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2. Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation

Author

Heinz, Amadeus T, primary, Calkoen, Friso G.J., additional, Derbich, Alexander, additional, Miltner, Lea, additional, Seitz, Christian, additional, Doering, Michaela, additional, Braun, Christiane, additional, Atar, Daniel, additional, Schumm, Michael, additional, Heubach, Florian, additional, Arendt, Anne-Marie, additional, Schulz, Ansgar, additional, Schuster, Friedhelm R, additional, Meisel, Roland, additional, Strahm, Brigitte, additional, Finke, Juergen, additional, Heineking, Beatrice, additional, Stetter, Susanne, additional, Silling, Gerda, additional, Stachel, Daniel, additional, Gruhn, Bernd, additional, Debatin, Klaus-Michael, additional, Foell, Juergen, additional, Schulte, Johannes H, additional, Woessmann, Wilhelm, additional, Mauz-Körholz, Christine, additional, Tischer, Johanna, additional, Feuchtinger, Tobias, additional, Handgretinger, Rupert, additional, and Lang, Peter, additional

Published
2023
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3. Microbiota-based markers predictive of development of Clostridioides difficile infection

Author

Berkell, Matilda, Mysara, Mohamed, Xavier, Britto Basil, van Werkhoven, Cornelis H., Monsieurs, Pieter, Lammens, Christine, Ducher, Annie, Vehreschild, Maria J.G.T., Goossens, Herman, de Gunzburg, Jean, Bonten, Marc J. M., Malhotra, Surbhi, Ahmed, Mohamed Mysara, Engbers, Annemarie, de Regt, Marieke, Biehl, Lena M., Cornely, Oliver A., Jazmati, Nathalie, Bouverne, Marie-Noelle, Sablier-Gallis, Frederique, Mentre, France, Merle, Uta, Stallmach, Andreas, Rupp, Jan, Bogner, Johannes, Lubbert, Christoph, Silling, Gerda, Witzke, Oliver, Gikas, Achilleas, Maraki, Sofia, Daikos, George, Tsiodras, Sotirios, Skoutelis, Athanasios, Sambatakou, Helen, Pujol, Miguel, Dominguez-Luzon, M. Angeles, Aguado, Jose M., Bouza, Emilio, Cobo, Javier, Rodriguez-Bano, Jesus, Almirante, Benito, de la Cisneros, Julian Torre, Florescu, Simin A., Nica, Maria, Vata, Andrei, Hristea, Adriana, Lupse, Mihaela, Herghea, Delia, Postil, Deborah, Barraud, Olivier, Molina, Jean-Michel, De Lastours, Victoire, Guimard, Thomas, Talarmin, Jean-Philippe, Duval, Xavier, Bernard, Louis, Launay, Odile, ANTICIPATE Study Group, Engbers, Annemarie, de Regt, Marieke, Biehl, Lena M., Cornely, Oliver A., Jazmati, Nathalie, Bouverne, Marie-Noelle, Sablier-Gallis, Frederique, Mentré, France, Merle, Uta, Stallmach, Andreas, Rupp, Jan, Bogner, Johannes, Lübbert, Christoph, Silling, Gerda, Witzke, Oliver, Gikas, Achilleas, Maraki, Sofia, Daikos, George, Tsiodras, Sotirios, Skoutelis, Athanasios, Sambatakou, Helen, Pujol, Miquel, Dominguez-Luzon, M. Angeles, Aguado, Jose M., Bouza, Emilio, Cobo, Javier, Rodríguez-Baño, Jesús, Almirante, Benito, de la Torre Cisneros, Julian, Florescu, Simin A., Nica, Maria, Vata, Andrei, Hristea, Adriana, Lupse, Mihaela, Herghea, Delia, Postil, Deborah, Barraud, Olivier, Molina, Jean-Michel, De Lastours, Victoire, Guimard, Thomas, Talarmin, Jean-Philippe, Duval, Xavier, Bernard, Louis, and Launay, Odile

Subjects
0301 basic medicine, Male, Malalties bacterianes grampositives, genetic structures, Antibiotics, Medizin, General Physics and Astronomy, Prevotella, Prospective Studies, Prospective cohort study, Bifidobacterium, Multidisciplinary, biology, Microbiota, Middle Aged, 3. Good health, Anti-Bacterial Agents, Diarrhea, Cohort, Female, medicine.symptom, Engineering sciences. Technology, medicine.medical_specialty, medicine.drug_class, Science, 030106 microbiology, Predictive markers, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Microbiome, Aged, Gram-positive bacterial infections, Bacteria, business.industry, Clostridioides difficile, General Chemistry, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Next-generation sequencing, Clostridium Infections, Human medicine, business, Dysbiosis, Biomarkers
Abstract

Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI., Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea (AAD); however, markers predictive of CDI or AAD development are as yet lacking. Here, to identify markers predictive of CDI, the authors profile the intestinal microbiota of 945 hospitalised patients from 34 hospitals in 6 different European countries and show distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients.

