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1. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Author

Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Al-Shemari, Salem, Aurran-Schleinitz, Thérèse, Bacchiarri, Francesca, Bellido, Mar, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofia, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, Maria, Donaldson, David, Santos, Gimena Dos, Dreta, Barbara, Efstathopoulou, Maria, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón-y-Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José-Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Laribi, Kamel, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, Maria, Konstantinou, Eliana, Koren-Michowitz, Maya, Kotsianidis, Ioannis, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, Lopez-Garcia, Alberto, Marquet, Juan, Martin-Rodríguez, Lucia, Maynadié, Marc, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Miras, Fatima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, Maria, Papajík, Tomas, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martin, Smirnova, Svetlana, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Tadmor, Tamar, Tomic, Kristina, Tse, Eric, Vassilakopoulos, Theodoros, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Panagiotidis, Panagiotis, Popov, Viola Maria, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine, Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2023
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3. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Author

Chatzikonstantinou, Thomas, Kapetanakis, Anargyros, Scarfò, Lydia, Karakatsoulis, Georgios, Allsup, David, Cabrero, Alejandro Alonso, Andres, Martin, Antic, Darko, Baile, Mónica, Baliakas, Panagiotis, Bron, Dominique, Capasso, Antonella, Chatzileontiadou, Sofia, Cordoba, Raul, Correa, Juan-Gonzalo, Cuéllar-García, Carolina, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Demosthenous, Christos, Dimou, Maria, Donaldson, David, Doubek, Michael, Efstathopoulou, Maria, Eichhorst, Barbara, El-Ashwah, Shaimaa, Enrico, Alicia, Espinet, Blanca, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Frederiksen, Henrik, Fürstenau, Moritz, García-Marco, José A., García-Serra, Rocío, Gentile, Massimo, Gimeno, Eva, Glenthøj, Andreas, Gomes da Silva, Maria, Gutwein, Odit, Hakobyan, Yervand K., Herishanu, Yair, Hernández-Rivas, José Ángel, Herold, Tobias, Innocenti, Idanna, Itchaki, Gilad, Jaksic, Ozren, Janssens, Ann, Kalashnikova, Оlga B., Kalicińska, Elżbieta, Karlsson, Linda Katharina, Kater, Arnon P., Kersting, Sabina, Labrador, Jorge, Lad, Deepesh, Laurenti, Luca, Levin, Mark-David, Lista, Enrico, Lopez-Garcia, Alberto, Malerba, Lara, Marasca, Roberto, Marchetti, Monia, Marquet, Juan, Mattsson, Mattias, Mauro, Francesca R., Milosevic, Ivana, Mirás, Fatima, Morawska, Marta, Motta, Marina, Munir, Talha, Murru, Roberta, Niemann, Carsten U., Rodrigues, Raquel Nunes, Olivieri, Jacopo, Orsucci, Lorella, Papaioannou, Maria, Pavlovsky, Miguel Arturo, Piskunova, Inga, Popov, Viola Maria, Quaglia, Francesca Maria, Quaresmini, Giulia, Qvist, Kristian, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Saghumyan, Gevorg, Shrestha, Amit, Šimkovič, Martin, Špaček, Martin, Sportoletti, Paolo, Stanca, Oana, Stavroyianni, Niki, Tadmor, Tamar, Te Raa, Doreen, Tonino, Sanne H., Trentin, Livio, Van Der Spek, Ellen, van Gelder, Michel, van Kampen, Roel, Varettoni, Marzia, Visentin, Andrea, Vitale, Candida, Wasik-Szczepanek, Ewa, Wróbel, Tomasz, San Segundo, Lucrecia Yáñez, Yassin, Mohamed, Coscia, Marta, Rambaldi, Alessandro, Montserrat, Emili, Foà, Robin, Cuneo, Antonio, Stamatopoulos, Kostas, and Ghia, Paolo

