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1. Consejo genético y detección de vías moleculares en pacientes con cáncer hereditario

Author

Lerda D, Pellicioni P, Biaggi M, Labrador J, Illescas E, Bella S, Llugdar J, and Cortes M

Subjects
BRCA 1 y 2, Inestabilidad de Microsatelites, BRAF cáncer hereditario de mama /ovario y colon, consejo genético., Science, Biology (General), QH301-705.5
Abstract

INTRODUCCIÓN: El cáncer de mama es la primera causa de muerte de la mujer en la Argentina, con una incidencia estimada de más de 19.000 casos nuevos por año. Dentro de estos, el tipo de cáncer hereditario más común es el de mama/ovario hereditario, provocado por mutaciones en los genes BRCA 1(Breast cáncer) y BRCA 2. A su vez el cáncer colorrectal es la segunda causa de muerte en Argentina, con una incidencia estimada de más de 11.000 casos nuevos por año. OBJETIVO: de la presente investigación es evaluar la utilidad de la realización de los estudios genéticos en personas con cáncer hereditario en el contexto del consejo genético, con un asesoramiento antes y después de realizarse la prueba genética POBLACIÓN Y MÉTODOS: Se estudiaron 34 mujeres con diagnóstico de cáncer de mama/ovario y 31 pacientes de ambos sexos con diagnóstico de cáncer colorrectal (CCR). En las mujeres se analizaron los genes BRCA 1 y 2 por secuenciación de próxima generación (NSG) y grandes rearreglos de los genes BRCA 1 y 2 por amplificación de sonda dependiente de la ligadura multiplex (MLPA). En las personas de ambos sexos se determinó la Inestabilidad de Microsatelites(IMS), el análisis de mismatch repair (MMR) por MLPA y la mutación del gen BRAF (Protooncogen B-Raf) RESULTADOS: Los resultados mostraron que las pacientes con cáncer de mama / ovario con antecedentes familiares tienen un alto porcentaje de BRCA negativo. En cuanto a los cambios fenotípicos, el más predominante en este estudio, fue el subtipo triple negativo y la paciente con BRCA 2 positivo presentó este fenotipo. Con respecto al estudio del cáncer de colon detectamos cuatro pacientes con IMS-alta y mutación del V600E del gen BRAF. Cuando se les realizó el análisis de MLPA en los genes MSH6, MLH1, MSH2 y PMS2 a los efectos de establecer la diferencia entre CCR y síndrome de Lynch, los resultados fueron negativos, por lo tanto, estos pacientes fueron diagnosticados como CCR esporádico. CONCLUSIONES: Como lo demuestra este trabajo, para el consejo genético, el estudio de vías moleculares en pacientes con cáncer hereditario es un instrumento de ayuda para la valoración del riesgo génico.

Published
2019

2. Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

Author

Suárez, E. U., Boluda, B., Lavilla, E., Tormo, M., Botella, C., Gil, C., Vives, S., Rodríguez, C., Serrano, J., Sayas, M. J., Martínez-Sánchez, P., Ramos, F., Bernal, T., Algarra, L., Bergua-Burgues, J. M., Pérez-Simón, J. A., Herrera, P., Barrios, M., Noriega-Concepción, V., Raposo-Puglia, J. A., Ayala, R., Barragán, E., Martínez-Cuadrón, D., Amigo, M. L., López-Lorenzo, J. L., Lázaro-García, A., Guimaraes, J. E., Colorado, M., García-Boyero, R., De Rueda-Ciller, B., Foncillas-García, M., Hong, A., Labrador, J., Alonso-Dominguez, J. M., and Montesinos, P.

Published
2024
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4. Nanosecond pulsed proton beam: upgrade of the accelerator-based neutron facility HiSPANOS at CNA (Spain)

Author

Macías, M., Fernández, B., Labrador, J. A., Romero, A., and Praena, J.

Subjects
Physics - Accelerator Physics
Abstract

The 3 MV Tandem Pelletron accelerator at the Spanish Accelerator Laboratory (CNA) has been recently upgraded to produce pulsed ion beams for neutron Time-Of-Flight (TOF) measurements. The upgrade has consisted of two actions: a pulsing system installed at the low energy part of the Tandem accelerator and a new line fully equipped. The pulsing system provides approximately one nanosecond pulse width of protons with variable repetition rates from kHz down to MHz. The new line is equipped with conventional devices and a pick-up for timing measurements with high resolution. The properties of the whole system have been tested under various working conditions and they are described in some detail., Comment: Accepted for publication in "Il Nuovo Cimento"

