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151. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and COVID-19: A study of ERIC, the European Research Initiative on CLL

Author

Antic, Darko, primary, Milic, Natasa, additional, Chatzikonstantinou, Thomas, additional, Scarfò, Lydia, additional, Otasevic, Vladimir, additional, Rajovic, Nina, additional, Allsup, David, additional, Cabrero, Alejandro Alonso, additional, Andres, Martin, additional, Gonzales, Monica Baile, additional, Capasso, Antonella, additional, Collado, Rosa, additional, Cordoba, Raul, additional, Cuéllar-García, Carolina, additional, Correa, Juan Gonzalo, additional, De Paoli, Lorenzo, additional, De Paolis, Maria Rosaria, additional, Poeta, Giovanni Del, additional, Dimou, Maria, additional, Doubek, Michael, additional, Efstathopoulou, Maria, additional, El-Ashwah, Shaimaa, additional, Enrico, Alicia, additional, Espinet, Blanca, additional, Farina, Lucia, additional, Ferrari, Angela, additional, Foglietta, Myriam, additional, Lopez-Garcia, Alberto, additional, García-Marco, José A., additional, García-Serra, Rocío, additional, Gentile, Massimo, additional, Gimeno, Eva, additional, Silva, Maria Gomes, additional, Gutwein, Odit, additional, Hakobyan, Yervand K., additional, Herishanu, Yair, additional, Hernández-Rivas, José Ángel, additional, Herold, Tobias, additional, Itchaki, Gilad, additional, Jaksic, Ozren, additional, Janssens, Ann, additional, Kalashnikova, Оlga B., additional, Kalicińska, Elżbieta, additional, Kater, Arnon P., additional, Kersting, Sabina, additional, Koren-Michowitz, Maya, additional, Gomez, Jorge Labrador, additional, Lad, Deepesh, additional, Laurenti, Luca, additional, Fresa, Alberto, additional, Levin, Mark-David, additional, Bastida, Carlota Mayor, additional, Malerba, Lara, additional, Marasca, Roberto, additional, Marchetti, Monia, additional, Marquet, Juan, additional, Mihaljevic, Biljana, additional, Milosevic, Ivana, additional, Mirás, Fatima, additional, Morawska, Marta, additional, Motta, Marina, additional, Munir, Talha, additional, Murru, Roberta, additional, Nunes, Raquel, additional, Olivieri, Jacopo, additional, Pavlovsky, Miguel Arturo, additional, Piskunova, Inga, additional, Popov, Viola Maria, additional, Quaglia, Francesca Maria, additional, Quaresmini, Giulia, additional, Reda, Gianluigi, additional, Rigolin, Gian Matteo, additional, Shrestha, Amit, additional, Šimkovič, Martin, additional, Smirnova, Svetlana, additional, Špaček, Martin, additional, Sportoletti, Paolo, additional, Stanca, Oana, additional, Stavroyianni, Niki, additional, Raa, Doreen Te, additional, Tomic, Kristina, additional, Tonino, Sanne, additional, Trentin, Livio, additional, Spek, Ellen Der, additional, Gelder, Michel, additional, Varettoni, Marzia, additional, Visentin, Andrea, additional, Vitale, Candida, additional, Vukovic, Vojin, additional, Wasik-Szczepanek, Ewa, additional, Wróbel, Tomasz, additional, Segundo, Lucrecia Yáñez San, additional, Yassin, Mohamed, additional, Coscia, Marta, additional, Rambaldi, Alessandro, additional, Montserrat, Emili, additional, Foà, Robin, additional, Cuneo, Antonio, additional, Carrier, Marc, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2022
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153. How COVID-19 pandemic changed our attitude to venetoclax-based treatment in chronic lymphocytic leukemia

Author

Deodato, Marina, primary, Frustaci, Anna Maria, additional, Sportoletti, Paolo, additional, Laurenti, Luca, additional, Murru, Roberta, additional, Visentin, Andrea, additional, Reda, Gianluigi, additional, Mauro, Francesca Romana, additional, Quaresmini, Giulia, additional, Vanazzi, Anna, additional, Vitale, Candida, additional, Orsucci, Lorella, additional, Massaia, Massimo, additional, Sanna, Alessandro, additional, Motta, Marina, additional, Ibatici, Adalberto, additional, Ferrarini, Isacco, additional, Borella, Chiara, additional, Varettoni, Marzia, additional, Tani, Monica, additional, Marinoni, Sara, additional, Ferrario, Andrea, additional, Zamprogna, Giulia, additional, Montillo, Marco, additional, and Tedeschi, Alessandra, additional

Published
2022
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155. From Biology to Treatment of Monoclonal Gammopathies of Neurological Significance

Author

Visentin, Andrea, primary, Pravato, Stefano, additional, Castellani, Francesca, additional, Campagnolo, Marta, additional, Angotzi, Francesco, additional, Cavarretta, Chiara Adele, additional, Cellini, Alessandro, additional, Ruocco, Valeria, additional, Salvalaggio, Alessandro, additional, Tedeschi, Alessandra, additional, Trentin, Livio, additional, and Briani, Chiara, additional

Published
2022
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157. sj-docx-1-tah-10.1177_20406207221127550 – Supplemental material for Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia

Author

Frustaci, Anna Maria, Del Poeta, Giovanni, Visentin, Andrea, Sportoletti, Paolo, Fresa, Alberto, Vitale, Candida, Murru, Roberta, Chiarenza, Annalisa, Sanna, Alessandro, Mauro, Francesca Romana, Reda, Gianluigi, Gentile, Massimo, Varettoni, Marzia, Baratè, Claudia, Borella, Chiara, Greco, Antonino, Deodato, Marina, Zamprogna, Giulia, Laureana, Roberta, Cipiciani, Alessandra, Galitzia, Andrea, Curto Pelle, Angelo, Morelli, Francesca, Malvisi, Lucio, Coscia, Marta, Laurenti, Luca, Trentin, Livio, Montillo, Marco, Cairoli, Roberto, and Tedeschi, Alessandra

