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101. Serum levels of soluble interleukin-2 receptor in Hodgkin disease. Relationship with clinical stage, tumor burden, and treatment outcome.

Author

Ambrosetti, Achille, Nadali, Gianpaolo, Vinante, Fabrizio, Carlini, Stefano, Veneri, Dino, Todeschini, Giuseppe, Morosato, Lorella, de Sabata, Donata, Chilosi, Marco, Maggi, Enrico, Parronchi, Paola, Romagnani, Sergio, Semenzato, Gianpietro, Perona, Giuseppe, Pizzolo, Giovanni, Ambrosetti, A, Nadali, G, Vinante, F, Carlini, S, and Veneri, D

Published
1993
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102. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation

Author

Trojani, A., Ripamonti, C. B., Silvana Penco, Beghini, A., Nadali, G., Di Bona, E., Viola, A., Castagnola, C., Colapietro, P., Grillo, G., Pezzetti, L., Ravelli, E., Patrosso, M. C., Marocchi, A., Cuneo, A., Ferrara, F., Lazzarino, M., Pizzolo, G., Cairoli, R., Morra, E., Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, and Morra, E

Subjects
Adult, Male, Kit, FLT 3, Leukemia, Receptor, Platelet-Derived Growth Factor alpha, Acute myeloid leukemia, PDGFR, Core Binding Factors, Core-binding factor, Middle Aged, NO, Receptor, Platelet-Derived Growth Factor beta, Proto-Oncogene Proteins c-kit, fms-Like Tyrosine Kinase 3, Leukemia, Myeloid, Acute Disease, Mutation, Humans, Female, PDGFR, acute myeloid leukemia, single-strand conformation polymorphism, core-binding factor, Polymorphism, Single-Stranded Conformational, Single-strand conformation polymorphism, Aged
Abstract

Background: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. Patients and Methods: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Results: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. Conclusion: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.

103. SEIFEM 2016 STUDY: INCIDENCE OF PROBABLE AND PROVEN INVASIVE ASPERGILLOSIS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA DURING CONSOLIDATION THERAPY

Author

Del Principe, M. I., Di Blasi, R., Verga, L., anna candoni, Potenza, L., Ballanti, S., Cattaneo, C., Delia, M., Decembrino, N., Melillo, L., Castagnola, C., Nadali, G., Fanci, R., Ferrari, A., Fracchiolla, N. S., Iovino, L., Lessi, F., Veggia, B., Offidani, M., Picardi, M., Prezioso, L., Rambaldi, B., Marchesi, F., Annibali, O., Zama, D., Mancini, V., Salutari, P., Garzia, M. G., Vacca, A., Cesaro, S., Paolis, M. R., Invernizzi, R., Perruccio, K., Mitra, M. E., Quinto, A. M., Venditti, A., Busca, A., Aversa, F., and Pagano, L.

Subjects
acute myeloid leukemia, aspergillosis, chemotherapy, aspergillosis, acute myeloid leukemia, chemotherapy

104. PRELIMINARY REPORT OF FUNGEMIA IN HEMATOLOGICAL MALIGNANCIES FROM SEIFEM-2015 SURVEY

Author

Criscuolo, M., Dragonetti, G., Fianchi, L., Verga, L., Del Principe, M. I., Picardi, M., Veggia, B., Ballanti, S., Marchesi, F., Delia, M., anna candoni, Nadali, G., Castagnola, C., Decembrino, N., Mancini, V., Ferrari, A., Busca, A., Vallero, S., Cattaneo, C., Giordano, A., Martino, B., Vacca, A., Iovino, L., Calore, E., Fanci, R., Lessi, F., Zama, D., Cesaro, S., Aversa, F., and Pagano, L.

105. SEIFEM 2016 STUDY: INCIDENCE AND MORTALITY OF PROBABLE AND PROVEN INVASIVE ASPERGILLOSIS DURING SALVAGE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA

Author

Del Principe, M. I., Dragonetti, G., Verga, L., Candoni, A., Potenza, L., Ballanti, S., Cattaneo, C., Delia, M., Decembrino, N., Valente, A., Castagnola, C., Nadali, G., Fanci, R., Piedimonte, M., Fracchiolla, N. S., Orciuolo, E., Lessi, F., Chierichini, A., Maracci, L., Della Pepa, R., Spolzino, A., Russo, D., Spadea, A., Sarlo, C., Zama, D., Mancini, V., Salutari, P., Garzia, M. G., Caria, R., Cesaro, S., Paolis, M. R., Invernizzi, R., Perruccio, K., Mitra, M. E., Quinto, A. M., Venditti, A., Busca, A., Aversa, F., and Livio PAGANO

107. Serum levels of soluble syndecan-1 in Hodgkin's lymphoma

Author

Vassilakopoulos, T. P., Kyrtsonis, M. -C, Papadogiannis, A., Nadali, G., Angelopoulou, M. K., Tzenou, T., Dimopoulou, M. N., Marina Siakantaris, Kontopidou, F. N., Kalpadakis, C., Kokoris, S. I., Dimitriadou, E. M., Tsaftaridis, P., Pizzolo, G., and Pangalis, G. A.

108. Clinical value of PCR in diagnosis and follow-up of leukaemia and lymphoma: Report of the third workshop of the molecular biology/BMT Study Group

Author

Hughes, T. P., Ambrosetti, A., Barbu, V., Bartram, C., Battista, R., Biondi, A., Chiamenti, A., Cimino, G., Ernst, P., Francesco Frassoni, Gasparini, P., Gentilini, I., Gluckman, E., Grosveld, G., Guerrasio, A., Hegewich, S., Janssen, J. W. G., Keating, A., Lo Coco, F., Martiat, P., Martinelli, G., Mills, K., Morgan, G., Nadali, G., Pelicci, P. G., Perona, G., Pignatti, P. F., Richard, P., Saglio, G., Trabetti, E., Turco, A., Veneri, D., Zaccaria, A., Zander, A., and Goldman, J. M.

109. CLINICAL CHARACTERISTICS AND OUTCOME OF INVASIVE INFECTIONS DUE TO SAPROCHAETE SPECIES IN PATIENTS AFFECTED BY HEMATOLOGICAL MALIGNANCIES. A MULTI-CENTER STUDY ON BEHALF OF SEIFEM/FUNGISCOPE REGISTRY

Author

Del Principe, M. I., Criscuolo, M., Seidel, D., Dargenio, M., Racil, Z., Piedimonte, M., Marchesi, F., Nadali, G., Koehler, P., Fracchiolla, N., Cattaneo, C., Klimko, N., Spolzino, A., Karapinar, D. Yilmaz, Demiraslan, H., Duarte, R., Demeter, J., Stanziani, M., Melillo, L., Basilico, C. M., Cesaro, S., Paterno, G., Oliver Cornely, Califano, C., Delia, M., Busca, A., and Pagano, L.

114. SEIFEM 2015-B: INCIDENCE AND MORTALITY FOR CANDIDEMIA IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

Author

Dragonetti, G., Cattaneo, C., Marchesi, F., Aversa, F., Busca, A., Candoni, A., Castagnola, C., Cesaro, S., Criscuolo, M., Del Principe, M. I., Decembrino, N., Delia, M., Fanci, R., Ferrari, A., Fracchiolla, N. S., Lessi, F., Mancini, V., Martino, B., Melillo, L., Nadali, G., Nosari, A., Perruccio, K., Picardi, M., Prezioso, L., Stanzani, M., Tumbarello, M., Veggia, B., and Livio PAGANO

116. Evaluation on 'real life' prescriptions of antifungal prophylaxis in high risk patients: preliminary results from a prospective survey Evaluation on 'real life' prescriptions of antifungal prophylaxis in high risk patients: preliminary results from a prospective survey

Author

Caira, M., Busca, A., Melillo, L., Candoni, A., Caramatti, C., Specchia, G., Fanci, R., Rossi, G., Cattaneo, C., Vacca, A., Quintavalle, C., Picardi, M., Mitra, M. E., Delia, M., Landini, B., Gasbarrino, C., Invernizzi, R., Salutari, P., Martino, B., Garzia, M. G., Chierichini, A., Venditti, A., Nadali, G., Luppi, M., Leone, G., Nosari, A. M., Aversa, F., Livio PAGANO, and Vianelli, N.

118. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS

Author

Pizzolo, G., Vinante, F., Morosato, L., Nadali, G., Gandini, G., Sinicco, A., Raiteri, R., and Perona, G.

Subjects
AIDS (Disease) -- Development and progression, Lymphocytes -- Physiological aspects, HIV infection -- Physiological aspects, Business, Health care industry
Abstract

AUTHORS: G. Pizzolo, F. Vinante, L. Morosato, G. Nadali, G. Gandini, A. Sinicco, R. Raiteri and G. Perona. Verona University, Verona, Italy; and Torino University, Torino, Italy. According to an [...]

Published
1994

120. Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study

Author

Maria Chiara Tisi, Michelina Dargenio, for Sorveglianza Epidemiologica Infezioni nelle Emopatie, Federica Lessi, Francesca Farina, Livio Pagano, Andrea Visentin, Angelica Spolzino, Luca Laurenti, Davide Facchinelli, M. Picardi, Gianpaolo Nadali, Chiara Cattaneo, Fabio Trastulli, Luisa Verga, Francesco Marchesi, Anna Candoni, Alessandro Busca, Lucia Prezioso, Gessica Marchesini, Rosa Fanci, Marchesini, G., Nadali, G., Facchinelli, D., Candoni, A., Cattaneo, C., Laurenti, L., Fanci, R., Farina, F., Lessi, F., Visentin, A., Marchesi, F., Prezioso, L., Spolzino, A., Tisi, M. C., Trastulli, F., Picardi, M., Verga, L., Dargenio, M., Busca, A., and Pagano, L.

Subjects
Male, medicine.medical_treatment, infections, lymphoproliferative diseases, targeted therapy, Targeted therapy, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Risk Factors, Agammaglobulinaemia Tyrosine Kinase, Medicine, Molecular Targeted Therapy, Enzyme Inhibitors, Aged, 80 and over, Bacterial Infections, Hematology, Middle Aged, Clinical Practice, Italy, Virus Diseases, 030220 oncology & carcinogenesis, Ibrutinib, Female, Idelalisib, Research Paper, medicine.medical_specialty, Lymphoproliferative disorders, Opportunistic Infections, 03 medical and health sciences, Internal medicine, Humans, In patient, Protein Kinase Inhibitors, lymphoproliferative disease, Aged, Quinazolinones, Retrospective Studies, business.industry, Adenine, Retrospective cohort study, medicine.disease, Haematological Malignancy – Clinical, Lymphoproliferative Disorders, infection, Settore MED/15 - MALATTIE DEL SANGUE, chemistry, Purines, Case-Control Studies, Frequent infections, business, Invasive Fungal Infections, 030215 immunology
Abstract

Summary We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P

Published
2020

121. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract

Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2021

122. Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper

Author

Elena De Carolis, Michele Malagola, Livio Pagano, Angelica Spolzino, Monica Piedimonte, Angela Maria Quinto, Roma Rosa Fanci, Eleonora Ceresoli, Francesca Farina, Ilaria Del Principe, Fabio Trastulli, Francesco Marchesi, Marco Picardi, Maria Chiara Tisi, Patrizia Zappasodi, Mario Delia, Anna Candoni, Mario Tumbarello, Lucia Prezioso, Marianna Criscuolo, Gianpaolo Nadali, Chiara Cattaneo, Roberta Della Pepa, Alessandro Busca, Claudia Giordano, Enrico Maria Trecarichi, Massimo Offidani, Nicola Stefano Fracchiolla, Busca, A., Cattaneo, C., De Carolis, E., Nadali, G., Offidani, M., Picardi, M., Candoni, A., Ceresoli, E., Criscuolo, M., Delia, M., Della Pepa, R., Del Principe, I., Fanci, R. R., Farina, F., Fracchiolla, N., Giordano, C., Malagola, M., Marchesi, F., Piedimonte, M., Prezioso, L., Quinto, A. M., Spolzino, A., Tisi, M. C., Trastulli, F., Trecarichi, E. M., Zappasodi, P., Tumbarello, M., and Pagano, L.

Subjects
Anti-Infective Agent, Lymphoproliferative disorders, 0301 basic medicine, medicine.medical_specialty, Antimicrobial prophylaxis, Antimicrobial stewardship, Bacterial, Fungal and viral infections, 03 medical and health sciences, 0302 clinical medicine, Fungal and viral infection, Anti-Infective Agents, Anti-Bacterial Agent, medicine, Humans, Antimicrobial prophylaxi, Antibiotic prophylaxis, Intensive care medicine, Antiinfective agent, business.industry, Anti-Bacterial Agents, Lymphoproliferative Disorders, Hematology, Settore MED/15, Antimicrobial, medicine.disease, Multiple drug resistance, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Lymphoproliferative disorder, Oncology, 030220 oncology & carcinogenesis, Position paper, business, Human
Abstract

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections.

Published
2021

123. Isavuconazole in Hematological Patients: Results of a Real-Life Multicentre Observational Seifem Study

Author

Nicola Stefano Fracchiolla, Monica Piedimonte, Valentina Mancini, Anna Candoni, Mario Tumbarello, Margherita Sciumé, Giuseppe Rossi, Livio Pagano, Stelvio Ballanti, Massimo Offidani, Chiara Pagani, Doriana Gramegna, Rosa Fanci, Francesco Marchesi, Maria Ilaria Del Principe, Francesca Farina, Alessandro Busca, Attilio Olivieri, Marco Picardi, Gianpaolo Nadali, Angelica Spolzino, Chiara Cattaneo, Marianna Criscuolo, Maria Chiara Tisi, Mario Delia, Cattaneo, C., Busca, A., Gramegna, D., Farina, F., Candoni, A., Piedimonte, M., Fracchiolla, N., Pagani, C., Principe, M. I. D., Tisi, M. C., Offidani, M., Fanci, R., Ballanti, S., Spolzino, A., Criscuolo, M., Marchesi, F., Nadali, G., Delia, M., Picardi, M., Sciume, M., Mancini, V., Olivieri, A., Tumbarello, M., Rossi, G., and Pagano, L.

Subjects
Response rate (survey), medicine.medical_specialty, Acute leukemia, Multivariate analysis, lcsh:RC633-647.5, business.industry, isavuconazole, Retrospective cohort study, lcsh:Diseases of the blood and blood-forming organs, isavuconazole, hematological malignancies, Hematology, Settore MED/15, Settore MED/17 - MALATTIE INFETTIVE, Article, Discontinuation, Tolerability, Internal medicine, Medicine, Observational study, hematological malignancies, business, Adverse effect
Abstract

Invasive fungal diseases (IFDs) remain a major clinical issue in patients with hematological malignancies (HMs). To confirm the efficacy and safety of the new azole isavuconazole (ISV) in a clinical care setting, we planned a multicenter retrospective study; we collected data on all possible/probable/proven IFDs in patients with HMs treated with ISV in 17 centers. Between July 2016 and November 2018, 128 patients were enrolled, and 122 were fully evaluable. ISV was employed as the 1st line therapy in 43 (35%) patients and as a subsequent therapy in 79 (65%) patients. The response rate was 82/122 patients (67.2%); it was similar when using ISV as a 1st or 2nd line treatment (60.5% vs 70.9%, respectively; p = 0.24). In multivariate analysis, both female sex (OR: 2.992; CI: 1.22–7.34) and induction phase of treatment (OR: 3.953; CI: 1.085–14.403) were predictive of a favorable response. At a median follow-up of 5 months, 43 (35.2%) patients were dead; the 1-year overall survival (OS) was 49.9%. In multivariate analysis, the response to ISV (OR: 0.103; CI: 0.041–0.262) and IFD refractoriness to previous antifungals (OR: 3.413; CI: 1.318–8.838) were statistically significant for OS. Adverse events (AEs) were reported in 15/122 patients (12.3%); grade 3–4 AEs were reported in 5 (4%) and led to ISV discontinuation. Our study confirms the safety and tolerability of ISV, also in diseases other than acute leukemia. Phase of hematological disease, gender and refractoriness to previous antifungals are the main predictive factors for the aforementioned response and outcome.