Published
2019

5. 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

6. 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

7. 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

8. Data-driven flow cytometry classification of blast differentiation in older patients with acute myeloid leukemia

Author

Rojas, F., Longoni, H., Milone, G., Fernández, I., Conciencia, Clínica, Ramirez, R., Canepa, C., Saba, S., Balladares, G., Ventiurini, C., Mariano, R., Negri, P., Prates, M.V., Milone, J., Fazio, P., Gelemur, M., Ciarlo, S., Bezares, F., López, L., García, J. J, Giunta, M., Kruss, M., Lafalse, D., Marquesoni, E., Casale, M.F., Gimenez, A., Brulc, E.B., Perusini, M.A., Palmer, L., Correa, M.E., Jaramillo, F.J., Rosales, J., Sossa, C., Herrera, J.C., Arango, M., Holojda, J., Golos, A., Ejduk, A., Ochrem, B., Małgorzata, G., Waszczuk-Gajda, A., Drozd-Sokolowska, J., Czemerska, M., Paluszewska, M., Zarzycka, E., Masternak, A., Hawrylecka, Dr., Podhoreka, M., Giannopoulos, K., Gromek, T., Oleksiuk, J., Armatys, bA., Helbig, G., Sobas, M., Szczepaniak, A., Rzenno, E., Rodzaj, M., Piatkowska-Jakubas, B., Skret, A., Pluta, A., Barańska, E., Vasconcelos, G., Brioso, J., Nunes, A., Bogalho, I., Espadana, A., Coucelo, M., Marini, S., Azevedo, J., Crisostomo, A.I., Ribeiro, L., Pereira, V., Botelho, A., Mariz, J.M., Guimaraes, J.E., Aguiar, E., Coutinho, J., Noriega, V., García, L., Varela, C., Debén, G., González, M.R., Encinas, M., Bendaña, A., González, S., Bello, J.L., Albors, M., Algarra, L., Romero, J.R., Bermon, J.S., Varo, M.J., López, V., López, E., Mora, C., Amorós, C., Romero, A., Jaramillo, A., Valdez, N., Molina, I., Fernández, A., Sánchez, B., García, A., Castaño, V., López, T., Bernabeu, J., Sánchez, M.J., Fernández, C., Gil, C., Botella, C., Fernández, P., Pacheco, M., Tarín, F., Verdú, J.J., García, M.J., Mellado, A., García, M.C., González, J., Castillo, T., Colado, E., Alonso, S., Recio, I., Cabezudo, M., Davila, J., Rodríguez, M.J., Barez, A., Díaz, B., Prieto, J., Arnan, M., Marín, C., Mansilla, M., Balaberdi, A., Amutio, M.E., del Orbe, R.A., Ancin, I., Ruíz, J.C., Olivalres, M., Gómez, C., gonzález, I., Celis, M., Atutxa, K., Carrascosa, T., Artola, T., Lizuain, M., Rodriguez, J .I., Arce, O., Márquez, J.A., Atuch, J., Marco de Lucas, F., Díez, Z., Dávila, B., Cantalejo, R., Díaz, M., Labrador, J., Serra, F., Hermida, G., Díaz, F.J., de Vicente, P., Álvarez, R., Alonso, C., Bergua, J.M., Ugalde, N., Pardal, E., Saldaña, R., Rodríguez, F., Martín, E., Hermosín, L., Garrastazul, M.P., Marchante, I., Raposo, J.A., Capote, F.J., Colorado, M., Batlle, A., Yañez, L., García, S., González, P., Ocio, E.M., Briz, M., Bermúdez, A., Jiménez, C., Beltrán, S., Montagud, M., Castillo, I., García, R., Gascón, A., Clavel, J., Lancharro, A., Lnares, L., Herráez, M.M., Milena, A., Romero, M.J., Hernández, B., Calle, C., Benegas, R., Bolívar, Dr., Serrano, J., Dorado, F.J., Sánchez, J., Martínez, M.C., Cerveró, C.J., Busto, M.J., Bernal, M., Moratalla, L., Mesa, Z., Jurado, M., De Miguel, D., Santos, A.B., Arbeteta, J., Pérez, E., Caminos, N., Uresandi, N., Argoitiaituart, N., Swen, J., Uranga, A., Olazaba, I., Gainza, E., Romero, P., Gil, E., Palma, A.J., Gómez, K.G., Solé, M., Rodríguez, J.N., Murillo, I.M., Marco, J., Serena, J., Marco, V., Perella, M., Costilla, L., López, J.A., Baena, A., Almagro, P., Hermosilla, M., Esteban, A., Campeny, B.A., Nájera, M.J., Herrra, P., Fernández, R., González, J.D., Torres, L., Jiménez, S., Gómez, M.T., Bilbao, C., Rodríguez, C., Hong, A., Ramos de Laón, Y., Afonso, V., Ramos, F., Fuertes, M., de Cabo, E., Aguilera, C., Megido, M., García, T., Lavilla, E., Varela, M., Ferrero, S., Arias, J., Vizcaya, L., Roldán, A., Vilches, A., Penalva, M.J., Vázquez, J., Calderón, M.T., Matilla, A., Serí, C., Otero, M.J., García, N., Sandoval, E., Franco, C., Flores, R., Bravo, P., López, A., López, J.L., Blas, C., Díez, A., Alonso, J.M., Soto, C., Arenas, A., García, J., Martín, Y., Villafuerte, P.S., Magro, E., Bautista, G., De