19 results on '"Zambrotta, G."'
Search Results
2. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022
- Author
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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
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- 2024
3. Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry
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Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., Pagano L. (ORCID:0000-0001-8287-928X), Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., and Pagano L. (ORCID:0000-0001-8287-928X)
- Abstract
Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.
- Published
- 2024
4. The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey
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El-Ashwah, S., Salmanton-Garcia, J., Bilgin, Y. M., Itri, F., Zak, P., Weinbergerova, B., Verga, L., Omrani, A. S., Silva, M. G. D., Szotkowski, T., Marchetti, M., Buquicchio, C., Nucci, M., Schonlein, M., Farina, F., Besson, C., Prezioso, L., Nizamuddin, S., Davila-Valls, J., Martin-Perez, S., Bonuomo, V., Van Doesum, J., Tisi, M. C., Passamonti, F., Mendez, G. -A., Meers, S., Maertens, J., Lopez-Garcia, A., Glenthoj, A., Bonnani, M., Rinaldi, I., Ormazabal-Velez, I., Labrador, J., Kulasekararaj, A., Espigado, I., Demirkan, F., De Jonge, N., Collins, G. P., Calbacho, M., Blennow, O., Al-Khabori, M., Adzic-Vukicevic, T., Arellano, E., Miskovic, B., Mladenovic, M., Nordlander, A., Racil, Z., Ammatuna, E., Cordoba, R., Hersby, D. S., Grafe, S., Emarah, Z., Hanakova, M., Sacchi, M. V., Ijaz, M., Rahimli, L., Nunes Rodrigues, R., Zambrotta, G. P. M., Marchesi, F., Cornely, O. A., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), El-Ashwah, S., Salmanton-Garcia, J., Bilgin, Y. M., Itri, F., Zak, P., Weinbergerova, B., Verga, L., Omrani, A. S., Silva, M. G. D., Szotkowski, T., Marchetti, M., Buquicchio, C., Nucci, M., Schonlein, M., Farina, F., Besson, C., Prezioso, L., Nizamuddin, S., Davila-Valls, J., Martin-Perez, S., Bonuomo, V., Van Doesum, J., Tisi, M. C., Passamonti, F., Mendez, G. -A., Meers, S., Maertens, J., Lopez-Garcia, A., Glenthoj, A., Bonnani, M., Rinaldi, I., Ormazabal-Velez, I., Labrador, J., Kulasekararaj, A., Espigado, I., Demirkan, F., De Jonge, N., Collins, G. P., Calbacho, M., Blennow, O., Al-Khabori, M., Adzic-Vukicevic, T., Arellano, E., Miskovic, B., Mladenovic, M., Nordlander, A., Racil, Z., Ammatuna, E., Cordoba, R., Hersby, D. S., Grafe, S., Emarah, Z., Hanakova, M., Sacchi, M. V., Ijaz, M., Rahimli, L., Nunes Rodrigues, R., Zambrotta, G. P. M., Marchesi, F., Cornely, O. A., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)
- Abstract
Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.
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- 2024
5. Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study
- Author
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Zambrotta, G, Nicolini, F, Assouline, S, Busque, L, Pungolino, E, Abruzzese, E, Miggiano, M, Elena, C, Alvarez-Larran, A, Triguero, A, Iurlo, A, Bucelli, C, Cerrano, M, Capodanno, I, Lunghi, F, le Coutre, P, Galimberti, S, Caocci, G, Maffioli, M, Stagno, F, Saussele, S, Piazza, R, Druker, B, Fava, C, Guglielmana, V, Colombo, F, Antolini, L, Gambacorti-Passerini, C, Zambrotta G. P. M., Nicolini F. E., Assouline S., Busque L., Pungolino E., Abruzzese E., Miggiano M. C., Elena C., Alvarez-Larran A., Triguero A., Iurlo A., Bucelli C., Cerrano M., Capodanno I., Lunghi F., le Coutre P., Galimberti S., Caocci G., Maffioli M., Stagno F., Saussele S., Piazza R., Druker B. J., Fava C., Guglielmana V., Colombo F., Antolini L., Gambacorti-Passerini C., Zambrotta, G, Nicolini, F, Assouline, S, Busque, L, Pungolino, E, Abruzzese, E, Miggiano, M, Elena, C, Alvarez-Larran, A, Triguero, A, Iurlo, A, Bucelli, C, Cerrano, M, Capodanno, I, Lunghi, F, le Coutre, P, Galimberti, S, Caocci, G, Maffioli, M, Stagno, F, Saussele, S, Piazza, R, Druker, B, Fava, C, Guglielmana, V, Colombo, F, Antolini, L, Gambacorti-Passerini, C, Zambrotta G. P. M., Nicolini F. E., Assouline S., Busque L., Pungolino E., Abruzzese E., Miggiano M. C., Elena C., Alvarez-Larran A., Triguero A., Iurlo A., Bucelli C., Cerrano M., Capodanno I., Lunghi F., le Coutre P., Galimberti S., Caocci G., Maffioli M., Stagno F., Saussele S., Piazza R., Druker B. J., Fava C., Guglielmana V., Colombo F., Antolini L., and Gambacorti-Passerini C.