Published
2019

124. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria

Author

Lucia Prezioso, Michele Malagola, Maria Alessandra Innocente, Edoardo Simonetti, Livio Pagano, Angelica Spolzino, R Di Blasi, Barbara Veggia, Angela Passi, Luca Facchini, Simone Cesaro, Gianpaolo Nadali, Doriana Gramegna, Marco Picardi, Gloria Turri, Antonio Spadea, Enrico Orciuolo, Stelvio Ballanti, Anna Candoni, Cristina Skert, Davide Lazzarotto, Enrico Maria Trecarichi, Francesco Marchesi, Vincenza Orlando, Rosa Fanci, Mario Delia, Maria Rosaria De Paolis, Domenico Russo, Bruno Martino, Valentina Mancini, N. Di Renzo, Anna Chierichini, Giorgio Rossi, Anna Pegoraro, Mario Tumbarello, Cristina Cattaneo, Francesco Mazziotta, Domenico Rotilio, Franco Aversa, Cattaneo, C., Di Blasi, R., Skert, C., Candoni, A., Martino, B., Di Renzo, N., Delia, M., Ballanti, S., Marchesi, F., Mancini, V., Orciuolo, E., Cesaro, S., Prezioso, L., Fanci, R., Nadali, G., Chierichini, A., Facchini, L., Picardi, M., Malagola, M., Orlando, V., Trecarichi, E. M., Tumbarello, M., Aversa, F., Rossi, G., Pagano, L., Passi, Angela, Gramegna, Doriana, Russo, Domenico, Lazzarotto, Davide, Rotilio, Domenico, De Paolis, Maria Rosaria, Simonetti, Edoardo, Innocente, Maria Alessandra, Spadea, Antonio, Mazziotta, Francesco, Pegoraro, Anna, Spolzino, Angelica, Turri, Gloria, and Veggia, Barbara

Subjects
0301 basic medicine, Male, Colonization, Multidrug-resistant bacteria, Antibiotics, Drug Resistance, Bacteremia, Bloodstream infections, Haematologic patients, Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Infections, Catheter-Related Infections, Child, Child, Preschool, Female, Hematologic Neoplasms, Humans, Infant, Infant, Newborn, Middle Aged, Young Adult, Drug Resistance, Multiple, Bacterial, 0302 clinical medicine, 80 and over, 030212 general & internal medicine, Young adult, Pathogen, Hematology, Incidence (epidemiology), Bacterial, General Medicine, Bloodstream infections, haematological cancer patients, multidrug-resistant bacteria, Haematologic patient, Multiple, Human, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Neutropenia, Bloodstream infection, Bacterial Infection, 03 medical and health sciences, Internal medicine, medicine, Preschool, Hematologic Neoplasm, Catheter-Related Infection, business.industry, biochemical phenomena, metabolism, and nutrition, medicine.disease, Newborn, bacterial infections and mycoses, business
Abstract

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Published
2018

125. Old and new prognostic factors in acute myeloid leukemia with deranged core-binding factor beta

Author

Giambattista Bertani, Alessandro Beghini, Giuseppe Rossi, Carlo Castagnola, Enrico Pogliani, Francesco Rodeghiero, Roberto Cairoli, Giovanni Martinelli, Gianpaolo Nadali, Mauro Turrini, Michele Nichelatti, Enrica Morra, Francesca Lazzaroni, Giovanni Pizzolo, Felicetto Ferrara, Cairoli, R, Beghini, A, Turrini, M, Bertani, G, Nadali, G, Rodeghiero, F, Castagnola, C, Lazzaroni, F, Nichelatti, M, Ferrara, F, Pizzolo, G, Pogliani, E, Rossi, G, Martinelli, G, and Morra, E

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Core Binding Factor beta Subunit, KIT mutation, Gene Expression, Antineoplastic Agents, Favorable prognosis, Gastroenterology, Leukocyte Count, Sex Factors, MED/15 - MALATTIE DEL SANGUE, Internal medicine, Leukocytes, medicine, Humans, Risk factor, Beta (finance), business.industry, Incidence (epidemiology), Age Factors, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Prognosis, Survival Analysis, Leukemia, Myeloid, Acute, Proto-Oncogene Proteins c-kit, Mutation, Immunology, Female, business, Core Binding Factor Leukemia, Follow-Up Studies
Abstract

Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50–70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. Increasing age was the only predictor for survival (P

Published
2013

126. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations

Author

Livio Pagano, Alessandro Busca, Anna Candoni, Chiara Cattaneo, Simone Cesaro, Rosa Fanci, Gianpaolo Nadali, Leonardo Potenza, Domenico Russo, Mario Tumbarello, Annamaria Nosari, Franco Aversa, Federica Lessi, Marianna Criscuolo, Francesca Farina, Maria Chiara Tisi, Gloria Turri, Angelica Barone, Angelica Spolzino, Maria Ilaria Del Principe, Angela Maria Quinto, Roberta Di Blasi, Laura Maracci, Mitja Nabergoj, Benedetta Cambò, Anna Pegoraro, Francesco Marchesi, Silvia Pascale, Angela Passi, Melania Carlisi, Nicola Polverelli, Barbara Beggia, Benedetta Rambaldi, Lucia Prezioso, Marco Sanna, Pagano, L., Busca, A., Candoni, A., Cattaneo, C., Cesaro, S., Fanci, R., Nadali, G., Potenza, L., Russo, D., Tumbarello, M., Nosari, A., Aversa, F., and Carlisi, M.

Subjects
Risk, medicine.medical_specialty, Settore MED/06 - Oncologia Medica, medicine.medical_treatment, Hematopoietic stem cell transplantation, Neutropenia, Settore MED/17 - MALATTIE INFETTIVE, Leukemia, Molds, Risk factors, Yeast, Antineoplastic Combined Chemotherapy Protocols, Disease Susceptibility, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Invasive Fungal Infections, Hematology, Oncology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, Aspergillus, biology, Incidence (epidemiology), hematopoietic stem cell transplantation, medicine.disease, biology.organism_classification, Settore MED/15 - MALATTIE DEL SANGUE, Mold, 030220 oncology & carcinogenesis, Risk stratification, Immunology, Risk factor, 030215 immunology
Abstract

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy.

Published
2016

127. Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey

Author

Livio Pagano, Prassede Salutari, Marco Picardi, Luisa Verga, Stelvio Ballanti, Chiara Cattaneo, Federica Lessi, Anna Candoni, Carlo Castagnola, Mario Tumbarello, Gianpaolo Nadali, Franco Aversa, Annamaria Nosari, Morena Caira, Alessandro Busca, Bruno Martino, Rosa Fanci, Maria E nza Mitra, Pagano, L, Verga, L, Busca, A, Martino, B, Mitra, Me, Fanci, R, Ballanti, S, Picardi, Marco, Castagnola, C, Cattaneo, C, Nadali, G, Nosari, A, Candoni, A, Caira, M, Salutari, P, Lessi, F, Aversa, F, and Tumbarello, M.

Subjects
Male, Myeloid, Posaconazole, empirical therapy, Antifungal Agents, medicine.medical_treatment, Antifungal drug, Targeted therapy, antifungal prophylaxis, Pharmacology (medical), Prospective Studies, Acute myeloid leukaemia, Antifungal prophylaxis, Empirical therapy, Data Collection, Incidence (epidemiology), leukemia, Middle Aged, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, Infectious Diseases, Female, prophylaxis, medicine.drug, Adult, Microbiology (medical), Antifungal, medicine.medical_specialty, Adolescent, medicine.drug_class, Intraoperative floppy iris syndrome, Acute, Young Adult, Internal medicine, medicine, Humans, acute myeloid leukaemia, Aged, Pharmacology, business.industry, fungal infection, Induction chemotherapy, Triazoles, medicine.disease, Surgery, Settore MED/15 - MALATTIE DEL SANGUE, Mycoses, business, Follow-Up Studies
Abstract

Objectives To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis. Methods From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925. Results In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities. Conclusions This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used.

