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1. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Author

Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., Cingolani A. (ORCID:0000-0002-3793-2755), Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., and Cingolani A. (ORCID:0000-0002-3793-2755)

Abstract

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe

Published
2024

2. Optimal Duration of CPX-351 Treatment and Best Timing for Consolidation with Allogeneic Stem Cell Transplantation: Evidence from a Large Real-World Italian Study

Author

Guolo, F, Fianchi, L, Martelli, M, Chiusolo, P, Lussana, F, Grimaldi, F, Pilo, F, Rondoni, M, Fili, C, Capelli, D, Breccia, M, Mastaglio, S, Bocchia, M, Fumagalli, M, Galimberti, S, Mancini, V, Piccioni, A, Maurillo, L, Palmieri, R, Corbingi, A, Vetro, C, Sperotto, A, Gigli, F, Zappasodi, P, Mulé, A, Borlenghi, E, Dargenio, M, Lessi, F, Cerrano, M, Isidori, A, Brunetti, L, Papayannidis, C, Lunghi, M, Alati, C, Gatani, S, Mannelli, F, Fracchiolla, N, Gottardi, M, Cairoli, R, Ferrara, F, Lemoli, R, Venditti, A, Pagano, L, Todisco, E, Guolo, Fabio, Fianchi, Luana, Martelli, Maria Paola, Chiusolo, Patrizia, Lussana, Federico, Grimaldi, Francesco, Pilo, Federica, Rondoni, Michela, Fili, Carla, Capelli, Debora, Breccia, Massimo, Mastaglio, Sara, Bocchia, Monica, Fumagalli, Monica, Galimberti, Sara, Mancini, Valentina, Piccioni, Anna Lina, Maurillo, Luca, Palmieri, Raffaele, Corbingi, Andrea, Vetro, Calogero, Sperotto, Alessandra, Gigli, Federica, Zappasodi, Patrizia, Mulé, Antonio, Borlenghi, Erika, Dargenio, Michelina, Lessi, Federica, Cerrano, Marco, Isidori, Alessandro, Brunetti, Lorenzo, Papayannidis, Cristina, Lunghi, Monia, Alati, Caterina, Gatani, Samuele, Mannelli, Francesco, Fracchiolla, Nicola, Gottardi, Michele, Cairoli, Roberto, Ferrara, Felicetto, Lemoli, Roberto Massimo, Venditti, Adriano, Pagano, Livio, Todisco, Elisabetta, Guolo, F, Fianchi, L, Martelli, M, Chiusolo, P, Lussana, F, Grimaldi, F, Pilo, F, Rondoni, M, Fili, C, Capelli, D, Breccia, M, Mastaglio, S, Bocchia, M, Fumagalli, M, Galimberti, S, Mancini, V, Piccioni, A, Maurillo, L, Palmieri, R, Corbingi, A, Vetro, C, Sperotto, A, Gigli, F, Zappasodi, P, Mulé, A, Borlenghi, E, Dargenio, M, Lessi, F, Cerrano, M, Isidori, A, Brunetti, L, Papayannidis, C, Lunghi, M, Alati, C, Gatani, S, Mannelli, F, Fracchiolla, N, Gottardi, M, Cairoli, R, Ferrara, F, Lemoli, R, Venditti, A, Pagano, L, Todisco, E, Guolo, Fabio, Fianchi, Luana, Martelli, Maria Paola, Chiusolo, Patrizia, Lussana, Federico, Grimaldi, Francesco, Pilo, Federica, Rondoni, Michela, Fili, Carla, Capelli, Debora, Breccia, Massimo, Mastaglio, Sara, Bocchia, Monica, Fumagalli, Monica, Galimberti, Sara, Mancini, Valentina, Piccioni, Anna Lina, Maurillo, Luca, Palmieri, Raffaele, Corbingi, Andrea, Vetro, Calogero, Sperotto, Alessandra, Gigli, Federica, Zappasodi, Patrizia, Mulé, Antonio, Borlenghi, Erika, Dargenio, Michelina, Lessi, Federica, Cerrano, Marco, Isidori, Alessandro, Brunetti, Lorenzo, Papayannidis, Cristina, Lunghi, Monia, Alati, Caterina, Gatani, Samuele, Mannelli, Francesco, Fracchiolla, Nicola, Gottardi, Michele, Cairoli, Roberto, Ferrara, Felicetto, Lemoli, Roberto Massimo, Venditti, Adriano, Pagano, Livio, and Todisco, Elisabetta