Published
2021
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7. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Scarfò, Lydia, Chatzikonstantinou, Thomas, Rigolin, Gian Matteo, Quaresmini, Giulia, Motta, Marina, Vitale, Candida, Garcia-Marco, Jose Antonio, Hernández-Rivas, José Ángel, Mirás, Fatima, Baile, Mónica, Marquet, Juan, Niemann, Carsten U., Reda, Gianluigi, Munir, Talha, Gimeno, Eva, Marchetti, Monia, Quaglia, Francesca Maria, Varettoni, Marzia, Delgado, Julio, Iyengar, Sunil, Janssens, Ann, Marasca, Roberto, Ferrari, Angela, Cuéllar-García, Carolina, Itchaki, Gilad, Špaček, Martin, De Paoli, Lorenzo, Laurenti, Luca, Levin, Mark-David, Lista, Enrico, Mauro, Francesca R., Šimkovič, Martin, Van Der Spek, Ellen, Vandenberghe, Elisabeth, Trentin, Livio, Wasik-Szczepanek, Ewa, Ruchlemer, Rosa, Bron, Dominique, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Farina, Lucia, Foglietta, Myriam, Gentile, Massimo, Herishanu, Yair, Herold, Tobias, Jaksic, Ozren, Kater, Arnon P., Kersting, Sabina, Malerba, Lara, Orsucci, Lorella, Popov, Viola Maria, Sportoletti, Paolo, Yassin, Mohamed, Pocali, Barbara, Barna, Gabor, Chiarenza, Annalisa, dos Santos, Gimena, Nikitin, Eugene, Andres, Martin, Dimou, Maria, Doubek, Michael, Enrico, Alicia, Hakobyan, Yervand, Kalashnikova, Olga, Ortiz Pareja, Macarena, Papaioannou, Maria, Rossi, Davide, Shah, Nimish, Shrestha, Amit, Stanca, Oana, Stavroyianni, Niki, Strugov, Vladimir, Tam, Constantine, Zdrenghea, Mihnea, Coscia, Marta, Stamatopoulos, Kostas, Rossi, Giuseppe, Rambaldi, Alessandro, Montserrat, Emili’, Foà, Robin, Cuneo, Antonio, and Ghia, Paolo

Published
2020
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9. Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide and rituximab (FCR) in patients with CLL. A retrospective multicenter 'real-world' study

Author

Levi, Shai, Bronstein, Yotam, Goldschmidt, Neta, Morabito, Fortunato, Ziv-Baran, Tomer, Del Poeta, Giovanni, Bairey, Osnat, Del Principe, Maria Ilaria, Fineman, Riva, Mauro, Francesca Romana, Gutwein, Odit, Reda, Gianluigi, Ruchlemer, Rosa, Sportoletti, Paolo, Laurenti, Luca, Shvidel, Lev, Coscia, Marta, Tadmor, Tamar, Varettoni, Marzia, Aviv, Ariel, Murru, Roberta, Braester, Andrei, Chiarenza, Annalisa, Visentin, Andrea, Pietrasanta, Daniela, Loseto, Giacomo, Zucchetto, Antonella, Bomben, Riccardo, Olivieri, Jacopo, Neri, Antonio, Rossi, Davide, Gaidano, Gianluca, Trentin, Livio, Foà, Robin, Cuneo, Antonio, Perry, Chava, Gattei, Valter, Gentile, Massimo, and Herishanu, Yair

Subjects
Settore MED/15
Published
2023

11. Differences in Clinical Course and Management of Sars-CoV2 Infection in Patients with Chronic Lymphocytic Leukemia between the Sequential Pandemic Phases: An Eric Study

Author

Visentin, Andrea, Scarfò, Lydia, Chatzikonstantinou, Thomas, Kapetanakis, Anargyros, Demosthenous, Christos, Karakatsoulis, Georgios, Andres, Martin, Antic, Darko, Allsup, David, Baile, Mónica, Bron, Dominique, Capasso, Antonella, Catherwood, Mark, Collado, Rosa, Cordoba, Raul, Cuéllar-García, Carolina, Delgado, Julio, Dimou, Maria, Doubek, Michael, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Efstathopoulou, Maria, Shimaa, El-Ashwah, Enrico, Alicia, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Furstenau, Moritz, Garcia-Marco, Jose A., Gentile, Massimo, Gimeno, Eva, Maria, Gomes da Silva, Gutwein, Odit, Hakobyan, Yervand, Herishanu, Yair, Hernandez, jose Angel, Herold, Tobias, Iyengar, Sunil, Itchaki, Gilad, Jaksic, Ozren, Janssens, Ann, Kalashnikova, Olga, Kalicinska, Elzbieta, Kater, Arnon P., Kersting, Sabina, Labrador, Jorge, Lad, Deepesh, Laurenti, Luca, Levin, Mark-David, Lista, Enrico, Malerba, Lara, Marasca, Roberto, Marchetti, Monia, Marquet Palomanes, Juan, Mattsson, Mattias, Mauro, Francesca Romana, Mayor-Bastida, Carlota, Morawska, Marta, Motta, Marina, Munir, Talha, Murru, Roberta, Milosevic, Ivana, Miras Calvo, Fatima, Niemann, Carsten Utoft, Olivieri, Jacopo, Orsucci, Lorella, Papaioannou, Maria, Pavlovsky, Miguel Arturo, Piskunova, Inga S., Pocali, Barbara, Popov, Viola Maria, Quaglia, Francesca Maria, Quaresmini, Giulia, Raa, Doreen te, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Shrestha, Amit, Šimkovič, Martin, Špaček, Martin, Sportoletti, Paolo, Stanca Ciocan, Oana, Tadmor, Tamar, Vandenberghe, Elisabeth, Varettoni, Marzia, Vitale, Candida, Van Der Spek, Ellen, Van Gelder, Michel, Wasik-Szczepanek, Ewa, Yáñez, Lucrecia, Yassin, Mohamed A, Coscia, Marta, Eichhorst, Barbara, Rambaldi, Alessandro, Stavroyianni, Niki, Trentin, Livio, Stamatopoulos, Kostas, and Ghia, Paolo

