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18 results on '"Chalandon, Y."'

1. Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G.J., Breems, D.A., Stuessi, G., Norden, Y. van, Bargetzi, M., Biemond, B.J., Borne, P.A. von dem, Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J.J.J.W., Jaspers, A., Jongen-Lavrencic, M., Jongh, E. de, Klein, S.K., Klift, M. van der, Kooy, M.V., Maertens, J., Micheaux, L., Poel, M.W.M. van der, Rhenen, A. van, Tick, L., Valk, P., Vekemans, M.C., Velden, W.J.F.M. van der, Weerdt, O. de, Pabst, T., Manz, M., Lowenberg, B., Havelange, Moors, I., Obberg, F. van, Maertens, J.A., Hodossy, B., Vansteenweghen, S., Lammertijn, L., Sonet, A., Triffet, A., Gjertsen, B.T., Passweg, J., Heim, D., Giovanni, S., Betticher, D., Spertini, O., Gregor, M., Hess, U., Manz, M.G., Loosdrecht, A. van de, Janssen, J.J.W.M., Esser, J.W.J. van, Brouwer, R.E., Lammeren-Venema, D. van, Levin, M.D., Tick, L.W., Legdeur, M.C.J.C., Vellenga, E., Hoogendoorn, M., Veelken, J.H., Schouten, H.C., Cornelissen, J., Wouters, B., Raaijmakers, H.G.M., Kuball, J., Dutch-Belgian Hemato-Oncology, Swiss Grp Clinical Canc Res SAKK, Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Haematology, CCA - Cancer Treatment and Quality of Life, CCA - Cancer Treatment and quality of life, Hematology laboratory, Hematology, Department of History, International Institute of Social Studies, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, and UCL - (SLuc) Service d'hématologie

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, HIGH-DOSE LENALIDOMIDE, ACUTE MYELOID-LEUKEMIA, THERAPY, 03 medical and health sciences, 0302 clinical medicine, Older patients, SDG 3 - Good Health and Well-being, Internal medicine, medicine, 610 Medicine & health, Adverse effect, Lenalidomide, Chemotherapy, business.industry, Intensive treatment, Myeloid leukemia, Hematology, ADULTS, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Cytarabine, business, medicine.drug
Abstract

Contains fulltext : 225470.pdf (Publisher’s version ) (Closed access) More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n = 222) to receive standard chemotherapy ("3 + 7") with or without lenalidomide at a dose of 20 mg/day 1-21. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without lenalidomide (20 mg/day 1-21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).

Published
2020
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2. Impact of primary disease on outcome after allogeneic stem cell transplantation for transformed secondary acute leukaemia

Author

Kroger, N., Eikema, D.J., Koster, L., Beelen, D., Wreede, L.C. de, Finke, J., Koenecke, C., Niederwieser, D., Bornhauser, M., Schoenland, S., Potter, V., Wolschke, C., Maertens, J., Theobald, M., Kobbe, G., Itala-Remes, M., Wulf, G., Kahls, P., Forcade, E., Greinix, H., Masszi, T., Yakoub-Agha, I., Chalandon, Y., Robin, M., and European Soc Blood Marrow Transpla

Subjects
Male, Chronic myelomonocytic leukaemia, myeloproliferative neoplasm, Medizin, Myeloproliferative neoplasm, Graft vs Host Disease, Gastroenterology, 0302 clinical medicine, allogeneic stem cell transplantation, hemic and lymphatic diseases, MDS, Medicine, Cumulative incidence, ddc:616, Hematopoietic Stem Cell Transplantation, Leukemia, Myelomonocytic, Chronic, Hematology, Middle Aged, Haematopoiesis, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Acute Disease, Disease Progression, Female, Stem cell, chronic myelomonocytic leukaemia, Adult, medicine.medical_specialty, Adolescent, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, Young Adult, Median follow-up, Statistical significance, Internal medicine, Humans, Aged, Secondary acute myeloid leukaemia, Myeloproliferative Disorders, secondary acute myeloid leukaemia, business.industry, Myelodysplastic syndromes, medicine.disease, Allogeneic stem cell transplantation, Transplantation, Myelodysplastic Syndromes, Chronic Disease, Neoplasm Recurrence, Local, business, 030215 immunology
Abstract

Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukaemia (CMML) can progress to secondary acute myeloid leukaemia (sAML). We compared the outcome of 4214 sAML patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) from an unrelated (62%) or human leucocyte antigen (HLA)-identical sibling donor (38%) according the underlying disease: MDS (n = 3541), CMML (n = 251) or MPN (n = 422). After a median follow up of 46·5 months, the estimated 3-year progression-free (PFS) and overall survival (OS) for the entire group was 36% (34-37%) and 41% (40-43%), respectively. The cumulative incidence of relapse and non-relapse mortality (NRM) was 37% (35-39%) and 27% (26-29%), respectively. In a multivariable analysis for OS, besides age (P

Published
2019

3. Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT

Author

Gelder, M. van, Ziagkos, D., Wreede, L. de, Biezen, A. van, Dreger, P., Gramatzki, M., Stelljes, M., Andersen, N.S., Schaap, N., Vitek, A., Beelen, D., Lindstrom, V., Finke, J., Passweg, J., Eder, M., Machaczka, M., Delgado, J., Kruger, W., Raida, L., Socie, G., Jindra, P., Afanasyev, B., Wagner, E., Chalandon, Y., Henseler, A., Schoenland, S., Kroger, N., Schetelig, J., CLL Subcomm Chronic Malignancies W, European Soc Blood Marrow Transpla, HUS Comprehensive Cancer Center, Clinicum, Department of Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde

Subjects
Male, Oncology, Cancer Research, Transplantation Conditioning, BLOOD, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], medicine.medical_treatment, Chronic lymphocytic leukemia, Medizin, MULTICENTER, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, THERAPY, chemistry.chemical_compound, 0302 clinical medicine, HLA Antigens, Risk Factors, IBRUTINIB, education.field_of_study, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, RELAPSED CLL, Tissue Donors, EUROPEAN-SOCIETY, 3. Good health, Risk factor analysis, Treatment Outcome, 030220 oncology & carcinogenesis, Ibrutinib, SURVIVAL, Female, Refractory Chronic Lymphocytic Leukemia, Adult, medicine.medical_specialty, 3122 Cancers, Population, HLA-matched donor, MARROW TRANSPLANTATION, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Non-relapse mortality, Internal medicine, medicine, Humans, Transplantation, Homologous, education, Aged, Retrospective Studies, Chromosome Aberrations, business.industry, Kinase- and BCL2 inhibitor refractory, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Confidence interval, Surgery, Transplantation, chemistry, MATCHED UNRELATED DONOR, del(17p), FOLLOW-UP, business, 030215 immunology
Abstract

Patients with chronic lymphocytic leukemia with del(17p) or del(11q) have poor long-term prognosis with targeted therapies. Conversely, this retrospective European Society for Blood and Marrow Transplantation registry study shows that young high cytogenetic risk responsive patients with human leukocyte antigen-matched donors have a high 8-year progression-free survival and low 2-year non-relapse mortality after allogeneic stem cell transplantation. This treatment then may compare favorably with targeted therapies for younger high cytogenetic risk patients.Background: Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase-and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. Patients and Methods: Risk factors for 2-year NRM and 8-year PFS were identified in patients