Laiglesia, A., Rodríguez, G., Solán, L., Chicano, M., Balsalobre, P., Monsalvo, S., Font, P., Carbonell, D., Martínez, C., Humala, K., Kerguelen, A.E., Hernández, D., Gasior, M., Gómez, P., Sánchez, I., Redondo, S., Llorente, L., Bengochea, M., Pérez, J., Sebrango, A., M. santero, Morales, A., Figuera, A., Villafuerte, P., Alegre, A., Fernández, E., Alonso, A., Martínez, M.P., Martínez, J., Cedena, M.T., Moreno, L., De la Fuente, A., García, D., Chamorro, C., Pradillo, V., Martí, E., Sánchez, J.M., Delgado, I., Rosado, B., Velasco, A., Miranda, C., Salvatierra, G., Foncillas, M., Hernández, J.A., Escolano, C., Benabente, C., Martínez, R., Polo, M., Anguita, E., Riaza, R., Amores, G., Requena, M.J., Javier, F., Villaloón, L., Aláez, C., Nistal, S., Navas, B., Andreu, M.A., Herrera, P., López, J., García, M., Moreno, M.J., Queipo, M.P., Hernández, A., Barrios, M., Heiniger, A., Jiménez, A., Contento, A., López, F., Alcalá, M., Lorente, S., González, M., Morales, E.M., Gutierrez, J., Serna, M.J., Beltrán, V., Romera, M., Berenguer, M., MArtínez, A., Tejedor, A., Amigo, M.L., Ortuño, F., Jerez, A., López, O., Moraleda, J.M., Rosique, P., Gómez, J., Garay, M.C., Cerezuela, P., MArtínez, A.B., González, A., Ibáñez, J., Alfaro, M.J., Mateos, M., Goñi, M.A., Araiz, M.A., Gorosquieta, A., Zudaire, M., Viguria, M., Zabala, A., Alvarellos, M., Quispe, I., Sánchez, M.P., Hurtado, G., Pérez, M., Burguete, Y., Areizaga, N., Galicia, T., Rifón, J., Alfonso, A., Prósper, F., Marcos, M., Tamariz, L.E., Riego, V., Manubens, A., Larrayoz, M.J., Calasanz, M.J., Mañú, A., Paiva, B., Vázquez, I., Burgos, L., Pereiro, M., Rodríguez, M., Pastoriza, M.C., Mendez, J.A., Sastre, J.L., Iglesias, M., Ulibarrena, C., Campoy, F., Jaimes, D., Albarrán, B., Solano, J., Silvestre, A., Albo, C., Suarez, S., Loureiro, C., Figueroa, I., Fernández, M.A., Martínez, A., Poderós, C., Vazquez, J., Iglesias, L., Nieto, A., Torrado, T., Martínez, A.M., Amador, M.L., Oubiña, P., Feijó, E., Dios, A., Loyola, I., Roreno, R., Simiele, A., Álvarez, L., Turcu, V., Vidriales, B., Avendaño, A., Chillón, C., González, V., Govantes, J.V., Rubio, S., Tapia, M., Olivier, C., Queizán, J.A., Pérez, O., Vera, J.A., Muñoz, C., rodriguez, A., González, N., Pérez, J.A., Soria, E., I.Espigado, Falantes, J., Montero, I., García, P., Rodríguez, E., Carrillo, E., Caballero, T., García, C., Couto, C., Simón, I., Gómez, M., Aguilar, C., González, B.J., Lakhwani, S., Bienert, A., González, B., Cabello, A., Oliva, A.Y., González, H., Sancho, L., Paricio, M., Perdiguer, L., Solano, F., Lerma, A., Martínez, M.D., Gómez, M.I., Yeguas, A., Montesinos, P., Barragán, E., Sargas, C., Amigo, R., Martinez, D., Boluda, B., Rodríguez, R., Acuña, E., Cano, I., Escrivá, A., Pedreño, M., Navalón, A., Orts, M., Sayas, M.J., Fernández, M.J., Juan, M.L., Gómez, E., Gimeno, M., Donato, E., Cejalvo, M., Tormo, M., Calabuig, M., Navarro, B., Martin, I., Villamont, E., Miralles, A., Lluch, R., Moragues, M., Ruiz, M.A., Benet, C., Valero, M., Linares, M., Collado, R., Orero, M., Ibañez, P., Lis, M.J., Pérez, P.L., Roig, M., López, M., Mena, A.V., Picón, I., Cánovas, V., Palacios, A., Cuello, R., Borrego, J., burgois, M., Cantalapiedra, A., Norberto, O., Angomas, E., Cidoncha, B., Cuevas, L., Robles, D., Mendiazabal, A., Oiartzabal, I., Guinea de Castro, J.M., Montes, C., Carrasco, V., Pérez, A., Moneva, J.J., Olave, M., Bonafonte, E., Mayor, L., Azaceta, G., Palomera, L., Malo, M., Escobar, M.J., Grasa, J.M., De Rueda, B., Aulés, A., Salvador, C., Ansó, V., Iborra, A., Delagado, P., Rubio, A., Stevenazzi, M., Alpire, I., Irigoin, V., Díaz, L., Guillermo, C., Guadagna, R., Grille, S., Oliver, C., Boada, M., Vales, V., Prado, A.I., De los Santos, A.P., Simoes, Catia, Gonzalez, Carmen, Vergez, François, Sarry, Audrey, Bertoli, Sarah, Ariceta, Beñat, Martínez-Cuadrón, David, Bergua, Juan-Miguel, Vives, Susana, Algarra, Lorenzo, Tormo, Mar, Martinez, Pilar, Serrano, Josefina, Herrera, Pilar, Ramos, Fernando, Salamero, Olga, Lavilla, Esperanza, Gil, Cristina, Lopez-Lorenzo, Jose-Luis, Vidriales, Maria-Belen, Chillon, Carmen, Labrador, Jorge, Falantes, Jose-Francisco, Sayas, María-José, Ayala, Rosa, Martinez-Lopez, Joaquin, Villar, Sara, Calasanz, Maria-Jose, Prosper, Felipe, San-Miguel, Jesús F., Sanz, Miguel Á., Récher, Christian, Paiva, Bruno, and Montesinos, Pau