Published
2021
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4. Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy

Author

Straka, Christian, Sandherr, Michael, Salwender, Hans, Wandt, Hannes, Metzner, Bernd, Hübel, Kai, Silling, Gerda, Hentrich, Marcus, Franke, Daniel, Schwerdtfeger, Rainer, Freund, Mathias, Sezer, Orhan, Giagounidis, Alexander, Ehninger, Gerhard, Grimminger, Wolfgang, Engert, Andreas, Schlimok, Günter, Scheid, Christof, Hellmann, Peter, Heinisch, Harald, Einsele, Hermann, Hinke, Axel, and Emmerich, Bertold

Published
2011
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5. Matched-paired analysis of patients treated for invasive mucormycosis: standard treatment versus posaconazole new formulations (MoveOn)

Author

Salmanton-García, Jon, Seidel, Danila, Koehler, Philipp, Mellinghoff, Sibylle, Herbrecht, Raoul, Klimko, Nikolai, Ráčil, Zdeněk, Falces-Romero, Iker, Ingram, Paul, Benítez-Peñuela, Miguel-Ángel, Rodríguez, José Yesid, Desoubeaux, Guillaume, Barać, Aleksandra, García-Vidal, Carolina, Hoenigl, Martin, Mehta, Sanjay, Cheng, Matthew, Klyasova, Galina, Heinz, Werner, Iqbal, Nousheen, Krause, Robert, Ostermann, Helmut, Penack, Olaf, Schalk, Enrico, Sheppard, Donald, Willinger, Birgit, Wisplinghoff, Hilmar, Vehreschild, J Janne, Cornely, Oliver, Vehreschild, Maria, Khedr, Reham Abdelaziz, Arencibia-Núñez, Alberto, Avilés-Robles, Martha, Banke, Ingo, Basher, Ariful, Benachinamardi, Keertilaxmi, Bertz, Harmut, Chakrabarti, Arunaloke, Drgona, Lubos, García-Martínez, Jesús, García-Rodríguez, Julio, Gräber, Sandra, Härter, Georg, Klein, Michael, Kouba, Michal, Lee, Dong-Gun, Le Govic, Yohann, Leo, Fabian, Maertens, Johan, Maschmeyer, Georg, Meintker, Lisa, Mo, Xiao-Dong, Müller, Lena-Katharina, Müller, Nicolas, Nel, Jeremy Stephen, Novák, Jan, Patel, Atul, Pfäfflin, Frieder, Pozo-Laderas, Juan-Carlos, Puerta-Alcalde, Pedro, Rodríguez-Guardado, Azucena, Schroers, Roland, Shekar, Vandana, Shenoi, Susan, Silling, Gerda, Vinh, Donald, Waizel-Haiat, Salomón, Yee Yee, Mandy Yap, Prakash, Peralam Yegneswaran, Žák, Pavel, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Service d'Hématologie, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine, Medical University Graz, Schwerpunkt Infektiologie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Department of Haematology and Oncology, Medical Clinic III, University Hospital Munich—Großhadern, Ludwig Maximilian University, Klinik für Hämatologie und Onkologie, Charité, Campus Benjamin Franklin, Department of Haematology/Oncology, Magdeburg University Hospital, McGill University = Université McGill [Montréal, Canada], Medizinische Universität Wien = Medical University of Vienna, University Hospital of Cologne [Cologne], Postgraduate Institute of Medical Education and Research, Laboratoire de psychologie cognitive (LPC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Anofel Cryptosporidium National Network, Department of Hematology, University Hospital Gasthuisberg, Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Real Expression Artificial Life (IRIT-REVA), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Medizinische Klinik A des Universitätsklinikums Münster, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University Hospital Gasthuisberg [Leuven], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Posaconazole, Antifungal Agents, [SDV]Life Sciences [q-bio], Gastroenterology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, Pharmacology (medical), Prospective Studies, Registries, 030212 general & internal medicine, Child, Prospective cohort study, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, ComputingMilieux_MISCELLANEOUS, Antiinfective agent, Standard treatment, Middle Aged, 3. Good health, Infectious Diseases, Tolerability, Child, Preschool, Mucorales, Female, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Adolescent, Drug Compounding, Matched-Pair Analysis, 030106 microbiology, Young Adult, 03 medical and health sciences, Pharmacokinetics, Internal medicine, parasitic diseases, medicine, Humans, Mucormycosis, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [INFO]Computer Science [cs], Aged, Pharmacology, business.industry, Infant, Newborn, Infant, Triazoles, medicine.disease, business, MESH: amphotericin b, antifungal agents, cancer, kidney failure, mucormycosis, surgical procedures, operative, suspensions, mortality, posaconazole, Invasive Fungal Infections
Abstract

