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

Author

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

Abstract

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

Published
2024

2. 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

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

Author

Busca, A., Salmanton-García, J., Marchesi, F., Farina, F., Seval, G.C., Doesum, J. Van, Jonge, N. de, Bahr, N.C., Maertens, J., Meletiadis, J., Fracchiolla, N.S., Weinbergerová, B., Verga, L., Ráčil, Z., Jiménez, M., Glenthøj, A., Blennow, O., Tanase, A.D., Schönlein, M., Prezioso, L., Khanna, N., Duarte, R.F., Žák, P., Nucci, M., Machado, M., Kulasekararaj, A., Espigado, I., Kort, E.A. de, 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, G., Cabirta, A., Berg Venemyr, C., Gräfe, S., Praet, J. Van, Tragiannidis, A., Petzer, V., López-García, A., Itri, F., Groh, A., Gavriilaki, E., Dargenio, M., Rahimli, L., Cornely, O.A., Pagano, L., Busca, A., Salmanton-García, J., Marchesi, F., Farina, F., Seval, G.C., Doesum, J. Van, Jonge, N. de, Bahr, N.C., Maertens, J., Meletiadis, J., Fracchiolla, N.S., Weinbergerová, B., Verga, L., Ráčil, Z., Jiménez, M., Glenthøj, A., Blennow, O., Tanase, A.D., Schönlein, M., Prezioso, L., Khanna, N., Duarte, R.F., Žák, P., Nucci, M., Machado, M., Kulasekararaj, A., Espigado, I., Kort, E.A. de, 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, G., Cabirta, A., Berg Venemyr, C., Gräfe, S., Praet, J. Van, Tragiannidis, A., Petzer, V., López-García, A., Itri, F., Groh, A., Gavriilaki, E., Dargenio, M., Rahimli, L., Cornely, O.A., and Pagano, L.

Abstract

Item does not contain fulltext, 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

6. Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002.

Author

Meyers, G., Hamadani, M., Martens, M., Ali, H., Chevallier, P., Choe, H., Harris, A.C., Holler, E., Hooren, E. van, Klaassen, W., Leifer, E., Oosterhout, Y. van, Perez, L., Pusic, I., Stelljes, M., Velden, W.J.F.M. van der, Ammatuna, E., Beauvais, D., Cornillon, J., Maziarz, R.T., Schetelig, J., Romeril, J., MacMillan, M.L., Levine, J.E., Socié, G., Meyers, G., Hamadani, M., Martens, M., Ali, H., Chevallier, P., Choe, H., Harris, A.C., Holler, E., Hooren, E. van, Klaassen, W., Leifer, E., Oosterhout, Y. van, Perez, L., Pusic, I., Stelljes, M., Velden, W.J.F.M. van der, Ammatuna, E., Beauvais, D., Cornillon, J., Maziarz, R.T., Schetelig, J., Romeril, J., MacMillan, M.L., Levine, J.E., and Socié, G.

Abstract

Contains fulltext : 299881.pdf (Publisher’s version ) (Closed access), 01 december 2023

Published
2023

7. 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial.

Author

Lübbert, M., Wijermans, P.W., Kicinski, M., Chantepie, S., Velden, W.J.F.M. van der, Noppeney, R., Griškevičius, L., Neubauer, A., Crysandt, M., Vrhovac, R., Luppi, M., Fuhrmann, S., Audisio, E., Candoni, A., Legrand, O., Foà, R., Gaidano, G., Lammeren-Venema, D. van, Posthuma, E.F.M., Hoogendoorn, M., Giraut, A., Stevens-Kroef, M.J.P.L., Jansen, J.H., Graaf, A.O. de, Efficace, F., Ammatuna, E., Vilque, J.P., Wäsch, R., Becker, H., Blijlevens, N., Dührsen, U., Baron, F., Suciu, S., Amadori, S., Venditti, A., Huls, G., Lübbert, M., Wijermans, P.W., Kicinski, M., Chantepie, S., Velden, W.J.F.M. van der, Noppeney, R., Griškevičius, L., Neubauer, A., Crysandt, M., Vrhovac, R., Luppi, M., Fuhrmann, S., Audisio, E., Candoni, A., Legrand, O., Foà, R., Gaidano, G., Lammeren-Venema, D. van, Posthuma, E.F.M., Hoogendoorn, M., Giraut, A., Stevens-Kroef, M.J.P.L., Jansen, J.H., Graaf, A.O. de, Efficace, F., Ammatuna, E., Vilque, J.P., Wäsch, R., Becker, H., Blijlevens, N., Dührsen, U., Baron, F., Suciu, S., Amadori, S., Venditti, A., and Huls, G.