Published
2023

3. Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in “Real-Life”: The SEIFEM Experience

Author

Fianchi, Luana, Guolo, F., Marchesi, F., Cattaneo, C., Gottardi, M., Restuccia, F., Candoni, A., Ortu La Barbera, E., Fazzi, R., Pasciolla, C., Finizio, O., Fracchiolla, N., Delia, M., Lessi, F., Dargenio, M., Bonuomo, V., Del Principe, M. I., Zappasodi, P., Picardi, M., Basilico, C., Piedimonte, M., Minetto, P., Giordano, A., Chiusolo, Patrizia, Prezioso, L., Buquicchio, C., Melillo, L. M. A., Zama, D., Farina, F., Mancini, V., Terrenato, I., Rondoni, M., Urbino, I., Tumbarello, Mario, Busca, A., Pagano, Livio, Fianchi L., Chiusolo P. (ORCID:0000-0002-1355-1587), Tumbarello M. (ORCID:0000-0002-9519-8552), Pagano L. (ORCID:0000-0001-8287-928X), Fianchi, Luana, Guolo, F., Marchesi, F., Cattaneo, C., Gottardi, M., Restuccia, F., Candoni, A., Ortu La Barbera, E., Fazzi, R., Pasciolla, C., Finizio, O., Fracchiolla, N., Delia, M., Lessi, F., Dargenio, M., Bonuomo, V., Del Principe, M. I., Zappasodi, P., Picardi, M., Basilico, C., Piedimonte, M., Minetto, P., Giordano, A., Chiusolo, Patrizia, Prezioso, L., Buquicchio, C., Melillo, L. M. A., Zama, D., Farina, F., Mancini, V., Terrenato, I., Rondoni, M., Urbino, I., Tumbarello, Mario, Busca, A., Pagano, Livio, Fianchi L., Chiusolo P. (ORCID:0000-0002-1355-1587), Tumbarello M. (ORCID:0000-0002-9519-8552), and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality–infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01–0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.

Published
2023

4. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author

Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Published
2023

5. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia–like or acute lymphoblastic leukemia–like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study

Author

Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment.

Published
2023

7. Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

Author

Minetto, P, Candoni, A, Guolo, F, Clavio, M, Zannier, M, Miglino, M, Dubbini, M, Carminati, E, Sicuranza, A, Ciofini, S, Colombo, N, Pugliese, G, Marcolin, R, Santoni, A, Ballerini, F, Lanino, L, Cea, M, Gobbi, M, Bocchia, M, Fanin, R, Lemoli, R, Minetto P., Candoni A., Guolo F., Clavio M., Zannier M. E., Miglino M., Dubbini M. V., Carminati E., Sicuranza A., Ciofini S., Colombo N., Pugliese G., Marcolin R., Santoni A., Ballerini F., Lanino L., Cea M., Gobbi M., Bocchia M., Fanin R., Lemoli R. M., Minetto, P, Candoni, A, Guolo, F, Clavio, M, Zannier, M, Miglino, M, Dubbini, M, Carminati, E, Sicuranza, A, Ciofini, S, Colombo, N, Pugliese, G, Marcolin, R, Santoni, A, Ballerini, F, Lanino, L, Cea, M, Gobbi, M, Bocchia, M, Fanin, R, Lemoli, R, Minetto P., Candoni A., Guolo F., Clavio M., Zannier M. E., Miglino M., Dubbini M. V., Carminati E., Sicuranza A., Ciofini S., Colombo N., Pugliese G., Marcolin R., Santoni A., Ballerini F., Lanino L., Cea M., Gobbi M., Bocchia M., Fanin R., and Lemoli R. M.

Abstract

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD.

