezeh Legrand, Valerio Maisano, Norbert Vey, Didier Blaise, Pierre-Jean Weiller, Claude Lemarie, Département d'Hématologie [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Unité de Transplantation et de Thérapie Cellulaire [Marseille], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Transplant Unit [Milano, Italy] (Department of Hemato-oncology), Humanitas Cancer Center [Milano, Italy], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Bidaut, Ghislain

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Human leukocyte antigen, Single Center, 03 medical and health sciences, High morbidity, 0302 clinical medicine, Unrelated Donor, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Sibling, Aged, Retrospective Studies, Transplantation, business.industry, Siblings, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Tissue Donors, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Female, business, Unrelated Donors, 030215 immunology
Abstract

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged >= 60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged >= 60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. (C) 2018 American Society for Blood and Marrow Transplantation.

Published
2018
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5. Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord

Author

S. Vigouroux, L Souchet, Patrice Chevallier, Anne Sirvent, C-E. Bulabois, Faezeh Legrand, Laurence Clement, Jérôme Cornillon, S. Furst, Sébastien Maury, Vivien Béziat, J Lejeune, Bernard Rio, Sylvie Chevret, G Margueritte, Sylvie François, Karin Bilger, Vincent Vieillard, G. Michel, Madalina Uzunov, Gérard Socié, Marie-Cécile Michallet, Patrice Ceballos, V. Rocha, J.-O. Bay, N. Maillard, Charles Dauriac, I. Yakoub-Agha, Abla Achour, Anne Huynh, Stéphanie Nguyen, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Semiconductor Photonics Research Group, Trinity College Dublin-Science Foundation Ireland-Enterprise Ireland-Higher Education Authority, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), STMicroelectronics, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Public Henri Tudor [Technoport] (CRP Henri Tudor), Centre de Recherche Public Henri-Tudor [Luxembourg] (CRP Henri-Tudor), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de sismologie (DS (UMR_7580)), Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Centre National de la Recherche Scientifique (CNRS), Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel Dieu, IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel Dieu, Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Adult, Male, 0301 basic medicine, Transplantation Conditioning, Myeloid, Cord Blood Stem Cell Transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Multicenter trial, Humans, Medicine, Prospective Studies, Registries, ComputingMilieux_MISCELLANEOUS, Transplantation, business.industry, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Recovery of Function, Hematology, Middle Aged, Allografts, medicine.disease, 3. Good health, Killer Cells, Natural, Survival Rate, Leukemia, Myeloid, Acute, Leukemia, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Immunology, Female, business, 030215 immunology
Abstract

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Published
2017
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6. Epidemiology of invasive fungal infections during induction therapy in adults with acute lymphoblastic leukemia: a GRAALL-2005 study

Author

Véronique Lhéritier, Clara Mariette, Anne Huynh, Jean-Yves Cahn, Françoise Isnard, Faezeh Legrand, Emmanuelle Tavernier, Didier Hocquet, Norbert Ifrah, Anne Thiebaut, Emmanuel Raffoux, Hervé Dombret, Service des Basses Températures ( SBT - UMR 9004 ), Institut Nanosciences et Cryogénie ( INAC ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ), Clinical Investigation Center - INSERM 1415, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Acoustique pour les nanosciences ( INSP-E3 ), Institut des Nanosciences de Paris ( INSP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Département d’Immunologie Biologique [AP-HP - Hôpital Saint-Antoine, Paris], Unité d’autoimmunité, AP-HP - Hôpital Saint-Antoine -AP-HP - Hôpital Saint-Antoine, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hôpital Michallon, CHU Grenoble, Service des Basses Températures (SBT ), Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Acoustique pour les nanosciences (INSP-E3), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE)

Subjects
Male, 0301 basic medicine, Cancer Research, Antifungal Agents, Time Factors, Lymphoblastic Leukemia, Acute lymphoblastic leukemia, Aspergillosis, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Induction therapy, Epidemiology, 030212 general & internal medicine, Candida albicans, Randomized Controlled Trials as Topic, biology, Induction Chemotherapy, Hematology, Invasive candidiasis, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, invasive candidiasis, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncology, Female, France, Adult, Antifungal, medicine.medical_specialty, Adolescent, medicine.drug_class, 030106 microbiology, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Candidiasis, Invasive, Retrospective Studies, invasive aspergillosis, invasive fungal infections, business.industry, Induction chemotherapy, medicine.disease, biology.organism_classification, Surgery, Clinical Trials, Phase III as Topic, business
Abstract