Abstract

Contains fulltext : 299611.pdf (Publisher’s version ) (Closed access), BACKGROUND: Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes. METHODS: This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. Patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an Eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. Patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). For the decitabine group, decitabine (20 mg/m(2)) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m(2)) was administered over the first 3 days and cytarabine (200 mg/m(2)) over the first 7 days, followed by 1-3 additional chemotherapy cycles. Allogeneic HSCT was strongly encouraged. Overall survival in the intention-to-treat population was the primary endpoint. Safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants. FINDINGS: Between Dec 1, 2014, and Aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. Following an interim analysis which showed futility, the IDMC recommended on May 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35, 01 november 2023

Published
2023

8. Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry

Author

Marchesi, F., Salmanton-Garcia, J., Buquicchio, C., Itri, F., Besson, C., Davila-Valls, J., Martin-Perez, S., Fianchi, Luana, Rahimli, L., Tarantini, G., Grifoni, F. I., Sciume, M., Labrador, J., Cordoba, R., Lopez-Garcia, A., Fracchiolla, N. S., Farina, F., Ammatuna, E., Cingolani, Antonella, Garcia-Bordallo, D., Grafe, S. K., Bilgin, Y. M., Dargenio, M., Gonzalez-Lopez, T. J., Guidetti, A., Lahmer, T., Lavilla-Rubira, E., Mendez, G. -A., Prezioso, L., Schonlein, M., Van Doesum, J., Wolf, D., Hersby, D. S., Magyari, F., Van Praet, J., Petzer, V., Tascini, C., Falces-Romero, I., Glenthoj, A., Cornely, O. A., Pagano, Livio, Fianchi L., Cingolani A. (ORCID:0000-0002-3793-2755), Pagano L. (ORCID:0000-0001-8287-928X), Marchesi, F., Salmanton-Garcia, J., Buquicchio, C., Itri, F., Besson, C., Davila-Valls, J., Martin-Perez, S., Fianchi, Luana, Rahimli, L., Tarantini, G., Grifoni, F. I., Sciume, M., Labrador, J., Cordoba, R., Lopez-Garcia, A., Fracchiolla, N. S., Farina, F., Ammatuna, E., Cingolani, Antonella, Garcia-Bordallo, D., Grafe, S. K., Bilgin, Y. M., Dargenio, M., Gonzalez-Lopez, T. J., Guidetti, A., Lahmer, T., Lavilla-Rubira, E., Mendez, G. -A., Prezioso, L., Schonlein, M., Van Doesum, J., Wolf, D., Hersby, D. S., Magyari, F., Van Praet, J., Petzer, V., Tascini, C., Falces-Romero, I., Glenthoj, A., Cornely, O. A., Pagano, Livio, Fianchi L., Cingolani A. (ORCID:0000-0002-3793-2755), and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.