Published
2022
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12. Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients

Author

Dann, Eldad J., Bairey, Osnat, Bar‐Shalom, Rachel, Mashiach, Tanya, Barzilai, Elinor, Kornberg, Abraham, Akria, Luiza, Tadmor, Tamar, Filanovsky, Kalman, Abadi, Uri, Kagna, Olga, Ruchlemer, Rosa, Abdah‐Bortnyak, Roxolyana, Goldschmidt, Neta, Epelbaum, Ron, Horowitz, Netanel A., Lavie, David, Ben‐Yehuda, Dina, Shpilberg, Ofer, and Paltiel, Ora

Published
2017
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15. Efficacy of front‐line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter "Real‐World" study.

Author

Levi, Shai, Bronstein, Yotam, Goldschmidt, Neta, Morabito, Fortunato, Ziv‐Baran, Tomer, Del Poeta, Giovanni, Bairey, Osnat, Del Principe, Maria Ilaria, Fineman, Riva, Mauro, Francesca Romana, Gutwein, Odit, Reda, Gianluigi, Ruchlemer, Rosa, Sportoletti, Paolo, Laurenti, Luca, Shvidel, Lev, Coscia, Marta, Tadmor, Tamar, Varettoni, Marzia, and Aviv, Ariel

Published
2023
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18. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Author

Chatzikonstantinou, Thomas Kapetanakis, Anargyros Scarfo, Lydia and Karakatsoulis, Georgios Allsup, David Alonso Cabrero, Alejandro Andres, Martin Antic, Darko Baile, Monica and Baliakas, Panagiotis Bron, Dominique Capasso, Antonella and Chatzileontiadou, Sofia Cordoba, Raul Correa, Juan-Gonzalo and Cuellar-Garcia, Carolina De Paoli, Lorenzo De Paolis, Maria Rosaria Del Poeta, Giovanni Demosthenous, Christos Dimou, Maria Donaldson, David Doubek, Michael Efstathopoulou, Maria and Eichhorst, Barbara El-Ashwah, Shaimaa Enrico, Alicia and Espinet, Blanca Farina, Lucia Ferrari, Angela Foglietta, Myriam Frederiksen, Henrik Furstenau, Moritz Garcia-Marco, Jose A. Garcia-Serra, Rocio Gentile, Massimo Gimeno, Eva and Glenthoj, Andreas da Silva, Maria Gomes Gutwein, Odit and Hakobyan, Yervand K. Herishanu, Yair Angel Hernandez-Rivas, Jose and Herold, Tobias Innocenti, Idanna Itchaki, Gilad Jaksic, Ozren Janssens, Ann Kalashnikova, Olga B. Kalicinska, Elzbieta Karlsson, Linda Katharina Kater, Arnon P. Kersting, Sabina Labrador, Jorge Lad, Deepesh Laurenti, Luca and Levin, Mark-David Lista, Enrico Lopez-Garcia, Alberto and Malerba, Lara Marasca, Roberto Marchetti, Monia Marquet, Juan Mattsson, Mattias Mauro, Francesca R. Milosevic, Ivana and Miras, Fatima Morawska, Marta Motta, Marina Munir, Talha and Murru, Roberta Niemann, Carsten U. Rodrigues, Raquel Nunes and Olivieri, Jacopo Orsucci, Lorella Papaioannou, Maria and Arturo Pavlovsky, Miguel Piskunova, Inga Popov, Viola Maria and Quaglia, Francesca Maria Quaresmini, Giulia Qvist, Kristian and Reda, Gianluigi Rigolin, Gian Matteo Ruchlemer, Rosa and Saghumyan, Gevorg Shrestha, Amit Simkovic, Martin Spacek, Martin Sportoletti, Paolo Stanca, Oana Stavroyianni, Niki and Tadmor, Tamar Te Raa, Doreen Tonino, Sanne H. Trentin, Livio Van der Spek, Ellen van Gelder, Michel van Kampen, Roel Varettoni, Marzia Visentin, Andrea Vitale, Candida and Wasik-Szczepanek, Ewa Wrobel, Tomasz Yanez San Segundo, Lucrecia and Yassin, Mohamed Coscia, Marta Rambaldi, Alessandro and Montserrat, Emili Foa, Robin Cuneo, Antonio Stamatopoulos, Kostas Ghia, Paolo

Abstract

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.