Published
2017

4. Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Author

Cusini, A, Béguelin, C, Stampf, S, Boggian, K, Garzoni, C, Koller, M, Manuel, O, Meylan, P, Mueller, NJ, Hirsch, HH, Weisser, M, Berger, C, van Delden, C, Achermann, R, Amico, P, Aubert, JD, Banz, V, Beldi, G, Benden, C, Binet, I, Bochud, PY, Bucher, H, Bühler, L, Carell, T, Catana, E, Chalandon, Y, de Geest, S, de Rougemont, O, Dickenmann, M, Duchosal, M, Elkrief, L, Fehr, T, Ferrari-Lacraz, S, Gasche Soccal, P, Gaudet, C, Giostra, E, Golshayan, D, Hadaya, K, Halter, J, Heim, D, Hess, C, Hillinger, S, Hofbauer, G, Huynh-Do, U, Immer, F, Klaghofer, R, Laesser, B, Lehmann, R, Lovis, C, Marti, HP, Martin, PY, Mohacsi, P, Morel, P, Mueller, U, Mueller-McKenna, H, Müller, A, Müller, T, Müllhaupt, B, Nadal, D, Pascual, M, Passweg, J, Rick, J, Roosnek, E, Rosselet, A, Rothlin, S, Ruschitzka, F, Schanz, U, Schaub, S, Schnyder, A, Seiler, C, Steiger, J, Stirnimann, G, Toso, C, Venetz, JP, Villard, J, Wick, M, Wilhelm, M, Yerly, P, Gasche-Soccal, Paola Marina Alessandra, University of Zurich, and van Delden, C

Subjects
Graft Rejection, Male, genetic structures, 2747 Transplantation, 10265 Clinic for Endocrinology and Diabetology, 030230 surgery, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Risk Factors, Medicine, 2736 Pharmacology (medical), Immunology and Allergy, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, 610 Medicine & health, Prospective cohort study, ddc:616, Incidence, Hazard ratio, Graft Survival, Clostridium difficile, Middle Aged, Prognosis, Anti-Bacterial Agents, Diarrhea, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, Female, medicine.symptom, 10178 Clinic for Pneumology, Switzerland, Cohort study, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Humans, Transplantation, business.industry, Clostridioides difficile, Case-control study, Organ Transplantation, Confidence interval, Transplant Recipients, 10036 Medical Clinic, Case-Control Studies, Clostridium Infections, business, Follow-Up Studies
Abstract

© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P =.02). These findings may help to improve the management of SOT recipients. ispartof: American Journal of Transplantation vol:18 issue:7 pages:1745-1754 ispartof: location:United States status: published

Published
2017

5. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders : current practice in Europe, 2019

Author

Duarte, R.F., Labopin, M., Bader, P., Basak, G.W., Bonini, C., Chabannon, C., Corbacioglu, S., Dreger, P., Dufour, C., Genneryl, A.R., Kuball, J., Lankester, A.C., Lanza, F., Montoto, S., Nagler, A., Latour, R.P. de, Snowden, J.A., Styczynski, J., Yakoub-Agha, I., Kroger, N., Mohty, M., Albert, M., Alexander, T., Averbuch, D., Baron, F., Bazarbachi, E., Beksac, M., Brissot, E., Bug, G., Cesaro, S., Chalandon, Y., Ciceri, F., Czerw, T., Dazzi, F., Esteve, J., Fleischhauer, K., Garderet, L., Giebel, S., Gil, L., Gilleece, M., Gorin, N.C., Hayden, P., Halter, J., Boluda, J.C.H., Hudecek, M., Kleinschmidt, K., Kenyon, M., Koenecke, C., Locatelli, F., Malard, F., McLornan, D., Mikulska, M., Murray, J., Onida, F., Pedrazzoli, P., Penack, O., Peric, Z., Risitano, A., Robin, M., Robinson, S., Ruggeri, A., Sanz, J., Savani, B., Schetelig, J., Schied, C., Schmid, C., Schoemans, H., Schonland, S., Sharrack, B., Shouval, R., Spyridonidis, A., Toubert, A., Tourniac, O., Urbano-Ispizua, A., Vago, L., Gelder, M. van, Verhoeven, B., Versluis, J., Wietten, L., Willasch, A., European Soc Blood Marrow Transpla, Duarte, R. F., Labopin, M., Bader, P., Basak, G. W., Bonini, C., Chabannon, C., Corbacioglu, S., Dreger, P., Dufour, C., Gennery, A. R., Kuball, J., Lankester, A. C., Lanza, F., Montoto, S., Nagler, A., Peffault de Latour, R., Snowden, J. A., Styczynski, J., Yakoub-Agha, I., Kroger, N., Mohty, M, and on behalf of the European Society forBlood and Marrow Transplantation, (EBMT)

Subjects
medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, MEDLINE, Disease, Hematopoietic stem cell transplantation, History, 21st Century, NO, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Humans, Intensive care medicine, Multiple myeloma, Accreditation, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Hematologic Diseases, Europe, Immune System Diseases, Hematologic disease, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract

This is the seventh special EBMT report on the indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on transplant indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. In over two decades since the first report, the EBMT indications manuscripts have incorporated changes in transplant practice coming from scientific and technical developments in the field. In this same period, the establishment of JACIE accreditation has promoted high quality and led to improved outcomes of patient and donor care and laboratory performance in transplantation and cellular therapy. An updated report with operating definitions, revised indications and an additional set of data with overall survival at 1 year and non-relapse mortality at day 100 after transplant in the commonest standard-of-care indications is presented. Additional efforts are currently underway to enable EBMT member centres to benchmark their risk-adapted outcomes as part of the Registry upgrade Project 2020 against national and/or international outcome data.

Published
2019
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6. Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for T Cell Acute Lymphoblastic Leukemia: A Report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party

Author

Ali Bazarbachi, Yener Koc, Concepcion Herrera, Luca de Rosa, Mutlu Arat, Rocco Pastano, Hakan Ozdogu, Mohamad Mohty, Paolo Bernasconi, Didier Blaise, Célestine Simand, Luca Castagna, J. L. Diez-Martin, Myriam Labopin, Antonin Vitek, Rovira Montserrat, Giuseppe Marotta, Gérard Socié, Eolia Brissot, Fabio Ciceri, Emanuele Angelucci, Andrew M. McDonald, Zafer Gulbas, Guiseppe Visani, Pietro Pioltelli, Arnon Nagler, Wolf Rösler, Sebastian Giebel, Yves Chalandon, Paola Carluccio, Boris V. Afanasyev, Massimo Martino, Bazarbachi, A., Labopin, M., Angelucci, E., Gulbas, Z., Ozdogu, H., Arat, M., de Rosa, L., Pastano, R., Pioltelli, P., Montserrat, R., Martino, M., Ciceri, F., Koc, Y., Socie, G., Blaise, D., Herrera, C., Chalandon, Y., Bernasconi, P., Marotta, G., Castagna, L., Mcdonald, A., Visani, G., Carluccio, P., Vitek, A., Simand, C., Afanasyev, B., Rosler, W., Diez-Martin, J. L., Nagler, A., Brissot, E., Giebel, S., Mohty, M., Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)

Subjects
Male, Oncology, Transplantation Conditioning, T-Lymphocytes, Lymphoblastic Leukemia, Graft vs Host Disease, Disease, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, 0302 clinical medicine, Bone Marrow, Haploidentical stem cell transplantation, ComputingMilieux_MISCELLANEOUS, ddc:616, Acute leukemia, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Total body irradiation, 3. Good health, Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Stem cell, T-ALL, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Cyclophosphamide, T cell, Disease-Free Survival, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Transplantation, business.industry, Transplantation, Haploidentical, business, Thiotepa, Conditioning, 030215 immunology
Abstract

Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting.