- Abstract
Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003–0.138]) in the overall group; 0.0 (95% CI [0–0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004–0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p <.0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated.
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- 2023
6. A monocentric analysis of the long-term safety and efficacy of crizotinib in relapsed/refractory ALK+ lymphomas
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Rindone, G, Aroldi, A, Bossi, E, Verga, L, Zambrotta, G, Tarantino, S, Piazza, R, Mussolin, L, Chiarle, R, Gambacorti-Passerini, C, Rindone, Giovanni, Aroldi, Andrea, Bossi, Elisa, Verga, Luisa, Zambrotta, Giovanni, Tarantino, Sara, Piazza, Rocco, Mussolin, Lara, Chiarle, Roberto, Gambacorti-Passerini, Carlo, Rindone, G, Aroldi, A, Bossi, E, Verga, L, Zambrotta, G, Tarantino, S, Piazza, R, Mussolin, L, Chiarle, R, Gambacorti-Passerini, C, Rindone, Giovanni, Aroldi, Andrea, Bossi, Elisa, Verga, Luisa, Zambrotta, Giovanni, Tarantino, Sara, Piazza, Rocco, Mussolin, Lara, Chiarle, Roberto, and Gambacorti-Passerini, Carlo
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- 2023
7. Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry
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Busca, A., Salmanton-Garcia, J., Marchesi, F., Farina, F., Seval, G. C., Van Doesum, J., De Jonge, N., Bahr, N. C., Maertens, J., Meletiadis, J., Fracchiolla, N. S., Weinbergerova, B., Verga, L., Racil, Z., Jimenez, M., Glenthoj, A., Blennow, O., Tanase, A. D., Schonlein, M., Prezioso, L., Khanna, N., Duarte, R. F., Zak, P., Nucci, M., Machado, M., Kulasekararaj, A., Espigado, I., De Kort, E., Ribera-Santa Susana, J. -M., Marchetti, M., Magliano, G., Falces-Romero, I., Ilhan, O., Ammatuna, E., Zompi, S., Tsirigotis, P., Antoniadou, A., Zambrotta, G. P. M., Nordlander, A., Karlsson, L. K., Hanakova, M., Dragonetti, Giulia, Cabirta, A., Berg Venemyr, C., Grafe, S., Van Praet, J., Tragiannidis, A., Petzer, V., Lopez-Garcia, A., Itri, F., Groh, A., Gavriilaki, E., Dargenio, M., Rahimli, L., Cornely, O. A., Pagano, Livio, Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Busca, A., Salmanton-Garcia, J., Marchesi, F., Farina, F., Seval, G. C., Van Doesum, J., De Jonge, N., Bahr, N. C., Maertens, J., Meletiadis, J., Fracchiolla, N. S., Weinbergerova, B., Verga, L., Racil, Z., Jimenez, M., Glenthoj, A., Blennow, O., Tanase, A. D., Schonlein, M., Prezioso, L., Khanna, N., Duarte, R. F., Zak, P., Nucci, M., Machado, M., Kulasekararaj, A., Espigado, I., De Kort, E., Ribera-Santa Susana, J. -M., Marchetti, M., Magliano, G., Falces-Romero, I., Ilhan, O., Ammatuna, E., Zompi, S., Tsirigotis, P., Antoniadou, A., Zambrotta, G. P. M., Nordlander, A., Karlsson, L. K., Hanakova, M., Dragonetti, Giulia, Cabirta, A., Berg Venemyr, C., Grafe, S., Van Praet, J., Tragiannidis, A., Petzer, V., Lopez-Garcia, A., Itri, F., Groh, A., Gavriilaki, E., Dargenio, M., Rahimli, L., Cornely, O. A., Pagano, Livio, Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)
- Abstract
Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.