Published
2024
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11. Heatwave breaks down the linearity between sun-induced fluorescence and gross primary production

Author

Martini, D, Sakowska, K, Wohlfahrt, G, Pacheco-Labrador, J, van der Tol, C, Porcar-Castell, A, Magney, T, Carrara, A, Colombo, R, El-Madany, T, Gonzalez-Cascon, R, Martin, M, Julitta, T, Moreno, G, Rascher, U, Reichstein, M, Rossini, M, Migliavacca, M, Martini D., Sakowska K., Wohlfahrt G., Pacheco-Labrador J., van der Tol C., Porcar-Castell A., Magney T. S., Carrara A., Colombo R., El-Madany T. S., Gonzalez-Cascon R., Martin M. P., Julitta T., Moreno G., Rascher U., Reichstein M., Rossini M., Migliavacca M., Martini, D, Sakowska, K, Wohlfahrt, G, Pacheco-Labrador, J, van der Tol, C, Porcar-Castell, A, Magney, T, Carrara, A, Colombo, R, El-Madany, T, Gonzalez-Cascon, R, Martin, M, Julitta, T, Moreno, G, Rascher, U, Reichstein, M, Rossini, M, Migliavacca, M, Martini D., Sakowska K., Wohlfahrt G., Pacheco-Labrador J., van der Tol C., Porcar-Castell A., Magney T. S., Carrara A., Colombo R., El-Madany T. S., Gonzalez-Cascon R., Martin M. P., Julitta T., Moreno G., Rascher U., Reichstein M., Rossini M., and Migliavacca M.

Abstract

Sun-induced fluorescence in the far-red region (SIF) is increasingly used as a remote and proximal-sensing tool capable of tracking vegetation gross primary production (GPP). However, the use of SIF to probe changes in GPP is challenged during extreme climatic events, such as heatwaves. Here, we examined how the 2018 European heatwave (HW) affected the GPP–SIF relationship in evergreen broadleaved trees with a relatively invariant canopy structure. To do so, we combined canopy-scale SIF measurements, GPP estimated from an eddy covariance tower, and active pulse amplitude modulation fluorescence. The HW caused an inversion of the photosynthesis–fluorescence relationship at both the canopy and leaf scales. The highly nonlinear relationship was strongly shaped by nonphotochemical quenching (NPQ), that is, a dissipation mechanism to protect from the adverse effects of high light intensity. During the extreme heat stress, plants experienced a saturation of NPQ, causing a change in the allocation of energy dissipation pathways towards SIF. Our results show the complex modulation of the NPQ–SIF–GPP relationship at an extreme level of heat stress, which is not completely represented in state-of-the-art coupled radiative transfer and photosynthesis models.

