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34 results on '"Zambrotta, G."'

1. Late relapse of chronic myeloid leukemia after allogeneic bone marrow transplantation points to KANSARL (KANSL1::ARL17A) alteration: a case report with insights on the molecular landscape

Author

Fontana, D, Zambrotta, G, Scannella, A, Piazza, R, Gambacorti-Passerini, C, Zambrotta, GPM, Fontana, D, Zambrotta, G, Scannella, A, Piazza, R, Gambacorti-Passerini, C, and Zambrotta, GPM

Abstract

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome and the consequent BCR::ABL1 oncoprotein. In the era before the introduction of tyrosine kinase inhibitors (TKIs), the only potentially curative treatment was allogeneic hematopoietic stem cell transplantation (HSCT). Here, we present the case of a patient affected by CML who experienced a relapse 20 years after allogeneic HSCT. Following relapse, the patient was treated with imatinib and bosutinib, resulting in a deep molecular response and successfully discontinued treatment. Additional analysis including whole-exome sequencing and RNA sequencing provided some insights on the molecular mechanisms of the relapse: the identification of the fusion transcript KANSL1::ARL17A (KANSARL), a cancer predisposition fusion gene, could justify a condition of genomic instability which may be associated with the onset and/or probably the late relapse of his CML.

Published
2024

2. 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

3. Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry

Author

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

Author

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.

Published
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

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.

Published
2023

6. A monocentric analysis of the long-term safety and efficacy of crizotinib in relapsed/refractory ALK+ lymphomas

Author

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

Published
2023

7. Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry

Author

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

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

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

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

11. COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

Author

Marchesi F, Salmanton-García J, Emarah Z, Piukovics K, Nucci M, López-García A, Ráčil Z, Farina F, Popova M, Zompi S, Audisio E, Ledoux MP, Verga L, Weinbergerová B, Szotkovski T, Da Silva MG, Fracchiolla N, De Jonge N, Collins G, Marchetti M, Magliano G, García-Vidal C, Biernat MM, Van Doesum J, Machado M, Demirkan F, Al- Khabori M, Žák P, Víšek B, Stoma I, Méndez GA, Maertens J, Khanna N, Espigado I, Dragonetti G, Fianchi L, Del Principe MI, Cabirta A, Ormazabal- Vélez I, Jaksic O, Buquicchio C, Bonuomo V, Batinić J, Omrani AS, Lamure S, Finizio O, Fernández N, Falces-Romero I, Blennow O, Bergantim R, Ali N, Win S, Van Praet J, Tisi MC, Shirinova A, Schönlein M, Prattes J, Piedimonte M, Petzer V, Navrátil M, Kulasekararaj A, Jindra P, Sramek J, Glenthøj A, Fazzi R, De Ramón-Sánchez C, Cattaneo C, Calbacho M, Bahr NC, El-Ashwah S, Cordoba R, Hanakova M, Zambrotta G, Sciumè M, Booth S, Rodrigues RN, Sacchi MV, García-Poutón N, Martín- González JA, Khostelidi S, Gräfe S, Rahimli L, Ammatuna E, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Cornely OA, Pagano L and EPICOVIDEHA working group.

Subjects
AML Covid 19
Abstract

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died ; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80% ; P

Published
2023

12. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Author

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., Hematology, Pagano L., Salmanton-García J., Marchesi F., Blennow O., Gomes da Silva M., Glenthøj A., van Doesum J., Bilgin Y. M. , López-García A., Itri F., et al., and Gilead Sciences