- Published
- 2023
8. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry
- Author
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Salmanton-Garcia, J., Marchesi, F., Gomes da Silva, M., Farina, F., Davila-Valls, J., Bilgin, Y. M., Glenthoj, A., Falces-Romero, I., Van Doesum, J., Labrador, J., Buquicchio, C., El-Ashwah, S., Petzer, V., Van Praet, J., Schonlein, M., Dargenio, M., Mendez, G. -A., Meers, S., Itri, F., Giordano, A., Pinczes, L. I., Espigado, I., Stojanoski, Z., Lopez-Garcia, A., Prezioso, L., Jaksic, O., Vena, A., Fracchiolla, N. S., Gonzalez-Lopez, T. J., Colovic, N., Delia, M., Weinbergerova, B., Marchetti, M., Marques de Almeida, J., Finizio, O., Besson, C., Biernat, M. M., Valkovic, T., Lahmer, T., Cuccaro, A., Ormazabal-Velez, I., Batinic, J., Fernandez, N., De Jonge, N., Tascini, C., Anastasopoulou, A. N., Dulery, R., Del Principe, M. I., Plantefeve, G., Papa, M. V., Nucci, M., Jimenez, M., Aujayeb, A., Hernandez-Rivas, J. -A., Merelli, M., Cattaneo, C., Blennow, O., Nordlander, A., Cabirta, A., Varricchio, G., Sacchi, M. V., Cordoba, R., Arellano, E., Grafe, S. K., Wolf, D., Emarah, Z., Ammatuna, E., Hersby, D. S., Martin-Perez, S., Nunes Rodrigues, R., Rahimli, L., Pagano, Livio, Cornely, O. A., Piukovics, K., De Ramon, C., Danion, F., Yahya, A., Guidetti, A., Garcia-Vidal, C., Sili, U., Meletiadis, J., De Kort, E., Verga, L., Serrano, L., Erben, N., Di Blasi, R., Tragiannidis, A., Ribera-Santa Susana, J. -M., Ommen, H. -B., Busca, A., Coppola, N., Bergantim, R., Dragonetti, Giulia, Criscuolo, Marianna, Fianchi, Luana, Bonanni, Matteo, Soto-Silva, A., Mikulska, M., Machado, M., Shan Kho, C., Hassan, N., Gavriilaki, E., Cordini, G., Chi, L. Y. A., Eggerer, M., Hoenigl, M., Prattes, J., Jimenez-Lorenzo, M. -J., Zompi, S., Zambrotta, G. P. M., Colak, G. M., Garcia-Pouton, N., Aiello, T. F., Prin, R., Stamouli, M., Samarkos, M., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Criscuolo M., Fianchi L., Bonanni M., Salmanton-Garcia, J., Marchesi, F., Gomes da Silva, M., Farina, F., Davila-Valls, J., Bilgin, Y. M., Glenthoj, A., Falces-Romero, I., Van Doesum, J., Labrador, J., Buquicchio, C., El-Ashwah, S., Petzer, V., Van Praet, J., Schonlein, M., Dargenio, M., Mendez, G. -A., Meers, S., Itri, F., Giordano, A., Pinczes, L. I., Espigado, I., Stojanoski, Z., Lopez-Garcia, A., Prezioso, L., Jaksic, O., Vena, A., Fracchiolla, N. S., Gonzalez-Lopez, T. J., Colovic, N., Delia, M., Weinbergerova, B., Marchetti, M., Marques de Almeida, J., Finizio, O., Besson, C., Biernat, M. M., Valkovic, T., Lahmer, T., Cuccaro, A., Ormazabal-Velez, I., Batinic, J., Fernandez, N., De Jonge, N., Tascini, C., Anastasopoulou, A. N., Dulery, R., Del Principe, M. I., Plantefeve, G., Papa, M. V., Nucci, M., Jimenez, M., Aujayeb, A., Hernandez-Rivas, J. -A., Merelli, M., Cattaneo, C., Blennow, O., Nordlander, A., Cabirta, A., Varricchio, G., Sacchi, M. V., Cordoba, R., Arellano, E., Grafe, S. K., Wolf, D., Emarah, Z., Ammatuna, E., Hersby, D. S., Martin-Perez, S., Nunes