Published
2022

12. 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

13. 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

14. Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry

Author

Salmanton-Garcia, J., Marchesi, F., Koehler, P., Weinbergerova, B., Colovic, N., Falces-Romero, I., Buquicchio, C., Farina, F., van Praet, J., Biernat, M. M., Itri, F., Prezioso, L., Tascini, C., Vena, A., Romano, A., Delia, M., Davila-Valls, J., Martin-Perez, S., Lavilla-Rubira, E., Adzic-vukicevic, T., Garcia-Bordallo, D., Lopez-Garcia, A., Criscuolo, Marianna, Petzer, V., Fracchiolla, N. S., Espigado, I., Sili, U., Meers, S., Erben, N., Cattaneo, C., Tragiannidis, A., Gavriilaki, E., Schonlein, M., Mitrovic, M., Pantic, N., Merelli, M., Labrador, J., Hernandez-Rivas, J. -A., Glenthoj, A., Fouquet, G., del Principe, M. I., Dargenio, M., Calbacho, M., Besson, C., Kohn, M., Grafe, S., Hersby, D. S., Arellano, E., Colak, G. M., Wolf, D., Marchetti, M., Nordlander, A., Blennow, O., Cordoba, R., Miskovic, B., Mladenovic, M., Bavastro, M., Limongelli, A., Rahimli, L., Pagano, Livio, Cornely, O. A., Criscuolo M., Pagano L. (ORCID:0000-0001-8287-928X), Salmanton-Garcia, J., Marchesi, F., Koehler, P., Weinbergerova, B., Colovic, N., Falces-Romero, I., Buquicchio, C., Farina, F., van Praet, J., Biernat, M. M., Itri, F., Prezioso, L., Tascini, C., Vena, A., Romano, A., Delia, M., Davila-Valls, J., Martin-Perez, S., Lavilla-Rubira, E., Adzic-vukicevic, T., Garcia-Bordallo, D., Lopez-Garcia, A., Criscuolo, Marianna, Petzer, V., Fracchiolla, N. S., Espigado, I., Sili, U., Meers, S., Erben, N., Cattaneo, C., Tragiannidis, A., Gavriilaki, E., Schonlein, M., Mitrovic, M., Pantic, N., Merelli, M., Labrador, J., Hernandez-Rivas, J. -A., Glenthoj, A., Fouquet, G., del Principe, M. I., Dargenio, M., Calbacho, M., Besson, C., Kohn, M., Grafe, S., Hersby, D. S., Arellano, E., Colak, G. M., Wolf, D., Marchetti, M., Nordlander, A., Blennow, O., Cordoba, R., Miskovic, B., Mladenovic, M., Bavastro, M., Limongelli, A., Rahimli, L., Pagano, Livio, Cornely, O. A., Criscuolo M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Methods: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. Results: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccina

Published
2023

15. SARS-CoV-2 Infection In Patients With Mastocytosis: An EPICOVIDEHA Report

Author

Criscuolo, Marianna, Salmanton-Garcia, J., Fracchiolla, N., Dragonetti, Giulia, Khanna, N., Weinbergerova, B., Schonlein, M., Machado, M., Labrador, J., Kolditz, M., Itri, F., Gomes Da Silva, M., Bonuomo, V., Sciume, M., Nunes Rodrigues, R., Grafe, S., Marchesi, F., Cornely, O. A., Pagano, Livio, Criscuolo M., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Criscuolo, Marianna, Salmanton-Garcia, J., Fracchiolla, N., Dragonetti, Giulia, Khanna, N., Weinbergerova, B., Schonlein, M., Machado, M., Labrador, J., Kolditz, M., Itri, F., Gomes Da Silva, M., Bonuomo, V., Sciume, M., Nunes Rodrigues, R., Grafe, S., Marchesi, F., Cornely, O. A., Pagano, Livio, Criscuolo M., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

N/A

Published
2023

16. 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

19. 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

20. Performance of Singular Spectrum Analysis in Separating Seasonal and Fast Physiological Dynamics of Solar-Induced Chlorophyll Fluorescence and PRI Optical Signals

Author

Biriukova, K, Pacheco-Labrador, J, Migliavacca, M, Mahecha, M, Gonzalez-Cascon, R, Martin, M, Rossini, M, Biriukova K., Pacheco-Labrador J., Migliavacca M., Mahecha M. D., Gonzalez-Cascon R., Martin M. P., Rossini M., Biriukova, K, Pacheco-Labrador, J, Migliavacca, M, Mahecha, M, Gonzalez-Cascon, R, Martin, M, Rossini, M, Biriukova K., Pacheco-Labrador J., Migliavacca M., Mahecha M. D., Gonzalez-Cascon R., Martin M. P., and Rossini M.