Subjects
Internal Diseases, Clinical Trials and Observations, CELL BIOLOGY, Cardiorespiratory Medicine and Haematology, Sağlık Bilimleri, Fundamental Medical Sciences, Biochemistry, İç Hastalıkları, Clinical Medicine (MED), COVID-19 Testing, BİYOKİMYA VE MOLEKÜLER BİYOLOJİ, Biyokimya, Monoclonal, Klinik Tıp (MED), 03.02. Klinikai orvostan, Viral, Lung, Cancer, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Lymphoid Neoplasia, Myeloid Neoplasia, Klinik Tıp, Hücre Biyolojisi, Temel Bilimler, HEMATOLOJİ, Life Sciences, HÜCRE BİYOLOJİSİ, Tıp, MOLECULAR BIOLOGY & GENETICS, Infectious Diseases, Hematologic Neoplasms, Medicine, Natural Sciences, Infection, BIOCHEMISTRY & MOLECULAR BIOLOGY, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Sitogenetik, Biotechnology, Adult, Clinical Sciences, Immunology, Temel Tıp Bilimleri, Histoloji-Embriyoloji, Life Sciences (LIFE), Molecular Biology and Genetics, Antiviral Agents, Antibodies, Vaccine Related, Paediatrics and Reproductive Medicine, HEMATOLOGY, Biodefense, Yaşam Bilimleri, Health Sciences, Humans, CVOID19, Cytogenetic, Free Research Articles, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Moleküler Biyoloji ve Genetik, Internal Medicine Sciences, İmmünoloji, SARS-CoV-2, Histology and Embryology, Prevention, COVID-19, Dahili Tıp Bilimleri, CLINICAL MEDICINE, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15 - MALATTIE DEL SANGUE, Emerging Infectious Diseases, Good Health and Well Being, Yaşam Bilimleri (LIFE), Hematoloji, Immunization
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., EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2022

13. S281: PRIOR EXPOSURE TO IMMUNOSUPPRESSIVE AGENTS AND COMORBIDITIES ARE ASSOCIATED WITH WORSE OUTCOMES OF SARS-COV2 INFECTION IN PH-NEG CHRONIC MYELOPROLIFERATIVE NEOPLASMS: RESULTS OF EPICOVIDEHA SURVEY

Author

Marchetti, M., primary, Salmanton-García, J., additional, El-Ashwah, S., additional, Sacchi, M. V., additional, Marchesi, F., additional, Ráčil, Z., additional, Hanakova, M., additional, Zambrotta, G., additional, Verga, L., additional, Passamonti, F., additional, Itri, F., additional, Van Doesum, J., additional, Martìn-Pérez, S., additional, López-García, A., additional, Dávila-Valls, J., additional, Cordoba, R., additional, Abu-Zeinah, G., additional, Dragonetti, G., additional, Cattaneo, C., additional, Bonuomo, V., additional, Prezioso, L., additional, Glenthøj, A., additional, Farina, F., additional, Duarte, R., additional, Blennow, O., additional, Cornely, O, additional, and Pagano, L., additional

Published
2022
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14. ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

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.

Published
2020

15. ETNK1 mutations in atypical chronic myeloid leukemia induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

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

16. B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)

Author

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

17. Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey

Author

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

18. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Author

Pagano L, Salmanton-García J, Marchesi F, Blennow O, Gomes da Silva M, Glenthøj A, van Doesum J, Bilgin YM, López-García A, Itri F, Nunes Rodrigues R, Weinbergerová B, Farina F, Dragonetti G, Berg Venemyr C, van Praet J, Jaksic O, Valković T, Falces-Romero I, Martín-Pérez S, Jiménez M, Dávila-Valls J, Schönlein M, Ammatuna E, Meers S, Delia M, Stojanoski Z, Nordlander A, Lahmer T, Imre Pinczés L, Buquicchio C, Piukovics K, Ormazabal-Vélez I, Fracchiolla N, Samarkos M, Méndez GA, Hernández-Rivas JÁ, Espigado I, Cernan M, Petzer V, Lamure S, di Blasi R, Marques de Almedia J, Dargenio M, Biernat MM, Sciumè M, de Ramón C, de Jonge N, Batinić J, Aujayeb A, Marchetti M, Fouquet G, Fernández N, Zambrotta G, Sacchi MV, Guidetti A, Demirkan F, Prezioso L, Ráčil Z, Nucci M, Mladenović M, Liévin R, Hanáková M, Gräfe S, Sili U, Machado M, Cattaneo C, Adžić- Vukičević T, Verga L, Labrador J, Rahimli L, Bonanni M, Passamonti F, Pagliuca A, Corradini P, Hoenigl M, Koehler P, Busca A, Cornely OA.