Rodrigues, R., Rahimli, L., Pagano, Livio, Cornely, O. A., Piukovics, K., De Ramon, C., Danion, F., Yahya, A., Guidetti, A., Garcia-Vidal, C., Sili, U., Meletiadis, J., De Kort, E., Verga, L., Serrano, L., Erben, N., Di Blasi, R., Tragiannidis, A., Ribera-Santa Susana, J. -M., Ommen, H. -B., Busca, A., Coppola, N., Bergantim, R., Dragonetti, Giulia, Criscuolo, Marianna, Fianchi, Luana, Bonanni, Matteo, Soto-Silva, A., Mikulska, M., Machado, M., Shan Kho, C., Hassan, N., Gavriilaki, E., Cordini, G., Chi, L. Y. A., Eggerer, M., Hoenigl, M., Prattes, J., Jimenez-Lorenzo, M. -J., Zompi, S., Zambrotta, G. P. M., Colak, G. M., Garcia-Pouton, N., Aiello, T. F., Prin, R., Stamouli, M., Samarkos, M., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Criscuolo M., Fianchi L., and Bonanni M.
- Abstract
Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mort
- Published
- 2023
9. DNA Damage Response (DDR) Is Associated With Treatment-free Remission in Chronic Myeloid Leukemia Patients
- Author
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Malighetti, F, Arosio, G, Manfroni, C, Mauri, M, Villa, M, Manghisi, B, Inzoli, E, Rindone, G, Zambrotta, G, Civettini, I, Guglielmana, V, Ramazzotti, D, Giudici, G, Bombelli, S, Perego, R, Piazza, R, Mologni, L, Gambacorti-Passerini, C, Malighetti, Federica, Arosio, Giulia, Manfroni, Chiara, Mauri, Mario, Villa, Matteo, Manghisi, Beatrice, Inzoli, Elena, Rindone, Giovanni, Zambrotta, Giovanni P M, Civettini, Ivan, Guglielmana, Veronica, Ramazzotti, Daniele, Giudici, Giovanni, Bombelli, Silvia, Perego, Roberto, Piazza, Rocco, Mologni, Luca, Gambacorti-Passerini, Carlo, Malighetti, F, Arosio, G, Manfroni, C, Mauri, M, Villa, M, Manghisi, B, Inzoli, E, Rindone, G, Zambrotta, G, Civettini, I, Guglielmana, V, Ramazzotti, D, Giudici, G, Bombelli, S, Perego, R, Piazza, R, Mologni, L, Gambacorti-Passerini, C, Malighetti, Federica, Arosio, Giulia, Manfroni, Chiara, Mauri, Mario, Villa, Matteo, Manghisi, Beatrice, Inzoli, Elena, Rindone, Giovanni, Zambrotta, Giovanni P M, Civettini, Ivan, Guglielmana, Veronica, Ramazzotti, Daniele, Giudici, Giovanni, Bombelli, Silvia, Perego, Roberto, Piazza, Rocco, Mologni, Luca, and Gambacorti-Passerini, Carlo
- Published
- 2023
10. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings
- Author
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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.
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- 2023
11. ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine
- Author
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Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Gambacorti-Passerini, C, Piazza, R, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Gambacorti-Passerini C., Piazza R., Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Gambacorti-Passerini, C, Piazza, R, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Gambacorti-Passerini C., and Piazza R.
- Abstract
Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype.