Published
2023

9. 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

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
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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
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15. P437: SURVIVAL-BASED 4-GENE PROGNOSTIC INDEX IMPROVES THE ELN-RISK CLASSIFICATION IN ACUTE MYELOID LEUKEMIA

Author

Ortiz Rojas, C. A., primary, Pereira-Martins, D. A., additional, Bellido More, C. C., additional, Hilberink, J. R., additional, Coelho-Silva, J. L., additional, Weinhäuser, I., additional, Yamamoto de Almeida, L., additional, de Deus Wagatsuma, V. M., additional, Hassibe Thomé, C., additional, Aguiar Ferreira, G., additional, Ammatuna, E., additional, Huls, G., additional, Schuringa, J. J., additional, and Magalhães Rego, E., additional

Published
2022
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16. S125: 10-DAY DECITABINE VS. CONVENTIONAL CHEMOTHERAPY (“3 + 7”) FOLLOWED BY ALLOGRAFTING (HSCT) IN AML PATIENTS ≥60 YEARS: A RANDOMIZED PHASE III STUDY OF THE EORTC LEUKEMIA GROUP, GIMEMA, CELG, AND GMDS-SG

Author

Lübbert, M., primary, Wijermans, P., additional, Kicinski, M., additional, Chantepie, S., additional, van der Velden, W., additional, Noppeney, R., additional, Griskevicius, L., additional, Neubauer, A., additional, Crysandt, M., additional, Vrhovac, R., additional, Luppi, M., additional, Fuhrmann, S., additional, Audisio, E., additional, Candoni, A., additional, Legrand, O., additional, Foà, R., additional, Gaidano, G., additional, van Lammeren-Venema, D., additional, Posthuma, E. F., additional, Hoogendoorn, M., additional, Giraut, A., additional, Stevens-Kroef, M., additional, Jansen, J. H., additional, Ammatuna, E., additional, Vilque, J.-P., additional, Wäsch, R., additional, Becker, H., additional, Blijlevens, N., additional, Dührsen, U., additional, Baron, F., additional, Suciu, S., additional, Amadori, S., additional, Venditti, A., additional, and Huls, G., additional

Published
2022
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18. S252: M2-POLARIZED MACROPHAGES CONTROL LEUKEMIC STEM CELL FATE BY PROMOTING METABOLIC REPROGRAMMING

Author

Weinhäuser, I., primary, Pereira-Martins, D. A., additional, Hilberink, J. R., additional, Almeida, L. Y., additional, Silveira, D. R. A., additional, Quek, L., additional, Hogeling, S. M, additional, Mota, J. M., additional, Ammatuna, E., additional, Lucena-Araujo, A. R., additional, Huls, G. A., additional, Rego, E. M., additional, and Schuringa, J. J., additional

Published
2022
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19. P439: ASSOCIATING EX VIVO DRUG SENSITIVITY WITH METABOLIC STATUS IDENTIFIES EFFECTIVE COMBINATION STRATEGIES IN ACUTE MYELOID LEUKEMIA

Author

Pereira-Martins, D. A., primary, Griessinger, E., additional, Weinhauser, I., additional, Coelho-Silva, J. L., additional, Silveira, D. R., additional, Quek, L., additional, Erdem, A., additional, Hilberink, J. R., additional, de Paula, E. V., additional, Olalla Saad, S. T., additional, Ammatuna, E., additional, Huls, G., additional, Rego, E. M., additional, Lucena-Araujo, A. R., additional, and Schuringa, J. J., additional

Published
2022
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20. Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: An EPICOVIDEHA survey report