Subjects
Covid-19
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

19. 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

20. Being a Myeloproliferative Patient in COVID-19 Era: The Mytico Study

Author

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

21. ETNK1 mutations promote ROS production and DNA damage through increased mitochondrial activity

Author

Fontana, D, Mauri, M, Niro, A, Massimino, L, Bertagna, M, Zambrotta, G, Bossi, M, CITTERIO, STEFANIA, Crescenzi, B, Signore, G, Piazza, V, 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, Mecucci, C, Cavaletti, G, Rea, D, Gambacorti-Passerini, C, and Piazza, R

Subjects
ETNK1, ROS
Abstract

Atypical chronic myeloid leukemia (aCML) is a clonal disorder belonging to the myelodysplastic/myeloproliferative syndromes. About 13% of aCML cases carry somatic mutations in ETNK1 gene, encoding for H243Y, N244S, and G245V substitutions. We previously showed that ETNK1 mutations cause a decreased catalytic activity of the enzyme. Despite this evidence however, their oncogenic role remained largely unexplained. Since ETNK1 activity is essential for the synthesis of phosphatidylethanolamine (PE) and given that PE is one of the most abundant phospholipids in the inner membrane of mitochondria, we focused our attention on mitochondrial activity. In order to characterize the oncogenic effect of ETNK1 variants we generated CRISPR/Cas9 clones carrying heterozygous N244S mutation and homozygous ETNK1 deletion (KO cells) on the 293 Flp-In™ cell-line. Both N244S and KO cells showed a significant increase in mitochondrial activity (1.78 and 2.13 fold increase, respectively; p= 0.0096 and p=0.0050) compared to WT, as assessed by MitoTracker™ Red. In line with this finding, electron microscopy revealed a significant modification in mitochondria morphology for N244S and KO cells, changing from an elongated, tubular shape to a round, swollen one. ATP (1.67 and 1.68 fold; p

Published
2018

22. ETNK1 mutations increase mitochondrial activity and promote DNA damage through ROS production

Author

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

Subjects
atypical chronic myeloid leukemia, mitochondrial activity
Published
2018

24. DNA Damage Response (DDR) Is Associated With Treatment-free Remission in Chronic Myeloid Leukemia Patients

Author

Federica Malighetti, Giulia Arosio, Chiara Manfroni, Mario Mauri, Matteo Villa, Beatrice Manghisi, Elena Inzoli, Giovanni Rindone, Giovanni P. M. Zambrotta, Ivan Civettini, Veronica Guglielmana, Daniele Ramazzotti, Giovanni Giudici, Silvia Bombelli, Roberto Perego, Rocco Piazza, Luca Mologni, Carlo Gambacorti-Passerini, 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, and Gambacorti-Passerini, C

Subjects
Chronic Myeloid Leukemia, Hematology
Published
2023

25. Being a Myeloproliferative Patient in COVID-19 Era: The Mytico Study

Author

Fabrizio Cavalca, Rossella Renso, Giovanni Paolo Maria Zambrotta, Carlo Gambacorti-Passerini, Elena Maria Elli, Cavalca, F, Renso, R, Zambrotta, G, Gambacorti Passerini, C, and Elli, E

Subjects
medicine.medical_specialty, Cancer Research, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Health care, medicine, burden of symptom, myeloproliferative disease, burden of symptoms, Myeloproliferative neoplasm, Original Research, business.industry, COVID-19, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, anxiety, medicine.disease, quality of life, Oncology, 030220 oncology & carcinogenesis, Chronic Myeloproliferative Neoplasm, Cohort, Anxiety, medicine.symptom, business, 030215 immunology
Abstract

IntroductionThe 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.MethodsWe 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].Results132 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 ConclusionThis 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
Full Text
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26. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author

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

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

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

Published
2021

27. ETNK1 mutations in atypical chronic myeloid leukemia induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

Clizia Chinello, Giovanni Zambrotta, Francesca Fanelli, Roberta Corti, Mi Jang, Steen Larsen, Carlo Gambacorti-Passerini, Rossella Renso, Rocco Piazza, Barbara Crescenzi, Mattia Docci, Lisa Marie Røst, Mayla Bertagna, Cristina Mecucci, Stefania Citterio, Deborah D'Aliberti, Francesco Mantegazza, Fulvio Magni, Ilaria Crespiatico, Guido Cavaletti, Antonio Niro, Diletta Fontana, Delphine Rea, Valeria Cassina, Mario Mauri, Domenico Salerno, Per Bruheim, M Bossi, Luca Nardo, Luca Massimino, 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, and Gambacorti-Passerini, C