Published
2020
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7. Cohort profile: The Swiss Transplant Cohort Study (STCS): A nationwide longitudinal cohort study of all solid organ recipients in Switzerland

Author

Stampf, Susanne, Mueller, Nicolas J., van Delden, Christian, Pascual, Manuel, Manuel, Oriol, Banz, Vanessa, Binet, Isabelle, De Geest, Sabina, Bochud, Pierre-Yves, Leichtle, Alexander, Schaub, Stefan, Steiger, Jürg, Koller, Michael, Swiss Transplant Cohort Study, members of the Swiss Transplant Cohort Study, Swiss Transplant Cohort Study, members of the Swiss Transplant Cohort Study, Amico, P., Axel, A., Aubert, J.D., Banz, V., Sonja, B., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carrel, T., Catana, E., Chalandon, Y., Geest, S., Rougemont, O., Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Franscini, N., Garzoni, C., Soccal, P.G., Gaudet, C., Golshayan, D., Goossens, N., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lehmann, R., Leichtle, A., Lovis, C., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., McLin, V., Mellac, K., Merçay, A., Mettler, K., Mueller, N., Müller, A., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirniman, G., Stürzinger, U., Delden, C.V., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhlem, M., Yerly, P., University of Zurich, and Stampf, Susanne

Subjects
PREVENTIVE STRATEGIES, 10255 Clinic for Thoracic Surgery, Epidemiology, CYTOMEGALOVIRUS, INVASIVE PULMONARY ASPERGILLOSIS, 610 Medicine & health, 2700 General Medicine, 030230 surgery, infectious diseases, 10234 Clinic for Infectious Diseases, immunology, 03 medical and health sciences, epidemiology, oncology, transplant medicine, Medicine, General & Internal, 0302 clinical medicine, General & Internal Medicine, INFECTION, Humans, Longitudinal Studies, Prospective Studies, PROTECTION, POLYMORPHISMS, OUTCOMES, Science & Technology, General Medicine, Transplant Recipients, 3. Good health, surgical procedures, operative, REJECTION, 10032 Clinic for Oncology and Hematology, 10209 Clinic for Cardiology, RISK-FACTORS, 030211 gastroenterology & hepatology, Life Sciences & Biomedicine, Switzerland
Abstract

PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine.ParticipantsOver 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients.Findings to dateDetailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the last decade. Interdisciplinary contributions in diverse fields of transplantation medicine such as infectious diseases, genomics, oncology, immunology and psychosocial science have resulted in approximately 70 scientific papers getting published in peer-review journals so far.Future plansThe STCS will deepen its efforts in personalised medicine and digital epidemiology, and will also focus on allocation research and the use of causal inference methods to make complex matters in transplant medicine more understandable and transparent.

Published
2021
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8. Outcomes following second allogeneic haematopoietic cell transplantation in patients with myelofibrosis: a retrospective study of the Chronic Malignancies Working Party of EBMT

Author

Nicolaus Kröger, Aleksandar Radujkovic, Jakob Passweg, Marie Robin, Tomasz Czerw, Patrick Hayden, Emanuele Angelucci, Alessandro Rambaldi, Katya Mauff, Liesebeth C. de Wreede, Ibrahim Yakoub-Agha, Juan Carlos Hernández-Boluda, Jiri Mayer, Yves Chalandon, Matthias Stelljes, Donal P. McLornan, Uwe Platzbecker, Mitja Nabergoj, Stephen P. Robinson, Xavier Poiré, Linda Koster, Fabio Ciceri, Søren Lykke Petersen, Marco Ladetto, Fridrich Stölzel, Nabergoj, M., Mauff, K., Robin, M., Kroger, N., Angelucci, E., Poire, X., Passweg, J., Radujkovic, A., Platzbecker, U., Robinson, S., Rambaldi, A., Petersen, S. L., Stolzel, F., Stelljes, M., Ciceri, F., Mayer, J., Ladetto, M., de Wreede, L. C., Koster, L., Hayden, P. J., Czerw, T., Hernandez-Boluda, J. C., Mclornan, D., Chalandon, Y., Yakoub-Agha, I., UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and Université Paris Cité (UPCité)

Subjects
medicine.medical_specialty, Graft failure, Transplantation Conditioning, [SDV]Life Sciences [q-bio], Primary Myelofibrosis / therapy, Graft vs Host Disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, In patient, Sibling, Myelofibrosis, Retrospective Studies, ddc:616, Transplantation, business.industry, Incidence (epidemiology), Haematopoietic cell transplantation, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, 3. Good health, surgical procedures, operative, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Chronic gvhd, business, 030215 immunology
Abstract

International audience; Therapeutic management of patients with primary or secondary myelofibrosis (MF) who experience relapse or graft failure following allogeneic haematopoietic cell transplantation (allo-HCT) remains heterogeneous. We retrospectively analyzed 216 patients undergoing a second allo-HCT for either relapse (56%) or graft failure (31%) between 2010 and 2017. Median age was 57.3 years (range 51–63). The same donor as for the first allo-HCT was chosen in 66 patients (31%) of whom 19 received an HLA-identical sibling donor, whereas a different donor was chosen for 116 patients (54%). Median follow-up was 40 months. Three-year overall survival (OS) and relapse-free survival (RFS) were 42% and 39%, respectively. Three-year non-relapse mortality (NRM) and relapse rates were 36% and 25%, respectively. Grade II-IV and III-IV acute GVHD occurred in 25% and 11% of patients, respectively, and the 3-year incidence of chronic GVHD was 33% including 14% for extensive grade. Graft-failure incidence at 1 year was 14%. In conclusion, our data suggest that a second allo-HCT is a potential option for patients failing first allo-HCT for MF albeit careful patient assessment is fundamental to identify individual patients who could benefit from this approach.