Abstract

High temporal resolution measurements of solar-induced chlorophyll fluorescence (F) and the Photochemical Reflectance Index (PRI) encode vegetation functioning. However, these signals are modulated by time-dependent processes. We tested the applicability of the Singular Spectrum Analysis (SSA) for disentangling fast components (physiology-driven) and slow components (controlled by structural and biochemical properties) from PRI, far-red F (F760), and far-red apparent fluorescence yield (Fy∗760). The proof of concept was developed on spectral and flux time series simulated with the Soil Canopy Observation of Photochemistry and Energy fluxes (SCOPE) model. This allowed the evaluation of SSA decomposition against variables that are independent of physiology or are modified by it. Slow SSA-decomposed components of PRI and Fy∗760 showed high correlations with the reference variables (R2 = 0.97 and 0.96, respectively). Fast SSA-decomposed components of PRI and Fy∗760 were better related to the physiological reference variables than the original signals during periods when leaf area index (LAI) was above 1 m2 m−2. The method was also successfully applied to predict light-use efficiency (LUE) from the fast SSA-decomposed components of PRI (R2 = 0.70) and Fy∗760 (R2 = 0.68) when discarding data modeled with LAI < 1 m2 m−2 and short-wave radiation Rin < 250 W m−2. The method was then tested on data acquired in a Mediterranean grassland. In this case, the fast SSA-decomposed component of apparent LUE∗ showed a stronger correlation with the fast SSA-decomposed component of Fy∗760 (R2 = 0.42) than with original Fy∗760 (R2 = 0.01). SSA-based approach is a promising tool for decoupling physiological information from measurements acquired with automated proximal sensing systems.

Published
2021

21. SARS-CoV-2 Infection among Patients with Mastocytosis: An EPICOVIDEHA Report

Author

Criscuolo, M, primary, Salmanton-García, J, additional, Fracchiolla, N, additional, Dragonetti, G, additional, Khanna, N, additional, Weinbergerová, B, additional, Schönlein, M, additional, Machado, M, additional, Labrador, J, additional, Kolditz, M, additional, Itri, F, additional, Gomes da Silva, M, additional, Bonuomo, V, additional, Sciumè, M, additional, Nunes Rodrigues, R, additional, Gräfe, S, additional, Marchesi, F, additional, Cornely, OA, additional, and Pagano, L, additional

Published
2022
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22. P523: MIDOSTAURIN PLUS INTENSIVE CHEMOTHERAPY IN FLT3 MUTATED AML. “REAL LIFE” DATA VERSUS THE RATIFY STUDY

Author

De La Fuente, A., primary, Diaz Beya, M., additional, Beneit, P., additional, Botella, C., additional, Fernandez Moreno, A., additional, Sampol, A., additional, Arnan Sangerman, M., additional, Yeguas Bermejo, A., additional, Amigo, M. D. L. L., additional, Labrador, J., additional, Garcia Guinon, A., additional, Garrido, A., additional, Serrano, J., additional, Vives Polo, S., additional, Garcia Fortes, M., additional, Sayas, M. J., additional, Bergua, J. M., additional, Olave, M. T., additional, Vall LLovera, F., additional, Bargay, J., additional, Pereiro Sanchez, M., additional, Garcia Boyero, R., additional, Diaz Lopez, A., additional, and Tormo, M., additional

Published
2022
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23. A Compact Detector for Studying Heavy Ion Reactions: GLORIA

Author

Marquínez-Durán, G., Acosta, L., Berjillos, R., Dueñas, J. A., Labrador, J. A., Rusek, K., Sánchez-Benítez, A. M., Martel, I., García-Ramos, José-Enrique, editor, Alonso, Clara E., editor, Andrés, María Victoria, editor, and Pérez-Bernal, Francisco, editor

Published
2016
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24. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), Foa R., Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), and Foa R.

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occu

Published
2022

25. Challenging the link between functional and spectral diversity with radiative transfer modeling and data

Author

Pacheco-Labrador, J., Migliavacca, M., Ma, X., Mahecha, Miguel Dario, Carvalhais, N., Weber, U., Benavides, R., Bouriaud, O., Barnoaiea, I., Coomes, D.A., Bohn, Friedrich, Kraemer, Guido, Heiden, U., Huth, Andreas, Wirth, C., Pacheco-Labrador, J., Migliavacca, M., Ma, X., Mahecha, Miguel Dario, Carvalhais, N., Weber, U., Benavides, R., Bouriaud, O., Barnoaiea, I., Coomes, D.A., Bohn, Friedrich, Kraemer, Guido, Heiden, U., Huth, Andreas, and Wirth, C.