Published
2014

128. Total serum tryptase: a predictive marker for KIT mutation in acute myeloid leukemia

Author

Felicetto Ferrara, Alessandro Beghini, Liliana Inropido, Enrica Morra, Laura Pezzetti, Alessandro Marocchi, Simonetta Granata, Gianpaolo Nadali, Carla B. Ripamonti, Erika Ravelli, Assunta Viola, Chiara Cattaneo, Roberto Cairoli, Anna Maria Nosari, Giovanni Pizzolo, Michele Nichelatti, Giuseppe Rossi, Giambattista Bertani, Giovanni Grillo, Matteo Brioschi, Cairoli, R, Ripamonti, C, Beghini, A, Granata, S, Grillo, G, Brioschi, M, Nadali, G, Viola, A, Cattaneo, C, Inropido, L, Ravelli, E, Bertani, G, Pezzetti, L, Nichelatti, M, Marocchi, A, Rossi, G, Pizzolo, G, Ferrara, F, Nosari, A, and Morra, E

Subjects
Adult, Male, Cancer Research, Myeloid, Adolescent, tryptase, Tryptase, Culture Media, Serum-Free, Young Adult, AML, MED/15 - MALATTIE DEL SANGUE, Precursor cell, Biomarkers, Tumor, medicine, Humans, Leukemia, myeloid, Aged, Serine protease, Predictive marker, biology, Myeloid leukemia, KIT, Hematology, Middle Aged, medicine.disease, Serum tryptase, Molecular biology, In vitro, Leukemia, Myeloid, Acute, Proto-Oncogene Proteins c-kit, medicine.anatomical_structure, Oncology, Mutation, Immunology, biology.protein, Female
Abstract

Human tryptase is a serine protease expressed in mast-cells. We previously observed that AML blast cells, cultured in vitro from a KIT D816Y patient, give rise to adherent cells with mast-cell like phenotype and tryptase was released in the serum-free medium. To correlate total serum tryptase (ts-try) levels with cytogenetic features and KIT mutational status, we analyzed serum samples from AML patients at diagnosis. In 70 out of 155 patients (45%) we detected elevated ts-try (>15 ng/mL), significantly linked to t(8;21) (P < .001) and inv(16) (P = .007). In patients that achieved complete remission the ts-try decreased to normal values. In 75 patients screened for KIT mutation, we found a clear relationship between elevated ts-try and mutated patients with t(8;21) (P < .001). In conclusion, we propose that checking for ts-try at diagnosis of AML may be a simple tool to select patients to be addressed to KIT mutation screening.

Published
2009

129. Prevalence and prognostic impact of KIT mutations in acute myeloid leukaemia with inv(16). A retrospective study

Author

Erika Ravelli, Giovanni Grillo, Enrico Di Bona, Emanuela Ottaviani, Gianbattista Bertani, Roberto Cairoli, Francesco Rodeghiero, Giovanni Martinelli, Antonio Cuneo, Mario Lazzarino, Pietro Pioltelli, Michele Nichelatti, Alessandro Beghini, Enrica Morra, Giuseppe Rossi, Felicetto Ferrara, Gianpaolo Nadali, Patrizia Colapietro, Giovanni Pizzolo, Carla B. Ripamonti, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Bertani, G, Ravelli, E, Cuneo, A, Ottaviani, E, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, and Morra, E

Subjects
Genetics, medicine.medical_specialty, brachial plexus neuritis, chemotherapy regimen, complete remission, follow-up, leukemia, myelocytic, acute, leukocyte count, mutation, polymerase chain reaction, screening, log rank test, business.industry, Incidence (epidemiology), Immunology, Retrospective cohort study, Cell Biology, Hematology, Biochemistry, Chemotherapy regimen, Gastroenterology, law.invention, Log-rank test, Exon, Exact test, law, Internal medicine, Mann–Whitney U test, Medicine, business, Polymerase chain reaction
Abstract

Introduction Several studies have recently pointed out the adverse impact of KIT mutations (mutKIT) on relapse incidence (RI) and overall survival (OS) in AML pts with t(8;21). By contrast, the prognostic significance of mutKIT in pts with inv(16) remains unclear. Purpose of this study is to evaluate the prevalence and the prognostic impact of mutKIT in inv(16)(p13q22). Patients and Methods Fifty adults with inv(16) AML at diagnosis (median age 46.6 yrs, range: 17–88; M/F: 30 /20), were centrally analyzed for mutKIT in exon 2, 8, 10, 11 and 17. Mutations were detected using sequencing and other sensitive assays such as ARMS (amplification refractory mutation system) PCR for D816Y and D816H and enzymatic digestion with HINFI for D816V and with Tsp509I for N822K. Results Data showed a prevalence of KIT mutation of 34% (17/50 pts). Among the mutKIT cases, we detected mutations in exon 17 (n=12), exon 8 (n= 4) and exon 10 (n=1). There was no difference between the mutKIT vs the unmutated (KIT-) patients in the median of WBC count at presentation (WBC 13.9 x109/L, range 4.4 to 277.5 vs 19.4 x109/L, range 2.5 to 130; Mann-Whitney U test: p = 0.649). Of the 42 patients (age < 60 years) who received intensive chemotherapy, 13 resulted mutKIT upon mutational screening. Complete remission (CR) was achieved in 13/13 (100%) mutKIT vs 27/29 (93%) KIT- patients (Fisher’s exact test: p > 0.999). At a median follow-up of 26 months (range: 2–144), 9/13 (69%) mutKIT and 8/27 (29%)KIT- pts relapsed;the Kaplan-Meier plots revealed KIT mutations to be a significant factor adversely affecting RI (log-rank test: p = 0.017) but not OS (61% in mutKIT vs 75% in KIT-;log-rank test: p = 0.331). Conclusion KIT mutations are associated with a greater probability of relapse following CR, without affecting OS, in AML pts with inv(16) aged

Published
2007

130. Serum tryptase levels in AML at diagnosis: A multicenter retrospective study

Author

Felicetto Ferrara, Alessandro Beghini, Giovanni Grillo, Giovanni Pizzolo, Liliana Intropido, Giuseppe Rossi, Carla B. Ripamonti, Laura Pezzetti, Gianbattista Bertani, Assunta Viola, Erika Ravelli, Enrica Morra, Gianpaolo Nadali, Chiara Cattaneo, Silvio Veronese, Annamaria Nosari, Michele Nichelatti, Alessandro Marocchi, Simonetta Granata, Patrizia Colapietro, Roberto Cairoli, Cairoli, R, Ripamonti, C, Granata, S, Beghini, A, Colapietro, P, Grillo, G, Nadali, G, Viola, A, Cattaneo, C, Intropido, L, Ravelli, E, Bertani, G, Pezzetti, L, Nichelatti, M, Veronese, S, Marocchi, A, Rossi, G, Pizzolo, G, Ferrara, F, Nosari, A, and Morra, E

Subjects
biology, medicine.diagnostic_test, business.industry, Immunology, Myeloid leukemia, Tryptase, Retrospective cohort study, Cell Biology, Hematology, Core binding factor, Biochemistry, Molecular biology, Exon, Exact test, serum tryptase, tryptase, ms-like tyrosine kinase 3, karyotype determination procedure, core-binding factor, immunoassay, leukemia, myeloid, screening, serine proteases, serum specimen, Chromosome 16, Immunoassay, biology.protein, medicine, business
Abstract

α and β-tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast-cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In an attempt at correlating the levels of tryptase with cytogenetic features and the KIT and FLT3 mutational status, we analyzed serum samples collected at diagnosis from 150 AML and 57 ALL adult patients. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml, ranging from 1 to 15 ng/ml. We detected elevated tryptase levels (more than 15 ng/ml) in 66 out of 150 AML-patients (44%) and in 1 out of 57 ALL-patients (1.75%; median value 1.2 ng/ml) (p = < 0.0005, Fisher’s exact test ). In AMLs data showed that elevated tryptase values are significantly bound to patients with t(8;21) (n = 26, p =

Published
2006

131. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study

Author

Felicetto Ferrara, Gianpaolo Nadali, Lidia Larizza, Antonio Cuneo, Assunta Viola, Carla B. Ripamonti, Monia Lunghi, Francesca Elice, Laura Pezzetti, Mario Lazzarino, Giovanni Pizzolo, Roberto Cairoli, Michele Nichelatti, Patrizia Colapietro, Alessandro Beghini, Giovanni Grillo, Francesco Rodeghiero, Enrica Morra, Cairoli, R, Beghini, A, Grillo, G, Nadali, G, Elice, F, Ripamonti, C, Colapietro, P, Nichelatti, M, Pezzetti, L, Lunghi, M, Cuneo, A, Viola, A, Ferrara, F, Lazzarino, M, Rodeghiero, F, Pizzolo, G, Larizza, L, and Morra, E