Published
2021
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9. Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study

Author

Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin J Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen R Spellman, Jean Villard, Phil Stevenson, Martin Maiers, Stephen Spellman, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven GE Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas PM Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, University of Washington [Seattle], Harvard University [Cambridge], Frederick National Laboratory for Cancer Research (FNLCR), Uppsala Universitet [Uppsala], PathWest Murdoch / Fiona Stanley Hospital [Perth, WA, Australia] (PMFSH), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical College of Wisconsin [Milwaukee] (MCW), Memorial Sloane Kettering Cancer Center [New York], Royal Free Hospital [London, UK], Center for International Blood and Marrow Transplant Research [Minneapolis, MN, USA] (CIBMTR), Aichi Medical University School of Medicine [Nagakute, Aichi, Japan] (AMUSM), Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Geneva University Hospital (HUG), International Histocompatibility Working Group in Hematopoietic Cell Transplantation: Effie W Petersdorf, Mary Carrington, Colm O'hUigin, Mats Bengtsson, Dianne De Santis, Valerie Dubois, Ted Gooley, Mary Horowitz, Katharine Hsu, J Alejandro Madrigal, Martin Maiers, Mari Malkki, Caroline McKallor, Yasuo Morishima, Machteld Oudshoorn, Stephen Spellman, Jean Villard, Phil Stevenson, Jane Apperley, Peter Bardy, Ghislaine Bernard, Yves Bertrand, Adrian Bloor, Chiara Bonini, Stephane Buhler, Laura Bungener, Helen Campbell, Kristina Carlson, Ben Carpenter, Anne Cesbron, Christian Chabannon, Yves Chalandon, Jeremy Chapman, Réda Chebel, Patrice Chevallier, Gerda Choi, Matt Collin, Jan J Cornelissen, Charles Crawley, Lloyd D'Orsogna, Jean-Hugues Dalle, Eric Deconinck, Muriel DeMatteis, Mary Diviney, Anne Dormoy, Katia Gagne, Brenda Gibson, Maria Gilleece, David Gottlieb, John Gribben, Tayfun Güngör, Mike Haagenson, Cathie Hart, Rhonda Holdsworth, Ian Humphreys, Yoshihisa Kodera, Mickey Koh, Hélène Labussière-Wallet, Arjan C Lankester, Neubery Lardy, Sarah Lawson, Xavier Leleu, Stephen MacKinnon, Ram Malladi, Steven Ge Marsh, Murray Martin, Neema P Mayor, I Grant McQuaker, Ellen Meijer, Satoko Morishima, Emmanouil Nikolousis, Kim Orchard, Jacob Passweg, Amit Patel, Katherine Patrick, Béatrice Pedron, Andy Peniket, Julia Perry, Eefke Petersen, Victoria Potter, Mike Potter, Rachel Protheroe, Nicole Raus, Carmen Ruiz de Elvira, Nigel Russell, Nicholaas Pm Schaap, Urs Schanz, Harry Schouten, Roderick Skinner, John Snowden, Eric Spierings, Colin Steward, Eleni Tholouli, Alycia Thornton, Marcel Tilanus, Arnold van de Meer, Hendrik Veelkens, Paul Veys, Narelle Watson, Lyanne Weston, Keith Wilson, Marie Wilson, Robert Wynn, József Zsiros, Leiden University Medical Center (LUMC), GAGNE, Katia, CCA - Cancer Treatment and quality of life, AII - Inflammatory diseases, Hematology, CCA - Cancer biology and immunology, Petersdorf, E. W., Carrington, M., O'Huigin, C., Bengtsson, M., De Santis, D., Dubois, V., Gooley, T., Horowitz, M., Hsu, K., Madrigal, J. A., Maiers, M. J., Malkki, M., Mckallor, C., Morishima, Y., Oudshoorn, M., Spellman, S. R., Villard, J., Stevenson, P., Maiers, M., Spellman, S., Apperley, J., Bardy, P., Bernard, G., Bertrand, Y., Bloor, A., Bonini, C., Buhler, S., Bungener, L., Campbell, H., Carlson, K., Carpenter, B., Cesbron, A., Chabannon, C., Chalandon, Y., Chapman, J., Chebel, R., Chevallier, P., Choi, G., Collin, M., Cornelissen, J. J., Crawley, C., D'Orsogna, L., Dalle, J. -H., Deconinck, E., Dematteis, M., Diviney, M., Dormoy, A., Gagne, K., Gibson, B., Gilleece, M., Gottlieb, D., Gribben, J., Gungor, T., Haagenson, M., Hart, C., Holdsworth, R., Humphreys, I., Kodera, Y., Koh, M., Labussiere-Wallet, H., Lankester, A. C., Lardy, N., Lawson, S., Leleu, X., Mackinnon, S., Malladi, R., Marsh, S. G., Martin, M., Mayor, N. P., Mcquaker, I. G., Meijer, E., Morishima, S., Nikolousis, E., Orchard, K., Passweg, J., Patel, A., Patrick, K., Pedron, B., Peniket, A., Perry, J., Petersen, E., Potter, V., Potter, M., Protheroe, R., Raus, N., Ruiz de Elvira, C., Russell, N., Schaap, N. P., Schanz, U., Schouten, H., Skinner, R., Snowden, J., Spierings, E., Steward, C., Tholouli, E., Thornton, A., Tilanus, M., van de Meer, A., Veelkens, H., Veys, P., Watson, N., Weston, L., Wilson, K., Wilson, M., Wynn, R., Zsiros, J., RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA TI Staf (9), University of Zurich, and Petersdorf, Effie W

Subjects
Oncology, Male, Hematopoietic Stem Cell Transplantation/methods, [SDV]Life Sciences [q-bio], 2720 Hematology, Graft vs Host Disease, Histocompatibility Testing, 0302 clinical medicine, Graft vs Host Disease/genetics, immune system diseases, unrelated donor, Exons/genetics, graft-versus-host disease, Medicine, ddc:616, Hematopoietic Stem Cell Transplantation, Exons, Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], surgical procedures, operative, 030220 oncology & carcinogenesis, Histocompatibility, HLA-B Antigens/genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, EXPRESSION, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, 610 Medicine & health, Human leukocyte antigen, Lower risk, Risk Assessment, Article, Graft vs Host Disease/genetics/immunology, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Retrospective Studies, RECEPTOR, business.industry, MORTALITY, RECOGNITION, Retrospective cohort study, Odds ratio, medicine.disease, Transplantation, Graft-versus-host disease, hematopoietic-cell transplantation, SEQUENCE-DERIVED PEPTIDES, 10036 Medical Clinic, HLA-B Antigens, 10032 Clinic for Oncology and Hematology, Multivariate Analysis, RESIDUES, HLA-B leader, business, 030215 immunology
Abstract

Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT. Methods: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, Japan, North America, and the UK between Jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50·3%) HLA-matched and 1457 (4·3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors. Findings: Between Jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909–2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3–4 acute GVHD (odds ratio [OR] 1·89, 95% CI 1·53–2·33; p

Published
2021
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10. Temporal trends, risk factors and outcomes of infections due to extended-spectrum β-lactamase producing Enterobacterales in Swiss solid organ transplant recipients between 2012 and 2018