Subjects
FOS: Clinical medicine, Cardiology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, sj-docx-1-tah-10.1177_20406207221127550 for Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia by Anna Maria Frustaci, Giovanni Del Poeta, Andrea Visentin, Paolo Sportoletti, Alberto Fresa, Candida Vitale, Roberta Murru, Annalisa Chiarenza, Alessandro Sanna, Francesca Romana Mauro, Gianluigi Reda, Massimo Gentile, Marzia Varettoni, Claudia Baratè, Chiara Borella, Antonino Greco, Marina Deodato, Giulia Zamprogna, Roberta Laureana, Alessandra Cipiciani, Andrea Galitzia, Angelo Curto Pelle, Francesca Morelli, Lucio Malvisi, Marta Coscia, Luca Laurenti, Livio Trentin, Marco Montillo, Roberto Cairoli and Alessandra Tedeschi in Therapeutic Advances in Hematology

Published
2022
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160. Prediction of outcomes in chronic lymphocytic leukemia patients treated with ibrutinib: Validation of current prognostic models and development of a simplified three‐factor model

Author

Molica, Stefano, primary, Giannarelli, Diana, additional, Visentin, Andrea, additional, Reda, Gianluigi, additional, Sportoletti, Paolo, additional, Frustaci, Anna Maria, additional, Chiarenza, Annalisa, additional, Ciolli, Stefania, additional, Vitale, Candida, additional, Laurenti, Luca, additional, De Paoli, Lorenzo, additional, Murru, Roberta, additional, Gentile, Massimo, additional, Moia, Riccardo, additional, Rigolin, Gian Matteo, additional, Levato, Luciano, additional, Giordano, Annamaria, additional, Del Poeta, Giovanni, additional, Stelitano, Caterina, additional, Deodato, Marina, additional, Ielo, Claudia, additional, Noto, Alessandro, additional, Guarente, Valerio, additional, Coscia, Marta, additional, Tedeschi, Alessandra, additional, Gaidano, Gianluca, additional, Cuneo, Antonio, additional, Foa', Robin, additional, Trentin, Livio, additional, and Mauro, Francesca Romana, additional

Published
2022
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161. Risk of hepatitis B virus reactivation in chronic lymphocytic leukemia patients receiving ibrutinib with or without antiviral prophylaxis. A retrospective multicentric GIMEMA study

Author

Innocenti, Idanna, primary, Reda, Gianluigi, additional, Visentin, Andrea, additional, Coscia, Marta, additional, Motta, Marina, additional, Murru, Roberta, additional, Moia, Riccardo, additional, Gentile, Massimo, additional, Pennese, Elsa, additional, Quaglia, Francesca Maria, additional, Albano, Francesco, additional, Cassin, Ramona, additional, Deodato, Marina, additional, Ielo, Claudia, additional, Frustaci, Anna Maria, additional, Piciocchi, Alfonso, additional, Rughini, Arianna, additional, Arena, Valentina, additional, Di Sevo, Daniela, additional, Tomasso, Annamaria, additional, Autore, Francesco, additional, Del Poeta, Giovanni, additional, Scarfò, Lydia, additional, Mauro, Francesca Romana, additional, Tedeschi, Alessandra, additional, Trentin, Livio, additional, Pompili, Maurizio, additional, Foà, Robin, additional, Ghia, Paolo, additional, Cuneo, Antonio, additional, and Laurenti, Luca, additional

Published
2022
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164. Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia

Author

Frustaci, Anna Maria, primary, Del Poeta, Giovanni, additional, Visentin, Andrea, additional, Sportoletti, Paolo, additional, Fresa, Alberto, additional, Vitale, Candida, additional, Murru, Roberta, additional, Chiarenza, Annalisa, additional, Sanna, Alessandro, additional, Mauro, Francesca Romana, additional, Reda, Gianluigi, additional, Gentile, Massimo, additional, Varettoni, Marzia, additional, Baratè, Claudia, additional, Borella, Chiara, additional, Greco, Antonino, additional, Deodato, Marina, additional, Zamprogna, Giulia, additional, Laureana, Roberta, additional, Cipiciani, Alessandra, additional, Galitzia, Andrea, additional, Curto Pelle, Angelo, additional, Morelli, Francesca, additional, Malvisi, Lucio, additional, Coscia, Marta, additional, Laurenti, Luca, additional, Trentin, Livio, additional, Montillo, Marco, additional, Cairoli, Roberto, additional, and Tedeschi, Alessandra, additional

Published
2022
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165. Continuous treatment with Ibrutinib in 100 untreated patients with TP 53 disrupted chronic lymphocytic leukemia: A real‐life campus CLL study

Author

Visentin, Andrea, primary, Mauro, Francesca Romana, additional, Cibien, Francesca, additional, Vitale, Candida, additional, Reda, Gianluigi, additional, Fresa, Alberto, additional, Ciolli, Stefania, additional, Pietrasanta, Daniela, additional, Marchetti, Monia, additional, Murru, Roberta, additional, Gentile, Massimo, additional, Rigolin, Gian Matteo, additional, Quaglia, Francesca Maria, additional, Scarfò, Lydia, additional, Sportoletti, Paolo, additional, Pravato, Stefano, additional, Piazza, Francesco, additional, Coscia, Marta, additional, Laurenti, Luca, additional, Molica, Stefano, additional, Foà, Robin, additional, Cuneo, Antonio, additional, and Trentin, Livio, additional