International audience; Little data have been published concerning invasive fungal infections during treatment of acute lymphoblastic leukemia (ALL). Patients included between May 2006 and October 2012 in the multicenter phase III trial for newly diagnosed ALL (GRAALL-2005) were retrospectively reviewed for the occurrence of IFI using the EORTC modified criteria. These patients did not routinely receive antifungal prophylaxis. Among 969 patients included (median age 47 years), 65 (6.7%) developed IFI during induction chemotherapy: 26 (3.3%) invasive aspergillosis (IA), 33 (3.4%) invasive candidiasis (IC) and six other IFI. For IA, the median time between induction therapy and IA diagnosis was 20 days. Diagnosis was probable in 22 cases and proven in four. Aspergillus antigen in serum was tested in all cases and positive in 24. Overall 12-week mortality after diagnosis of IA was 5/26 and attributable mortality related to the infection was 4/26 (15.4%). For IC, the median time between induction therapy and diagnosis was 19 days. Diagnosis was proven in 29 episodes. Candida albicans was the major pathogen in yeast infections (16/27). Overall 12-week mortality after diagnosis of IC was 8/33 (24.2%) and attributable mortality related to the infection was 7/33. The median delay between induction chemotherapy initiation and attributable death related to IC was 15 days. These findings may help to optimize the future management of ALL patients, and as in AML advocate systematic monitoring and the development of prophylactic or preemptive antifungal treatments.

Published
2017
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7. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients

Author

Etienne Daguindau, Fabrice Larosa, Steffi Rocchi, Laurence Millon, Faezeh Legrand, Emeline Scherer, Frédéric Grenouillet, Joel Leroy, Anne-Pauline Bellanger, Quentin Lepiller, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Parasitologie-Mycologie CHU Besançon, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Agents pathogènes et inflammation - UFC (EA 4266) ( API ), Université de Franche-Comté ( UFC ), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques

Subjects
Male, MESH : Retrospective Studies, MESH : Aged, Polymerase Chain Reaction, law.invention, 0302 clinical medicine, Absidia, law, Limit of Detection, MESH: Immunocompromised Host, MESH : Female, 030212 general & internal medicine, DNA, Fungal, Mycological Typing Techniques, MESH : Mycological Typing Techniques, MESH : Polymerase Chain Reaction, Polymerase chain reaction, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Mucor, MESH: Aged, 0303 health sciences, MESH: Middle Aged, biology, MESH : Immunocompromised Host, Middle Aged, MESH : Adult, 3. Good health, MESH: Reproducibility of Results, Infectious Diseases, Real-time polymerase chain reaction, MESH : Mucorales, MESH: Mucorales, Mucorales, Female, Microbiology (medical), Adult, Adolescent, MESH : Male, MESH: Limit of Detection, Microbiology, MESH : Limit of Detection, 03 medical and health sciences, Immunocompromised Host, Rhizopus, MESH: Mycological Typing Techniques, MESH : Adolescent, medicine, Humans, Mucormycosis, MESH : Mucormycosis, MESH : Middle Aged, MESH: Mucormycosis, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, 030306 microbiology, business.industry, MESH : Reproducibility of Results, MESH : Humans, Reproducibility of Results, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Retrospective Studies, medicine.disease, biology.organism_classification, Virology, MESH: Male, Rhizomucor, MESH: DNA, Fungal, MESH : DNA, Fungal, business, MESH: Female
Abstract