Published
2021

21. Worldwide Examination of Patients with CLL Hospitalized for COVID-19

Author

Roeker, Lindsey E, Scarfo, Lydia, Chatzikonstantinou, Thomas, Abrisqueta, Pau, Eyre, Toby A., Cordoba, Raul, Muntañola Prat, Ana, Villacampa, Guillermo, Leslie, Lori A., Koropsak, Michael, Quaresmini, Giulia, Allan, John N., Furman, Richard R., Bhavsar, Erica B, Pagel, John M., Hernandez-Rivas, Jose Angel, Patel, Krish, Motta, Marina, Bailey, Neil, Miras, Fatima, Lamanna, Nicole, Alonso, Rosalia, Osorio-Prendes, Santiago, Vitale, Candida, Kamdar, Manali, Baltasar, Patricia, Österborg, Anders, Hanson, Lotta, Baile, Mónica, Rodríguez-Hernández, Ines, Valenciano, Susana, Popov, Viola Maria, Barez Garcia, Abelardo, Alfayate, Ana, Oliveira, Ana C, Eichhorst, Barbara, Quaglia, Francesca M., Reda, Gianluigi, Lopez Jimenez, Javier, Varettoni, Marzia, Marchetti, Monia, Romero, Pilar, Riaza Grau, Rosalía, Munir, Talha, Zabalza, Amaya, Janssens, Ann, Niemann, Carsten U, Perini, Guilherme Fleury, Delgado, Julio, Yanez San Segundo, Lucrecia, Gómez Roncero, Ma Isabel, Wilson, Matthew, Patten, Piers, Marasca, Roberto, Iyengar, Sunil, Seddon, Amanda, Torres, Ana, Ferrari, Angela, Cuéllar-García, Carolina, Wojenski, Daniel, El-Sharkawi, Dima, Itchaki, Gilad, Parry, Helen, Mateos-Mazón, Juan José, Martinez-Calle, Nicolas, Ma, Shuo, Naya, Daniel, Van Der Spek, Ellen, Seymour, Erlene K., Gimeno Vázquez, Eva, Rigolin, Gian Matteo, Mauro, Francesca Romana, Walter, Harriet S, Labrador, Jorge, De Paoli, Lorenzo, Laurenti, Luca, Ruiz, Elena, Levin, Mark-David, Šimkovič, Martin, Špaček, Martin, Andreu, Rafa, Walewska, Renata, Perez-Gonzalez, Sonia, Sundaram, Suchitra, Wiestner, Adrian, Cuesta, Amalia, Broom, Angus, Kater, Arnon P., Muiña, Begoña, Velasquez, César A, Ujjani, Chaitra S., Seri, Cristina, Antic, Darko, Bron, Dominique, Vandenberghe, Elisabeth, Chong, Elise A., Lista, Enrico, García, Fiz Campoy, Del Poeta, Giovanni, Ahn, Inhye, Pu, Jeffrey J., Brown, Jennifer R, Soler Campos, Juan Alfonso, Malerba, Lara, Trentin, Livio, Orsucci, Lorella, Farina, Lucia, Villalon, Lucia, Vidal, Maria Jesus, Sanchez, Maria Jose, Terol, Maria Jose, De Paolis, Maria Rosaria, Gentile, Massimo, Davids, Matthew S., Shadman, Mazyar, Yassin, Mohamed A, Foglietta, Myriam, Jaksic, Ozren, Sportoletti, Paolo, Barr, Paul M., Ramos, Rafael, Santiago, Raquel, Ruchlemer, Rosa, Kersting, Sabina, Huntington, Scott F., Herold, Tobias, Herishanu, Yair, Thompson, Meghan C., Lebowitz, Sonia, Ryan, Christine, Jacobs, Ryan W., Portell, Craig A., Isaac, Krista, Rambaldi, Alessandro, Nabhan, Chadi, Brander, Danielle M., Montserrat, Emili, Rossi, Giuseppe, Garcia-Marco, Jose A., Sr., Coscia, Marta, Malakhov, Nikita, Fernandez-Escalada, Noemi, Skånland, Sigrid Strand, Coombs, Callie C., Ghione, Paola, Schuster, Stephen J., Foà, Robin, Cuneo, Antonio, Bosch, Francesc, Stamatopoulos, Kostas, Ghia, Paolo, Mato, Anthony R., and Patel, Meera

Published
2020
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33. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.