Author

Kohler, Philipp, Wolfensberger, Aline, Stampf, Susanne, Brönnimann, Andreas, Boggian, Katia, van Delden, Christian, Favre, Melody, Hirzel, Cédric, Khanna, Nina, Kuster, Stefan P, Manuel, Oriol, Neofytos, Dionysios, Ragozzino, Silvio, Schreiber, Peter W, Walti, Laura, Mueller, Nicolas J, Swiss Transplant Cohort Study, Chalandon, Yves, Gasche-Soccal, Paola Marina Alessandra, Gaudet-Blavignac, Christophe, Lovis, Christian, Martin, Pierre-Yves, Posfay Barbe, Klara, Simonetta, Federico, Toso, Christian, Villard, Jean, Swiss Transplant Cohort Study, Amico, P., Axel, A., Aubert, J.D., Banz, V., Sonja, B., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carrel, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laesser, B., Lang, B., Lehmann, R., Leichtle, A., Lovis, C., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., Mellac, K., Merçay, A., Mettler, K., Meylan, P., Mueller, N., Müller, A., Müller, T., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Pascual, M., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Simonetta, F., Staufer, K., Stampf, S., Steiger, J., Stirniman, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Kohler, Philipp

Subjects
Graft Rejection, Male, 0301 basic medicine, 10255 Clinic for Thoracic Surgery, Antibiotics, Drug resistance, 030230 surgery, 2726 Microbiology (medical), Organ transplantation, 10234 Clinic for Infectious Diseases, Enterobacterales, 0302 clinical medicine, Medical microbiology, Risk Factors, 2736 Pharmacology (medical), Medicine, Pharmacology (medical), Prospective Studies, Prospective cohort study, 610 Medicine & health, Escherichia coli Infections, ddc:616, Enterobacteriaceae Infections, Middle Aged, Anti-Bacterial Agents, Extended-spectrum beta-lactamase, Renal transplant, Infectious Diseases, 10209 Clinic for Cardiology, Female, Switzerland, Cohort study, Adult, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, beta-Lactamases, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Enterobacteriaceae, Internal medicine, Drug Resistance, Bacterial, Humans, lcsh:RC109-216, Risk factor, Aged, business.industry, Research, Public Health, Environmental and Occupational Health, Organ Transplantation, 2739 Public Health, Environmental and Occupational Health, 2725 Infectious Diseases, Transplant Recipients, Solid organ transplant, Transplantation, Case-Control Studies, 10032 Clinic for Oncology and Hematology, bacteria, business
Abstract

Background The burden of antimicrobial resistance is high in solid organ transplant (SOT) recipients. Among Swiss SOT recipients, we assessed temporal trends of ESBL-producing Enterobacterales (ESBL-E), identified risk factors for ESBL-E, and assessed the impact of resistance on patient outcome. Methods Data from the Swiss Transplant Cohort Study (STCS), a nationwide prospective cohort of SOT-recipients, were analysed. Temporal trends were described for ESBL-detection among Escherichia coli and non-Escherichia coli. In a nested case–control study, cases with ESBL-E infection were 1:1 matched (by time since transplantation, organ transplant, pathogen) to controls infected with non-ESBL-E. Factors associated with resistance and with unfavourable 30-day outcome (death, infection relapse, graft loss) were assessed. Results From 2012 to 2018, we identified 1′212 infection episodes caused by Enterobacterales in 1′074 patients, thereof 11.4% (138/1′212) caused by ESBL-E. The proportion of ESBL-production among Escherichia coli remained stable over time (p = 0.93) but increased for non-E. coli (p = 0.02) Enterobacterales. In the case–control study (n = 102), antibiotic pre-treatment was independently associated with ESBL-production (aOR = 2.6, 95%-CI: 1.0–6.8, p = 0.046). Unfavourable outcome occurred in 24/51 (47%) cases and 9/51 (18%) controls (p = 0.003). Appropriate empiric antibiotic therapy was the only modifiable factor associated with unfavourable outcome. Conclusions In Swiss SOT-recipients, proportion of infections with ESBL-producing non-E. coli Enterobacterales increased in recent years. Antibiotic pre-treatment represents a risk factor for ESBL-E. Improving appropriateness of empiric antibiotic treatment might be an important measure to reduce unfavourable outcome, which was observed in almost half of SOT-recipients with ESBL-E infections.

Published
2021
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11. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Author

Tschopp, Jonathan, LHuillier, Arnaud G., Mombelli, Matteo, Mueller, Nicolas J., Khanna, Nina, Garzoni, Christian, Meloni, Dario, Papadimitriou‐Olivgeris, Matthaios, Neofytos, Dionysios, Hirsch, Hans H., Schuurmans, Macé M., Müller, Thomas, Berney, Thierry, Steiger, Jürg, Pascual, Manuel, Manuel, Oriol, Delden, Christian, Amico, Patrizia, Aubert, John‐David, Banz, Vanessa, Beldi, Guido, Benden, Christian, Berger, Christoph, Binet, Isabelle, Bochud, Pierre‐Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, Geest, Sabina, Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari‐Lacraz, Sylvie, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Déla, Hadaya, Karine, Halter, Jörg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Günther, Huynh‐Do, Uyen, Immer, Franz, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Marti, Hans‐Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Mueller, Nicolas J, Müller, Antonia, Müllhaupt, Beat, Passweg, Jakob, Posfay‐Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Schuurmans, Macé, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steinack, Carolin, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean‐Pierre, Villard, Jean, Wick, Madeleine, Wilhelm, Markus, Yerly, Patrick, University of Zurich, Swiss Transplant Cohort Study (STCS), Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., Meylan, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Seiler, C., Sprachta, J., Stampf, S., Steinack, C., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., and Yerly, P.

Subjects
Male, 10255 Clinic for Thoracic Surgery, Comorbidity, 030230 surgery, Infection and infectious agents/ Viral, Organ transplantation, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Epidemiology, Immunology and Allergy, Medicine, Pharmacology (medical), Prospective Studies, Prospective cohort study, ddc:616, Infectious disease, education.field_of_study, ddc:618, ddc:617, Incidence, Clinical research/ practice, Middle Aged, 3. Good health, Survival Rate, 10209 Clinic for Cardiology, Female, medicine.symptom, 10178 Clinic for Pneumology, Coronavirus Infections, infectious [Complication], infectious, infection and infectious agents, infection and infectious agents - viral, infectious disease [Aged, Betacoronavirus, Coronavirus Infections/epidemiology, Disease Transmission, Infectious/prevention & control, Follow-Up Studies, Humans, Organ Transplantation/methods, Pandemics, Pneumonia, Viral/epidemiology, Postoperative Complications/epidemiology, Survival Rate/trends, Switzerland/epidemiology, Transplant Recipients, clinical research/ practice, complication], Switzerland, Cohort study, medicine.medical_specialty, Nausea, Population, Pneumonia, Viral, Infection and infectious agents, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Disease Transmission, Infectious, education, Survival rate, Aged, Transplantation, business.industry, SARS-CoV-2, COVID-19, Organ Transplantation, medicine.disease, 10032 Clinic for Oncology and Hematology, business
Abstract

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.