Author

Blennow, O., Salmanton-García, J., Nowak, P., Itri, F., Doesum, J. Van, López-García, A., Farina, F., Jaksic, O., Pinczés, L.I., Bilgin, Y.M., Falces-Romero, I., Jiménez, M., Ormazabal-Vélez, I., Weinbergerová, B., Duléry, R., Stojanoski, Z., Lahmer, T., Fernández, N., Hernández-Rivas, J., Petzer, V., Jonge, N. de, Glenthøj, A., Ramón, C. De, Biernat, M.M., Fracchiolla, N., Aujayeb, A., Praet, J. Van, Schönlein, M., Méndez, G.A., Cattaneo, C., Guidetti, A., Sciumè, M., Ammatuna, E., Cordoba, R., García-Poutón, N., Gräfe, S., Cabirta, A., Wolf, D., Nordlander, A., García-Sanz, R., Delia, M., Venemyr, C. Berg, Brones, C., Blasi, R. Di, Kort, E.A. de, Meers, S., Lamure, S., Serrano, L., Merelli, M., Coppola, N., Bergantim, R., Besson, C., Kohn, M., Petiti, J., Garcia-Vidal, C., Dargenio, M., Danion, F., Machado, M., Bailén-Almorox, R., Hoenigl, M., Dragonetti, G., Chai, L.Y., Kho, C.S., Bonanni, M., Liévin, R., Marchesi, F., Cornely, O.A., Pagano, L., Blennow, O., Salmanton-García, J., Nowak, P., Itri, F., Doesum, J. Van, López-García, A., Farina, F., Jaksic, O., Pinczés, L.I., Bilgin, Y.M., Falces-Romero, I., Jiménez, M., Ormazabal-Vélez, I., Weinbergerová, B., Duléry, R., Stojanoski, Z., Lahmer, T., Fernández, N., Hernández-Rivas, J., Petzer, V., Jonge, N. de, Glenthøj, A., Ramón, C. De, Biernat, M.M., Fracchiolla, N., Aujayeb, A., Praet, J. Van, Schönlein, M., Méndez, G.A., Cattaneo, C., Guidetti, A., Sciumè, M., Ammatuna, E., Cordoba, R., García-Poutón, N., Gräfe, S., Cabirta, A., Wolf, D., Nordlander, A., García-Sanz, R., Delia, M., Venemyr, C. Berg, Brones, C., Blasi, R. Di, Kort, E.A. de, Meers, S., Lamure, S., Serrano, L., Merelli, M., Coppola, N., Bergantim, R., Besson, C., Kohn, M., Petiti, J., Garcia-Vidal, C., Dargenio, M., Danion, F., Machado, M., Bailén-Almorox, R., Hoenigl, M., Dragonetti, G., Chai, L.Y., Kho, C.S., Bonanni, M., Liévin, R., Marchesi, F., Cornely, O.A., and Pagano, L.

Abstract

Contains fulltext : 282572.pdf (Publisher’s version ) (Open Access)

Published
2022

21. 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

22. 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

24. Reduced SLIT2 is associated with increased cell proliferation and arsenic trioxide resistance in acute promyelocytic Leukemia

Author

Weinhäuser, I., Pereira-Martins, D.A., Ortiz, C., Silveira, D.R., Simões, L.A.A., Bianco, T.M., Araujo, C.L., Koury, L.C.D., Melo, R.A. (Raul), Bittencourt, R.I., Pagnano, K. (Katia), Pasquini, R. (Ricardo), Nunes, E.C., Fagundes, E.M. (Evandro), Gloria, ABF, Kerbauy, F., De Lourdes Chauffaille, M., Keating, A, Tallman, M.S. (Martin), Ribeiro, R.C. (Raul), Dillon, R, Ganser, A. (Arnold), Löwenberg, B., Valk, P.J.M. (Peter), Lo-Coco, F. (Francesco), Sanz, M.A. (Miguel Angel), Berliner, N. (Nancy), Ammatuna, E., Lucena-Araujo, A.R. (Antonio), Schuringa, J.J. (Jan Jacob), Rego, E.M. (Eduardo), Weinhäuser, I., Pereira-Martins, D.A., Ortiz, C., Silveira, D.R., Simões, L.A.A., Bianco, T.M., Araujo, C.L., Koury, L.C.D., Melo, R.A. (Raul), Bittencourt, R.I., Pagnano, K. (Katia), Pasquini, R. (Ricardo), Nunes, E.C., Fagundes, E.M. (Evandro), Gloria, ABF, Kerbauy, F., De Lourdes Chauffaille, M., Keating, A, Tallman, M.S. (Martin), Ribeiro, R.C. (Raul), Dillon, R, Ganser, A. (Arnold), Löwenberg, B., Valk, P.J.M. (Peter), Lo-Coco, F. (Francesco), Sanz, M.A. (Miguel Angel), Berliner, N. (Nancy), Ammatuna, E., Lucena-Araujo, A.R. (Antonio), Schuringa, J.J. (Jan Jacob), and Rego, E.M. (Eduardo)

Abstract

The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2high transcript levels were associated with cell cycle arrest, while SLIT2low APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92–0.97; p < 0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated.