Author

Herishanu, Yair, Shaulov, Adir, Fineman, Riva, Bašić‐Kinda, Sandra, Aviv, Ariel, Wasik‐Szczepanek, Ewa, Jaksic, Ozren, Zdrenghea, Mihnea, Greenbaum, Uri, Mandac, Inga, Simkovic, Martin, Morawska, Marta, Benjamini, Ohad, Spacek, Martin, Nemets, Anatoly, Bairey, Osnat, Trentin, Livio, Ruchlemer, Rosa, Laurenti, Luca, and Stanca Ciocan, Oana

Published
2020
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34. Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study.

Author

Ruchlemer, Rosa, Ben‐Ami, Ronen, Bar‐Meir, Maskit, Brown, Jennifer R., Malphettes, Marion, Mous, Rogier, Tonino, Sanne H., Soussain, Carole, Barzic, Noelie, Messina, Julia A., Jain, Preetesh, Cohen, Regev, Hill, Brian, Mulligan, Stephen P., Nijland, Marcel, Herishanu, Yair, Benjamini, Ohad, Tadmor, Tamar, Okamoto, Koh, and Arthurs, Benjamin

Subjects
*PULMONARY aspergillosis, *MYCOSES, *CHRONIC diseases, *LEUKEMIA, *LYMPHOMAS, *SCIENTIFIC observation
Abstract

Summary: Background: Invasive fungal diseases (IFD) are life‐threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. Objectives: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. Methods: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non‐Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. Result: Thirty‐five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1‐540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. Conclusions: The prevalence of IFD among chronic lymphocytic leukaemia/non‐Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib‐associated IFD. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Author

WEINKOVE, Robert, PRISTUPA, Alexander, KASYCH, Muzhdaba, YAGCI, Munci, MARCO, Jose Antonio Garcia, Vural, Filiz, Kaynar, Leylagül, BURGER, J. A., ROBAK, T., TEDESCHI, A., Barr, P. M., Owen, C., GHIA, P., Bairey, O., HILLMEN, P., BARTLETT, N. L., LI, J., SIMPSON, D., GROSICKI, S., HAMBLIN, Michael, ATKINS, James, BARRIENTOS, Jaqueline, DUNCOMBE, Andrew, GASIC, Slavisa, HOU, Jing-Zhou, KINGSLEY, Edwin, SHADMAN, Mazyar, BADOUX, Xavier, GILL, Devinder, OPAT, Stephen, BRON, Dominique, VAN DEN NESTE, Eric, JING, Hongmei, ZHU, Jun, VANDENBERGHE, Elisabeth, TADMOR, Tamar, CORTELEZZI, Agostino, GANLY, Peter, PLUTA, Andrzej, DEVEREUX, S., MCCARTHY, H., COUTRE, S., QUACH, H., GAIDANO, G., MASLYAK, Z., STEVENS, D. A., JANSSENS, A., OFFNER, F., MAYER, J., O'DWYER, M., HELLMANN, A., Schuh, A., SIDDIQI, T., POLLIACK, A., TAM, C. S., SURI, D., CHENG, M., CLOW, F., STYLES, L., JAMES, D. F., KIPPS, T. J., TIRUMALI, Nagendra, QUACKENBUSH, Robert, FEGAN, Christopher, KEATING, Michael, JEN, Jie, JINDRA, Pavel, SIMKOVIC, Martin, BRAESTER, Andrei, RUCHLEMER, Rosa, FOA, Roberto, SEMENZATO, Gianpietro, HAWKINS, Timothy, ATANASIO, Carolina Moreno, Demirkan, Fatih, PYLYPENKO, Halyna, FOX, Christopher, THIRMAN, Michael, CAMPBELL, Philip, COUGHLIN, Paul, HARRUP, Rosemary, KUSS, Bryone, TURNER, Paul, WU, Ka Lung, LARRATT, Loree, FINEMAN, Riva, MARASCA, Roberto, ZINZANI, Pier Luigi, CORBETT, Gillian, ABRISQUETA, Pau, DELGADO, Julio, GONZALEZ-BARCA, Eva, DE OTEYZA, Jaime Perez, ARSLAND, Onder, KAPLAN, Polina, OLIYNYK, Hanna, Burger, Jan A, Tedeschi, Alessandra, Barr, Paul M, Robak, Tadeusz, Owen, Carolyn, Ghia, Paolo, Bairey, Osnat, Hillmen, Peter, Bartlett, Nancy L, Li, Jianyong, Simpson, David, Grosicki, Sebastian, Devereux, Stephen, Mccarthy, Helen, Coutre, Steven, Quach, Hang, Gaidano, Gianluca, Maslyak, Zvenyslava, Stevens, Don A, Janssens, Ann, Offner, Fritz, Mayer, Jiří, O'Dwyer, Michael, Hellmann, Andrzej, Schuh, Anna, Siddiqi, Tanya, Polliack, Aaron, Tam, Constantine S, Suri, Deepali, Cheng, Mei, Clow, Fong, Styles, Lori, James, Danelle F, Kipps, Thomas J, M.D., Ph.D., for the RESONATE-2 Investigators [.., Pier Luigi Zinzani, Antonietta Tedeschi, ], Burger, Ja, Tedeschi, A, Barr, Pm, Robak, T, Owen, C, Ghia, P, Bairey, O, Hillmen, P, Bartlett, Nl, Li, J, Simpson, D, Grosicki, S, Devereux, S, Mccarthy, H, Coutre, S, Quach, H, Gaidano, G, Maslyak, Z, Stevens, Da, Janssens, A, Offner, F, Mayer, J, O'Dwyer, M, Hellmann, A, Schuh, A, Siddiqi, T, Polliack, A, Tam, C, Suri, D, Cheng, M, Clow, F, Styles, L, James, Df, Kipps, Tj, and for the RESONATE-2, Investigators