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- 2020
12. ETNK1 mutations in atypical chronic myeloid leukemia induce a mutator phenotype that can be reverted with phosphoethanolamine
- Author
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Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Piazza, R, Gambacorti-Passerini, C, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Piazza R., Gambacorti-Passerini C., Fontana, D, Mauri, M, Renso, R, Docci, M, Crespiatico, I, Rost, L, Jang, M, Niro, A, D'Aliberti, D, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Fanelli, F, Cassina, V, Corti, R, Salerno, D, Nardo, L, Chinello, C, Mantegazza, F, Mecucci, C, Magni, F, Cavaletti, G, Bruheim, P, Rea, D, Larsen, S, Piazza, R, Gambacorti-Passerini, C, Fontana D., Mauri M., Renso R., Docci M., Crespiatico I., Rost L. M., Jang M., Niro A., D'Aliberti D., Massimino L., Bertagna M., Zambrotta G., Bossi M., Citterio S., Crescenzi B., Fanelli F., Cassina V., Corti R., Salerno D., Nardo L., Chinello C., Mantegazza F., Mecucci C., Magni F., Cavaletti G., Bruheim P., Rea D., Larsen S., Piazza R., and Gambacorti-Passerini C.
- Published
- 2020
13. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey
- Author
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Pagano, Livio, Salmanton-Garcia, J., Marchesi, F., Blennow, O., Gomes da Silva, M., Glenthoj, A., van Doesum, J., Bilgin, Y. M., Lopez-Garcia, A., Itri, F., Nunes Rodrigues, R., Weinbergerova, B., Farina, F., Dragonetti, Giulia, Berg Venemyr, C., van Praet, J., Jaksic, O., Valkovic, T., Falces-Romero, I., Martin-Perez, S., Jimenez, M., Davila-Valls, J., Schonlein, M., Ammatuna, E., Meers, S., Delia, M., Stojanoski, Z., Nordlander, A., Lahmer, T., Imre Pinczes, L., Buquicchio, C., Piukovics, K., Ormazabal-Velez, I., Fracchiolla, N., Samarkos, M., Mendez, G. -A., Hernandez-Rivas, J. -A., Espigado, I., Cernan, M., Petzer, V., Lamure, S., di Blasi, R., Marques de Almedia, J., Dargenio, M., Biernat, M. M., Sciume, M., de Ramon, C., de Jonge, N., Batinic, J., Aujayeb, A., Marchetti, M., Fouquet, G., Fernandez, N., Zambrotta, G., Sacchi, M. V., Guidetti, A., Demirkan, F., Prezioso, L., Racil, Z., Nucci, M., Mladenovic, M., Lievin, R., Hanakova, M., Grafe, S., Sili, U., Machado, M., Cattaneo, C., Adzic-Vukicevic, T., Verga, L., Labrador, J., Rahimli, L., Bonanni, Matteo, Passamonti, F., Pagliuca, A., Corradini, P., Hoenigl, M., Koehler, P., Busca, A., Cornely, O. A., Serrano, L., Ribera-Santa Susana, J. -M., Meletiadis, J., Tsirigotis, P., Coppola, N., Mikulska, M., Erben, N., Besson, C., Merelli, M., Gonzalez-Lopez, T. -J., Loureiro-Amigo, J., Garcia-Vidal, C., Kort, E. D., Cuccaro, A., Zompi, S., Reizine, F., Finizio, O., Dulery, R., Calbacho, M., Abu-Zeinah, G., Malak, S., Zdziarski, P., Varrichio, G., Tragiannidis, A., Plantefeve, G., Duarte, R., Danion, F., Tisi, M. C., Sakellari, I., Karthaus, M., Groh, A., Fung, M., Emarah, Z., Coronel-Ayala, O. -F., Ann Chai, L. Y., Brehon, M., Bonuomo, V., Wolf, D., Wittig, J., Vehreschild, M., Papa, M. V., Neuhann, J., Jimenez-Lorenzo, M. -J., Grothe, J., Gavriilaki, E., Garcia-Sanz, R., Garcia-Pouton, N., El-Ashwah, S. S., Eggerer, M., Cordoba, R., Colak, G. M., Arellano, E., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Bonanni M., Pagano, Livio, Salmanton-Garcia, J., Marchesi, F., Blennow, O., Gomes da Silva, M., Glenthoj, A., van