Abstract

In a context of accelerated human-induced biodiversity loss, remote sensing (RS) is emerging as a promising tool to map plant biodiversity from space. Proposed approaches often rely on the Spectral Variation Hypothesis (SVH), linking the heterogeneity of terrestrial vegetation to the variability of the spectroradiometric signals. Yet, due to observational limitations, the SVH has been insufficiently tested, remaining unclear which metrics, methods, and sensors could provide the most reliable estimates of plant biodiversity. Here we assessed the potential of RS to infer plant biodiversity using radiative transfer simulations and inversion. We focused specifically on “functional diversity,” which represents the spatial variability in plant functional traits. First, we simulated vegetation communities and evaluated the information content of different functional diversity metrics (FDMs) derived from their optical reflectance factors (R) or the corresponding vegetation “optical traits,” estimated via radiative transfer model inversion. Second, we assessed the effect of the spatial resolution, the spectral characteristics of the sensor, and signal noise on the relationships between FDMs derived from field and remote sensing datasets. Finally, we evaluated the plausibility of the simulations using Sentinel-2 (multispectral, 10 m pixel) and DESIS (hyperspectral, 30 m pixel) imagery acquired over sites of the Functional Significance of Forest Biodiversity in Europe (FunDivEUROPE) network. We demonstrate that functional diversity can be inferred both by reflectance and optical traits. However, not all the FDMs tested were suited for assessing plant functional diversity from RS. Rao's Q index, functional dispersion, and functional richness were the best-performing metrics. Furthermore, we demonstrated that spatial resolution is the most limiting RS feature. In agreement with simulations, Sentinel-2 imagery provided better estimates of plant diversity than DESIS, despite the c

Published
2022

26. Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis

Author

Universitat Rovira i Virgili, Palazón-Carrión N; Martín García-Sancho A; Nogales-Fernández E; Jiménez-Cortegana C; Carnicero-González F; Ríos-Herranz E; de la Cruz-Vicente F; Rodríguez-García G; Fernández-Álvarez R; Martínez-Banaclocha N; Gumà-Padrò J; Gómez-Codina J; Salar-Silvestre A; Rodríguez-Abreu D; Gálvez-Carvajal L; Labrador J; Guirado-Risueño M; García-Domínguez DJ; Hontecillas-Prieto L; Espejo-García P; Fernández-Román I; Provencio-Pulla M; Sánchez-Beato M; Navarro M; Marylene L; Álvaro-Naranjo T; Casanova-Espinosa M; Sánchez-Margalet V; Rueda-Domínguez A; de la Cruz-Merino L, Universitat Rovira i Virgili, and Palazón-Carrión N; Martín García-Sancho A; Nogales-Fernández E; Jiménez-Cortegana C; Carnicero-González F; Ríos-Herranz E; de la Cruz-Vicente F; Rodríguez-García G; Fernández-Álvarez R; Martínez-Banaclocha N; Gumà-Padrò J; Gómez-Codina J; Salar-Silvestre A; Rodríguez-Abreu D; Gálvez-Carvajal L; Labrador J; Guirado-Risueño M; García-Domínguez DJ; Hontecillas-Prieto L; Espejo-García P; Fernández-Román I; Provencio-Pulla M; Sánchez-Beato M; Navarro M; Marylene L; Álvaro-Naranjo T; Casanova-Espinosa M; Sánchez-Margalet V; Rueda-Domínguez A; de la Cruz-Merino L

Abstract

New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma.In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29).After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells.R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.©2022 The Authors; Published by the American Association for Cancer Research.

Published
2022

27. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Author

Flores-Montero, J, Sanoja-Flores, L, Paiva, B, Puig, N, García-Sánchez, O, Böttcher, S, van der Velden, V HJ, Pérez-Morán, J-J, Vidriales, M-B, García-Sanz, R, Jimenez, C, González, M, Martínez-López, J, Corral-Mateos, A, Grigore, G-E, Fluxá, R, Pontes, R, Caetano, J, Sedek, L, del Cañizo, M-C, Bladé, J, Lahuerta, J-J, Aguilar, C, Bárez, A, García-Mateo, A, Labrador, J, Leoz, P, Aguilera-Sanz, C, San-Miguel, J, Mateos, M-V, Durie, B, van Dongen, J JM, and Orfao, A

Published
2017
Full Text
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28. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic D, Milic N, Chatzikonstantinou T, Scarfò L, Otasevic V, Rajovic N, Allsup D, Alonso Cabrero A, Andres M, Baile Gonzales M, Capasso A, Collado R, Cordoba R, Cuéllar-García C, Correa JG, De Paoli L, De Paolis MR, Del Poeta G, Dimou M, Doubek M, Efstathopoulou M, El-Ashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Lopez-Garcia A, García-Marco JA, García-Serra R, Gentile M, Gimeno E, da Silva MG, Gutwein O, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Itchaki G, Jaksic O, Janssens A, Kalashnikova OB, Kalicińska E, Kater AP, Kersting S, Koren- Michowitz M, Labrador J, Lad D, Laurenti L, Fresa A, Levin MD, Mayor Bastida C, Malerba L, Marasca R, Marchetti M, Marquet J, Mihaljevic B, Milosevic I, Mirás F, Morawska M, Motta M, Munir T, Murru R, Nunes R, Olivieri J, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Reda G, Rigolin GM, Shrestha A, Šimkovič M, Smirnova S, Špaček M, Sportoletti P, Stanca O, Stavroyianni N, Te Raa D, Tomic K, Tonino S, Trentin L, Van Der Spek E, van Gelder M, Varettoni M, Visentin A, Vitale C, Vukovic V, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Coscia M, Rambaldi A, Montserrat E, Foà R, Cuneo A, Carrier M, Ghia P, Stamatopoulos K.