Background First-line antifungal treatment for invasive mucormycosis (IM) consists of liposomal amphotericin B. Salvage treatment options are limited and often based on posaconazole oral suspension. With the approval of posaconazole new formulations, patients could benefit from improved pharmacokinetics, safety and tolerability. Objectives Our aim was to assess the effectiveness of posaconazole new formulations for IM treatment. Methods We performed a case-matched analysis with proven or probable IM patients from the FungiScope® Registry. First-line posaconazole new formulations (1st-POSnew) and first-line amphotericin B plus posaconazole new formulations (1st-AMB+POSnew) cases were matched with first-line amphotericin B-based (1st-AMB) treatment controls. Salvage posaconazole new formulations (SAL-POSnew) cases were matched with salvage posaconazole oral suspension (SAL-POSsusp) controls. Each case was matched with up to three controls (based on severity, haematological/oncological malignancy, surgery and/or renal dysfunction). Results Five patients receiving 1st-POSnew, 18 receiving 1st-AMB+POSnew and 22 receiving SAL-POSnew were identified. By day 42, a favourable response was reported for 80.0% (n = 4/5) of patients receiving 1st-POSnew, for 27.8% (n = 5/18) receiving 1st-AMB+POSnew and for 50.0% (n = 11/22) receiving SAL-POSnew. Day 42 all-cause mortality of patients receiving posaconazole new formulations was lower compared with controls [20.0% (n = 1/5) in 1st-POSnew versus 53.3% (n = 8/15) in 1st-AMB; 33.3% (n = 6/18) in 1st-AMB+POSnew versus 52.0% (n = 26/50) in 1st-AMB; and 0.0% (n = 0/22) in SAL-POSnew versus 4.4% (n = 2/45) in SAL-POSsusp]. Conclusions Posaconazole new formulations were effective in terms of treatment response and associated mortality of IM. While posaconazole new formulations may be an alternative for treatment of IM, the limited sample size of our study calls for a cautious interpretation of these observations.

Published
2019

6. Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Author

van Werkhoven, Cornelis H., Ducher, Annie, Berkell, Matilda, Mysara, Mohamed, Lammens, Christine, Torre-Cisneros, Julian, Rodríguez-Baño, Jesús, Herghea, Delia, Cornely, Oliver A., Biehl, Lena M., Bernard, Louis, Dominguez-Luzon, M. Angeles, Maraki, Sofia, Barraud, Olivier, Nica, Maria, Jazmati, Nathalie, Sablier-Gallis, Frederique, de Gunzburg, Jean, Mentré, France, Malhotra-Kumar, Surbhi, Bonten, Marc J. M., Vehreschild, Maria J. G. T., Engbers, Annemarie M. S., de Regt, Marieke J. A., Goossens, Herman, Xavier, Basil Britto, Bouverne, Marie-Noelle, Monsieurs, Pieter, Merle, Uta, Stallmach, Andreas, Rupp, Jan, Bogner, Johannes, Lübbert, Christoph, Silling, Gerda, Witzke, Oliver, Gikas, Achilleas, Daikos, George, Tsiodras, Sotirios, Skoutelis, Athanasios, Sambatakou, Helen, Pujol, Miquel, Aguado, Jose M., Bouza, Emilio, Cobo, Javier, Almirante, Benito, Florescu, Simin A., Vata, Andrei, Hristea, Adriana, Lupse, Mihaela, Postil, Deborah, Molina, Jean-Michel, De Lastours, Victoire, Guimard, Thomas, Talarmin, Jean-Philippe, Duval, Xavier, Launay, Odile, Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, and ANTICIPATE Study Group

Subjects
Male, 0301 basic medicine, Carbapenem, genetic structures, Antibiotics, Medizin, General Physics and Astronomy, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Multidisciplinary, Incidence, Incidence (epidemiology), Microbiota, Hazard ratio, Middle Aged, Anti-Bacterial Agents, Hospitalization, Drug Therapy, Combination, Female, Engineering sciences. Technology, Fluoroquinolones, Cohort study, medicine.drug, medicine.medical_specialty, medicine.drug_class, Science, 030106 microbiology, Bacterial diseases, Antibiòtics, Penicillins, Predictive markers, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Malalties bacterianes, Clostridioides difficile, business.industry, Clindamycin, Clostridium difficile, General Chemistry, Cephalosporins, Gastrointestinal Microbiome, Carbapenems, Clostridium Infections, Human medicine, business, Biomarkers, Follow-Up Studies
Abstract

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk., Here, the authors report the incidence of Clostridioides difficile infection (CDI) and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients of 50 years and above receiving newly initiated antibiotic treatment.