Published
2020
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25. Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

Author

Huls, G. (Gerwin), Chitu, D.A., Pabst, T. (Thomas), Klein, SK, Stussi, G. (Georg), Griskevicius, L., Valk, P.J.M. (Peter), Cloos, J. (Jacqueline), de Loosdrecht, AAV, Breems, D.A. (Dimitri), van Lammeren - Venema, D. (Danielle), van Zeventer, I., Boersma, R., Jongen-Lavrencic, M. (Mojca), Fehr, M., Hoogendoorn, M. (Martine), Manz, MG, Söhne, M. (Maaike), Kooy, RV, Deeren, D., van der Poel, M.W.M., Legdeur, MC, Tick, L.W. (Lidwine), Chalandon, Y. (Yves), Ammatuna, E., Blum, S., Löwenberg, B. (Bob), Ossenkoppele, G.J. (Gert), Huls, G. (Gerwin), Chitu, D.A., Pabst, T. (Thomas), Klein, SK, Stussi, G. (Georg), Griskevicius, L., Valk, P.J.M. (Peter), Cloos, J. (Jacqueline), de Loosdrecht, AAV, Breems, D.A. (Dimitri), van Lammeren - Venema, D. (Danielle), van Zeventer, I., Boersma, R., Jongen-Lavrencic, M. (Mojca), Fehr, M., Hoogendoorn, M. (Martine), Manz, MG, Söhne, M. (Maaike), Kooy, RV, Deeren, D., van der Poel, M.W.M., Legdeur, MC, Tick, L.W. (Lidwine), Chalandon, Y. (Yves), Ammatuna, E., Blum, S., Löwenberg, B. (Bob), and Ossenkoppele, G.J. (Gert)

Abstract

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85.

Published
2020
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26. Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

Author

Huls, G, Chitu, Dana, Pabst, T, Klein, SK, Stussi, G, Griskevicius, L, Valk, Peter, Cloos, J, de Loosdrecht, AAV, Breems, D, van Lammeren-Venema, D, van Zeventer, I, Boersma, R, Jongen - Lavrencic, Mojca, Fehr, M, Hoogendoorn - Lips, EJI, Manz, MG, Sohne, M, Kooy, RV, Deeren, D, van der Poel, MWM, Legdeur, MC, Tick, L, Chalandon, Y, Ammatuna, E, Blum, S, Löwenberg, Bob, Ossenkoppele, GJ, Huls, G, Chitu, Dana, Pabst, T, Klein, SK, Stussi, G, Griskevicius, L, Valk, Peter, Cloos, J, de Loosdrecht, AAV, Breems, D, van Lammeren-Venema, D, van Zeventer, I, Boersma, R, Jongen - Lavrencic, Mojca, Fehr, M, Hoogendoorn - Lips, EJI, Manz, MG, Sohne, M, Kooy, RV, Deeren, D, van der Poel, MWM, Legdeur, MC, Tick, L, Chalandon, Y, Ammatuna, E, Blum, S, Löwenberg, Bob, and Ossenkoppele, GJ

Published
2020

27. Reduced SLIT2 is associated with increased cell proliferation and arsenic trioxide resistance in acute promyelocytic Leukemia

Author

Weinhäuser, I, Pereira-Martins, DA, Ortiz, C, Silveira, DR, Simões, LAA, Bianco, TM, Araujo, CL, Koury, LCD, Melo, RA, Bittencourt, RI, Pagnano, K, Pasquini, R, Nunes, EC, Fagundes, EM, Gloria, ABF, Kerbauy, F, De Lourdes Chauffaille, M, Keating, A, Tallman, MS, Ribeiro, RC, Dillon, R, Ganser, A, Löwenberg, Bob, Valk, Peter, Lo-Coco, F, Sanz, MA, Berliner, N, Ammatuna, E, Lucena-Araujo, AR, Schuringa, JJ, Rego, EM, Weinhäuser, I, Pereira-Martins, DA, Ortiz, C, Silveira, DR, Simões, LAA, Bianco, TM, Araujo, CL, Koury, LCD, Melo, RA, Bittencourt, RI, Pagnano, K, Pasquini, R, Nunes, EC, Fagundes, EM, Gloria, ABF, Kerbauy, F, De Lourdes Chauffaille, M, Keating, A, Tallman, MS, Ribeiro, RC, Dillon, R, Ganser, A, Löwenberg, Bob, Valk, Peter, Lo-Coco, F, Sanz, MA, Berliner, N, Ammatuna, E, Lucena-Araujo, AR, Schuringa, JJ, and Rego, EM