Subjects
business.industry, Kinase, Somatic cell, Immunology, Mutator phenotype, Chronic myelomonocytic leukemia, Cell Biology, Hematology, medicine.disease, Biochemistry, medicine, Atypical chronic myeloid leukemia, Cancer research, Eosinophilia, Phosphorylation, Systemic mastocytosis, medicine.symptom, business, ETNK1, chronic myeloid leukemia
Abstract

ETNK1 kinase is responsible for the phosphorylation of ethanolamine to phosphoethanolamine (P-Et) (Kennedy, 1956, J Biol Chem). Recurrent somatic mutations occurring on ETNK1 were identified in about 13% of patients affected by atypical chronic myeloid leukemia (aCML), in 3-14% of chronic myelomonocytic leukemia (CMML), and in 20% of systemic mastocytosis (SM) patients with eosinophilia (Gambacorti-Passerini, 2015, Blood; Lasho, 2015, Blood Cancer J). ETNK1 mutations, encoding for H243Y, N244S/T/K, and G245V/A amino acid substitutions, cluster in a very narrow region of the ETNK1 catalytic domain and cause an impairment of ETNK1 enzymatic activity leading to a significant decrease in the intracellular concentration of P-Et (Gambacorti-Passerini, 2015, Blood). Despite this evidence, however, their oncogenic role remained largely unexplained. Here, we investigated the specific role of these mutations by using cellular CRISPR/Cas9 and ETNK1 overexpression models as well as aCML patients' samples. We showed that mutated ETNK1 causes a significant increase in mitochondrial activity (1.87 fold increase compared to WT; p=0.0002) and in ROS production (2.05 fold increase compared to WT; p Disclosures Rea: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Gambacorti-Passerini:Bristol-Myers Squibb: Consultancy; Pfizer: Honoraria, Research Funding.

Published
2020

28. ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine

Author

Francesca Fanelli, Steen Larsen, Stefania Citterio, Lisa Marie Røst, Roberta Corti, Barbara Crescenzi, Mattia Docci, Deborah D'Aliberti, Mi Jang, Delphine Rea, Rocco Piazza, Clizia Chinello, Mayla Bertagna, Guido Cavaletti, Fulvio Magni, Antonio Niro, M Bossi, Ilaria Crespiatico, Rossella Renso, Carlo Gambacorti-Passerini, Giovanni Zambrotta, Francesco Mantegazza, Domenico Salerno, Luca Massimino, Mario Mauri, Per Bruheim, Luca Nardo, Valeria Cassina, Cristina Mecucci, Diletta Fontana, 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, and Piazza, R

Subjects
0301 basic medicine, Myeloid, Cancer therapy, Somatic cell, Succinic Acid, General Physics and Astronomy, Cell Line, Cell Respiration, DNA Breaks, Electron Transport Complex II, Ethanolamines, Humans, Leukemia, Myeloid, Mitochondria, Mutation, Phenotype, Phosphotransferases (Alcohol Group Acceptor), Reactive Oxygen Species, Tigecycline, Mitochondrion, medicine.disease_cause, MITOCHONDRIAL, 0302 clinical medicine, PHOSPHATIDYLETHANOLAMINE, Ethanolamine, PHOSPHOMETABOLOME, Multidisciplinary, Leukemia, Hyperactivation, Molecular medicine, Chemistry, DNA Break, Cell biology, 030220 oncology & carcinogenesis, Phosphorylation, Reactive Oxygen Specie, Intracellular, Human, DNA damage, Science, HIGH-THROUGHPUT, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, TANDEM MASS-SPECTROMETRY, PATHWAYS, LEUKEMIA, LIPIDOME, REPAIR, Haematological cancer, General Chemistry, 030104 developmental biology
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., ETNK1 mutations are recurrent in leukemia but how they contribute to oncogenesis is still unclear. Here, the authors show that ETNK1 mutations increase mitochondrial activity, ROS and H2AX levels and that these effects can be rescued upon phosphoethanolamine supplementation.