Published
2021
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166. Computing optimal (R,s,S) Policy Parameters by a hybrid of branch-and-bound and stochastic dynamic programming

Author

Visentin, Andrea, Prestwich, Steven, Rossi, Roberto, and Tarim, S. Armagan

Subjects
inventory, (R,s,S) policy, Optimization and Control (math.OC), FOS: Mathematics, stochastic lot sizing, Mathematics - Optimization and Control, demand uncertainty
Abstract

A well-know control policy in stochastic inventory control is the (R, s, S) policy, in which inventory is raised to an order-up-to-level S at a review instant R whenever it falls below reorder-level s. To date, little or no work has been devoted to developing approaches for computing (R, s, S) policy parameters. In this work, we introduce a hybrid approach that exploits tree search to compute optimal replenishment cycles, and stochastic dynamic programming to compute (s, S) levels for a given cycle. Up to 99.8% of the search tree is pruned by a branch-and-bound technique with bounds generated by dynamic programming. A numerical study shows that the method can solve instances of realistic size in a reasonable time.

Published
2021

167. A Retrospective Study on the Efficacy of Subcutaneous Immunoglobulin as Compared to Intravenous Formulation in Patients with Chronic Lymphocytic Leukemia and Secondary Antibody Deficiency.

Author

Visentin, Andrea, Molinari, Maria Chiara, Pravato, Stefano, Cellini, Alessandro, Angotzi, Francesco, Cavaretta, Chiara Adele, Ruocco, Valeria, Imbergamo, Silvia, Piazza, Francesco, Proietti, Giulia, Mauro, Francesca Romana, and Trentin, Livio

Subjects
*IMMUNOGLOBULINS, *CHRONIC lymphocytic leukemia, *HEALTH outcome assessment, *MEDICAL care, *MEDICAL personnel
Abstract

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L. [ABSTRACT FROM AUTHOR]

Published
2023
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169. Efficacy of Front-Line Ibrutinib Versus Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients with CLL. a Multicenter "Real-World" Study

Author

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

Published
2021
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170. Real-World Evidence on Therapeutic Strategies and Treatment-Sequencing in Patients with Chronic Lymphocytic Leukemia: An International Study of Eric, the European Research Initiative on CLL

Author

Chatzikonstantinou, Thomas, primary, Scarfo, Lydia, additional, Demosthenous, Christos, additional, Kotaskova, Jana, additional, Iacoboni, Gloria, additional, Minga, Evangelia, additional, Chammou, Dimitra, additional, Karakatsoulis, Georgios, additional, Albi, Elisa, additional, Alcoceba, Miguel, additional, El-Ashwah, Shaimaa, additional, Bacchiarri, Francesca, additional, Khan, Mehreen Ali, additional, Aurran, Thérèse, additional, Calleja, Anne, additional, Cassin, Ramona, additional, Chatzileontiadou, Sofia, additional, Christian, Amy, additional, Claus, Rainer, additional, Collado, Rosa, additional, De Deus Santos, Marcos Daniel, additional, Davis, Zadie, additional, Dimou, Maria, additional, Donaldson, David, additional, Dos Santos, Gimena, additional, Dreta, Barbara, additional, Efstathopoulou, Maria, additional, Enrico, Alicia, additional, Fresa, Alberto, additional, Galimberti, Sara, additional, García-Serra, Rocío, additional, González-Gascón Y Marín, Isabel, additional, Gozzetti, Alessandro, additional, Guarente, Valerio, additional, Harrop, Sean, additional, Hatzimichael, Eleftheria, additional, Herishanu, Yair, additional, Inchiappa, Luca, additional, Iskas, Michalis, additional, Jaksic, Ozren, additional, Janssen, Susanne R., additional, Kalicinska, Elzbieta, additional, Karakus, Volkan, additional, Kater, Arnon P., additional, Kho, Bonnie, additional, Konstantinou, Iliana, additional, Longval, Thomas, additional, Koren-Michowitz, Maya, additional, Kotsianidis, Ioannis, additional, Kreitman, Robert J., additional, Nath, Uttam Kumar, additional, Labrador, Jorge, additional, Lad, Deepesh, additional, Laribi, Kamel, additional, Levy, Ilana, additional, Lopez-Garcia, Alberto, additional, Marquet Palomanes, Juan, additional, Maslejova, Stanislava, additional, Mayor-Bastida, Carlota, additional, Merabet, Fatiha, additional, Mihaljevic, Biljana, additional, Milosevic, Ivana, additional, Miras, Fatima, additional, Moia, Riccardo, additional, Morawska, Marta, additional, Navarro-Bailón, Almudena, additional, Oscier, David, additional, Olivieri, Jacopo, additional, Papajík, Tomáš, additional, Papaioannou, Maria, additional, Pierie, Cheyenne, additional, Puiggros, Anna, additional, Reda, Gianluigi, additional, Rigolin, Gian Matteo, additional, Ruchlemer, Rosa, additional, Schiattone, Luana, additional, Sevindik, Omur Gokmen, additional, Shen, Yandong, additional, Šimkovič, Martin, additional, Smirnova, Svetlana, additional, Soliman, Dina Sameh, additional, Špaček, Martin, additional, Schiwitza, Annett, additional, Tadmor, Tamar, additional, Tourjeman, Liat, additional, Tse, Eric, additional, Visentin, Andrea, additional, Tomic, Kristina, additional, Van Gelder, Michel, additional, Vassilakopoulos, Theodoros P., additional, Vitale, Candida, additional, Vrachiolias, George, additional, Vukovic, Vojin, additional, Xu, Zhenshu, additional, Yáñez, Lucrecia, additional, Yagci, Munci, additional, Yassin, Mohamed A, additional, Zuchnicka, Jana, additional, Angelopoulou, Maria K., additional, Antic, Darko, additional, Biderman, Bella V., additional, Catherwood, Mark, additional, Coscia, Marta, additional, Cuneo, Antonio, additional, Demirkan, Fatih, additional, Espinet, Blanca, additional, Gaidano, Gianluca, additional, Guièze, Romain, additional, Kalashnikova, Olga, additional, Laurenti, Luca, additional, Mulligan, Stephen, additional, Murru, Roberta, additional, Nikitin, Eugene A., additional, Panayiotidis, Panayiotis, additional, Pangalis, Gerasimos, additional, Panovska, Irina, additional, Popov, Viola Maria, additional, Pospíšilová, Šárka, additional, Smolej, Lukas, additional, Sportoletti, Paolo, additional, Stavroyianni, Niki, additional, Tam, Constantine S., additional, Trentin, Livio, additional, Trněný, Marek, additional, Bosch Albareda, Francesc, additional, Doubek, Michael, additional, Chatzidimitriou, Anastasia, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2021
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171. Brentuximab vedotin consolidation after autologous stem cell transplantation for Hodgkin lymphoma: A Fondazione Italiana Linfomi real‐life experience