Doesum, J., Bilgin, Y. M., Lopez-Garcia, A., Itri, F., Nunes Rodrigues, R., Weinbergerova, B., Farina, F., Dragonetti, Giulia, Berg Venemyr, C., van Praet, J., Jaksic, O., Valkovic, T., Falces-Romero, I., Martin-Perez, S., Jimenez, M., Davila-Valls, J., Schonlein, M., Ammatuna, E., Meers, S., Delia, M., Stojanoski, Z., Nordlander, A., Lahmer, T., Imre Pinczes, L., Buquicchio, C., Piukovics, K., Ormazabal-Velez, I., Fracchiolla, N., Samarkos, M., Mendez, G. -A., Hernandez-Rivas, J. -A., Espigado, I., Cernan, M., Petzer, V., Lamure, S., di Blasi, R., Marques de Almedia, J., Dargenio, M., Biernat, M. M., Sciume, M., de Ramon, C., de Jonge, N., Batinic, J., Aujayeb, A., Marchetti, M., Fouquet, G., Fernandez, N., Zambrotta, G., Sacchi, M. V., Guidetti, A., Demirkan, F., Prezioso, L., Racil, Z., Nucci, M., Mladenovic, M., Lievin, R., Hanakova, M., Grafe, S., Sili, U., Machado, M., Cattaneo, C., Adzic-Vukicevic, T., Verga, L., Labrador, J., Rahimli, L., Bonanni, Matteo, Passamonti, F., Pagliuca, A., Corradini, P., Hoenigl, M., Koehler, P., Busca, A., Cornely, O. A., Serrano, L., Ribera-Santa Susana, J. -M., Meletiadis, J., Tsirigotis, P., Coppola, N., Mikulska, M., Erben, N., Besson, C., Merelli, M., Gonzalez-Lopez, T. -J., Loureiro-Amigo, J., Garcia-Vidal, C., Kort, E. D., Cuccaro, A., Zompi, S., Reizine, F., Finizio, O., Dulery, R., Calbacho, M., Abu-Zeinah, G., Malak, S., Zdziarski, P., Varrichio, G., Tragiannidis, A., Plantefeve, G., Duarte, R., Danion, F., Tisi, M. C., Sakellari, I., Karthaus, M., Groh, A., Fung, M., Emarah, Z., Coronel-Ayala, O. -F., Ann Chai, L. Y., Brehon, M., Bonuomo, V., Wolf, D., Wittig, J., Vehreschild, M., Papa, M. V., Neuhann, J., Jimenez-Lorenzo, M. -J., Grothe, J., Gavriilaki, E., Garcia-Sanz, R., Garcia-Pouton, N., El-Ashwah, S. S., Eggerer, M., Cordoba, R., Colak, G. M., Arellano, E., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., and Bonanni M.
- Abstract
Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.
- Published
- 2022
14. B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)
- Author
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Infante, M. S., Salmanton-Garcia, J., Fernandez-Cruz, A., Marchesi, F., Jaksic, O., Weinbergerova, B., Besson, C., Duarte, R. F., Itri, F., Valkovic, T., Szotkovski, T., Busca, A., Guidetti, A., Glenthoj, A., Collins, G. P., Bonuomo, V., Sili, U., Seval, G. C., Machado, M., Cordoba, R., Blennow, O., Abu-Zeinah, G., Lamure, S., Kulasekararaj, A., Falces-Romero, I., Cattaneo, C., Van Doesum, J., Piukovics, K., Omrani, A. S., Magliano, G., Ledoux, M. -P., de Ramon, C., Cabirta, A., Verga, L., Lopez-Garcia, A., Da Silva, M. G., Stojanoski, Z., Meers, S., Lahmer, T., Martin-Perez, S., Davila-Vals, J., Van Praet, J., Samarkos, M., Bilgin, Y. M., Karlsson, L. K., Batinic, J., Nordlander, A., Schonlein, M., Hoenigl, M., Racil, Z., Mladenovic, M., Hanakova, M., Zambrotta, G. P. M., De Jonge, N., Adzic-Vukicevic, T., Nunes-Rodrigues, R., Prezioso, L., Navratil, M., Marchetti, M., Cuccaro, A., Calbacho, M., Giordano, A., Cornely, O. A., Hernandez-Rivas, J. -A., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Infante, M. S., Salmanton-Garcia, J., Fernandez-Cruz, A., Marchesi, F., Jaksic, O., Weinbergerova, B., Besson, C., Duarte, R. F., Itri, F., Valkovic, T., Szotkovski, T., Busca, A., Guidetti, A., Glenthoj, A., Collins, G. P., Bonuomo, V., Sili, U., Seval, G. C., Machado, M., Cordoba, R., Blennow, O., Abu-Zeinah, G., Lamure, S., Kulasekararaj, A., Falces-Romero, I., Cattaneo, C., Van