International audience; BACKGROUND: The aim of our study was to assess the detection of circulating DNA from the most common species of Mucorales for early diagnosis of mucormycosis in at-risk patients. METHODS: We retrospectively evaluated a combination of 3 quantitative polymerase chain reaction (qPCR) assays using hydrolysis probes targeting Mucor/Rhizopus, Lichtheimia (formerly Absidia), and Rhizomucor for circulating Mucorales detection. Serial serum samples from 10 patients diagnosed with proven mucormycosis (2-9 samples per patient) were analyzed. RESULTS: No cross-reactivity was detected in the 3 qPCR assays using 19 reference strains of opportunistic fungi, and the limit of detection ranged from 3.7 to 15 femtograms/10 µL, depending on the species. DNA from Mucorales was detected in the serum of 9 of 10 patients between 68 and 3 days before mucormycosis diagnosis was confirmed by histopathological examination and/or positive culture. All the qPCR results were concordant with culture and/or PCR-based identification of the causing agents in tissue (Lichtheimia species, Rhizomucor species, and Mucor/Rhizopus species in 4, 3, and 2 patients, respectively). Quantitative PCR was negative in only 1 patient with proven disseminated mucormycosis caused by Lichtheimia species. CONCLUSION: Our study suggests that using specific qPCR targeting several species of Mucorales according to local ecology to screen at-risk patients could be useful in a clinical setting. The cost and efficacy of this strategy should be evaluated. However, given the human and economic cost of mucormycosis and the need for rapid diagnosis to initiate prompt directed antifungal therapy, this strategy could be highly attractive.

Published
2013
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8. Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Author

E. Deconinck, Faezeh Legrand, Frédéric Grenouillet, Frédéric Dalle, Fabrice Larosa, Philippe Saas, Laurence Millon, Pierre Rohrlich, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), and Université de Bourgogne (UB)

Subjects
Male, medicine.medical_treatment, MESH : Cryptosporidium parvum, Cryptosporidiosis, Graft vs Host Disease, Hematopoietic stem cell transplantation, Azithromycin, Gastroenterology, 0302 clinical medicine, immune system diseases, MESH : Thiazoles, MESH: Animals, MESH : Female, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH : Azithromycin, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Antibacterial agent, 0303 health sciences, MESH: Middle Aged, biology, MESH : Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, MESH: Immunosuppression, Nitazoxanide, Immunosuppression, Hematology, Middle Aged, MESH : Adult, Nitro Compounds, MESH : Diagnosis, Differential, 3. Good health, Cryptosporidium parvum, surgical procedures, operative, MESH: Young Adult, Female, medicine.symptom, MESH : Lymphopenia, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Homologous, MESH : Male, MESH : Young Adult, MESH: Thiazoles, MESH: Graft vs Host Disease, Asymptomatic, MESH: Lymphopenia, Diagnosis, Differential, 03 medical and health sciences, Young Adult, MESH: Diagnosis, Differential, Internal medicine, MESH: Azithromycin, Lymphopenia, MESH : Hematopoietic Stem Cell Transplantation, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Cryptosporidiosis, MESH: Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy, Transplantation, MESH: Humans, 030306 microbiology, business.industry, MESH: Cryptosporidiosis, MESH : Humans, MESH: Adult, biology.organism_classification, MESH: Male, Thiazoles, Immunology, MESH : Immunosuppression, MESH: Cryptosporidium parvum, MESH : Animals, business, MESH: Female
Abstract

International audience; Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Published
2011
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9. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial

Author

Carine, Domenech, Xavier, Thomas, Sylvie, Chabaud, Andre, Baruchel, François, Gueyffier, Françoise, Mazingue, Anne, Auvrignon, Selim, Corm, Herve, Dombret, Patrice, Chevallier, Claire, Galambrun, Françoise, Huguet, Faezeh, Legrand, Françoise, Mechinaud, Norbert, Vey, Irène, Philip, David, Liens, Yann, Godfrin, Dominique, Rigal, Yves, Bertrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Children's Cancer Center, The Royal Children's Hospital, Hematology (IPC-Marseille), Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Adult, Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Erythrocytes, Adolescent, MESH: Drug Delivery Systems, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, MESH: Dose-Response Relationship, Drug, Young Adult, MESH: Bioreactors, Bioreactors, Drug Delivery Systems, MESH: Child, Asparaginase, Humans, MESH: Asparaginase, Child, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Drug Carriers, MESH: Humans, MESH: Middle Aged, Dose-Response Relationship, Drug, MESH: Erythrocytes, MESH: Child, Preschool, Infant, MESH: Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Infant, MESH: Male, MESH: Drug Carriers, MESH: Young Adult, Child, Preschool, MESH: Antineoplastic Agents
Abstract

International audience; l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .

Published
2011
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10. Ribosomal and mitochondrial DNA target for real-time PCR diagnosis of invasive aspergillosis

Author

Faezeh Legrand, Laurence Millon, T. Henon, E. Deconinck, Houssein Gbaguidi-Haore, Anne-Pauline Bellanger, Frédéric Grenouillet, Stéphane Loewert, Emeline Scherer, Pierre-Simon Rohrlich, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Parasitologie-Mycologie CHU Besançon, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de parasitologie et mycologie [CHRU de Besançon], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Mitochondrial DNA, Adolescent, Mycology, Biology, Aspergillosis, Gastroenterology, DNA, Mitochondrial, DNA, Ribosomal, Polymerase Chain Reaction, Sensitivity and Specificity, law.invention, Mannans, 03 medical and health sciences, Galactomannan, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Child, DNA, Fungal, Ribosomal DNA, Polymerase chain reaction, Mycosis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, ComputingMilieux_MISCELLANEOUS, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Invasive Pulmonary Aspergillosis, 0303 health sciences, 030306 microbiology, Galactose, Ribosomal RNA, Middle Aged, medicine.disease, Molecular biology, 3. Good health, Real-time polymerase chain reaction, Aspergillus, chemistry, Female
Abstract

The aim of the present study was to assess the diagnostic efficacy of a combination of two quantitative Aspergillus PCR assays, targeting a mitochondrial and a ribosomal target, in patients with risk factors for invasive aspergillosis (IA) and positive galactomannan (GM) antigen. Forty-four patients with hematological malignancies and risk factors for IA according to revised European Organization for Research on Treatment of Cancer and the Mycoses Study Group criteria (EORTC/MSG) criteria and presenting at least two sequential GM-positive sera were included in the study. Mitochondrial PCR was carried out prospectively on all GM-positive serum samples. Ribosomal PCR was carried out retrospectively on frozen stored sera. The sensitivities of mitochondrial and ribosomal PCRs were 58% and 50%, respectively. The diagnostic test performance was improved by using a combination of both PCR assays and by considering a patient PCR positive when at least two positive results were obtained. The sensitivity, specificity, and positive and negative likelihood ratios were 65%, 94%, and 11.8 and 0.37, respectively. A significant association between fatal outcome at 90 days and positive results of ribosomal PCR assays was observed (adjusted hazard ratio = 8.2; 95% confidence interval [CI] = 1.0 to 65.8; P = 0.048). Our results showed that the combination of two PCR assays targeting mitochondrial and ribosomal Aspergillus DNA improves the sensitivity of PCR in the diagnosis of IA in hematological patients with risk factors and positive GM results. This study also confirms that a positive PCR result is associated with a poor prognosis in these patients and should lead to specific antifungal therapy being introduced immediately.

Published
2011
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11. G-CSF-induced aneuploidy does not affect CD34+ cells and does not require cell division

Author

Maribel Tavernier, Fabienne Pouthier, Faezeh Legrand, Olivier Hequet, Franck Vitte, Pierre Tiberghien, Dana Ranta, Jean-Luc Bresson, Caroline Marmier-Savet, Nicole Raus, Pascale Louvat, Eric Robinet, Marie-Agnès Collonge-Rame, Fabrice Larosa, Mauricette Michallet, Eric Deconinck, Jean-René Pallandre, Brigitte Witz, Marc Puyraveau, Suzanne Mathieu-Nafissi, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), EFS Rhône-Alpes, EFS, Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saas, Philippe, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)

Subjects
Male, Cell division, Cd34 cells, Aneuploidy, Antigens, CD34, 030204 cardiovascular system & hematology, Biochemistry, MESH: Hematopoietic Stem Cells, 0302 clinical medicine, Granulocyte Colony-Stimulating Factor, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, ComputingMilieux_MISCELLANEOUS, Leukemia, MESH: Middle Aged, Hematology, Middle Aged, Hematopoietic Stem Cell Mobilization, 3. Good health, Granulocyte colony-stimulating factor, medicine.anatomical_structure, MESH: Young Adult, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cell Division, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Biology, Granulocyte, MESH: Hematopoietic Stem Cell Mobilization, 03 medical and health sciences, Young Adult, MESH: Leukemia, medicine, MESH: Aneuploidy, Humans, Epigenetics, MESH: Humans, Cell growth, MESH: Adult, Cell Biology, MESH: Antigens, CD34, medicine.disease, Hematopoietic Stem Cells, MESH: Male, MESH: Granulocyte Colony-Stimulating Factor, MESH: Female, 030215 immunology
Abstract