Published
2021

8. P539: PROGNOSTIC RELEVANCE OF MINIMAL RESIDUAL DISEASE IN THERAPY RELATED AND SECONDARY ACUTE MYELOID LEUKEMIA RECEIVING CPX-351 OR FLUDARABINE-BASED INDUCTION.

Author

Guolo, F., primary, Minetto, P., additional, Riva, C., additional, Parodi, F., additional, Miglino, M., additional, Tedone, E., additional, Colombo, N., additional, Carminati, E., additional, Nurra, C., additional, Cagnetta, A., additional, Cea, M., additional, and Lemoli, R. M., additional

Published
2022
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9. P1709: FERTILITY PRESERVATION FOR YOUNG ADULT ACUTE LYMPHOBLASTIC LEUKEMIAS IN ITALY: A CAMPUS ALL SURVEY.

Author

Giglio, F., primary, Bruno, A., additional, Dargenio, M., additional, Cerrano, M., additional, Del Principe, M. I., additional, Forghieri, F., additional, Fumagalli, M., additional, Guolo, F., additional, Imovilli, A., additional, Lunghi, M., additional, Mazzone, C., additional, Papayannidis, C., additional, Pasciolla, C., additional, Trappolini, S., additional, Lazzarotto, D., additional, Bonifacio, M., additional, Candoni, A., additional, Ciceri, F., additional, Pizzolo, G., additional, Vitale, A., additional, and Foà, R., additional

Published
2022
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10. P357: MULTICENTER RETROSPECTIVE ANALYSIS OF CLINICAL OUTCOME OF ADULT PATIENS WITH MIXED-PHENOTYPE ACUTE LEUKEMIA (MPAL) DIAGNOSED AND TREATED IN THE LAST TEN YEARS. A CAMPUS-ALL STUDY.

Author

Lazzarotto, D., primary, Tanasi, I., additional, Vitale, A., additional, Piccini, M., additional, Dargenio, M., additional, Giglio, F., additional, Forghieri, F., additional, Fracchiolla, N., additional, Cerrano, M., additional, Todisco, E., additional, Papayannidis, C., additional, Leoncin, M., additional, Defina, M., additional, Guolo, F., additional, Pasciolla, C., additional, Delia, M., additional, Chiusolo, P., additional, Mulè, A., additional, Candoni, A., additional, Bonifacio, M., additional, Pizzolo, G., additional, and Foà, R., additional

Published
2022
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11. INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph1 acute lymphoblastic leukemia

Author

Martinelli, G., Papayannidis, C., Piciocchi, A., Robustelli, V., Soverini, S., Terragna, C., Marconi, G., Lemoli, R. M., Guolo, F., Fornaro, A., Lunghi, M., de Fabritiis, P., Candoni, A., Selleri, C., Simonetti, F., Bocchia, M., Vitale, A., Frison, L., Tedeschi, A., Cuneo, A., Bonifacio, M., Martelli, M. P., D'Ardia, S., Trappolini, S., Tosi, P., Galieni, P., Fabbiano, F., Abbenante, M. C., Granier, M., Zhu, Z., Wang, M., Sartor, C., Paolini, S., Cavo, M., Foa, R., Fazi, P., Vignetti, M., and Baccarani, M.

Published
2022

12. Blastic plasmocitoid dendritic cell neoplasm with leukemic spread: a GIMEMA survey

Author

Valentini, C. G., Piciocchi, A., Facchetti, F., Guolo, F., Pulsoni, A., Vignetti, M., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Valentini, C. G., Piciocchi, A., Facchetti, F., Guolo, F., Pulsoni, A., Vignetti, M., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

no abstract

Published
2021

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

Author

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., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., 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., Pagano L. (ORCID:0000-0001-8287-928X), and Dragonetti G.