Author

Massaro, Fulvio, primary, Pavone, Vincenzo, additional, Stefani, Piero Maria, additional, Botto, Barbara, additional, Pulsoni, Alessandro, additional, Patti, Caterina, additional, Cantonetti, Maria, additional, Visentin, Andrea, additional, Scalzulli, Potito Rosario, additional, Rossi, Andrea, additional, Galimberti, Sara, additional, Cimminiello, Michele, additional, Gini, Guido, additional, Musso, Maurizio, additional, Sorio, Marco, additional, Arcari, Annalisa, additional, Zilioli, Vittorio Ruggero, additional, Luppi, Mario, additional, Mannina, Donato, additional, Fabbri, Alberto, additional, Pietrantuono, Giuseppe, additional, Annibali, Ombretta, additional, Tafuri, Agostino, additional, Prete, Eleonora, additional, Mulè, Antonino, additional, Barbolini, Elisa, additional, Marcheselli, Luigi, additional, Luminari, Stefano, additional, and Merli, Francesco, additional

Published
2021
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173. Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia

Author

Frezzato, Federica, primary, Visentin, Andrea, additional, Severin, Filippo, additional, Pizzo, Serena, additional, Ruggeri, Edoardo, additional, Mouawad, Nayla, additional, Martinello, Leonardo, additional, Pagnin, Elisa, additional, Trimarco, Valentina, additional, Tonini, Alessia, additional, Carraro, Samuela, additional, Pravato, Stefano, additional, Imbergamo, Silvia, additional, Manni, Sabrina, additional, Piazza, Francesco, additional, Brunati, Anna Maria, additional, Facco, Monica, additional, and Trentin, Livio, additional

Published
2021
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174. Protein Kinase CK1α Sustains B-Cell Receptor Signaling in Mantle Cell Lymphoma

Author

Manni, Sabrina, primary, Fregnani, Anna, additional, Quotti Tubi, Laura, additional, Spinello, Zaira, additional, Carraro, Marco, additional, Scapinello, Greta, additional, Visentin, Andrea, additional, Barilà, Gregorio, additional, Pizzi, Marco, additional, Dei Tos, Angelo Paolo, additional, Vianello, Fabrizio, additional, Zambello, Renato, additional, Gurrieri, Carmela, additional, Semenzato, Gianpietro, additional, Trentin, Livio, additional, and Piazza, Francesco, additional

Published
2021
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177. Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells

Author

Dalla Pietà, Anna, primary, Cappuzzello, Elisa, additional, Palmerini, Pierangela, additional, Ventura, Annavera, additional, Visentin, Andrea, additional, Astori, Giuseppe, additional, Chieregato, Katia, additional, Mozzo, Valentina, additional, Perbellini, Omar, additional, Tisi, Maria Chiara, additional, Trentin, Livio, additional, Visco, Carlo, additional, Ruggeri, Marco, additional, Sommaggio, Roberta, additional, and Rosato, Antonio, additional

Published
2021
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178. Prognostic Impact and Risk Factors of Infections in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib

Author

Mauro, Francesca Romana, primary, Giannarelli, Diana, additional, Visentin, Andrea, additional, Reda, Gianluigi, additional, Sportoletti, Paolo, additional, Frustaci, Anna Maria, additional, Chiarenza, Annalisa, additional, Ciolli, Stefania, additional, Vitale, Candida, additional, Laurenti, Luca, additional, De Paoli, Lorenzo, additional, Murru, Roberta, additional, Gentile, Massimo, additional, Rigolin, Gian Matteo, additional, Levato, Luciano, additional, Giordano, Annamaria, additional, Del Poeta, Giovanni, additional, Stelitano, Caterina, additional, Ielo, Claudia, additional, Noto, Alessandro, additional, Guarente, Valerio, additional, Molica, Stefano, additional, Coscia, Marta, additional, Tedeschi, Alessandra, additional, Gaidano, Gianluca, additional, Cuneo, Antonio, additional, Foà, Robin, additional, Martelli, Maurizio, additional, Girmenia, Corrado, additional, Gentile, Giuseppe, additional, and Trentin, Livio, additional

Published
2021
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179. Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs

Author

Vitale, Candida, primary, Salvetti, Chiara, additional, Griggio, Valentina, additional, Porrazzo, Marika, additional, Schiattone, Luana, additional, Zamprogna, Giulia, additional, Visentin, Andrea, additional, Vassallo, Francesco, additional, Cassin, Ramona, additional, Rigolin, Gian Matteo, additional, Murru, Roberta, additional, Laurenti, Luca, additional, Rivela, Paolo, additional, Marchetti, Monia, additional, Pennese, Elsa, additional, Gentile, Massimo, additional, Boccellato, Elia, additional, Perutelli, Francesca, additional, Montalbano, Maria Chiara, additional, De Paoli, Lorenzo, additional, Reda, Gianluigi, additional, Orsucci, Lorella, additional, Trentin, Livio, additional, Cuneo, Antonio, additional, Tedeschi, Alessandra, additional, Scarfò, Lydia, additional, Gaidano, Gianluca, additional, Mauro, Francesca Romana, additional, Foà, Robin, additional, Boccadoro, Mario, additional, and Coscia, Marta, additional

Published
2021
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180. The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation

Author

Visentin, Andrea, primary, Bonaldi, Laura, additional, Rigolin, Gian Matteo, additional, Mauro, Francesca Romana, additional, Martines, Annalisa, additional, Frezzato, Federica, additional, Pravato, Stefano, additional, Gargarella, Leila Romano, additional, Bardi, Maria Antonella, additional, Cavallari, Maurizio, additional, Volta, Eleonora, additional, Cavazzini, Francesco, additional, Nanni, Mauro, additional, Facco, Monica, additional, Piazza, Francesco, additional, Guarini, Anna, additional, Foà, Robin, additional, Semenzato, Gianpietro, additional, Cuneo, Antonio, additional, and Trentin, Livio, additional

Published
2021
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181. 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

182. CD49d Expression Is Included in a Revised 4-Factor Model Predicting Outcome in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Multi-Center Real-World Experience

Author

Bomben, Riccardo, Zucchetto, Antonella, Laureana, Roberta, Chiarenza, Annalisa, Olivieri, Jacopo, Tissino, Erika, Rossi, Francesca, Vit, Filippo, Bittolo, Tamara, Papotti, Robel, Pozzo, Federico, Gaglio, Annalisa, Degan, Massimo, Polesel, Jerry, Marasca, Roberto, Reda, Gianluigi, Visentin, Andrea, Moia, Riccardo, Innocenti, Idanna, Vitale, Candida, Murru, Roberta, Varettoni, Marzia, Tafuri, Agostino, Zaja, Francesco, Postorino, Massimiliano, Martino, Enrica Antonia, Condolucci, Adalgisa, Rossi, Davide, Cuneo, Antonio, Di Raimondo, Francesco, Sportoletti, Paolo, Del Giudice, Ilaria, Foa, Robin, Mauro, Francesca Romana, Coscia, Marta, Laurenti, Luca, Gaidano, Gianluca, Trentin, Livio, Del Principe, Maria Ilaria, Gentile, Massimo, and Gattei, Valter

Published
2023
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183. Ibrutinib As First Line Therapy in Chronic Lymphocytic Leukemia Patients over 80 Years Old: A Retrospective Real-Life Multicenter Italian Cohort

Author

Martino, Enrica Antonia, Mauro, Francesca Romana, Reda, Gianluigi, Laurenti, Luca, Visentin, Andrea, Frustaci, Annamaria, Vigna, Ernesto, Pepe, Sara, Catania, Gioacchino, Loseto, Giacomo, Murru, Roberta, Chiarenza, Annalisa, Sportoletti, Paolo, Del Principe, Maria Ilaria, Coscia, Marta, Galimberti, Sara, Tedeschi, Alessandra, Rossi, Davide, Trentin, Livio, Morabito, Fortunato, Gattei, Valter, and Gentile, Massimo

Published
2023
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184. Patients with Chronic Lymphocytic Leukemia Carrying t(14;19) Display a Distinctive Transcriptomic Profile and Adverse Outcome, Which Might be Overcome Continuous Therapy with BTK Inhibitors. an Italian Campus CLL and Eric Study

Author

Visentin, Andrea, Gaffo, Enrico, Furstenau, Moritz, Woyach, Jennifer A., Baliakas, Panagiotis, Rogers, Kerry A, Miller, Cecelia, Haferlach, Claudia, Plevova, Karla, Oscier, David Graham, Davis, Zadie, Nguyen Khac, Florence, Roncaglia, Eleonora, Rigolin, Gian Matteo, Athanasiadou, Anastasia, Baran-Marszak, Fanny, Valiente, Alberto, Terol, Maria Jose, Abrisqueta, Pau, Espinet, Blanca, Puiggros, Anna, Martines, Annalisa, Bonaldi, Laura, Mauro, Francesca Romana, Scarfo, Lydia, Chatzikonstantinou, Thomas, Tausch, Eugen, Kreuzer, Karl Anton, Kater, Arnon P., Bosch, Francesc, Doubek, Michael, Panayiotidis, Panayiotis, Kalashnikova, Olga, Frezzato, Federica, Facco, Monica, Ruocco, Valeria, Buratin, Alessia, Orsi, Silvia, Cellini, Alessandro, Angotzi, Francesco, Cavarretta, Chiara Adele, Zatta, Ivan, Serafin, Andrea, Foa, Robin, Eichhorst, Barbara F., Cuneo, Antonio, Stamatopoulos, Kostas, Ghia, Paolo, Bortoluzzi, Stefania, and Trentin, Livio

Published
2023
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185. Real-Life Efficacy and Safety of Vemurafenib Plus Rituximab (V+R) in Relapsed or Refractory Hairy Cell Leukemia: A Multi-Center Retrospective Study (HCL-PG03R)