Subjects
Oncology, leukocyte count, Myeloid, Chromosomes, Human, Pair 21, Core binding factor, chemotherapy, Biochemistry, Translocation, Genetic, MED/15 - MALATTIE DEL SANGUE, gene mutation, FRENCH AML INTERGROUP, Aged, 80 and over, Incidence (epidemiology), adult, article, leukemia, Myeloid leukemia, Hematology, Middle Aged, Prognosis, acute granulocytic leukemia, HIGH-DOSE CYTARABINE, Leukemia, Myeloid, Acute, Proto-Oncogene Proteins c-kit, Leukemia, aged, medicine.anatomical_structure, female, Italy, priority journal, T(8, 21)(q22, q22), prognosi, Chromosomes, Human, Pair 8, medicine.medical_specialty, Immunology, ACUTE MYELOID-LEUKEMIA, survival, male, Internal medicine, White blood cell, RAS GENE-MUTATIONS, medicine, Humans, follow up, controlled study, human, Core binding factor acute myeloid leukemia, Retrospective Studies, REMISSION DURATION, business.industry, Core Binding Factors, 8-21 TRANSLOCATION, treatment response, Cell Biology, BLOOD-CELL INDEX, medicine.disease, ACUTE MYELOID-LEUKEMIA, FRENCH AML INTERGROUP, HIGH-DOSE CYTARABINE, RAS GENE-MUTATIONS, BLOOD-CELL INDEX, CYTOLOGIC CHARACTERIZATION, EXTRAMEDULLARY LEUKEMIA, REMISSION DURATION, 8-21 TRANSLOCATION, GROUP-B, major clinical study, GROUP-B, adolescent, Mutation, treatment outcome, EXTRAMEDULLARY LEUKEMIA, codon, business, CYTOLOGIC CHARACTERIZATION
Abstract

Distinct forms of tyrosine kinase domain (TKD), juxtamembrane domain, exon 8, and internal tandem duplication (ITD) mutations of c-KIT, were observed in about 46% of core binding factor leukemia (CBFL) patients. To evaluate their prognostic significance, 67 adult patients with CBFL were analyzed to ascertain the c-KIT mutation status. In acute myeloid leukemia (AML) with t(8;21), the presence of c-KIT TKD mutation at codon 816 (TKD(816)) was associated with a high white blood cell count at diagnosis (median, 29.60 x 10(9)/L) and a higher incidence (33%) of extramedullary leukemia (EML) during the course of the disease. Data also showed that the TKD(816) mutated patients (n = 12) had a significantly higher incidence of relapse and a lower overall survival (OS) at 24 months, compared with the 17 c-KIT unmutated (c-KIT(-)) patients (90% vs 35.3%, P = .002; 25% vs 76.5%, P = .006, respectively). No difference in relapse incidence (P = .126) and OS (P = .474) was observed between the c-KIT mutated other than TKD(816) (n = 7) and the c-KIT(-) patients. These findings indicate that c-KIT TKD(816) mutation has a negative impact on the outcome of AML with t(8;21).

Published
2006

132. Prognostic Impact of C-Kit Mutations in Core Binding Factor-Leukemia

Author

Roberto Cairoli, Francesca Elice, Lidia Larizza, Alessandro Beghini, Maria Lunghi, Giovanni Pizzolo, Enrica Morra, Carla B. Ripamonti, Giovanni Grillo, Gianpaolo Nadali, Mario Lazzarino, Michele Nichelatti, Francesco Rodeghiero, Antonio Cuneo, Cairoli, R, Beghini, A, Nadali, G, Elice, F, Lunghi, M, Cuneo, A, Grillo, G, Nichelatti, M, Ripamonti, C, Lazzarino, M, Rodeghiero, F, Pizzolo, G, Larizza, L, and Morra, E

Subjects
medicine.medical_specialty, Pathology, Incidence (epidemiology), Immunology, Cell Biology, Hematology, Biology, Gene mutation, Core binding factor, medicine.disease, Biochemistry, Gastroenterology, Leukemia, Exon, medicine.anatomical_structure, Internal medicine, c-kit mutation, leukemia, proto-oncogene protein c-kit, core-binding factor, dna analysis, follow-up, leukocyte count, blast cells, bone marrow, correlation studies, medicine, Mutational status, Bone marrow, Statistical correlation
Abstract

C-KIT gene mutations are not a rare event in Core Binding Factor Leukemia (CBFL). To investigate their prognostic impact in this setting , we attempted at correlating the KIT mutational status with the WBC count, the level of the WBC-index, the presence of extramedullary disease (EMD) and the outcome, in t(8;21)(n=30) and inv(16) (n=20) AML patients. On the basis of genomic DNA analysis of c-KIT gene exons 2, 8, 10, 11, 17 for mutation detection, we categorized 21 patients (42%) in the “KIT mutated group” (KIT+) and 29 patients (58%) in the “KIT unmutated group” (KIT−). The median age at diagnosis was 46.4 and 45.6 years for the KIT(+) and KIT(−) groups, respectively (P=0.872). Among the KIT(+) patients, we found mutations in exon 8 (n = 4), exon 10 (n =1), exon 11 (n = 1) and exon 17 (n = 15). We recorded mean WBC counts of 28.6 x 109/L vs 34.5 x 109/L (P=0.051), and a mean WBC-index, expressed as WBC x (% Bone Marrow blasts/100), of 37.2 vs 15.5 (P=0.0395), for KIT(+) and KIT(−), respectively. Seven out of 50 patients experienced an EMD: in 6 cases (28.57%) this event occurred in the KIT(+) group. 40 patients (age < 60 years) were evaluable for clinical response; 18 out of them were KIT mutated. At a median follow-up of 24 months (range 10–107), we recorded for KIT(+) and KIT(−), respectively: CR incidence of 88.8 % (16/18) vs 100% (22/22) (P=0.38); Relapse Incidence 81.3% (13/16) vs 31.81% (7/22), P=0.0072; OS 27.7% (5/18) vs 77.3% (17/22), P=0.0049; DFS 16.7% (3/18) vs 77.3% (17/22), P=0.0005. Using a log-it linear model for univariate and multivariate regression analysis, we found a significant contribution to death (P=0.048) and relapse (P= 0.045) exerted by mutation in the whole group of patients; this effect was more evident when the analysis was restricted to patients

Published
2004

133. Long-term remissions with Gilteritinib in early relapse after allogeneic stem cell transplantation of FLT3/NPM1 mutated acute myeloid leukemia.

Author

Tamellini E, Sorio M, Andreini A, Tecchio C, Nadali G, Bernardelli A, Ferrarini I, Crosera L, Vatteroni A, Simio C, Benedetti F, Krampera M, and Tanasi I

Abstract

Early post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) relapse in patients with acute myeloid leukemia (AML) has an almost invariably dismal prognosis. Recent studies have demonstrated that FLT3 inhibition enhances the graft-versus-leukemia effect in vitro and in vivo. Thus, FLT-3 inhibitors may be viable treatment options in this setting. Here, we report three patients with FLT3 and NPM1 mutated AML who relapsed early after allo-HSCT and were treated with gilteritinib (associated with donor lymphocyte Infusion in two patients) to achieve long-term remission without a second transplantation., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

Published
2024
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134. Posaconazole and midostaurin in patients with FLT3-mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study.

Author

Menna P, Marchesi F, Cattaneo C, Candoni A, Delia M, Nadali G, Vatteroni A, Pasciolla C, Perrone S, Verga L, Armiento D, Del Principe MI, Fracchiolla NS, Salvatorelli E, Lupisella S, Terrenato I, Busca A, Minotti G, and Pagano L

Subjects
Humans, Antifungal Agents adverse effects, Micafungin therapeutic use, Prospective Studies, fms-Like Tyrosine Kinase 3 genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute diagnosis, Neutropenia
Abstract

Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Chemotherapy-induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin-related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real-life study to evaluate (i) how often concerns around PCZ-midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ-midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p < 0.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ-midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (C min ) was greater than three times higher than reported; moreover, midostaurin C min , maximum plasma concentration, and area under the curve were more than or equal to four times higher with PCZ than micafungin. Hematologic outcomes (complete remission and duration of severe neutropenia) and safety outcomes (midostaurin-related any grade or grade ≥3 AEs) were nonetheless similar for patients exposed to PCZ or micafungin, as was the number of breakthrough IFIs. In waiting for randomized phase III trials of new prophylaxis regimens, these findings show that PCZ should remain the antifungal of choice for the midostaurin-treated patient., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Published
2023
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135. Prospective multicenter study on infectious complications and clinical outcome of 230 unfit acute myeloid leukemia patients receiving first-line therapy with hypomethylating agents alone or in combination with Venetoclax.