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. Ho

Published
2021

14. Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen

Author

Chiusolo, Patrizia, Bregante, S., Giammarco, S., Lamparelli, T., Casarino, L., Dominietto, A., Raiola, A. M., Metafuni, Elisabetta, Di Grazia, C., Gualandi, F., Sora', Federica, Laurenti, Luca, Sica, Simona, Barosi, G., Guolo, F., Rossi, M., Rossi, Elena, Vannucchi, A., Signori, A., De Stefano, Valerio, Bacigalupo, Andrea, Angelucci, E., Chiusolo P. (ORCID:0000-0002-1355-1587), Metafuni E., Sora F. (ORCID:0000-0002-9607-5298), Laurenti L. (ORCID:0000-0002-8327-1396), Sica S. (ORCID:0000-0003-2426-3465), Rossi E. (ORCID:0000-0002-7572-9379), De Stefano V. (ORCID:0000-0002-5178-5827), Bacigalupo A. (ORCID:0000-0002-9119-567X), Chiusolo, Patrizia, Bregante, S., Giammarco, S., Lamparelli, T., Casarino, L., Dominietto, A., Raiola, A. M., Metafuni, Elisabetta, Di Grazia, C., Gualandi, F., Sora', Federica, Laurenti, Luca, Sica, Simona, Barosi, G., Guolo, F., Rossi, M., Rossi, Elena, Vannucchi, A., Signori, A., De Stefano, Valerio, Bacigalupo, Andrea, Angelucci, E., Chiusolo P. (ORCID:0000-0002-1355-1587), Metafuni E., Sora F. (ORCID:0000-0002-9607-5298), Laurenti L. (ORCID:0000-0002-8327-1396), Sica S. (ORCID:0000-0003-2426-3465), Rossi E. (ORCID:0000-0002-7572-9379), De Stefano V. (ORCID:0000-0002-5178-5827), and Bacigalupo A. (ORCID:0000-0002-9119-567X)

Abstract

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P <.001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P <.001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P =.004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.

Published
2021

16. Cancer immunotherapy by blocking immune checkpoints on innate lymphocytes

Author

Pesce, S., Trabanelli, S., Di Vito, C., Greppi, M., Obino, V., Guolo, F., Minetto, P., Bozzo, M., Calvi, M., Zaghi, E., Candiani, S., Lemoli, R.M., Jandus, C., Mavilio, D., and Marcenaro, E.

Subjects
KIR, NKG2A, PD-1, immune checkpoint, immune escape, immunotherapy, innate immunity, innate lymphoid cells, miRNA, natural killer cells, animal diseases, bacteria, chemical and pharmacologic phenomena, biochemical phenomena, metabolism, and nutrition, ddc:616.07
Abstract

Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

Published
2020

17. PB1730 A SIMPLE FLOW CYTOMETRY-BASED SCORE MAY OPTIMIZE TESTING FOR BIALLELIC CEBPA MUTATIONS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA PATIENTS

Author

Marcolin, R., primary, Guolo, F., additional, Minetto, P., additional, Clavio, M., additional, Ballerini, F., additional, Kunkl, A., additional, Tedone, E., additional, Contini, P., additional, Mangerini, R., additional, Colombo, N., additional, Cagnetta, A., additional, Cea, M., additional, Pugliese, G., additional, Carminati, E., additional, Gobbi, M., additional, Miglino, M., additional, and Lemoli, R.M., additional

Published
2019
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18. PS1535 AUTOLOGOUS STEM CELL TRANSPLANT FOLLOWED BY POST-TRANSPLANT IMMUNOTHERAPY WITH NIVOLUMAB AND UNSELECTED AUTOLOGOUS LYMPHOCYTES INFUSION AS SALVAGE THERAPY FOR RELAPSED/REFRACTORY HODGKIN LYMPHOMA

Author

Guolo, F., primary, Minetto, P., additional, Ballerini, F., additional, Canale, F.A., additional, Frello, M., additional, Coviello, E., additional, Manconi, L., additional, Kunkl, A., additional, Tedone, E., additional, Contini, P., additional, Mangerini, R., additional, Fenoglio, D., additional, Bo, A., additional, Luigi, M.C. De, additional, Ruzzenenti, M.R., additional, Carlier, P., additional, Serio, A., additional, Lucchetti, S., additional, Strada, P., additional, Gobbi, M., additional, Ravetti, J.L., additional, Marcenaro, E., additional, and Lemoli, R.M., additional