Doesum, J., Piukovics, K., Omrani, A. S., Magliano, G., Ledoux, M. -P., de Ramon, C., Cabirta, A., Verga, L., Lopez-Garcia, A., Da Silva, M. G., Stojanoski, Z., Meers, S., Lahmer, T., Martin-Perez, S., Davila-Vals, J., Van Praet, J., Samarkos, M., Bilgin, Y. M., Karlsson, L. K., Batinic, J., Nordlander, A., Schonlein, M., Hoenigl, M., Racil, Z., Mladenovic, M., Hanakova, M., Zambrotta, G. P. M., De Jonge, N., Adzic-Vukicevic, T., Nunes-Rodrigues, R., Prezioso, L., Navratil, M., Marchetti, M., Cuccaro, A., Calbacho, M., Giordano, A., Cornely, O. A., Hernandez-Rivas, J. -A., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)
- Abstract
Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.
- Published
- 2022
15. Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey
- Author
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Cattaneo, C., Salmanton-Garcia, J., Marchesi, F., El-Ashwah, S., Itri, F., Weinbergerova, B., Gomes Da Silva, M., Dargenio, M., Davila-Valls, J., Martin-Perez, S., Farina, F., Van Doesum, J., Valkovic, T., Besson, C., Poulsen, C. B., Lopez-Garcia, A., Zak, P., Schonlein, M., Piukovics, K., Jaksic, O., Cabirta, A., Ali, N., Sili, U., Fracchiolla, N., Dragonetti, Giulia, Adzic-Vukicevic, T., Marchetti, M., Machado, M., Glenthoj, A., Finizio, O., Demirkan, F., Blennow, O., Tisi, M. C., Omrani, A. S., Navratil, M., Racil, Z., Novak, J., Magliano, G., Jimenez, M., Garcia-Vidal, C., Erben, N., Del Principe, M. I., Buquicchio, C., Bergantim, R., Batinic, J., Al-Khabori, M., Verga, L., Szotkowski, T., Samarkos, M., Ormazabal-Velez, I., Meers, S., Maertens, J., Pinczes, L. I., Hoenigl, M., Drgona, L., Cuccaro, A., Bilgin, Y. M., Aujayeb, A., Rahimli, L., Grafe, S., Sciume, M., Mladenovic, M., Colak, G. M., Sacchi, M. V., Nordlander, A., Berg Venemyr, C., Hanakova, M., Garcia-Pouton, N., Emarah, Z., Zambrotta, G. P. M., Nunes Rodrigues, R., Cordoba, R., Mendez, G. -A., Biernat, M. M., Cornely, O. A., Pagano, Livio, Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Cattaneo, C., Salmanton-Garcia, J., Marchesi, F., El-Ashwah, S., Itri, F., Weinbergerova, B., Gomes Da Silva, M., Dargenio, M., Davila-Valls, J., Martin-Perez, S., Farina, F., Van Doesum, J., Valkovic, T., Besson, C., Poulsen, C. B., Lopez-Garcia, A., Zak, P., Schonlein, M., Piukovics, K., Jaksic, O., Cabirta, A., Ali, N., Sili, U., Fracchiolla, N., Dragonetti, Giulia, Adzic-Vukicevic, T., Marchetti, M., Machado, M., Glenthoj, A., Finizio, O., Demirkan, F., Blennow, O., Tisi, M. C., Omrani, A. S., Navratil, M., Racil, Z., Novak, J., Magliano, G., Jimenez, M., Garcia-Vidal, C., Erben, N., Del Principe, M. I., Buquicchio, C., Bergantim, R., Batinic, J., Al-Khabori, M., Verga, L., Szotkowski, T., Samarkos, M., Ormazabal-Velez, I., Meers, S., Maertens, J., Pinczes, L. I., Hoenigl, M., Drgona, L., Cuccaro, A., Bilgin, Y. M., Aujayeb, A., Rahimli, L., Grafe, S., Sciume, M., Mladenovic, M., Colak, G. M., Sacchi, M. V., Nordlander, A., Berg Venemyr, C., Hanakova, M., Garcia-Pouton, N., Emarah, Z., Zambrotta, G. P. M., Nunes Rodrigues, R., Cordoba, R., Mendez, G. -A., Biernat, M. M., Cornely, O. A., Pagano, Livio, Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)
- Abstract
Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.