Author

Candoni A, Lazzarotto D, Papayannidis C, Piccini M, Nadali G, Dargenio M, Riva M, Fracchiolla N, Mellillo L, Dragonetti G, Del Principe MI, Cattaneo C, Stulle M, Pasciolla C, De Marchi R, Delia M, Tisi MC, Bonuomo V, Sciumè M, Spadea A, Sartor C, Griguolo D, Buzzatti E, Basilico CM, Sarlo C, Piccioni AL, Cerqui E, Lessi F, Olivieri A, Fanin R, Luppi M, and Pagano L

Subjects
Humans, Prospective Studies, Azacitidine adverse effects, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute etiology
Published
2023
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136. Clinical features and prognostic factors of Magnusiomyces (Saprochaete) infections in haematology. A multicentre study of SEIFEM/Fungiscope.

Author

Del Principe MI, Seidel D, Criscuolo M, Dargenio M, Rácil Z, Piedimonte M, Marchesi F, Nadali G, Koehler P, Fracchiolla N, Cattaneo C, Klimko N, Spolzino A, Yilmaz Karapinar D, Demiraslan H, Duarte RF, Demeter J, Stanzani M, Melillo LMA, Basilico CM, Cesaro S, Paterno G, Califano C, Delia M, Buzzatti E, Busca A, Alakel N, Arsenijevi'c VA, Camus V, Falces-Romero I, Itzhak L, Kouba M, Martino R, Sedlacek P, Weinbergerová B, Cornely OA, and Pagano L

Subjects
Humans, Female, Child, Preschool, Child, Adolescent, Young Adult, Adult, Middle Aged, Aged, Male, Antifungal Agents therapeutic use, Prognosis, Echinocandins therapeutic use, Candidemia drug therapy, Hematology
Abstract

Background: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies., Methods: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia., Results: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015)., Conclusions: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome., (© 2022 Wiley-VCH GmbH.)

Published
2023
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137. High Incidence of Invasive Fungal Diseases in Patients with FLT3-Mutated AML Treated with Midostaurin: Results of a Multicenter Observational SEIFEM Study.

Author

Cattaneo C, Marchesi F, Terrenato I, Bonuomo V, Fracchiolla NS, Delia M, Criscuolo M, Candoni A, Prezioso L, Facchinelli D, Pasciolla C, Del Principe MI, Dargenio M, Buquicchio C, Mitra ME, Farina F, Borlenghi E, Nadali G, Gagliardi VP, Fianchi L, Sciumè M, Menna P, Busca A, Rossi G, and Pagano L

Abstract

The potential drug-drug interactions of midostaurin may impact the choice of antifungal (AF) prophylaxis in FLT3-positive acute myeloid leukemia (AML) patients. To evaluate the incidence of invasive fungal diseases (IFD) during the treatment of FLT3-mutated AML patients and to correlate it to the different AF prophylaxis strategies, we planned a multicenter observational study involving 15 SEIFEM centers. One hundred fourteen patients treated with chemotherapy + midostaurin as induction/reinduction, consolidation or both were enrolled. During induction, the incidence of probable/proven and possible IFD was 10.5% and 9.7%, respectively; no statistically significant difference was observed according to the different AF strategy adopted. The median duration of neutropenia was similar in patients with or without IFD. Proven/probable and possible IFD incidence was 2.4% and 1.8%, respectively, during consolidation. Age was the only risk factor for IFD (OR, 95% CI, 1.10 [1.03-1.19]) and complete remission achievement after first induction the only one for survival (OR, 95% CI, 5.12 [1.93-13.60]). The rate of midostaurin discontinuation was similar across different AF strategies. The IFD attributable mortality during induction was 8.3%. In conclusion, the 20.2% overall incidence of IFD occurring in FLT3-mutated AML during induction with chemotherapy + midostaurin, regardless of AF strategy type, was noteworthy, and merits further study, particularly in elderly patients.

Published
2022
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138. A High-Risk Profile for Invasive Fungal Infections Is Associated with Altered Nasal Microbiota and Niche Determinants.

Author

Costantini C, Nunzi E, Spolzino A, Merli F, Facchini L, Spadea A, Melillo L, Codeluppi K, Marchesi F, Marchesini G, Valente D, Dragonetti G, Nadali G, Englmaier L, Coufalikova K, Spáčil Z, Bellet MM, Pariano M, Renga G, Stincardini C, D'Onofrio F, Bozza S, Pagano L, Aversa F, and Romani L

Subjects
Bacteria, Humans, Nose microbiology, Prospective Studies, Invasive Fungal Infections, Microbiota
Abstract

It is becoming increasingly clear that the communities of microorganisms that populate the surfaces exposed to the external environment, termed microbiota, are key players in the regulation of pathogen-host cross talk affecting the onset as well as the outcome of infectious diseases. We have performed a multicenter, prospective, observational study in which nasal and oropharyngeal swabs were collected for microbiota predicting the risk of invasive fungal infections (IFIs) in patients with hematological malignancies. Here, we demonstrate that the nasal and oropharyngeal microbiota are different, although similar characteristics differentiate high-risk from low-risk samples at both sites. Indeed, similar to previously published results on the oropharyngeal microbiota, high-risk samples in the nose were characterized by low diversity, a loss of beneficial bacteria, and an expansion of potentially pathogenic taxa, in the presence of reduced levels of tryptophan (Trp). At variance with oropharyngeal samples, however, low Trp levels were associated with defective host-derived kynurenine production, suggesting reduced tolerance mechanisms at the nasal mucosal surface. This was accompanied by reduced levels of the chemokine interleukin-8 (IL-8), likely associated with a reduced recruitment of neutrophils and impaired fungal clearance. Thus, the nasal and pharyngeal microbiomes of hematological patients provide complementary information that could improve predictive tools for the risk of IFI in hematological patients.

Published
2022
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139. Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: Results from SEIFEM 2016-B survey.

Author

Del Principe MI, Dragonetti G, Conti A, Verga L, Ballanti S, Fanci R, Candoni A, Marchesi F, Cattaneo C, Lessi F, Fracchiolla N, Spolzino A, Prezioso L, Delia M, Potenza L, Decembrino N, Castagnola C, Nadali G, Picardi M, Zama D, Orciulo E, Veggia B, Garzia M, Dargenio M, Melillo L, Manetta S, Russo D, Mancini V, Piedimonte M, Tisi MC, Toschi N, Busca A, and Pagano L

Subjects
Humans, Retrospective Studies, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis epidemiology, Invasive Fungal Infections drug therapy, Invasive Fungal Infections epidemiology, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute microbiology
Abstract

Background: In patients with relapsed/refractory acute myeloid leukaemia (R/R AML) who received salvage chemotherapy, limited and not updated studies explored the incidence of invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP). The aims of this multicentre retrospective 'SEIFEM 2016-B' study were as follows: (1) to evaluate the current rate and the outcome of proven/probable IA and (2) to assess the efficacy of AP, in a large 'real life' series of patient with R/R AML submitted to salvage chemotherapy., Results: Of 2250 R/R AML patients, a total of 74 cases of IA (5.1%) were recorded as follows: 10 (0.7%) proven and 64 (4.3%) probable. Information about AP were available in 73/74 (99%) patients. Fifty-eight (79%) breakthrough infections occurred, mainly during AP with posaconazole [25 (43%)]. The patients who received AP during salvage chemotherapy showed a benefit from antifungal therapy (AT) than patients who did not received AP [43 (86%) vs 7 (14%); p < .033]. In a multivariate analysis, AP and absence of severe mucositis had a significant favourable effect on overall response rate., Conclusion: Our data demonstrated that the incidence of IA during the salvage chemotherapy is similar to the past. Nevertheless, the attributable mortality rate (AMR) appears to be lower than that previously reported in R/R AML. Further prospective studies should be performed to confirm our preliminary observation and understand and the why a decreased AMR is reported in this setting of high-risk patients., (© 2021 Wiley-VCH GmbH.)