Subjects
Male, pci-32765, previously untreated patients, Lymphoma, Gastroenterology, Medical and Health Sciences, Medicaments antineoplàstics, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, chlorambucil, Piperidines, Obinutuzumab, immune system diseases, hemic and lymphatic diseases, Antineoplastic agents, Chronic, Fatigue, Cancer, cll, 0303 health sciences, Leukemia, Medicine (all), Hazard ratio, tyrosine kinase, Leucèmia, General Medicine, Hematology, Duvelisib, Lymphocytic, 3. Good health, Fludarabine, Aged, Antineoplastic Agents, Chlorambucil, Diarrhea, Disease-Free Survival, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Neutropenia, Pyrazoles, Pyrimidines, Survival Analysis, 030220 oncology & carcinogenesis, Ibrutinib, 6.1 Pharmaceuticals, RESONATE-2 Investigators, Acalabrutinib, medicine.drug, Human, medicine.medical_specialty, Cèl·lules B, Clinical Trials and Supportive Activities, open-label, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, General & Internal Medicine, medicine, cancer, Survival rate, 030304 developmental biology, B cells, business.industry, Adenine, B-Cell, fludarabine, Evaluation of treatments and therapeutic interventions, phase-3 trial, Pirimidines, Orphan Drug, chemistry, Pyrimidine, Immunology, Pyrazole, cyclophosphamide, business
Abstract

Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Background Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. METHODS We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P

Published
2015

37. A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain.

Author

Tadmor, Tamar, Braester, Andrei, Najib, Dally, Aviv, Ariel, Herishanu, Yair, Yuklea, Mona, Shvidel, Lev, Rahimi‐Levene, Naomi, Ruchlemer, Rosa, Arad, Ariela, Fogl, Claudia, Henig, Clara, Barak, Mira, Magal, Lee, Polliack, Aaron, and Townsend, Kelly

Subjects
CHRONIC lymphocytic leukemia, MULTIVARIATE analysis
Abstract

Background: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. Aims: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment‐naïve patients with CLL. Results: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra‐high‐risk group with a median TTFT of only 1.3 months. Conclusion: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL. [ABSTRACT FROM AUTHOR]

Published
2019
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38. Low-dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD-FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience.

Author

Herishanu, Yair, Tadmor, Tamar, Braester, Andrei, Bairey, Osnat, Aviv, Ariel, Rahimi‐Levene, Naomi, Fineman, Riva, Levi, Itai, Yuklea, Mona, Ruchlemer, Rosa, Shvidel, Lev, Polliack, Aaron, and Rahimi-Levene, Naomi

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single-arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL. Forty patients received LD-FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression-free survival (PFS) was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment-related neutropenia occurred in 20 (47.6%) patients. During the entire study follow-up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non-neutropenic infections. In conclusion, LD-FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both "time and cost limited" and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high-risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard. [ABSTRACT FROM AUTHOR]

Published
2019
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39. Outcomes of second‐line treatment after fludarabine cyclophosphamide and rituximab in patients with chronic lymphocytic leukemia outside clinical trials.