Published
2020

29. ETNK1 MUTATIONS INCREASE MITOCHONDRIAL ACTIVITY AND PROMOTE DNA DAMAGE THROUGH ROS PRODUCTION

Author

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, and Piazza, R

Subjects
acml
Published
2018

31. COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Author

Marchesi F, Salmanton-García J, Emarah Z, Piukovics K, Nucci M, López-García A, Ráčil Z, Farina F, Popova M, Zompi S, Audisio E, Ledoux MP, Verga L, Weinbergerová B, Szotkovski T, Da Silva MG, Fracchiolla N, De Jonge N, Collins G, Marchetti M, Magliano G, García-Vidal C, Biernat MM, Van Doesum J, Machado M, Demirkan F, Al-Khabori M, Žák P, Víšek B, Stoma I, Méndez GA, Maertens J, Khanna N, Espigado I, Dragonetti G, Fianchi L, Del Principe MI, Cabirta A, Ormazabal-Vélez I, Jaksic O, Buquicchio C, Bonuomo V, Batinić J, Omrani AS, Lamure S, Finizio O, Fernández N, Falces-Romero I, Blennow O, Bergantim R, Ali N, Win S, Van Praet J, Tisi MC, Shirinova A, Schönlein M, Prattes J, Piedimonte M, Petzer V, Navrátil M, Kulasekararaj A, Jindra P, Sramek J, Glenthøj A, Fazzi R, De Ramón-Sánchez C, Cattaneo C, Calbacho M, Bahr NC, El-Ashwah S, Cordoba R, Hanakova M, Zambrotta G, Sciumè M, Booth S, Rodrigues RN, Sacchi MV, García-Poutón N, Martín-González JA, Khostelidi S, Gräfe S, Rahimli L, Ammatuna E, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Cornely OA, and Pagano L

Subjects
Humans, Adult, Follow-Up Studies, COVID-19 Testing, COVID-19, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Hematology
Abstract

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Published
2023
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32. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey.

Author

Pagano L, Salmanton-García J, Marchesi F, Blennow O, Gomes da Silva M, Glenthøj A, van Doesum J, Bilgin YM, López-García A, Itri F, Nunes Rodrigues R, Weinbergerová B, Farina F, Dragonetti G, Berg Venemyr C, van Praet J, Jaksic O, Valković T, Falces-Romero I, Martín-Pérez S, Jiménez M, Dávila-Valls J, Schönlein M, Ammatuna E, Meers S, Delia M, Stojanoski Z, Nordlander A, Lahmer T, Imre Pinczés L, Buquicchio C, Piukovics K, Ormazabal-Vélez I, Fracchiolla N, Samarkos M, Méndez GA, Hernández-Rivas JÁ, Espigado I, Cernan M, Petzer V, Lamure S, di Blasi R, Marques de Almedia J, Dargenio M, Biernat MM, Sciumè M, de Ramón C, de Jonge N, Batinić J, Aujayeb A, Marchetti M, Fouquet G, Fernández N, Zambrotta G, Sacchi MV, Guidetti A, Demirkan F, Prezioso L, Ráčil Z, Nucci M, Mladenović M, Liévin R, Hanáková M, Gräfe S, Sili U, Machado M, Cattaneo C, Adžić-Vukičević T, Verga L, Labrador J, Rahimli L, Bonanni M, Passamonti F, Pagliuca A, Corradini P, Hoenigl M, Koehler P, Busca A, and Cornely OA

Subjects
Adult, Humans, SARS-CoV-2, COVID-19 Testing, Antibodies, Monoclonal, Antiviral Agents, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention & control, Hematologic Neoplasms complications, Hematologic Neoplasms therapy
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., (© 2022 by The American Society of Hematology.)

Published
2022
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33. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

Author

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

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

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

Published
2021
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34. ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine.

Author

Fontana D, Mauri M, Renso R, Docci M, Crespiatico I, Røst LM, 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

Subjects
Cell Line, Cell Respiration drug effects, Cell Respiration genetics, DNA Breaks drug effects, Electron Transport Complex II drug effects, Electron Transport Complex II metabolism, Ethanolamines metabolism, Humans, Leukemia, Myeloid genetics, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Mitochondria genetics, Mitochondria pathology, Mutation, Phenotype, Phosphotransferases (Alcohol Group Acceptor) metabolism, Reactive Oxygen Species metabolism, Succinic Acid metabolism, Tigecycline pharmacology, Ethanolamines pharmacology, Mitochondria drug effects, Mitochondria metabolism, Phosphotransferases (Alcohol Group Acceptor) genetics
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.

Published
2020
Full Text
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