Published
2022
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140. A 58-year-old man with B-cell chronic lymphocytic leukemia and multiple strokes.

Author

Magrinelli F, Mariotto S, Nadali G, Todeschini G, Lanzafame M, Cavallaro T, Monaco S, and Ferrari S

Subjects
Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnostic imaging, Magnetic Resonance Imaging, Male, Middle Aged, Stroke diagnostic imaging, Tomography, X-Ray Computed, Brain diagnostic imaging, Leukemia, Lymphocytic, Chronic, B-Cell complications, Stroke complications
Abstract

A 58-year-old male with B-cell chronic lymphocytic leukemia presented with fever, chest pain, and acute-onset neurological deficits suggestive of multiple strokes (A). Brain autopsy revealed softening areas in the brain parenchyma (B, C) corresponding to extensive necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F) necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F)., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Published
2021
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141. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

Author

Pagano L, Salmanton-García J, Marchesi F, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Verga L, Víšek B, Ilhan O, Nadali G, Weinbergerová B, Córdoba-Mascuñano R, Marchetti M, Collins GP, Farina F, Cattaneo C, Cabirta A, Gomes-Silva M, Itri F, van Doesum J, Ledoux MP, Čerňan M, Jakšić O, Duarte RF, Magliano G, Omrani AS, Fracchiolla NS, Kulasekararaj A, Valković T, Poulsen CB, Machado M, Glenthøj A, Stoma I, Ráčil Z, Piukovics K, Navrátil M, Emarah Z, Sili U, Maertens J, Blennow O, Bergantim R, García-Vidal C, Prezioso L, Guidetti A, Del Principe MI, Popova M, de Jonge N, Ormazabal-Vélez I, Fernández N, Falces-Romero I, Cuccaro A, Meers S, Buquicchio C, Antić D, Al-Khabori M, García-Sanz R, Biernat MM, Tisi MC, Sal E, Rahimli L, Čolović N, Schönlein M, Calbacho M, Tascini C, Miranda-Castillo C, Khanna N, Méndez GA, Petzer V, Novák J, Besson C, Duléry R, Lamure S, Nucci M, Zambrotta G, Žák P, Seval GC, Bonuomo V, Mayer J, López-García A, Sacchi MV, Booth S, Ciceri F, Oberti M, Salvini M, Izuzquiza M, Nunes-Rodrigues R, Ammatuna E, Obr A, Herbrecht R, Núñez-Martín-Buitrago L, Mancini V, Shwaylia H, Sciumè M, Essame J, Nygaard M, Batinić J, Gonzaga Y, Regalado-Artamendi I, Karlsson LK, Shapetska M, Hanakova M, El-Ashwah S, Borbényi Z, Çolak GM, Nordlander A, Dragonetti G, Maraglino AME, Rinaldi A, De Ramón-Sánchez C, and Cornely OA

Subjects
Adult, Aged, Aged, 80 and over, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 therapy, Europe epidemiology, Female, Hematologic Neoplasms epidemiology, Hematologic Neoplasms therapy, Hospitalization, Humans, Intensive Care Units, Male, Middle Aged, Registries, Risk Factors, SARS-CoV-2 isolation & purification, Young Adult, COVID-19 complications, Hematologic Neoplasms complications
Abstract

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality., Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020., Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases., Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases., (© 2021. The Author(s).)

Published
2021
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142. Pharyngeal Microbial Signatures Are Predictive of the Risk of Fungal Pneumonia in Hematologic Patients.

Author

Costantini C, Nunzi E, Spolzino A, Palmieri M, Renga G, Zelante T, Englmaier L, Coufalikova K, Spáčil Z, Borghi M, Bellet MM, Acerbi E, Puccetti M, Giovagnoli S, Spaccapelo R, Talesa VN, Lomurno G, Merli F, Facchini L, Spadea A, Melillo L, Codeluppi K, Marchesi F, Marchesini G, Valente D, Dragonetti G, Nadali G, Pagano L, Aversa F, and Romani L

Subjects
Animals, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Disease Models, Animal, Hematologic Neoplasms complications, Humans, Metagenome, Metagenomics methods, Mice, Mycoses diagnosis, Mycoses drug therapy, Pneumonia diagnosis, Pneumonia drug therapy, Risk Assessment, Risk Factors, Hematologic Diseases complications, Microbiota, Mycoses etiology, Pharynx microbiology, Pneumonia etiology
Abstract

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes , along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.

Published
2021
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143. Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study.

Author

Marchesini G, Nadali G, Facchinelli D, Candoni A, Cattaneo C, Laurenti L, Fanci R, Farina F, Lessi F, Visentin A, Marchesi F, Prezioso L, Spolzino A, Tisi MC, Trastulli F, Picardi M, Verga L, Dargenio M, Busca A, and Pagano L

Subjects
Adenine administration & dosage, Adenine adverse effects, Adenine therapeutic use, Agammaglobulinaemia Tyrosine Kinase antagonists & inhibitors, Aged, Aged, 80 and over, Bacterial Infections chemically induced, Bacterial Infections epidemiology, Case-Control Studies, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors adverse effects, Enzyme Inhibitors therapeutic use, Female, Humans, Invasive Fungal Infections chemically induced, Invasive Fungal Infections epidemiology, Italy epidemiology, Lymphoproliferative Disorders complications, Lymphoproliferative Disorders microbiology, Lymphoproliferative Disorders mortality, Male, Middle Aged, Molecular Targeted Therapy methods, Molecular Targeted Therapy statistics & numerical data, Piperidines administration & dosage, Piperidines therapeutic use, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Purines administration & dosage, Purines therapeutic use, Quinazolinones administration & dosage, Quinazolinones therapeutic use, Retrospective Studies, Risk Factors, Virus Diseases chemically induced, Virus Diseases epidemiology, Adenine analogs & derivatives, Lymphoproliferative Disorders drug therapy, Molecular Targeted Therapy adverse effects, Opportunistic Infections chemically induced, Piperidines adverse effects, Purines adverse effects, Quinazolinones adverse effects
Abstract

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2021
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144. Do high MICs predict the outcome in invasive fusariosis?

Author

Nucci M, Jenks J, Thompson GR, Hoenigl M, Dos Santos MC, Forghieri F, Rico JC, Bonuomo V, López-Soria L, Lass-Flörl C, Candoni A, Garcia-Vidal C, Cattaneo C, Buil J, Rabagliati R, Roiz MP, Gudiol C, Fracchiolla N, Campos-Herrero MI, Delia M, Farina F, Fortun J, Nadali G, Sastre E, Colombo AL, Pérez Nadales E, Alastruey-Izquierdo A, and Pagano L

Subjects
Antifungal Agents therapeutic use, Humans, Itraconazole, Microbial Sensitivity Tests, Retrospective Studies, Voriconazole pharmacology, Fusariosis drug therapy
Abstract

Background: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established., Objective: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF., Methods: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF., Results: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality., Conclusions: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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145. Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper.

Author

Busca A, Cattaneo C, De Carolis E, Nadali G, Offidani M, Picardi M, Candoni A, Ceresoli E, Criscuolo M, Delia M, Della Pepa R, Del Principe I, Fanci RR, Farina F, Fracchiolla N, Giordano C, Malagola M, Marchesi F, Piedimonte M, Prezioso L, Quinto AM, Spolzino A, Tisi MC, Trastulli F, Trecarichi EM, Zappasodi P, Tumbarello M, and Pagano L

Subjects
Anti-Bacterial Agents therapeutic use, Humans, Anti-Infective Agents therapeutic use, Lymphoproliferative Disorders drug therapy, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders etiology
Abstract

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections., (Copyright © 2020. Published by Elsevier B.V.)

Published
2021
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146. Infections in patients with lymphoproliferative diseases treated with brentuximab vedotin: SEIFEM multicentric retrospective study.