Published
2021

7. Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography

Author

Stelljes, Matthias, Hermann, Sven, Albring, Jörn, Köhler, Gabriele, Löffler, Markus, Franzius, Christiane, Poremba, Christopher, Schlösser, Verena, Volkmann, Sarah, Opitz, Corinna, Bremer, Christoph, Kucharzik, Torsten, Silling, Gerda, Schober, Otmar, Berdel, Wolfgang E., Schäfers, Michael, and Kienast, Joachim

Published
2008
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9. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation A Randomized Clinical Trial

Author

Bastidas, Adriana de la Serna, Javier El Idrissi, Mohamed and Oostvogels, Lidia Quittet, Philippe Lopez-Jimenez, Javier and Vural, Filiz Pohlreich, David Zuckerman, Tsila Issa, Nicolas C. Gaidano, Gianluca Lee, Je-Jung Abhyankar, Sunil and Solano, Carlos Perez de Oteyza, Jaime Satlin, Michael J. and Schwartz, Stefan Campins, Magda Rocci, Alberto Llamas, Carlos Vallejo Lee, Dong-Gun Tan, Sen Mui Johnston, Anna M. and Grigg, Andrew Boeckh, Michael J. Campora, Laura and Lopez-Fauqued, Marta Heineman, Thomas C. Stadtmauer, Edward A. and Sullivan, Keith M. Alonso Alonso, Aranzazu Anagnostopoulos, Achilles Andreadis, Charalambos (Babis) Angelopoulou, Maria and Anttila, Veli-Jukka Aoun, Mickael Barista, Ibrahim Berkahn, Leanne Bloor, Adrian J. C. Broady, Raewyn Brossart, Peter and Buadi, Francis K. Bulabois, Claude-Eric Cantin, Guy and Cellini, Claudia Chandrasekar, Pranatharthi Haran Chauncey, Thomas Cuneo, Antonio Dadwal, Sanjeet Singh Dickinson, Michael Eom, HyeonSeok Esquirol Sanfeliu, Albert Ferra Coll, Christelle Flomenberg, Phyllis R. Pilar Gonzalez-Rodriguez, Ana and Gottlieb, David J. Grisariu, Sigal Guenther, Andreas and Gutman, Jonathan Hahn, Uwe Heinz, Werner J. Heras, Inmaculada Ikeda, Takashi Jarque, Isidro Karthaus, Meinolf and Kerre, Tessa Kiani, Alexander Klein, Andreas K. Kofla, Grzegorz Kryuchkova, Irina V. Kuo, Ching-Yuan Kuruvilla, John Kuvshinov, Aleksey Kwak, Jae-Yong Lee, Jae Hoon and Lepretre, Stephane Lie, Albert Kwok-Wai Lucchesi, Alessandro and Maertens, Johan Marijt, Erik W. A. Martinez Munoz, Carmen and Michieli, Mariagrazia Milliken, Samuel T. Milpied, Noel and Monserrat Coll, Jorge Mossad, Sherif Beniameen Murphy, John and Navarro Matilla, Maria Belen Novak, Jan Olney, Harold J. Ona Navarrete, Raquel Pascual Cascon, Maria Jesus Peniket, Andy and Penka, Ganeva Piatkowska-Jakubas, Beata Polo Zarzuela, Marta and Quiel, Dimas Rowley, Scott D. Sabry, Waleed Salmi, Tommi Mikael Selleslag, Dominik L. D. Shea, Thomas C. Silling, Gerda Sinisalo, Ulla Marjatta Sohn, Sang Kyun Staib, Peter and Szer, Jeff Theunissen, Koen Topcuoglu, Pervin Tyurina, Natalya G. Uvarov, Mikhail Wahid, Fadilah S. Abdul Yanez San Segundo, Lucrecia Yegin, Zeynep Arzu Yeh, Su-Peng Yip, Sze-Fai Yoon, Sung Soo Young, Jo-Anne H. Zachee, Pierre and Zaja, Francesco ZOE-HSCT Study Grp Collaborators

Abstract

IMPORTANCE Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n=922) or placebo (n=924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURES The primary end point was occurrence of confirmed herpes zoster cases. RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

Published
2019

10. Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets

Author

Stelljes, Matthias, Strothotte, Robert, Pauels, Hans-Gerd, Poremba, Christopher, Milse, Michaela, Specht, Christiane, Albring, Jörn, Bisping, Guido, Scheffold, Christian, Kammertoens, Thomas, Oelmann, Elisabeth, Silling, Gerda, Berdel, Wolfgang E., and Kienast, Joachim

Published
2004
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11. CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation) - Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Author

Schmidt-Hieber, Martin, Silling, Gerda, Wolf, H. H., Ruhnke, M., Schwartz, S., Maschmeyer, G., Schalk, E., Heinz, W., Panse, Jens, Penack, O., Christopeit, M., Buchheidt, D., Meyding-Lamadé, U., and Hähnel, S.