Published
2020

33. Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107)

Author

Amadori, S, Stasi, R, Martelli, Am, Venditti, A, Meloni, G, Pane, F, Martinelli, G, Lunghi, M, Pagano, L, Cilloni, D, Rossetti, E, DI RAIMONDO, Francesco, Fozza, C, Annino, L, Chiarini, F, Ricci, F, Ammatuna, E, La Sala, E, Fazi, P, Vignetti, M., Amadori, S, Stasi, R, Martelli, Am, Venditti, A, Meloni, G, Pane, Fabrizio, Martinelli, G, Lunghi, M, Pagano, L, Cilloni, D, Rossetti, E, Di Raimondo, F, Fozza, C, Annino, L, Chiarini, F, Ricci, F, Ammatuna, E, La Sala, E, Fazi, P, Vignetti, M., Amadori S., Stasi R., Martelli A.M., Venditti A., Meloni G., Pane F., Martinelli G., Lunghi M., Pagano L., Cilloni D., Rossetti E., Di Raimondo F., Fozza C., Annino L., Chiarini F., Ricci F., Ammatuna E., La Sala E., Fazi P., and Vignetti M.

Subjects
age factors, tor serine-threonine kinases, adenine nucleotides, disease-free survival, antineoplastic combined chemotherapy protocols, acute, acute myeloid leukaemia, administration /&/ dosage/adverse effects, administration /&/ dosage/adverse effects/analogs /&/ derivatives, adverse effects/therapeutic use, aged, antagonists /&/ inhibitors, arabinonucleosides, clofarabine, drug therapy, elderly patients, female, humans, leukemia, male, mammalian target of rapamycin, methods, middle aged, myeloid, salvage therapy, sirolimus, temsirolimus, temsirolimu, ACUTE MYELOID LEUKEMIA, AKT/MAMMALIAN TARGET OF RAPAMYCIN (MTOR), Clofarabine, ELDERLY PATIENTS, Adenine Nucleotides, administration /&/ dosage/adverse effects, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols, adverse effects/therapeutic use, Arabinonucleosides, administration /&/ dosage/adverse effects, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute, drug therapy, Male, Middle Aged, Salvage Therapy, methods, Sirolimus, administration /&/ dosage/adverse effects/analogs /&/ derivatives, TOR Serine-Threonine Kinases, Leukemia, Myeloid, Acute, Settore MED/15 - Malattie del Sangue
Abstract

The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20 mg/m2 on days 15 and temsirolimus 25 mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3.5 months, and median overall survival was 4 months (9.1 months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P = 0.0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.

Published
2012

35. Disseminated fusariosis

Author

Sandberg, Y. (Yorick), Clahsen-van Groningen, M.C. (Marian), Ammatuna, E. (E.), Sandberg, Y. (Yorick), Clahsen-van Groningen, M.C. (Marian), and Ammatuna, E. (E.)