Author

Marchesini G, Nadali G, Facchinelli D, Candoni A, Cattaneo C, Cuccaro A, Fanci R, Farina F, Lessi F, Visentin A, Marchesi F, Prezioso L, Spolzino A, Tisi MC, Trastulli F, Verga L, Dargenio M, Busca A, and Pagano L

Subjects
Brentuximab Vedotin, Humans, Retrospective Studies, Hodgkin Disease complications, Hodgkin Disease drug therapy, Immunoconjugates adverse effects, Lymphoproliferative Disorders drug therapy
Published
2020
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147. Impact of invasive aspergillosis occurring during first induction therapy on outcome of acute myeloid leukaemia (SEIFEM-12B study).

Author

Candoni A, Farina F, Perruccio K, Di Blasi R, Criscuolo M, Cattaneo C, Delia M, Zannier ME, Dragonetti G, Fanci R, Martino B, Del Principe MI, Fianchi L, Vianelli N, Chierichini A, Garzia M, Petruzzellis G, Nadali G, Verga L, Busca A, and Pagano L

Subjects
Aged, Antifungal Agents pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Aspergillosis drug therapy, Aspergillosis etiology, Case-Control Studies, Female, Humans, Induction Chemotherapy, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Mortality, Remission Induction, Treatment Outcome, Invasive Fungal Infections drug therapy, Invasive Fungal Infections etiology, Leukemia, Myeloid, Acute complications
Abstract

Background: Acute myeloid leukaemia (AML) patients are at high risk of invasive aspergillosis (IA) after first induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during induction phase, on overall AML outcome., Patients and Results: The end point of this multicentre, case-control, study was to evaluate whether IA, occurring after first induction CHT, can affect treatment schedule and patient's outcome. We identified 40 AML patients (cases) who developed IA during first induction phase, 31 probable (77.5%) and 9 proven (22.5%). These cases were matched with a control group (80 AML) without IA, balanced according to age, type of CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups. In the 40 cases with IA, the overall response rate to antifungal treatment was favourable (80%) but it was significantly affected by the achievement of leukaemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction treatment (P < .0001). The adherence to the schedule and full doses of CHT were reported in 35% of cases (14/40) and in 76% of controls (61/80) (P = .0001; OR 6.7; 95% CI 2.7-16.6). After first induction CHT, a significant higher number of cases (15/40; 37.5%) compared to controls (9/80; 11%) could not receive additional cycles of CHT (P = .0011, OR 4.8; 95% CI 1.9-12.3). The IA-related mortality was 22.5%. The median OS of cases was significantly worse than OS of controls with a difference of 12.3 months (12.1 vs 24.4 months, P = .04). However, the occurrence of IA during first induction phase did not have a significant impact on the OS of cases who achieved a CR of AML with induction CHT which are able to proceed, despite the IA, with their therapeutic program, achieving the same OS as the control group with AML in CR (P = ns)., Conclusions: These data show that IA during first induction CHT can delay the subsequent therapeutic program and has a significant impact on OS, specifically in AML patients who did not achieved a CR of AML with the first course of CHT., (© 2020 Blackwell Verlag GmbH.)

Published
2020
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148. Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis.

Author

Posteraro B, De Carolis E, Criscuolo M, Ballanti S, De Angelis G, Del Principe MI, Delia M, Fracchiolla N, Marchesi F, Nadali G, Picardi M, Piccioni AL, Verga L, Candoni A, Busca A, Sanguinetti M, and Pagano L

Subjects
Adult, Aged, Candida classification, Candida isolation & purification, Chemoprevention, Drug Resistance, Fungal, Female, Humans, Italy epidemiology, Male, Microbial Sensitivity Tests, Middle Aged, Retrospective Studies, Antifungal Agents therapeutic use, Candida drug effects, Candidemia epidemiology, Candidemia prevention & control, Hematologic Neoplasms complications, Hematologic Neoplasms microbiology
Abstract

Background: Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia., Objective: To analyse the Candida species' distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres., Methodology: This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data., Results: Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for C parapsilosis (35, 26.3%), C glabrata (16, 12.0%), C krusei (14, 10.5%), C tropicalis (13, 9.8%) and uncommon species (11, 8.3%). C albicans caused the remaining 44 (33.1%) episodes. Excluding 2 C albicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 C krusei, 6 C glabrata, 2 C parapsilosis and 1 C tropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a C krusei infection (10/56, P = .02) or a fluconazole-resistant isolate's infection (14/50, P = .04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia., Conclusions: Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates' infections in haematological malignancy patients., (© 2020 Blackwell Verlag GmbH.)

Published
2020
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149. Central nervous system fungal infections in allogeneic stem cell transplantation. Outcome of 24 recent cases and literature review.

Author

Candoni A, Facchin G, Busca A, Lazzarotto D, Cattaneo C, Nadali G, Klimko N, Del Principe MI, Castagnola C, Verga L, Zannier ME, Calore E, Capelli D, Perruccio K, Melillo L, Fanin R, and Pagano L

Subjects
Adolescent, Adult, Allografts, Child, Disease-Free Survival, Female, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Male, Middle Aged, Survival Rate, Amphotericin B administration & dosage, Central Nervous System Fungal Infections drug therapy, Central Nervous System Fungal Infections etiology, Central Nervous System Fungal Infections mortality, Hematopoietic Stem Cell Transplantation, Voriconazole administration & dosage
Published
2020
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150. Outbreak of Saprochaete clavata Sepsis in Hematology Patients: Combined Use of MALDI-TOF and Sequencing Strategy to Identify and Correlate the Episodes.

Author

Lo Cascio G, Vincenzi M, Soldani F, De Carolis E, Maccacaro L, Sorrentino A, Nadali G, Cesaro S, Sommavilla M, Niero V, Naso L, Grancini A, Azzini AM, Sanguinetti M, Tacconelli E, and Cornaglia G

Abstract

Introduction: New fungal species are increasingly reported in immunocompromised patients. Saprochaete clavata ( S. clavata ), an ascomycetous fungus formerly called Geotrichum clavatum , is intrinsically resistant to echinocandins and is often misidentified., Objective: We describe a cluster of seven S. clavata infections in hospitalized hematology patients who developed this rare fungemia within a span of 11 months. Three of the seven patients died. Identification of the isolates was determined only with the Saramis database of VitekMS system and sequencing of the internal transcribed spacer (ITS) region. Clonal relatedness of the isolates was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) analysis; clonal correlation between the strains was investigated by means of phylogenetic analysis, based on single-nucleotide variants (SNPs). Clinical presentation, 1-3 β-D-glucan (BG) and galactomannan (GM) antigen results and analysis of possible sources of contamination are also described with a prospective case-control study of the outbreak., Results: MALDI-TOF MS-Vitek (bioMerieux, Marcy l'Etoile, France) failed to identify the six isolates, while SARAMIS (bioMerieux, Marcy l'Etoile, France) identified the isolates as S. clavata . Initially, Vitek 2 identified the strains as Geotrichum capitatum in two of the seven cases. Molecular identification gave 99% homology with S. clavata . BG was positive in three out of six patients (range 159 to >523 pg/ml), GM results were always negative. All the isolates were resistant to echinocandins (anidulafungin, micafungin, and caspofungin) and Fluconazole, but susceptible to Flucytosine and Voriconazole. One isolate showed acquired resistance to Flucytosine and Amphotericin B during treatment. Both the correlation-based dendrograms obtained by MALDI-TOF MS (Bruker Daltonics) and MS-Vitek not only clustered six of the seven bloodstream infection (BSI) isolates in the same group, but also showed their strong relatedness. Phylogenetic analysis using SNPrelate showed that the seven samples recorded during the investigation period clustered together. We observed a split between one case and the remainder with a node supported by a z -score of 2.3 ( p -value = 0.021) and 16 mutations unique to each branch., Conclusion: The use of proteomics for identification and evaluation of strain clonality in outbreaks of rare pathogens is a promising alternative to laborious and time-consuming molecular methods, even if molecular whole-genome sequencing (WGS) typing will still remain the reference method for rare emergent pathogens., (Copyright © 2020 Lo Cascio, Vincenzi, Soldani, De Carolis, Maccacaro, Sorrentino, Nadali, Cesaro, Sommavilla, Niero, Naso, Grancini, Azzini, Sanguinetti, Tacconelli and Cornaglia.)

Published
2020
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