Published
2020

12. Management of allergy transfer upon solid organ transplantation

Author

Muller, Yannick D, Vionnet, Julien, Beyeler, Franziska, Eigenmann, Philippe, Caubet, Jean-Christoph, Villard, Jean, Berney, Thierry, Scherer, Kathrin, Spertini, Francois, Fricker, Michael P, Lang, Claudia, Schmid-Grendelmeier, Peter, Benden, Christian, Lombard, Pascale Roux, Aubert, Vincent, Immer, Franz, Pascual, Manuel, Harr, Thomas, Amico, Patrizia, Aubert, John-David, Banz, Vanessa, Beldi, Guido, Berger, Christoph, Binet, Isabelle, Bochud, Pierre-Yves, Branca, Sanda, Bucher, Heiner, Carell, Thierry, Catana, Emmanuelle, Chalandon, Yves, de Geest, Sabina, de Rougemont, Olivier, Dickenmann, Michael, Duchosal, Michel, Elkrief, Laure, Fehr, Thomas, Ferrari-Lacraz, Sylvie, Garzoni, Christian, Soccal, Paola Gasche, Gaudet, Christophe, Giostra, Emiliano, Golshayan, Dela, Hadaya, Karine, Halter, Joerg, Hauri, Dimitri, Heim, Dominik, Hess, Christoph, Hillinger, Sven, Hirsch, Hans H, Hofbauer, Guenther, Huynh-Do, Uyen, Klaghofer, Richard, Koller, Michael, Laesser, Bettina, Laube, Guido, Lehmann, Roger, Lovis, Christian, Majno, Pietro, Manuel, Oriol, Marti, Hans-Peter, Martin, Pierre Yves, Martinelli, Michele, Meylan, Pascal, Morel, Philippe, Mueller, Nicolas J, Mueller, Antonia, Mueller, Thomas, Muellhaupt, Beat, Yerly, Patrick, Passweg, Jakob, Posfay-Barbe, Klara, Rick, Juliane, Roosnek, Eddy, Rosselet, Anne, Rothlin, Silvia, Ruschitzka, Frank, Schanz, Urs, Schaub, Stefan, Schnyder, Aurelia, Seiler, Christian, Sprachta, Jan, Stampf, Susanne, Steiger, Juerg, Stirnimann, Guido, Toso, Christian, Van Delden, Christian, Venetz, Jean-Pierre, Wick, Madeleine, Wilhelm, Markus, Swiss Transplant Cohort Study, Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Gasche Soccal, P., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Hauri, D., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Laube, G., Lehmann, R., Lovis, C., Majno, P., Manuel, O., Marti, H.P., Yves Martin, P., Martinelli, M., Meylan, P., Morel, P., Mueller, N.J., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Seiler, C., Sprachta, J., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, Muller, Yannick D, Gasche-Soccal, Paola Marina Alessandra, Posfay Barbe, Klara, and Lovis, Christian

Subjects
Allergy, diagnostic techniques and imaging, IgE, Immunoglobulin E, allergy transfer, anaphylaxis, immunosuppression, management, solid organ transplantation, allergy, business/management, clinical decision-making, clinical research/practice, guidelines, immunoglobulin E, immunosuppression/immune modulation, organ transplantation in general, patient safety, 10255 Clinic for Thoracic Surgery, 2747 Transplantation, medicine.medical_treatment, 030230 surgery, INCREASE, Cohort Studies, 0302 clinical medicine, Solid organ transplantation, Immunology and Allergy, Medicine, 2736 Pharmacology (medical), Pharmacology (medical), LUNG TRANSPLANTATION, ddc:616, Kidney, ddc:618, biology, ddc:617, PEANUT ALLERGY, 10177 Dermatology Clinic, Immunosuppression, practice, Management, clinical decision‐making, medicine.anatomical_structure, B-CELLS, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, 10178 Clinic for Pneumology, Brief Communications, Life Sciences & Biomedicine, Anaphylaxis, medicine.medical_specialty, 610 Medicine & health, Brief Communication, 03 medical and health sciences, Internal medicine, Humans, Peanut Hypersensitivity, Allergy transfer, business, Retrospective Studies, Transplantation, Lung, Science & Technology, immune modulation, business.industry, Organ Transplantation, medicine.disease, clinical research, 10036 Medical Clinic, 10032 Clinic for Oncology and Hematology, biology.protein, ASTHMA, Surgery, IMMUNOGLOBULIN-E
Abstract

Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor‐Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut‐specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living‐donor kidney recipients. All pollen‐specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor‐derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid‐organ transplantation from donors with a history of fatal anaphylaxis., Based on the Swisstransplant donor registry, the Swiss‐Transplant‐Cohort‐Study, and a prospective analysis on allergy maintenance in atopic recipients, this study makes new recommendations for the management of allergy transfer upon solid organ transplantation, emphasizing the poor effect of immunosuppression on IgE sensitization and the need of early allergological investigation in the donor and respective recipients.

Published
2020

13. γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Author

Jean-Pierre Bourquin, Beat Bornhauser, Beena Jeevan-Raj, Oliver Hantschel, Werner Held, Joerg Huelsken, Maxime Danilo, Margot Thome, Georgi S Angelov, Anja Irmisch, Noemie Luong-Gardiol, Gianni Cazzaniga, Sara Curtet, Mélanie Charmoy, Yuna Huang, Yves Chalandon, Irene Pizzitola, Imran Siddiqui, Mélanie Juilland, University of Zurich, Held, Werner, Luong-Gardiol, N, Siddiqui, I, Pizzitola, I, Jeevan-Raj, B, Charmoy, M, Huang, Y, Irmisch, A, Curtet, S, Angelov, G, Danilo, M, Juilland, M, Bornhauser, B, Thome, M, Hantschel, O, Chalandon, Y, Cazzaniga, G, Bourquin, J, Huelsken, J, and Held, W

Subjects
0301 basic medicine, Cancer Research, Survivin, Fusion Proteins, bcr-abl, MYC, Mice, SCID, 1307 Cell Biology, 0302 clinical medicine, Animals, Fusion Proteins, bcr-abl/genetics, Fusion Proteins, bcr-abl/metabolism, Gene Expression Regulation, Leukemic, Humans, K562 Cells, Mice, Inbred NOD, Mice, Transgenic, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, Survivin/genetics, Survivin/metabolism, Wnt Signaling Pathway, beta Catenin/genetics, beta Catenin/metabolism, gamma Catenin/genetics, gamma Catenin/metabolism, B cell acute lymphoblastic leukemia (B-ALL), BCR-ABL1, BIRC5 (Survivin), chronic myeloid leukemia (CML), junction plakoglobin, β-catenin, γ-catenin, hemic and lymphatic diseases, Chronic myeloid leukemia (CML), 1306 Cancer Research, beta Catenin, ddc:616, biology, Wnt signaling pathway, Myeloid leukemia, 3. Good health, Oncology, 030220 oncology & carcinogenesis, 2730 Oncology, Junction plakoglobin, Β-catenin, Human, Beta-catenin, Plakoglobin, 610 Medicine & health, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, K562 Cell, Animal, Cell Biology, Fusion protein, 030104 developmental biology, 10036 Medical Clinic, Catenin, biology.protein, Cancer research, gamma Catenin, K562 cells
Abstract

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ-catenin in the initiation and maintenance of BCR-ABL1 + B-ALL but not CML. The selectivity was explained by a partial γ-catenin dependence of MYC expression together with the susceptibility of B-ALL, but not CML, to reduced MYC levels. MYC and γ-catenin enabled B-ALL maintenance by augmenting BIRC5 and enforced BIRC5 expression overcame γ-catenin loss. Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1 + B-ALL.