Abstract

Annals of oncology 27(7), 1207-1225 (2016). doi:10.1093/annonc/mdw155, Published by Oxford Univ. Press, Oxford

Published
2016
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12. The Epidemiology of Invasive Aspergillosis and Resistance Patterns of Aspergillus spp. in Germany - Interim Analysis of a Multicenter Observational Study

Author

Vehreschild, Maria J.G.T., Hamprecht, Axel, Adam, Thomas, Bader, Oliver, Becker, Caroline, Bekerdijan-Ding, Isabelle, Buchheidt, Dieter, Doelken, Gottfried, Elias, Johannes, Haase, Gerhard, Hahn-Ast, Corinna, Karthaus, Meinolf, Kekulé, Alexander, Krause, Stefan, Neumann, Silke, Keller, Peter, Kiehl, Michael, Rohde, Holger, La Rosée, Paul, Ruhnke, Markus, Schalk, Enrico, Schafhausen, Philippe, Schwartz, Stefan, Silling, Gerda, Schulz, Katrin, Staib, Peter, Ullmann, Andrew, Weber, Thomas, and Cornely, Oliver A.

Subjects
ddc: 610, 610 Medical sciences, Medicine, skin and connective tissue diseases
Abstract

Introduction: Reports on increasing identification of azole-resistant Aspergillus fumigatus in clinical and environmental isolates have raised concerns with respect to the frequency and clinical relevance of resistant Aspergillus spp. in hematological high-risk patient populations. Methods: In an[for full text, please go to the a.m. URL], Frühjahrstagung der Sektion Antimykotische Chemotherapie 2014

Published
2014

13. Treatment of invasive fungal infections in cancer patients : updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Author

Mousset, Sabine, Buchheidt, Dieter, Heinz, Werner, Ruhnke, Markus, Cornely, Oliver Andreas, Egerer, Gerlinde, Krüger, William, Link, Hartmut, Neumann, Silke, Ostermann, Helmut, Panse, Jens, Penack, Olaf, Rieger, Christina, Schmidt-Hieber, Martin, Silling, Gerda, Südhoff, Thomas, Ullmann, Andrew J., Wolf, Hans-Heinrich, Maschmeyer, Georg, and Böhme, Angelika

Subjects
ddc:610
Abstract

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.

Published
2013

14. Control of Multidrug Resistant Pseudomonas Aeruginosa through Hospital Construction Design and Extensive Environmental and Clinical Surveillance in an Allogeneic Transplantat Unit

Author

Kossow, Annelene, primary, Kipp, Frank, additional, Silling, Gerda, additional, Groll, Andreas H, additional, Rössig, Claudia, additional, Jürgens, Heribert, additional, Mellmann, Alexander, additional, Karch, Helge, additional, Berdel, Wolfgang E, additional, and Stelljes, Matthias, additional

Published
2014
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15. Targeting Interleukin-2 to the Bone Marrow Stroma for Therapy of Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation

Author

Schliemann, Christoph, primary, Gutbrodt, Katrin, additional, Kerkhoff, Andrea, additional, Pohlen, Michele, additional, Wiebe, Stefanie, additional, Silling, Gerda, additional, Angenendt, Linus, additional, Kessler, Torsten, additional, Mesters, Rolf M, additional, Giovannoni, Leonardo, additional, Schäfers, Michael, additional, Altvater, Bianca, additional, Rössig, Claudia, additional, Grünewald, Inga, additional, Wardelmann, Eva, additional, Köhler, Gabriele, additional, Neri, Dario, additional, Stelljes, Matthias, additional, and Berdel, Wolfgang E, additional

Published
2014
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16. Comparison Of Different Pretransplant Predictive Scores In Patients With Refractory Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation Including Highdose Melphalan: Results Of a Double-Center Observational Study

Author

Steckel, Nina Kristin, primary, Ditschkowski, Markus, additional, Groth, Christoph, additional, Silling, Gerda, additional, Krug, U., additional, Trenschel, Rudolf, additional, Ottinger, Hellmut, additional, Berdel, Wolfgang E, additional, Koldehoff, Michael, additional, Elmaagacli, Ahmet H., additional, Beelen, Dietrich, additional, and Stelljes, Matthias, additional

Published
2013
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17. Acute Myeloid Leukemia: Longterm Outcome Predicted by Age and Genetic Groups