Published
2019
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19. PB2097 METABOLIC STARVATION TRIGGERED BY L-ASPARAGINASE SENSITIZES MULTIPLE MYELOMA CELLS TO PROTEASOME INHIBITORS BY INDUCING DNA DAMAGE ACCUMULATION

Author

Minetto, P., primary, Soncini, D., additional, Guolo, F., additional, Ruberti, S., additional, Retali, V., additional, Contini, P., additional, Rivoli, G., additional, Bisso, N., additional, Di Felice, N., additional, Cagnetta, A., additional, Gobbi, M., additional, Lemoli, R. M., additional, and Cea, M., additional

Published
2019
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24. De novo AML patients with favourable-intermediate karyotype may benefit from the addition of low-dose gemtuzumab ozogamicin (GO) to fludarabine, Ara-C and idarubicin (FLAI): a contribution to the reopened 'GO question'

Author

Clavio, M, Cruciani, F, Minetto, P, Guolo, F, Ballerini, F, Marani, C, De Astis, E, Aquino, S, Bergamaschi, M, Mitscheunig, L, Grasso, R, Colombo, N, Ghiggi, C, Lovera, D, Pastori, G, Avenoso, D, Miglino, M, Gobbi, M, Clavio, Marino, Cruciani, Fabio, Minetto, Paola, Guolo, Fabio, Ballerini, Filippo, Marani, Carlo, De Astis, Enrico, Aquino, Sara, Bergamaschi, Micaela, Mitscheunig, Laura, Grasso, Raffaella, Colombo, Nicoletta, Ghiggi, Chiara, Lovera, Davide, Pastori, Giordana, Avenoso, Daniele, Miglino, Maurizio, Gobbi, Marco, Clavio, M, Cruciani, F, Minetto, P, Guolo, F, Ballerini, F, Marani, C, De Astis, E, Aquino, S, Bergamaschi, M, Mitscheunig, L, Grasso, R, Colombo, N, Ghiggi, C, Lovera, D, Pastori, G, Avenoso, D, Miglino, M, Gobbi, M, Clavio, Marino, Cruciani, Fabio, Minetto, Paola, Guolo, Fabio, Ballerini, Filippo, Marani, Carlo, De Astis, Enrico, Aquino, Sara, Bergamaschi, Micaela, Mitscheunig, Laura, Grasso, Raffaella, Colombo, Nicoletta, Ghiggi, Chiara, Lovera, Davide, Pastori, Giordana, Avenoso, Daniele, Miglino, Maurizio, and Gobbi, Marco

Abstract

We report the final results of a prospective trial testing the combination of fludarabine, Ara-C and idarubicin (FLAI) followed by low-dose gemtuzumab ozogamicin (FLAI-GO) in 85 patients aged 60 years or more with CD33+ acute myeloid leukaemia (AML). Median age was 68 years (60-82); karyotype was unfavourable in 21 patients (24 %), intermediate in 63 (74 %) and favourable in 1 (2 %). There were five therapy-related deaths. Of the 80 evaluable patients, 47 achieved complete response (CR) (58 %); CR rates were 65 and 32 % in good-intermediate/poor karyotype patients, respectively. Median length of CR was 7 months (3-76). The cumulative incidence of relapse was 84 % with an actuarial survival of 50.3 % at 1 year and 14.4 % at 2 years. The study control population is an unselected consecutive historic cohort of 104 patients treated with the FLAI regimen, who were matched for age and prognostic factors. CR rates after FLAI-GO and FLAI were comparable. However, patients with de novo AML and intermediate-favourable karyotype receiving GO had a significantly lower risk of relapse at 2 years as compared to patients not receiving GO (n = 77) (40 vs 80 %, p = 0.01) and significantly better disease-free survival (p = 0.018) and overall survival (p = 0.022).