Published
2019
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14. Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort

Author

Neofytos, Dionysios, Hirzel, Cédric, Boely, Elsa, Lecompte, Thanh, Khanna, Nina, Mueller, Nicolas J, Boggian, Katia, Cusini, Alexia, Manuel, Oriol, Banz Wüthrich, Vanessa, Beldi, Guido, Stirnimann, Guido, van Delden, Christian, Swiss Transplant, Cohort Study, Swiss Transplant Cohort Study, Amico, P., Aubert, J.D., Banz, V., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Boëly, E., Bucher, H., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Lehmann, R., Lovis, C., Majno, P., Marti, H.P., Martin, P.Y., Meylan, P., Mohacsi, P., Morel, P., Mueller, U., Mueller-McKenna, H., Müller, A., Müller, T., Müllhaupt, B., Pascual, M., Passweg, J., Posfay-Barbe, K., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Seiler, C., Sprachta, J., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Neofytos, Dionysios

Subjects
0301 basic medicine, Male, Epidemiology, 2747 Transplantation, Pneumocystis carinii, Adult, Aged, Anti-Bacterial Agents/therapeutic use, Antibiotic Prophylaxis/methods, Antibiotic Prophylaxis/standards, Female, Humans, Incidence, Middle Aged, Mortality, Organ Transplantation/adverse effects, Pneumocystis carinii/isolation & purification, Pneumonia, Pneumocystis/drug therapy, Pneumonia, Pneumocystis/epidemiology, Pneumonia, Pneumocystis/microbiology, Pneumonia, Pneumocystis/prevention & control, Practice Guidelines as Topic, Prospective Studies, Switzerland/epidemiology, Treatment Outcome, Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use, Young Adult, Pneumocystis jirovecii pneumonia, Solid organ transplant recipients, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, 030212 general & internal medicine, Prospective cohort study, 610 Medicine & health, education.field_of_study, ddc:617, Incidence (epidemiology), Pneumonia, Pneumocystis, Anti-Bacterial Agents, Infectious Diseases, 10219 Clinic for Gastroenterology and Hepatology, Cohort, 10209 Clinic for Cardiology, 10178 Clinic for Pneumology, Switzerland, medicine.drug, medicine.medical_specialty, 030106 microbiology, Population, 03 medical and health sciences, Internal medicine, parasitic diseases, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, education, Transplantation, business.industry, 2725 Infectious Diseases, Organ Transplantation, Antibiotic Prophylaxis, medicine.disease, Trimethoprim, Pneumonia, Complication, business
Abstract

BACKGROUND Descriptive data on Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients (SOTr) in the era of routine Pneumocystis-prophylaxis are lacking. METHODS All adult SOTr between 2008-2016 were included. PJP was diagnosed based on consensus guidelines. Early-onset PJP was defined as PJP within the 1st-year-post-transplant. RESULTS 41/2842 SOTr (1.4%) developed PJP (incidence rate: 0.01/1000 person-days) at a mean of 493-days post-transplant: 21 (51.2%) early vs 20 (48.8%) late-onset PJP. 2465 (86.7%) SOTr received Pneumocystis-prophylaxis for a mean 316 days. PJP incidence was 0.001% and 0.003% (log-rank

Published
2018
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15. CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation

Author

Zoltán Kutalik, Pierre-Yves Bochud, Séverine Crettol, Nicolas J. Mueller, Roger Lehmann, Manuel Pascual, Jean-François Dufour, Paola M. Soccal, Isabelle Binet, Andrea Treyer, Jürg Steiger, Dela Golshayan, Lina Quteineh, Chin B. Eap, Jean-Pierre Venetz, C. van Delden, Paul Mohacsi, Oriol Manuel, and The Swiss Transplant Cohort Study, Achermann, R., Aubert, J.D., Baumann, P., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Boely, E., Bucher, H., Bühler, L., Carell, T., Catana, E., Chalandon, Y., Geest, S., Rougemont, O., Dickenmann, M., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Gasche, Y., Soccal, P.G., Giostra, E., Golshayan, D., Good, D., Hadaya, K., Hess, C., Hillinger, S., Hirsch, H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Kuntzen, T., Laesser, B., Lehmann, R., Lovis, C., Manuel, O., Marti, H.P., Martin, P.Y., Meylan, P., Mohacsi, P., Morard, I., Morel, P., Mueller, U., Mueller, N., Mueller-McKenna, H., Müller, T., Müllhaupt, B., Nadal, D., Nair, G., Pascual, M., Passweg, J., Ziegler, C.P., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Seiler, C., Semmo, N., Stampf, S., Steiger, J., Toso, C., Tsinalis, D., Delden, C.V., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Eap, C B

Subjects
0301 basic medicine, Time Factors, Physiology, Pharmacology, Organ transplantation, 10234 Clinic for Infectious Diseases, Diabetes mellitus genetics, Gene Frequency, Risk Factors, Odds Ratio, Prevalence, ddc:616, Metabolic Syndrome, 2. Zero hunger, education.field_of_study, Incidence, Homozygote, 3. Good health, 10219 Clinic for Gastroenterology and Hepatology, 3004 Pharmacology, Phenotype, Treatment Outcome, 10209 Clinic for Cardiology, Molecular Medicine, 10178 Clinic for Pneumology, Switzerland, Heterozygote, medicine.medical_specialty, Population, 610 Medicine & health, Biology, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Insulin resistance, 1311 Genetics, Diabetes mellitus, Diabetes Mellitus, Genetics, medicine, Humans, Diabetes Mellitus/epidemiology, Diabetes Mellitus/genetics, Dyslipidemias/epidemiology, Dyslipidemias/genetics, Genetic Predisposition to Disease, Linear Models, Logistic Models, Metabolic Syndrome X/diagnosis, Metabolic Syndrome X/epidemiology, Metabolic Syndrome X/genetics, Multivariate Analysis, Obesity/epidemiology, Obesity/genetics, Organ Transplantation/adverse effects, Switzerland/epidemiology, Transcription Factors/genetics, Obesity, education, Dyslipidemias, Organ Transplantation, Odds ratio, medicine.disease, 10020 Clinic for Cardiac Surgery, Transplantation, 030104 developmental biology, 1313 Molecular Medicine, Metabolic syndrome, Transcription Factors
Abstract

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (PcorrectedA was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.The Pharmacogenomics Journal advance online publication, 8 December 2015; doi:10.1038/tpj.2015.82.