Author

Joffe, Erel, Goldschmidt, Neta, Bairey, Osnat, Fineman, Riva, Ruchlemer, Rosa, Rahimi‐Levene, Naomi, Shvidel, Lev, Greenbaum, Uri, Aviv, Ariel, Tadmor, Tamar, Braester, Andrea, Arad, Ariela, Polliack, Aaron, Herishanu, Yair, and The Israeli CLL Study Group

Subjects
FLUDARABINE, CYCLOPHOSPHAMIDE, RITUXIMAB, CHRONIC lymphocytic leukemia, IMMUNOTHERAPY
Abstract

Abstract: Objective: To evaluate disease characteristics and long‐term outcomes in patients requiring second‐line treatment following fludarabine, cyclophosphamide, and rituximab (FCR), for relapsed/refractory disease (R/R), or following discontinuation due to toxicities. Method: A retrospective analysis of 126 chronic lymphocytic leukemia patients treated with frontline FCR: 63 received second‐line treatment (41 relapsed, nine refractory [SD/PD], 13 prior toxicity). Time to next treatment (TTNT) was calculated from beginning FCR to initiation of second‐line therapy. Overall and event‐free survival was calculated from initiation of salvage treatment (OS2/EFS2). Results: Median follow‐up for the entire cohort was 67 and 37 months from second‐line therapy. TTNT < 24 months was associated with shorter OS2 and EFS2 similar to those observed with primary refractory disease (OS2 19 and 23 months; EFS2 12 and 9 months for TTNT < 24 months and SD/PD, respectively). TTNT ≥ 24 months (71% chemotherapy‐based second‐line), had longer OS2 and EFS2 (48 and 20 months). Among the 13 patients receiving second‐line therapy after discontinuing FCR due to toxicity EFS2 was 41 months (59 months from initiation of FCR). Conclusion: With limitations of sample size and treatment heterogeneity, patients progressing <24 months following FCR have poor outcomes, similar to refractory patients, while longer remissions are indicative of a chemoimmunotherapy sensitive disease. Patients who discontinue FCR for toxicities may achieve excellent outcomes with subsequent treatment. [ABSTRACT FROM AUTHOR]

Published
2018
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40. A phase I‐II clinical trial of the anti‐CD74 monoclonal antibody milatuzumab in frail patients with refractory chronic lymphocytic leukaemia: A patient based approach.

Author

Haran, Michal, Mirkin, Vita, Braester, Andrei, Harpaz, Nurith, Shevetz, Olga, Shtreiter, Marina, Greenberg, Shulamit, Mordich, Orly, Amram, Orna, Binsky‐Ehrenreich, Inbal, Marom, Ayelet, Shachar, Idit, Herishanu, Yair, Ruchlemer, Rosa, Berrebi, Alain, Valinsky, Liora, Shtalrid, Mordechai, and Shvidel, Lev

Subjects
CLINICAL trials, CHRONIC lymphocytic leukemia treatment, DRUG side effects, THERAPEUTIC complications, APOPTOSIS
Abstract

The article discusses a patient-centered phase I-II clinical protocol of milatuzumab combined with comfort care in elderly patients with refractory chronic lymphocytic leukemia (CLL), who were not eligible for any other form of treatment. Topics covered include patient characteristics and response to milatuzumab treatment, the most common significant adverse event, and the effect of milatuzumab on apoptosis.

Published
2018
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41. Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival.

Author

Joffe, Erel, Ariela Arad, N., Bairey, Osnat, Fineman, Riva, Ruchlemer, Rosa, Rahimi‐Levene, Naomi, Shvidel, Lev, Greenbaum, Uri, Aviv, Ariel, Tadmor, Tamar, Braester, Andrei, Goldschmidt, Neta, Polliack, Aaron, Herishanu, Yair, and Rahimi-Levene, Naomi

Subjects
THERAPEUTIC use of antimetabolites, ANTIMETABOLITES, ANTIVIRAL agents, CHRONIC lymphocytic leukemia, PROGNOSIS, SURVIVAL analysis (Biometry), RETROSPECTIVE studies, CYCLOPHOSPHAMIDE, LYMPHOCYTE count, PHARMACODYNAMICS
Abstract

Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR). We evaluated 99 patients who achieved a partial response without lymphocytosis (<4.0 × 103 cells/μL) or better after FCR. Absolute lymphocyte counts were recorded at 3-, 6-, 9-, and 12-month posttreatment and correlated with overall survival (OS) and event-free survival (EFS). For each time point, analyses were limited to patients without lymphocytosis, so as to avoid possible biases from undocumented disease progressions. Lymphopenia (ALC < 1.0 × 103 cells/μL) at 3 m after FCR (69% of patients n = 68), was associated with a longer OS (5y OS 91% vs 64%, P = .001), as were ALC ≤ 2 × 103 cells/μL at 6 m (5y OS 85% vs 48%, P = .004) and ALC ≤ 1.8 × 103 cells/μL at 9 m (5y OS 93% vs 54%, P = .009). A normal-range ALC (≤4 × 103 cells/μL) at 12 m was also associated with a 91% 5y OS. Higher ALCs (but without lymphocytosis) were associated with shorter EFS (median EFS 27 months for ALC > 1.8 vs not reached for ALC ≤ 0.7 at 9 months, P < .0001). In conclusion, lower ALC levels in the first few months following frontline FCR therapy were associated with longer OS and EFS. Possible explanations may be that lower ALCs reflect deeper clonal suppression or protracted Treg depletion. Absolute lymphocyte count levels may be a cheap and widely available prognostic marker, though the added value for clinical practice is the minimal residual disease era needs to be explored. [ABSTRACT FROM AUTHOR]

Published
2018
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42. Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/ CT is beneficial: a prospective multicentre trial of 355 patients.

Author

Dann, Eldad J., Bairey, Osnat, Bar‐Shalom, Rachel, Mashiach, Tanya, Barzilai, Elinor, Kornberg, Abraham, Akria, Luiza, Tadmor, Tamar, Filanovsky, Kalman, Abadi, Uri, Kagna, Olga, Ruchlemer, Rosa, Abdah‐Bortnyak, Roxolyana, Goldschmidt, Neta, Epelbaum, Ron, Horowitz, Netanel A., Lavie, David, Ben‐Yehuda, Dina, Shpilberg, Ofer, and Paltiel, Ora

Subjects
CLINICAL trials, HODGKIN'S disease treatment, POSITRON emission tomography, COMPUTED tomography, RADIOTHERAPY
Abstract

This multicentre study evaluated 5-year progression-free ( PFS) and overall survival ( OS) in early and advanced Hodgkin lymphoma ( HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles ( PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early- HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy ( ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced- HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early- HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced- HL, the PFS was 81% and 68%, respectively ( P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early- HL, even with additional ABVD and ISRT. Advanced- HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients. [ABSTRACT FROM AUTHOR]

Published
2017
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46. Cancer Registries Often Underestimate the True Incidence of CLL

Author

Ruchlemer, Rosa, Zatlawi, Miri, Fishler, Yehudit, Dichtiar, Rita, Silverman, Barbara, Aviv, Ariel, Arad, Ariella, Bairey, Osnat, Binyamini, Ohad, Braester, Andre, Fineman, Riva, Goldshmidt, Neta, Herishanu, Yair, Rahimi-Levene, Naomi, Shvidel, Lev, Tadmor, Tamar, Yuklea, Mona, Polliack, Aaron, and Keinan-Boker, Lital

Published
2014
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50. Polymorphisms in the human organic cation transporter and the multidrug resistance gene: correlation with imatinib levels and clinical course in patients with chronic myeloid leukemia.

Author

Vine, Jacob, Cohen, Sara Bar, Ruchlemer, Rosa, Goldschmidt, Neta, Levin, Moshe, Libster, Diana, Gural, Alexander, Gatt, Moshe E., Lavie, David, Ben-Yehuda, Dina, and Rund, Deborah

Subjects
CHRONIC myeloid leukemia, GENETIC polymorphism research, MULTIDRUG resistance, CATIONS, IMATINIB, PROTEIN-tyrosine kinases, PHARMACOGENOMICS, HEALTH outcome assessment
Abstract

The optimal tyrosine kinase inhibitor for any individual patient with chronic myeloid leukemia (CML) is not predictable. Pharmacogenetic parameters and trough levels of imatinib (IM) have each been independently correlated with response. We therefore studied the human organic cation transporter (h OCT1) and multidrug resistance ( MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians. We studied MDR1 G2677T and C3435T, and for h OCT1, C480G and A1222G. IM levels varied significantly with dose (< or > 400 mg/day) ( p = 0.038) and were significantly lower in 20 patients who lost MMR ( p = 0.042). Adjusting for dose, trough IM levels were not significantly correlated with SNPs. Patients with MDR1 3435 TT had significantly longer times to MMR compared to CC/CT genotypes ( p = 0.047). Genotypes did not predict treatment failure when controlling for IM levels. We conclude that IM levels, but not the SNPs studied here, determine IM failure. [ABSTRACT FROM AUTHOR]

Published
2014
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