To the editor: Lymphocytes from granulocyte colony-stimulating factor (G-CSF)–mobilized donors display epigenetic and genetic alterations similar to those observed in leukemia patients.[1][1] To further evaluate the scope and duration of G-CSF–induced genetic alterations, 24 healthy donors were

Published
2010
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12. Early immune reconstitution and efficient graft vs tumor effect after unrelated partially matched double cord blood transplantation in refractory 8p11 syndrome

Author

Sandrine Hayette, Pierre-Simon Rohrlich, Christophe Ferrand, Fabienne Pouthier, Fabrice Larosa, Pierre Tiberghien, Philippe Saas, Faezeh Legrand, Jacqueline Chabod, Stéphane Maddens, Eric Deconinck, Saas, Philippe, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), EFS Rhône-Alpes, EFS, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Biologie Moléculaire, Hospices Civils de Lyon (HCL), Laboratoire HLA, Service d'hématologie pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
medicine.medical_specialty, Pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Umbilical cord, Blood cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Refractory, Unrelated Donor, Internal medicine, medicine, Cord blood transplantation, ComputingMilieux_MISCELLANEOUS, Transplantation, Hematology, business.industry, 3. Good health, surgical procedures, operative, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, business, 030215 immunology
Abstract

Early immune reconstitution and efficient graft vs tumor effect after unrelated partially matched double cord blood transplantation in refractory 8p11 syndrome

Published
2010
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13. Adjuvant corticosteroid therapy for chronic disseminated candidiasis

Author

Olivier Lortholary, Erianna Bellaton, Bertrand Dupont, Marc Lecuit, Faezeh Legrand, Pierre-Simon Rohrlich, Michel Huerre, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Histotechnologie et Pathologie, Institut Pasteur [Paris] (IP), Service d'hémato-onco-pédiatrie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Saas, Philippe, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, Abdominal pain, MESH : Retrospective Studies, MESH: Spleen, medicine.medical_treatment, MESH : Aged, MESH : Immune Reconstitution Inflammatory Syndrome, MESH: Length of Stay, MESH : Child, Adrenal Cortex Hormones, MESH: Child, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, Child, 0303 health sciences, MESH: Middle Aged, Candidiasis, MESH : Chemotherapy, Adjuvant, 3. Good health, MESH : Length of Stay, C-Reactive Protein, Child, Preschool, MESH : Fever, Microbiology (medical), medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Abdominal Pain, Liver Abscess, MESH : Adrenal Cortex Hormones, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, MESH : Adolescent, MESH: Fever, Humans, MESH : Middle Aged, Mycosis, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, 030306 microbiology, MESH : Humans, MESH : Leukemia, MESH : Liver Abscess, MESH: Child, Preschool, MESH: Retrospective Studies, MESH: Adult, Length of Stay, medicine.disease, MESH: Antifungal Agents, MESH: Abdominal Pain, MESH: Fibrinogen, MESH: Female, Antifungal Agents, Time Factors, MESH : Fibrinogen, MESH : Child, Preschool, MESH : Candidiasis, Prednisone, Immune Reconstitution Inflammatory Syndrome, MESH : Female, MESH: Aged, Acute leukemia, Leukemia, MESH : Adult, Middle Aged, MESH: Candidiasis, Infectious Diseases, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH: Immune Reconstitution Inflammatory Syndrome, Corticosteroid, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, MESH : Time Factors, medicine.drug, MESH : Spleen, Adult, Adolescent, Fever, medicine.drug_class, MESH : Male, MESH : Antifungal Agents, MESH: Liver Abscess, Immune reconstitution inflammatory syndrome, Internal medicine, MESH: Leukemia, MESH: C-Reactive Protein, 030304 developmental biology, Chemotherapy, business.industry, MESH: Time Factors, Fibrinogen, Retrospective cohort study, MESH : C-Reactive Protein, MESH: Male, Surgery, Abdominal Pain, business, Spleen
Abstract

International audience; BACKGROUND: Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. OBJECTIVE: Our objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. METHODS: We performed a retrospective, multicenter study involving 10 pediatric and adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST was initiated. RESULTS: All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia. CDC-attributable clinical symptoms resolved with CST, which was started a mean of 33.8 days after antifungal therapy had been initiated. Fever and abdominal pain disappeared a median of 4-5 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14-30 days. The median duration of hospitalization after CST initiation was 8.8 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 107 days (range, 30-210 days). No relapses of CDC were observed during a median duration of follow-up of 6.5 years (range, 4-9 years). CONCLUSIONS: In children and adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of > or =0.5 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome.