Author

Tiacci, Enrico, De Carolis, Luca, Capponi, Monia, Bernardelli, Andrea, Visentin, Andrea, D'Elia, Gianna Maria, Ferrero, Simone, Cimminiello, Michele, Romeo, Azzurra Anna, Pocali, Barbara, Falcinelli, Flavio, Sanna, Alessandro, Frustaci, Annamaria, Maschio, Nilla, Stelitano, Caterina, Olivieri, Jacopo, Visco, Carlo, Pulsoni, Alessandro, Foa, Robin, Trentin, Livio, and Falini, Brunangelo

Published
2023
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187. Real-World Venetoclax-Obinutuzumab in 232 Treatment Naive CLL Patients: Feasibility and Tolerability

Author

Tedeschi, Alessandra, Galitzia, Andrea, Frustaci, Annamaria, Patti, Caterina, Sanna, Alessandro, Appio, Lorena, Schiattone, Luana, Sportoletti, Paolo, Barate', Claudia, Casadei, Beatrice, Ferrarini, Isacco, Figuera, Amalia, Stelitano, Caterina, Loseto, Giacomo, Visentin, Andrea, Coscia, Marta, Moia, Riccardo, Motta, Marina, Russo, Filomena, Tani, Monica, Capochiani, Enrico, Ferrari, Angela, Gentile, Massimo, Giacchetti, Roberta, Giordano, Annamaria, Innao, Vanessa, Varettoni, Marzia, Vozzella, Federico, Cibien, Francesca, Gottardi, Daniela, Lista, Enrico, Nocilli, Laura, Pasquini, Cristina, Vanazzi, Anna, Santambrogio, Elisa, Murru, Roberta, Mauro, Francesca Romana, Lucignano, Mariano, and Laurenti, Luca

Published
2023
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188. 36-Month Follow-up Results of the Gimema ‘Veritas’ Trial of Front-Line Venetoclax and Rituximab (VenR) in Young and Fit Patients with Chronic Lymphocytic Leukemia and an Adverse Biologic Profile

Author

Mauro, Francesca Romana, Della Starza, Irene, Messina, Monica, Reda, Gianluigi, Trentin, Livio, Coscia, Marta, Sportoletti, Paolo, Orsucci, Lorella, Arena, Valentina, Gaidano, Gianluca, Marasca, Roberto, Murru, Roberta, Laurenti, Luca, Stelitano, Caterina, Mannina, Donato, Ilariucci, Fiorella, Massaia, Massimo, Rigolin, Gian Matteo, Scarfo, Lydia, Marchetti, Monia, Levato, Luciano, Tani, Monica, Arcari, Annalisa, Musuraca, Gerardo, Deodato, Marina, Galieni, Piero, Belsito Patrizi, Valeria, Gottardi, Daniela, Liberati, Anna Marina, Giordano, Annamaria, Molinari, Maria Chiara, Pepe, Sara, Andriola, Costanza, Mattiello, Veronica, Visentin, Andrea, Vitale, Candida, Albano, Francesco, Neri, Antonino, De Propris, Maria Stefania, Nanni, Mauro, Del Giudice, Ilaria, Guarini, Anna, Fazi, Paola, Vignetti, Marco, Piciocchi, Alfonso, Cuneo, Antonio, and Foà, Robin

Published
2023
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189. Efficacy and Safety of Front-Line Venetoclax and Rituximab (VenR) for the Treatment of Young Patients with Chronic Lymphocytic Leukemia and an Unfavorable Biologic Profile. Preliminary Results of the Gimema Study ‘Veritas‘

Author

Mauro, Francesca Romana, Reda, Gianluigi, Arena, Valentina, Trentin, Livio, Coscia, Marta, Sportoletti, Paolo, Laurenti, Luca, Gaidano, Gianluca, Marasca, Roberto, Orsucci, Lorella, Murru, Roberta, Stelitano, Caterina, Ilariucci, Fiorella, Mannina, Donato, Massaia, Massimo, Rigolin, Gian Matteo, Scarfo, Lydia, Marchetti, Monia, Levato, Luciano, Tani, Monica, Arcari, Annalisa, Musuraca, Gerardo, Deodato, Marina, Galieni, Piero, Califano, Catello, Gottardi, Daniela, Liberati, Anna Marina, Pietrasanta, Daniela, Molica, Stefano, Cassin, Ramona, Visentin, Andrea, Vitale, Candida, Lapietra, Gianfranco, Della Starza, Irene, De Propris, Maria Stefania, Raponi, Sara, Nanni, Mauro, Del Giudice, Ilaria, Giuliani, Giorgia, Vignetti, Marco, Guarini, Anna, Albano, Francesco, Neri, Antonino, Cuneo, Antonio, and Foà, Robin

Published
2020
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191. TP53 disruption as a risk factor in the era of targeted therapies: A multicenter retrospective study of 525 chronic lymphocytic leukemia cases

Author

Morabito, Fortunato, primary, Del Poeta, Giovanni, additional, Mauro, Francesca Romana, additional, Reda, Gianluigi, additional, Sportoletti, Paolo, additional, Laurenti, Luca, additional, Coscia, Marta, additional, Herishanu, Yair, additional, Bossio, Sabrina, additional, Varettoni, Marzia, additional, Murru, Roberta, additional, Chiarenza, Annalisa, additional, Visentin, Andrea, additional, Condoluci, Adalgisa, additional, Moia, Riccardo, additional, Pietrasanta, Daniela, additional, Loseto, Giacomo, additional, Consoli, Ugo, additional, Scortechini, Ilaria, additional, Recchia, Anna Grazia, additional, Rossi, Francesca Maria, additional, Zucchetto, Antonella, additional, Al‐Janazreh, Hamdi, additional, Martino, Enrica Antonia, additional, Vigna, Ernesto, additional, Tripepi, Giovanni, additional, D'Arrigo, Graziella, additional, Galimberti, Sara, additional, Rago, Angela, additional, Angeletti, Ilaria, additional, Biagi, Annalisa, additional, Del Giudice, Ilaria, additional, Bomben, Riccardo, additional, Neri, Antonino, additional, Fronza, Gilberto, additional, Cutrona, Giovanna, additional, Jaksic, Ozren, additional, Olivieri, Jacopo, additional, Rossi, Davide, additional, Di Raimondo, Francesco, additional, Cuneo, Antonio, additional, Gaidano, Gianluca, additional, Polliack, Aaron, additional, Trentin, Livio, additional, Foà, Robin, additional, Ferrarini, Manlio, additional, Gattei, Valter, additional, and Gentile, Massimo, additional