Author

Buchner, Thomas, primary, Berdel, Wolfgang E., additional, Krug, Utz, additional, Haferlach, Claudia, additional, Schnittger, Susanne, additional, Stelljes, Matthias, additional, Silling, Gerda, additional, Staib, Peter, additional, Grueneisen, Andreas, additional, Reichle, Albrecht, additional, Balleisen, Leopold, additional, Eimermacher, Hartmut, additional, Giagounidis, Aristoteles, additional, Rasche, Herbert, additional, Lengfelder, Eva, additional, Sauerland, Cristina, additional, Heinecke, Achim, additional, Woermann, Bernhard Josef, additional, and Hiddemann, Wolfgang, additional

Published
2012
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18. Population Pharmacokinetics of Liposomal Amphotericin B and Caspofungin in Allogeneic Hematopoietic Stem Cell Recipients

Author

Würthwein, Gudrun, primary, Young, Charlotte, additional, Lanvers-Kaminsky, Claudia, additional, Hempel, Georg, additional, Trame, Mirjam N., additional, Schwerdtfeger, Rainer, additional, Ostermann, Helmut, additional, Heinz, Werner J., additional, Cornely, Oliver A., additional, Kolve, Hedwig, additional, Boos, Joachim, additional, Silling, Gerda, additional, and Groll, Andreas H., additional

Published
2012
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20. Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Author

Groll, Andreas H., primary, Silling, Gerda, additional, Young, Charlotte, additional, Schwerdtfeger, Rainer, additional, Ostermann, Helmut, additional, Heinz, Werner J., additional, Gerss, Joachim, additional, Kolve, Hedwig, additional, Lanvers-Kaminsky, Claudia, additional, Vieira Pinheiro, João Paulo, additional, Gammelin, Sibylle, additional, Cornely, Oliver A., additional, and Wuerthwein, Gudrun, additional

Published
2010
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21. Immunological Intervention Triggered by Decreasing CD34 + Lineage-Specific Donor Cell Chimerism to Prevent Relapse of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Author

Rosenow, Felix, primary, Silling, Gerda, additional, Almut, Berkemeier, additional, Mueller-Tidow, Carsten, additional, Koschmieder, Steffen, additional, Bisping, Guido, additional, Krug, Utz, additional, Buechner, Thomas, additional, Berdel, Wolfgang E, additional, Kienast, Joachim, additional, and Stelljes, Matthias, additional

Published
2009
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22. Forty-One Recent Cases of Invasive Zygomycosis From a Global Clinical Registry.

Author

Rueping, Maria J.G.T., primary, Heinz, Werner J., additional, Kindo, Anupma J., additional, Rickerts, Volker, additional, Lass-Floerl, Cornelia, additional, Beisel, Claudia, additional, Herbrecht, Raoul, additional, Roth, Yehudah, additional, Silling, Gerda, additional, Ullmann, Andrew, additional, Borchert, Kersten, additional, Egerer, Gerlinda, additional, Maertens, Johann, additional, Maschmeyer, Georg, additional, Simon, Arne, additional, Wattad, Morad, additional, Fischer, Guido, additional, Vehreschild, Joerg J., additional, Karthaus, Meinolf, additional, and Cornely, Oliver A., additional

Published
2009
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23. Conditioning with 8 Gy Total Body Irradiation and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: Projected 4-Year Update.

Author

Stelljes, Matthias, primary, Bornhaeuser, Martin, additional, Kroger, Matthias, additional, Beyer, Joerg, additional, Sauerland, Maria C., additional, Heinecke, Achim, additional, Berning, Bjorna, additional, Scheffold, Christian, additional, Silling, Gerda, additional, Buchner, Thomas, additional, Neubauer, Andreas, additional, Fauser, Axel Arthur, additional, Ehninger, Gerhard, additional, Berdel, Wolfgang E., additional, and Kienast, Joachim, additional

Published
2006
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24. Forodesine in Patients with Refractory/Relapsed T-ALL Can Induce Prolonged Stable Remission with Minimal Toxicity before and after Allogeneic Hematopoietic Stem Cell Transplantation.

Author

Stelljes, Mattias, primary, Kienast, Joachim, additional, Berning, Björna, additional, Gokbuget, Nicola, additional, Hoelzer, Dieter, additional, Silling, Gerda, additional, Berdel, Wolfgang E., additional, Van Houten Dahl, Gary, additional, Schissel, Debra, additional, Hemenway, Molly, additional, and Gore, Lia, additional

Published
2006
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25. Noninvasive Assessment of Intestinal Graft-Versus-Host Disease Activity by 18F-Fluorodeoxyglucose Positron Emission Tomography.