Published
2008
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14. L'impact d'une situation de précarité sociale de patients recevant une allogreffe de cellules souches hématopoïétiques sur leur qualité de vie liée à la santé (PRECALLO)

Author

Nykolyszyn, Charlotte, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), and Faezeh Legrand

Subjects
Précarité sociale, [SDV]Life Sciences [q-bio], Qualité de vie liée à la santé, Allogreffe de cellules souches hématopoïétiques, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Bien que l’allogreffe de cellules souches hématopoïétiques (ACSH) puisse sauver des vies, il est désormais bien établi que la qualité de vie (QDV) des patients est fortement impactée par cette procédure. L'association du statut socio-économique avec la qualité de vie liée à la santé (QVLS) n'a pas été décrite précédemment. Nous avons évalué ici l'impact de la précarité des patients sur la QVLS durant les cent premiers jours suivant une ACSH.Nous avons réalisé une analyse rétrospective monocentrique des patients allogreffés en routine dans notre centre. L’évaluation de la QVLS se faisait par questionnaires auto-administrés à l'entrée dans l'unité de transplantation, à la sortie, et cent jours après la transplantation.35,9 % de nos patients (n=85) étaient en situation de précarité. A l'entrée, les patients défavorisés présentaient une QVLS significativement plus mauvaise que les patients non défavorisés (p

Published
2022

15. Épidémiologie des infections bactériennes pendant les phases de consolidations et d'intensification retardée chez les patients adultes atteints de leucémies aiguës lymphoblastiques (LAL) : une étude issue du protocole GRAALL-2005

Author

Richez, Valentine, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Faezeh Legrand, and Thomas Cluzeau

Subjects
Épidémiologie, Infections bactériennes, Protocole GRAALL, Leucémie aiguë lymphoblastique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Nous avons rétrospectivement étudié le profil des infections bactériennes (BI) survenues au cours des phases de consolidations et d’intensification retardée (IR) du protocole GRAALL-2005, étude incluant des patients adultes atteints de LAL non Ph1. Les BI ont été définies par l’identification microbiologique de bactéries chez les patients en cours de traitement. 126 BI ont été analysées : 37 (29%) au cours de la première consolidation, 22 (17%) au cours de la seconde consolidation, 44 (34%) au cours de l’IR et 29 (23%) au cours de la troisième consolidation. Le compartiment le plus colonisé par les bactéries était le sang et 68 (54%) infections de cathéters veineux centraux (CVC) ont été décrites. Les bactéries Gram-positives (BGP) étaient plus fréquemment décrites que les bactéries Gram-négatives (BGN) avec une majorité de Staphylococci coagulase négative. 71 (42%) BGN ont été décrits avec une majorité d’entérobactéries et de Pseudomonas aeruginosa. Pratiquement aucune antibioprophylaxie n’a été prescrite ; l’antibiothérapie empirique à type d’escalade avec l’utilisation d’une Bêta-lactamine en mono-thérapie a été utilisée pour 91% des BI. 14 (8%) des germes identifiés étaient multi résistants. La majorité des BI ont évolué favorablement entraînant un retard sur la cure suivante dans 75% des cas mais sans impact sur le devenir des patients. L’épidémiologie des BI des LAL traitées semble être similaire à celle décrite chez les patients atteints de LAM et/ou allogreffés. En respectant les recommandations de l’ECIL (European Conference on Infections in Leukemia), la plupart des BI ont évolué favorablement. Antibiothérapie empirique en mono-thérapie et absence d’antibioprophylaxie semblent être des stratégies indispensables pour lutter contre l’émergence des résistances bactériennes.

Published
2017

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