Published
2021
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192. Effectiveness of ibrutinib as first‐line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab‐bendamustine: Results of study on 486 cases outside clinical trials

Author

Morabito, Fortunato, primary, Tripepi, Giovanni, additional, Del Poeta, Giovanni, additional, Mauro, Francesca Romana, additional, Reda, Gianluigi, additional, Sportoletti, Paolo, additional, Laurenti, Luca, additional, Coscia, Marta, additional, Herishanu, Yair, additional, Bossio, Sabrina, additional, Varettoni, Marzia, additional, Murru, Roberta, additional, Chiarenza, Annalisa, additional, Visentin, Andrea, additional, Condoluci, Adalgisa, additional, Moia, Riccardo, additional, Pietrasanta, Daniela, additional, Loseto, Giacomo, additional, Consoli, Ugo, additional, Scortechini, Ilaria, additional, Rossi, Francesca Maria, additional, Zucchetto, Antonella, additional, Al‐Janazreh, Hamdi, additional, Vigna, Ernesto, additional, Martino, Enrica Antonia, additional, Cassin, Ramona, additional, D′Arrigo, Graziella, additional, Galimberti, Sara, additional, Rago, Angela, additional, Angeletti, Ilaria, additional, Biagi, Annalisa, additional, Del Giudice, Ilaria, additional, Bomben, Riccardo, additional, Neri, Antonino, additional, Fronza, Gilberto, additional, Monti, Paola, additional, Menichini, Paola, additional, Olivieri, Jacopo, additional, Cutrona, Giovanna, additional, Rossi, Davide, additional, Cuneo, Antonio, additional, Di Raimondo, Francesco, additional, Gaidano, Gianluca, additional, Polliack, Aaron, additional, Trentin, Livio, additional, Foà, Robin, additional, Ferrarini, Manlio, additional, Gattei, Valter, additional, and Gentile, Massimo, additional

Published
2021
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193. Enhanced IL-9 secretion by p66Shc-deficient CLL cells modulates the chemokine landscape of the stromal microenvironment

Author

Patrussi, Laura, primary, Manganaro, Noemi, additional, Capitani, Nagaja, additional, Ulivieri, Cristina, additional, Tatangelo, Vanessa, additional, Libonati, Francesca, additional, Finetti, Francesca, additional, Frezzato, Federica, additional, Visentin, Andrea, additional, D’Elios, Mario Milco, additional, Trentin, Livio, additional, Semenzato, Gianpietro, additional, and Baldari, Cosima T., additional

Published
2021
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194. Incidental lymphomas in surgical pathology: diagnostic clues and clinical-pathological correlations

Author

Pizzi, Marco, primary, Sbaraglia, Marta, additional, Bellan, Alberto, additional, Santoro, Luisa, additional, Dal Santo, Luca, additional, De Bartolo, Debora, additional, Carraro, Elisa, additional, Zoletto, Simone, additional, Visentin, Andrea, additional, Marino, Dario, additional, Trentin, Livio, additional, and Dei Tos, Angelo Paolo, additional

Published
2021
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195. Subcutaneous immunoglobulins replacement therapy in secondary antibody deficiencies: Real life evidence as compared to primary antibody deficiencies

Author

Cinetto, Francesco, primary, Neri, Raffaella, additional, Vianello, Fabrizio, additional, Visentin, Andrea, additional, Barilà, Gregorio, additional, Gianese, Sabrina, additional, Lanciarotta, Alison, additional, Milito, Cinzia, additional, Rattazzi, Marcello, additional, Piazza, Francesco, additional, Trentin, Livio, additional, Zambello, Renato, additional, Agostini, Carlo, additional, and Scarpa, Riccardo, additional

Published
2021
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196. Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia

Author

Visentin,Andrea, Frezzato,Federica, Severin,Filippo, Imbergamo,Silvia, Pravato,Stefano, Romano Gargarella,Leila, Manni,Sabrina, Pizzo,Serena, Ruggieri,Edoardo, Facco,Monica, Brunati,Anna Maria, Semenzato,Gianpietro, Piazza,Francesco, and Trentin,Livio