Author

Stelljes, Matthias, primary, Albring, Jorn, additional, Hermann, Sven, additional, Poremba, Christopher, additional, Kohler, Gabiele, additional, Bremer, Christoph, additional, Kucharzik, Thorsten, additional, Silling, Gerda, additional, Berdel, Wolfgang E., additional, Schober, Otmar, additional, Schafers, Michael, additional, and Kienast, Joachim, additional

Published
2006
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26. Population Pharmacokinetics of Liposomal Amphotericin B and Caspofungin in Allogeneic Hematopoietic Stem Cell Recipients

Author

Würthwein, Gudrun, Young, Charlotte, Lanvers-Kaminsky, Claudia, Hempel, Georg, Trame, Mirjam N., Schwerdtfeger, Rainer, Ostermann, Helmut, Heinz, Werner J., Cornely, Oliver A., Kolve, Hedwig, Boos, Joachim, Silling, Gerda, and Groll, Andreas H.

Abstract

ABSTRACTLiposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population. The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk-stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB (n= 17; 3 mg/kg once a day [QD]), CAS (n= 19; 50 mg QD; day 1, 70 mg), or the combination of both (CAS-LAMB; n= 17) for a median duration of 10 to 13 days (range, 4 to 28 days) until defervescence and granulocyte recovery. PK sampling was performed on days 1 and 4. Drug concentrations in plasma (LAMB, 405 samples; CAS, 458 samples) were quantified by high-pressure liquid chromatography and were analyzed using population pharmacokinetic modeling. CAS concentration data best fitted a two-compartment model with a proportional error model and interindividual variability (IIV) for clearance (CL) and central volume of distribution (V1) (CL, 0.462 liter/h ± 25%; V1, 8.33 liters ± 29%; intercompartmental clearance [Q], 1.25 liters/h; peripheral volume of distribution [V2], 3.59 liters). Concentration data for LAMB best fitted a two-compartment model with a proportional error model and IIV for all parameters (CL, 1.22 liters/h ± 64%; V1, 19.2 liters ± 38%; Q, 2.18 liters/h ± 47%; V2, 52.8 liters ± 84%). Internal model validation showed predictability and robustness of both models. None of the covariates tested (LAMB or CAS comedication, gender, body weight, age, body surface area, serum bilirubin, and creatinine clearance) further improved the models. In summary, the disposition of LAMB and CAS was best described by two-compartment models. Drug exposures in aHSCT patients were comparable to those in other populations, and no PK interactions were observed between the two compounds.

Published
2011
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27. Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets

Author

Stelljes, Matthias, Strothotte, Robert, Pauels, Hans-Gerd, Poremba, Christopher, Milse, Michaela, Specht, Christiane, Albring, Jörn, Bisping, Guido, Scheffold, Christian, Kammertoens, Thomas, Oelmann, Elisabeth, Silling, Gerda, Berdel, Wolfgang E., and Kienast, Joachim

Abstract

Cure of hematologic malignancies after allogeneic hematopoietic stem cell transplantation is partially attributable to immunocellular antitumor reactions termed graft-versus-tumor (GvT) effect. GvT effects are heterogeneous with respect to effector cell populations, target antigens, and their interrelation with graft-versus-host disease (GvHD). In the present study, allogeneic parent-into-F1murine transplantation models (BALB/c or C57BL/6 → [C57BL/6 × BALB/c]F1) with different tumors derived from either parental strain were used to evaluate tumor-specific GvT effects. Compared with syngeneic F1-into-F1controls, significant CD8+T cell-mediated GvT effects occurred in both allogeneic transplantation models, even in the absence of histoincompatibilities between donor cells and host tumor. Identical genetic background of donor and tumor precluded allorecognition of tumor cells, indicating that tumor-associated antigens (TAAs) were targeted. With allowance made for selective major histocompatibility complex (MHC) disparities between donor cells and normal host tissue, GvHD was identified as a driving force for TAA-specific GvT effects. Adoptive transfer of the effector cells into secondary tumor-bearing recipients confirmed sustained antitumor activity and specificity of the T-cell response. The results provide experimental proof of a donor CD8+T cell-mediated TAA-specific antitumor response in vivo that is driven by GvHD. It may represent one of the mechanisms contributing to GvT effects observed in allogeneic transplant recipients. (Blood. 2004;104:1210-1216)

Published
2004
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29. Immunological Intervention Triggered by Decreasing CD34 +Lineage-Specific Donor Cell Chimerism to Prevent Relapse of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Author

Rosenow, Felix, Silling, Gerda, Almut, Berkemeier, Mueller-Tidow, Carsten, Koschmieder, Steffen, Bisping, Guido, Krug, Utz, Buechner, Thomas, Berdel, Wolfgang E, Kienast, Joachim, and Stelljes, Matthias

Abstract

Abstract 3317

Published
2009
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30. Allogeneic transplantation as post-remission therapy for cytogenetically high-risk acute myeloid leukemia: landmark analysis from a single prospective multicenter trial.