Published
2013

25. Nucleophosmin gene-based monitoring in de novo cytogenetically normal acute myeloid leukemia with nucleophosmin gene mutations: comparison with cytofluorimetric analysis and study of Wilms tumor gene 1 expression

Author

Miglino, M, Colombo, N, Grasso, R, Marani, C, Clavio, M, Pica, G, Ballerini, F, Ghiggi, C, Minetto, P, Guolo, F, Carella, A, Gobbi, M, Miglino, Maurizio, Colombo, Nicoletta, Grasso, Raffaella, Marani, Carlo, Clavio, Marino, Pica, Gian Matteo, Ballerini, Filippo, Ghiggi, Chiara, Minetto, Paola, Guolo, Fabio, Carella, Angelo Michele, Gobbi, Marco, Miglino, M, Colombo, N, Grasso, R, Marani, C, Clavio, M, Pica, G, Ballerini, F, Ghiggi, C, Minetto, P, Guolo, F, Carella, A, Gobbi, M, Miglino, Maurizio, Colombo, Nicoletta, Grasso, Raffaella, Marani, Carlo, Clavio, Marino, Pica, Gian Matteo, Ballerini, Filippo, Ghiggi, Chiara, Minetto, Paola, Guolo, Fabio, Carella, Angelo Michele, and Gobbi, Marco

Abstract

We compared the clinical value of minimal residual disease (MRD) monitoring by cytofluorimetric methods, Wilms tumor gene 1 (WT1) expression and the study of nucleophosmin gene (NPM) mutations in a series of 26 patients with NPM-mutated de novo acute myeloid leukemia (NPM-AML) who achieved complete hematological remission after conventional chemotherapy. The relapse risk was significantly lower only in patients achieving a NPM molecular complete response (NPM mol-CR) and confirmed NPM mol-CR (non-detectable NPM mutations in two consecutive marrow samples). The disease-free survival (DFS) of patients achieving a <4-log or >= 4-log reduction in NPM value after induction therapy was 12.6 % and 50%, respectively, at 36 months (p = 0.009). The attainment of a confirmed NPM-CR had a significant influence on overall survival (OS at 36 months was 64.3% and 11.9% in patients obtaining or not obtaining confirmed NPM-CR, respectively, p < 0.03). We confirm that NPM-molecular relapse (NPM-rel) is always followed by hematological relapse (H-rel), but longitudinal studies of NPM mutations may predict an impending H-rel earlier than flow cytometric- or WT1-based methods.

Published
2012

26. P-294 Azacytidine therapy for MDS and AML patients: Retrospective multicentre regional experience in patients not enrolled into clinical trials

Author

Clavio, M., primary, Aquino, S., additional, Minetto, P., additional, Bergamaschi, M., additional, Del Corso, L., additional, Balleari, E., additional, Miglino, M., additional, De Astis, E., additional, Galaverna, F., additional, Arboscello, E., additional, Mitscheunig, L., additional, Guolo, F., additional, Goretti, R., additional, Ghio, R., additional, and Gobbi, M., additional

Published
2013
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28. Bloodstream Infections Are an Improbable Cause of Positive Serum (1,3)-ß-d-Glucan in Hematology Patients

Author

Furfaro, E., Mikulska, M., Del Bono, V., Guolo, F., Minetto, P., Gobbi, M., Ghiso, A., Bacigalupo, A., and Viscoli, C.

Abstract

ABSTRACTNinety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-ß-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results.

Published
2014
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32. PROGNOSTIC VALUE OF MINIMAL RESIDUAL DISEASE BEFORE ALLOGENEIC MARROW TRANSPLANTATION IN ACUTE MYELOID LEUKEMIA BY COMBINEDWT1 EXPRESSION LEVELS AND FLOW CYTOMETRY ASSESMENT

Author

Guolo, F., Minetto, P., Galaverna, F., Giannoni, L., Ghiggi, C., Clavio, M., Beltrami, G., Ibatici, A., Carmela Di Grazia, Raiola, A. M., Mitscheunig, L., Grasso, R., Colombo, N., Astis, E., Avenoso, D., Cruciani, F., Lovera, D., Pastori, G., Ballerini, F., Aquino, S., Kunkl, A., Miglino, M., Lemoli, R. M., Gobbi, M., Carella, A. M., and Bacigalupo, A.

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