Subjects
OncoTargets and Therapy
Abstract

Andrea Visentin,1,2 Federica Frezzato,1,2 Filippo Severin,1,2 Silvia Imbergamo,1 Stefano Pravato,1 Leila Romano Gargarella,1 Sabrina Manni,1,2 Serena Pizzo,1,2 Edoardo Ruggieri,1,2 Monica Facco,1,2 Anna Maria Brunati,3 Gianpietro Semenzato,1,2 Francesco Piazza,1,2 Livio Trentin1,2 1Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Padua, Italy; 2Veneto Institute of Molecular Medicine, Padua, Italy; 3Department of Molecular Medicine, University of Padua, Padua, ItalyCorrespondence: Livio TrentinHematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Via Giustiniani, 2 Padova, Padua 35128, ItalyTel +39 049 821 2298Fax +39 049 821 1970Email livio.trentin@unipd.itAbstract: The treatment (i.e. therapy and management) of chronic lymphocytic leukemia (i.e. the disease) has been improved thanks to the introduction (i.e. approval) of kinase inhibitors during the last years. PI3K is one of the most important kinases at the crossroad to the B-cell receptor and cytokine receptor which play a key role in CLL cell survival, proliferation and migration. Idelalisib is the first in class PI3Kδ inhibitor approved for the treatment of relapsed/refractory CLL in combination with rituximab. Idelalisib activity in heavily treated patients is balanced by recurrent adverse events which limit its long-term use. These limitations prompt the investigation on novel PI3K inhibitors, also targeting different protein isoforms, and alternative schedule strategies. In this regard, duvelisib is the only PI3K γ and δ inhibitor approved as single agent for relapsed CLL. In this review, we will address novel insights on PI3K structure, isoforms, regulating signaling and the most updated data of next-generation PI3K inhibitors in CLL.Keywords: chronic lymphocytic leukemia, PI3K inhibitor, duvelisib, umbralisib, copanlisib

Published
2020

197. Computing policy parameters for stochastic inventory control using stochastic dynamic programming approaches

Author

Visentin, Andrea, Prestwich, Steven David, and Brown, Kenneth N.

Subjects
Stochastic programming, Stochastic lot sizing, Dynamic programming, Inventory control
Abstract

The objective of this work is to introduce techniques for the computation of optimal and near-optimal inventory control policy parameters for the stochastic inventory control problem under Scarf’s setting. A common aspect of the solutions presented herein is the usage of stochastic dynamic programming approaches, a mathematical programming technique introduced by Bellman. Stochastic dynamic programming is hybridised with branch-and-bound, binary search, constraint programming and other computational techniques to develop innovative and competitive solutions. In this work, the classic single-item, single location-inventory control with penalty cost under the independent stochastic demand is extended to model a fixed review cost. This cost is charged when the inventory level is assessed at the beginning of a period. This operation is costly in practice and including it can lead to significant savings. This makes it possible to model an order cancellation penalty charge. The first contribution hereby presented is the first stochastic dynamic program- ming that captures Bookbinder and Tan’s static-dynamic uncertainty control policy with penalty cost. Numerous techniques are available in the literature to compute such parameters; however, they all make assumptions on the de- mand probability distribution. This technique has many similarities to Scarf’s stochastic dynamic programming formulation, and it does not require any ex- ternal solver to be deployed. Memoisation and binary search techniques are deployed to improve computational performances. Extensive computational studies show that this new model has a tighter optimality gap compared to the state of the art. The second contribution is to introduce the first procedure to compute cost- optimal parameters for the well-known (R, s, S) policy. Practitioners widely use such a policy; however, the determination of its parameters is considered com- putationally prohibitive. A technique that hybridises stochastic dynamic pro- gramming and branch-and-bound is presented, alongside with computational enhancements. Computing the optimal policy allows the determination of op- timality gaps for future heuristics. This approach can solve instances of consid- erable size, making it usable by practitioners. The computational study shows the reduction of the cost that such a system can provide. Thirdly, this work presents the first heuristics for determining the near-optimal parameters for the (R,s,S) policy. The first is an algorithm that formally models the (R,s,S) policy computation in the form of a functional equation. The second is a heuristic formed by a hybridisation of (R,S) and (s,S) policy parameters solvers. These heuristics can compute near-optimal parameters in a fraction of time compared to the exact methods. They can be used to speed up the optimal branch-and-bound technique. The last contribution is the introduction of a technique to encode dynamic programming in constraint programming. Constraint programming provides the user with an expressive modelling language and delegates the search for the solution to a specific solver. The possibility to seamlessly encode dynamic programming provides new modelling options, e.g. the computation of optimal (R,s,S) policy parameters. The performances in this specific application are not competitive with the other techniques proposed herein; however, this encoding opens up new connections between constraint programming and dynamic programming. The encoding allows deploying DP based constraints in modelling languages such as MiniZinc. The computational study shows how this technique can outperform a similar encoding for mixed-integer programming.

Published
2020

199. Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia

Author

Visentin, Andrea, Frezzato, Federica, Severin, Filippo, Imbergamo, Silvia, Pravato, Stefano, Romano Gargarella, Leila, Manni, Sabrina, Pizzo, Serena, Ruggieri, Edoardo, Facco, Monica, Brunati, Anna Maria, Semenzato, Gianpietro, Piazza, Francesco, and Trentin, Livio

Subjects
copanlisib, duvelisib, hemic and lymphatic diseases, chronic lymphocytic leukemia, Review, PI3K inhibitor, umbralisib
Abstract

The treatment (i.e. therapy and management) of chronic lymphocytic leukemia (i.e. the disease) has been improved thanks to the introduction (i.e. approval) of kinase inhibitors during the last years. PI3K is one of the most important kinases at the crossroad to the B-cell receptor and cytokine receptor which play a key role in CLL cell survival, proliferation and migration. Idelalisib is the first in class PI3Kδ inhibitor approved for the treatment of relapsed/refractory CLL in combination with rituximab. Idelalisib activity in heavily treated patients is balanced by recurrent adverse events which limit its long-term use. These limitations prompt the investigation on novel PI3K inhibitors, also targeting different protein isoforms, and alternative schedule strategies. In this regard, duvelisib is the only PI3K γ and δ inhibitor approved as single agent for relapsed CLL. In this review, we will address novel insights on PI3K structure, isoforms, regulating signaling and the most updated data of next-generation PI3K inhibitors in CLL.

Published
2020

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