Author

Stelljes M, Beelen DW, Braess J, Sauerland MC, Heinecke A, Berning B, Kolb HJ, Holler E, Schwerdtfeger R, Arnold R, Spiekermann K, Müller-Tidow C, Serve HL, Silling G, Hiddemann W, Berdel WE, Büchner T, and Kienast J

Subjects
Adult, Cytogenetics, Female, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Monosomy genetics, Neoadjuvant Therapy, Recurrence, Remission Induction, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
Abstract

Unlabelled: Background Allogeneic hematopoietic cell transplantation is considered the preferred post-remission therapy in patients with acute myeloid leukemia cytogenetically defined as being at high risk. To substantiate evidence for allogeneic hematopoietic cell transplantation in first complete remission in these high-risk patients we performed a landmark analysis within a single prospective multicenter treatment trial., Design and Methods: By the time of analysis, 2,347 patients had been accrued into the AMLCG 99 trial between 1999 - 2007. Out of this population, 243 patients under 60 years old fulfilled the criteria for high-risk cytogenetics. Landmark analyses were performed with a control cohort, who remained in first complete remission at least the median time from complete remission to transplantation in the intervention group., Results: After standardized induction therapy, 111 patients under 60 years old achieved complete remission. A matched allogeneic donor was identified for 59 patients (30 sibling donors, 29 unrelated donors). Fifty-five patients received an allogeneic hematopoietic cell transplant after a median time of 88 days in first complete remission. Of the remaining 56 patients, 21 relapsed within 90 days after achieving first complete remission and for 7 patients with relevant comorbidities no donors search was initiated, leaving 28 patients given conventional post-remission therapy as the control cohort. The median follow-up of surviving patients was 60.4 months. Patients with an allogeneic donor had substantially better 5-year overall and relapse-free survival rates than the control group (48% versus 18%, P=0.004 and 39% versus 10%, P<0.001, respectively). A survival benefit from transplantation was evident regardless of donor type, age and monosomal karyotype. Conclusions Beyond evidence available for subgroups of high-risk patients, the findings of this study establish in a broader manner that allogeneic hematopoietic cell transplantation is a preferable consolidation treatment for patients with acute myeloid leukemia and high-risk cytogenetics. The study was registered at Clinicaltrials.gov as NCT00266136.

Published
2011
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31. Viral encephalitis after allogeneic stem cell transplantation: a rare complication with distinct characteristics of different causative agents.

Author

Schmidt-Hieber M, Schwender J, Heinz WJ, Zabelina T, Kühl JS, Mousset S, Schüttrumpf S, Junghanss C, Silling G, Basara N, Neuburger S, Thiel E, and Blau IW

Subjects
Adolescent, Adult, Aged, Alemtuzumab, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm therapeutic use, Antineoplastic Agents therapeutic use, Antiviral Agents therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Encephalitis, Viral drug therapy, Female, Hematologic Neoplasms therapy, Humans, Immunosuppressive Agents therapeutic use, Infant, Lymphocyte Depletion, Male, Middle Aged, Muromonab-CD3 therapeutic use, Retrospective Studies, Survival Rate, Transplantation, Homologous, Treatment Outcome, Virus Activation, Young Adult, Encephalitis, Viral etiology, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
Abstract

Background: Limited data are available on characteristics of viral encephalitis in patients after allogeneic stem cell transplantation., Design and Methods: We analyzed 2,628 patients after allogeneic stem cell transplantation to identify risk factors and characteristics of viral encephalitis., Results: Viral encephalitis occurred in 32 patients (1.2%, 95% confidence interval 0.8%-1.6%) and was associated with the use of OKT-3 or alemtuzumab for T-cell depletion (P < 0.001) and an increased mortality (P = 0.011) in comparison to patients without viral encephalitis. Detected viruses included human herpesvirus-6 (28%), Epstein-Barr virus (19%), herpes simplex virus (13%), JC virus (9%), varicella zoster virus (6%), cytomegalovirus (6%) and adenovirus (3%). More than one virus was identified in 16% of the patients. The median onset time was 106 days after allogeneic stem cell transplantation for the total group of 32 patients, but onset times were shortest in those with human herpesvirus-6 encephalitis and longest in those with JC virus-associated progressive multifocal leukoencephalopathy. The probability of a sustained response to treatment was 63% (95% confidence interval 44%-82%) with a median survival of 94 (95% confidence interval 36-152) days after onset, but significant variation was found when considering different causative viruses. Patients with herpes simplex virus encephalitis had the most favorable outcome with no encephalitis-related deaths., Conclusions: The use of OKT-3 or alemtuzumab for in vivo T-cell depletion is associated with an increased risk of viral encephalitis after allogeneic stem cell transplantation. Different viruses are frequently associated with distinct characteristics such as onset time, response to treatment and outcome.

Published
2011
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