Published
2015
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36. Molecular characterization of paediatric idiopathic hypereosinophilia

Author

Rapanotti, M, Caruso, R, Ammatuna, E, Zaza, S, Trotta, L, Divona, M, Cicconi, L, Funaro, D, Federici, G, Amadori, S, De Rossi, G, and LO COCO, F

Subjects
Gene Rearrangement, Male, Lymphoma, B-Cell, Adolescent, Infant, lymphoma, B-cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, preschool, Immunophenotyping, prognosis, adolescent, male, infant, female, child, preschool, gene rearrangement, hypereosinophilic syndrome, precursor cell lymphoblastic leukemia-lymphoma, humans, follow-up studies, lymphoma, B-cell, child, immunophenotyping, immunoglobulin heavy chains, Child, Preschool, Hypereosinophilic Syndrome, Humans, Female, Child, Immunoglobulin Heavy Chains, Settore MED/15 - Malattie del Sangue, Follow-Up Studies
Abstract

The hypereosinophilic syndromes (HES) include a group of heterogeneous diseases characterized by the persistent increase of the number of eosinophils in blood and bone marrow. Few cases of paediatric hypereosinophilia (pHES) have been described in the literature. Early identification of pHES that may evolve towards a lymphomyeloproliferative disease is relevant in light of prognostic and therapeutic implications. Molecular features of 10 pHES patients were analysed at presentation and during their clinical course, including analysis of BCR-ABL1 and FIP1L1/PDGFRA fusion genes, quantitation of WT1 gene copy number and clonality of T-cell receptor (TCR) and immunoglobulin heavy chain (IGH). All patients had normal karyotype and germline TCR configuration. Five children showed IGH clonality at presentation: of these, two developed a B non-Hodgkin lymphoma and a B-lineage acute lymphocytic leukaemia at six and 12 months respectively, two spontaneously reverted to a polyclonal IGH profile during the follow-up, and the last one persisted with pHES without B-clonal evolution after 19 months. One patient had a PDGFRA/FIP1L1 fusion and achieved hematologic and molecular remission after imatinib therapy. IGH rearrangement was observed to be a frequent molecular feature of pHES and may precede B-cell clonal expansion and evolution into B-cell malignancies in children.

Published
2010

38. Identification of a potential 'Hotspot' DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation

Author

Ottone, T, Hasan, Sk, Montefusco, E, Curzi, P, Mays, An, Chessa, L, Ferrari, A, Conte, E, Noguera, Ni, Lavorgna, S, Ammatuna, E, Divona, M, Bovetti, K, Amadori, S, Grimwade, D, and LO COCO, F

Subjects
Myeloid, Male, genomic DNA, sequence analysis, polymerase chain reaction, complementary DNA, multiple sclerosis, granulocyte colony stimulating factor, gene targeting, cytarabine, In Situ Hybridization, Oncogene Proteins, Leukemia, adult, article, Middle Aged, acute granulocytic leukemia, leukemia cell, priority journal, Core Binding Factor Alpha 2 Subunit, Cytogenetic Analysis, transcription factor RUNX1, intron, DNA sequence, Translocation, Acute, Type II, mitoxantrone, Fluorescence, Databases, Genetic, human genome, DNA, fludarabine, case report, chromosome translocation, gene, gene fusion, gene identification, gene translocation, human, male, nucleotide sequence, RUNXI gene, Databases, Genetic, DNA Topoisomerases, Type II, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myeloid, Acute, Mitoxantrone, Multiple Sclerosis, Oncogene Proteins, Fusion, Phosphoproteins, Repressor Proteins, Sequence Analysis, DNA, Translocation, Genetic, Tumor Suppressor Proteins, Fusion, Neoplastic, Gene Expression Regulation, Settore MED/15 - Malattie del Sangue, DNA Topoisomerases
Published
2009

40. Front line clinical trials and minimal residual disease monitoring in acute promyelocytic leukemia

Author

LO COCO, F and Ammatuna, E

Subjects
Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Humans, Leukemia, Promyelocytic, Acute, Monitoring, Physiologic, Neoplasm, Residual, Oncogene Proteins, Fusion, Reverse Transcriptase Polymerase Chain Reaction, Treatment Outcome, Promyelocytic, Oncogene Proteins, Leukemia, Monitoring, Acute, Residual, Neoplasm, Physiologic, Fusion, Settore MED/15 - Malattie del Sangue
Abstract