Published
2015
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16. Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation

Author

Beaume, M, Köhler, T, Greub, G, Manuel, O, Aubert, J-D, Baerlocher, L, Farinelli, L, Buckling, A, van Delden, C, Stirnimann, Guido, Beldi, Guido, Huynh-Do, Uyen, Swiss Transplant, Cohort Study, Swiss Transplant Cohort Study, Achermann, R., Amico, P., Baumann, P., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, P.Y., Boely, E., Bucher, H., Bühler, L., Carell, T., Catana, E., Chalandon, Y., Geest, S., Rougemont, O., Dickenmann, M., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P.G., Giostra, E., Golshayan, D., Good, D., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Lehmann, R., Lovis, C., Marti, H.P., Martin, P.Y., Martinolli, L., Meylan, P., Mohacsi, P., Morard, I., Morel, P., Mueller, U., Mueller, N.J., Mueller-McKenna, H., Müller, A., Müller, T., Müllhaupt, B., Nadal, D., Pascual, M., Passweg, J., Ziegler, C.P., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Seiler, C., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Tsinalis, D., Venetz, J.P., Villard, J., Wick, M., Wilhelm, M., and Yerly, P.

Subjects
0301 basic medicine, Adult, Cystic Fibrosis, medicine.medical_treatment, 030106 microbiology, Colony Count, Microbial, Motility, 610 Medicine & health, Cystic fibrosis, Adaptation, Physiological, Allografts, Cystic Fibrosis/microbiology, Female, Genome, Bacterial, Humans, Lung/microbiology, Lung Transplantation, Microbiota, Phenotype, Pseudomonas/isolation & purification, Pseudomonas/physiology, Tissue Donors, Article, Microbiology, 03 medical and health sciences, Pseudomonas, medicine, Lung transplantation, Lung, ddc:616, Multidisciplinary, biology, ddc:617, Biofilm, biology.organism_classification, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Actinobacillus, Immunology
Abstract

In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft.

Published
2017
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17. Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections

Author

Héquet, Delphine, Kralidis, Georg, Carrel, Thierry, Cusini, Alexia, Garzoni, Christian, Hullin, Roger, Meylan, Pascal R, Mohacsi, Paul, Mueller, Nicolas J, Ruschitzka, Frank, Tozzi, Piergiorgio, van Delden, Christian, Weisser, Maja, Wilhelm, Markus J, Pascual, Manuel, Beldi, Guido, Stirnimann, Guido, Manuel, Oriol, Swiss Transplant Cohort Study, STCS, Swiss Transplant Cohort Study (STCS), Achermann, R., Amico, P., Aubert, JD., Baumann, P., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, PY., Boely, E., Bucher, H., Bühler, L., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Elkrief, L., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Soccal, P., Gaudet, C., Giostra, E., Golshayan, D., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Laesser, B., Lehmann, R., Lovis, C., Manuel, O., Marti, HP., Martin, P., Martinolli, L., Meylan, P., Mohacsi, P., Morel, P., Mueller, U., Mueller, N., Mueller-McKenna, H., Müller, A., Müller, T., Müllhaupt, B., Nadal, D., Pascual, M., Passweg, J., Ziegler, C., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Seiler, C., Stampf, S., Steiger, J., Stirnimann, G., Toso, C., Van Delden, C., Venetz, JP., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Manuel, Oriol

Subjects
Male, 10255 Clinic for Thoracic Surgery, medicine.medical_treatment, 030204 cardiovascular system & hematology, 030230 surgery, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Postoperative Complications, Risk Factors, Clinical endpoint, Medicine, Cumulative incidence, 610 Medicine & health, Outcome, Heart transplantation, ddc:616, Mechanical heart support, Incidence (epidemiology), Incidence, Bacterial Infections, Middle Aged, 3. Good health, 10219 Clinic for Gastroenterology and Hepatology, Infectious Diseases, surgical procedures, operative, Virus Diseases, Cohort, 10209 Clinic for Cardiology, Cardiac transplantation, Female, biological phenomena, cell phenomena, and immunity, Cohort study, Research Article, Adult, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, parasitic diseases, Humans, cardiovascular diseases, Aged, Proportional Hazards Models, Retrospective Studies, Heart Failure, business.industry, 2725 Infectious Diseases, medicine.disease, Surgery, Transplantation, Mycoses, 10036 Medical Clinic, Heart failure, Multivariate Analysis, Heart Transplantation, Heart-Assist Devices, business
Abstract

Background Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. Methods Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. Results Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p

Published
2016
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18. Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine

Author

Cécile Delhumeau, Christian van Delden, Christophe Combescure, Claire-Anne Siegrist, Olivier F. Clerc, Paola M. Soccal, Karine Hadaya, Matthias Cavassini, Sara Meier, Laurent Kaiser, Alexandra Calmy, Michael Bel, Bernard Hirschel, Sabine Yerly, H1N1 Study Group, Swiss HIV Cohort Study (SHCS), Siegrist, CA., Posfay-Barbe, K., Meier, S., Bel, M., Grillet, S., Sealy, G., Demeules, J., Charvat, S., Verdon, M., Combescure, C., Hirschel, B., Calmy, A., Delhumeau-Cartier, C., Gabay, C., Guerne, PA., Seebach, J., Ribi, C., Villard, J., Dietrich, PY., George, AC., Favet, L., van Delden, C., Morard, I., Mentha, G., Giostra, E., Hadaya, K., Martin, PY., Soccal, P., Berney, T., Noble, S., Mohty, B., Nagy, M., Chalandon, Y., Roosnek, E., Passweg, J., Kaiser, L., Yerly, S., Thomas, Y., Wunderli, W., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Posfay Barbe, Klara, and Grillet, Stéphane

Subjects
Male, lcsh:Medicine, Adult, Aged, Antibodies, Viral/blood, Antibodies, Viral/immunology, Female, HIV Infections/blood, HIV Infections/immunology, Humans, Immunocompromised Host, Immunologic Memory/drug effects, Influenza Vaccines/administration & dosage, Influenza, Human/blood, Influenza, Human/immunology, Kidney Transplantation/immunology, Middle Aged, Pandemics, HIV Infections/blood/immunology, HIV Infections, ddc:616.07, Antibodies, Viral, 0302 clinical medicine, Pandemic, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, Kidney transplantation, ddc:616, 0303 health sciences, Multidisciplinary, ddc:617, biology, Vaccination, Antibody titer, HIV diagnosis and management, 3. Good health, Titer, Influenza, Human/blood/immunology/prevention & control, Influenza Vaccines, Medicine, Infectious diseases, HIV clinical manifestations, Antibody, Research Article, Retrovirology and HIV immunopathogenesis, Viral diseases, 03 medical and health sciences, Immune system, Influenza, Human, medicine, Antibodies, Viral/blood/immunology, 030306 microbiology, business.industry, lcsh:R, Immunity, HIV, medicine.disease, Kidney Transplantation, Institutional repository, Immunology, biology.protein, lcsh:Q, Clinical Immunology, business, Immunologic Memory
Abstract

BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.

Published
2012

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