- Published
- 2022
16. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)
- Author
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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
17. Being a Myeloproliferative Patient in COVID-19 Era: The Mytico Study
- Author
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Cavalca, F, Renso, R, Zambrotta, G, Gambacorti Passerini, C, Elli, E, Zambrotta, GPM, Elli, EM, Cavalca, F, Renso, R, Zambrotta, G, Gambacorti Passerini, C, Elli, E, Zambrotta, GPM, and Elli, EM
- Abstract
Introduction: The Coronavirus disease 2019 (COVID-19) pandemic and the resulting social distancing, determined a reduction in access to care and limitations of individual freedom, with a consequent strong impact on quality of life (QoL), anxiety levels and medical management of onco-hematological people. In particular, in the case of patients with chronic myeloproliferative neoplasm (MPN), concern about SARS-CoV-2 infection added to the burden of symptoms (BS) which already weights on the QoL of these patients. We designed a cross-sectional survey in order to investigate the impact of the COVID-19 pandemic on status of anxiety, BS and QoL in MPN patients. Methods: We analyzed the anxiety levels using the Zung Self-Rating Anxiety Scale (SAS); BS modifications were studied using the 18 items of the Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF]. Results: 132 people answered to the survey: 27 (20.4%) patients achieved a moderate to marked anxiety index value: this group described a greater worsening of symptoms than the rest of the cohort (p <0.0001). Women showed a higher level of anxiety than men (p = 0.01). A trend for lower level of anxiety was reported by patients who performed habitual physical activity (p = 0.06). A total of 98 (74.2%) patients described worsening of their symptoms during the quarantine period; 94 (71.2%) patients had postponed appointments or visits: they showed a significant worsening of their BS (p =0.01). Conclusion: This study first showed that the COVID-19 quarantine had a significant negative impact on the level of anxiety and BS in MPN patients. We identified female gender, absence of physical activity, the need for frequent visit to the hospital and the absence of a direct access to healthcare staff as the main factors associated to a higher anxiety index and worst BS.
- Published
- 2021
18. ETNK1 mutations increase mitochondrial activity and promote DNA damage through ROS production
- Author
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Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Fanelli, F, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti Passerini, C, Piazza, R, Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Fanelli, F, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti Passerini, C, and Piazza, R
- Published
- 2018
19. ETNK1 MUTATIONS INCREASE MITOCHONDRIAL ACTIVITY AND PROMOTE DNA DAMAGE THROUGH ROS PRODUCTION
- Author
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Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti-Passerini, C, Piazza, R, D. Fontana, M. Mauri, A. Niro, L. Massimino, M. Bertagna, G. Zambrotta, M. Bossi, S. Citterio, B. Crescenzi, G. Signore, V. Piazza, C. Mecucci, G. Cavaletti, D. Rea, C. Gambacorti-Passerini, R. Piazza, Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, Citterio, S, Crescenzi, B, Signore, G, Piazza, V, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti-Passerini, C, Piazza, R, D. Fontana, M. Mauri, A. Niro, L. Massimino, M. Bertagna, G. Zambrotta, M. Bossi, S. Citterio, B. Crescenzi, G. Signore, V. Piazza, C. Mecucci, G. Cavaletti, D. Rea, C. Gambacorti-Passerini, and R. Piazza
- Published
- 2018
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