In spite of the very high cure rate (70%-80%) achieved in APL with combinatorial all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens, a number of issues are still open for investigation in front-line therapy of this disease. These include, among others, improvements in early death rate, the role of arsenic trioxide (ATO) and maintenance treatment, and, finally, optimization of molecular monitoring to better identify patients at increased risk of relapse. The current consensus on the most appropriate induction therapy consists of the concomitant administration of ATRA and anthracycline-based chemotherapy. Although the antileukemic benefit provided by the addition of ATRA to consolidation therapy has not been demonstrated in randomized studies, historical comparisons of consecutive studies carried out by Spanish and Italian cooperative groups suggest that the combination of ATRA and chemotherapy for consolidation may also contribute to improving therapeutic results. While a variety of distinct treatments are being investigated for front-line therapy, most experts agree that a risk-adapted therapy represents the optimal approach, through the use of more intensive therapy in patients with initial hyperleukocytosis. Longitudinal RT-PCR of PML/RARalpha allows sensitive assessment of response to treatment and minimal residual disease (MRD) monitoring in APL. Achievement of negative PCR status or molecular remission at the end of consolidation is now universally accepted and recommended as a therapeutic objective in this disease. On the other hand, persistence of, or conversion to, PCR positive in the marrow during follow-up is associated with impending relapse. Preliminary studies on therapy of molecular relapse indicate a survival advantage as compared to administering salvage treatment at time of hematologic relapse. The more accurate and reproducible real-time PCR method to detect at quantitative levels the PML/RARalpha hybrid will likely provide better inter-laboratory standardization and trial results comparison in the near future.

Published
2007

47. Front Line Clinical Trials and Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia.

Author

Compans, R. W., Cooper, M. D., Honjo, T., Koprowski, H., Melchers, F., Oldstone, M. B. A., Olsnes, S., Svanborg, C., Vogt, P. K., Wagner, H., Pandolfi, Pier Paolo, Vogt, Peter K., Lo-Coco, F., and Ammatuna, E.

Abstract

In spite of the very high cure rate (70%-80%) achieved in APL with combinatorial all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens, a number of issues are still open for investigation in front-line therapy of this disease. These include, among others, improvements in early death rate, the role of arsenic trioxide (ATO) and maintenance treatment, and, finally, optimization of molecular monitoring to better identify patients at increased risk of relapse. The current consensus on the most appropriate induction therapy consists of the concomitant administration of ATRA and anthracycline-based chemotherapy. Although the antileukemic benefit provided by the addition of ATRA to consolidation therapy has not been demonstrated in randomized studies, historical comparisons of consecutive studies carried out by Spanish and Italian cooperative groups suggest that the combination of ATRA and chemotherapy for consolidation may also contribute to improving therapeutic results. While a variety of distinct treatments are being investigated for front-line therapy, most experts agree that a risk-adapted therapy represents the optimal approach, through the use of more intensive therapy in patients with initial hyperleukocytosis. Longitudinal RT-PCR of PML/RARα allows sensitive assessment of response to treatment and minimal residual disease (MRD) monitoring in APL. Achievement of negative PCR status or molecular remission at the end of consolidation is now universally accepted and recommended as a therapeutic objective in this disease. On the other hand, persistence of, or conversion to, PCR positive in the marrow during follow-up is associated with impending relapse. Preliminary studies on therapy of molecular relapse indicate a survival advantage as compared to administering salvage treatment at time of hematologic relapse. The more accurate and reproducible real-time PCR method to detect at quantitative levels the PML/RARα hybrid will likely provide better inter-laboratory standardization and trial results comparison in the near future. [ABSTRACT FROM AUTHOR]

Published
2007
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50. Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary electrophoresis in acute myeloid leukemia.

Author

Noguera, N I, Ammatuna, E, Zangrilli, D, Lavorgna, S, Divona, M, Buccisano, F, Amadori, S, Mecucci, C, Falini, B, and Lo-Coco, F

Subjects
*ACUTE myeloid leukemia
Abstract

A correction to the article "Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary electrophoresis in acute myeloid leukemia" that was published in a previous issue of the periodical is presented.

Published
2007
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