Subjects
Age, Anticoagulation therapy, Bleeding, CLL, COVID-19, D-dimer, LMWH, Thromboprophylaxis, Thrombosis
Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment- related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS- CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C- reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Published
2022

29. AML-122 Midostaurin Maintenance versus Allo SCT versus W&W in FLT3-Mutated AML: A 'Real-Life' Multicenter Study

Author

de la Fuente A, Beya M, Beneit P, Moreno A, Sangerman M, Garrido A, Polo S, Fortes M, Mayol A, Labrador J, Guinon A, Cortes C, Bergua J, Olave M, Amigo M, Ortin X, Vall-LLovera F, Estevez M, Diaz-Lopez A, Serrano J, and Tormo M

Abstract

INTRODUCTION: FLT3-ITD mutation is associated with adverse prognosis (ELN2017, Dohner et al., Blood 2017) and SCT has been the standard of treatment for FLT3-mutated AML for decades. Midostaurin (Midos) has been approved in combination with intensive chemotherapy (IC) for FLT3-mutated AML; Midos maintenance was part of the treatment schedule in the RATIFY trial but not randomly explored (Stone et al., N Engl J Med 2017).; AIMS: The aims of this study are to analyze the safety and effectiveness of Midos maintenance in FLT3 AML in a real-world setting and evaluate maintenance versus allogeneic stem cell transplantation (alloSCT) versus watch and wait (W&W) and the impact of risk factors.; METHODS: We carried out a retrospective multicenter study (MDA-AML-2018-06) in 27 Spanish centers.; INCLUSION CRITERIA: age >18 years, FLT3-mutated AML diagnosis according to WHO criteria, and start of treatment with Midos in combination with IC between June 2016 and December 2020. We evaluated the response according to 2017 ELN criteria, toxicity according to CTCAE v4.0, and overall survival (OS) by Kaplan-Meier. Statistical analysis was performed using SPSS version 20.0.; RESULTS: A total of 175 (93 female) patients with a median age of 53 years (18-76 years) were included. The median OS for the whole population was not reached; 24-month OS was 68%. Of those who achieved CR after Induction 1 or 2 (144 patients, 81.4%), 24 received maintenance, 76 were consolidated with alloSCT, and 41 proceeded to W&W.; SAFETY: The only AE during maintenance was one case of QT prolongation, which required Midos discontinuation. There were no cases of febrile neutropenia nor deaths related to Midos. Regarding OS, the ELN2017 classification resulted in a trend of differences in all groups: maintenance, alloSCT, and W&W. We observed significant differences for maintenance versus W&W (P=0.001) in low- and intermediate-risk patients. Comparing maintenance and alloSCT, we observe no differences in the Int ELN2017 group.; CONCLUSIONS: Our experience confirms the safety of maintenance therapy in AML FLT3 patients after IC. We also observed a benefit for maintenance versus W&W in the low- and intermediate-risk population. Copyright © 2022 Elsevier Inc. All rights reserved.

Published
2022

30. Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives

Author

Pinto-Merino Á, Labrador J, Zubiaur P, Alcaraz R, Herrero MJ, Montesinos P, Abad-Santos F, and Saiz-Rodríguez M

Subjects
BCL2 inhibitors, CD33 inhibitors, FLT3 inhibitors, IDH inhibitors, acute myeloid leukemia, anthracyclines, cytarabine, hypomethylating agents, pharmacogenetics
Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.

Published
2022

31. 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

33. Sun-induced chlorophyll fluorescence II: Review of passive measurement setups, protocols, and their application at the leaf to canopy level

Author

Aasen, H, Van Wittenberghe, S, Medina, N, Damm, A, Goulas, Y, Wieneke, S, Hueni, A, Malenovsky, Z, Alonso, L, Pacheco-Labrador, J, Cendrero-Mateo, M, Tomelleri, E, Burkart, A, Cogliati, S, Rascher, U, Arthur, A, Aasen H., Van Wittenberghe S., Medina N. S., Damm A., Goulas Y., Wieneke S., Hueni A., Malenovsky Z., Alonso L., Pacheco-Labrador J., Cendrero-Mateo M. P., Tomelleri E., Burkart A., Cogliati S., Rascher U., Arthur A. M., Aasen, H, Van Wittenberghe, S, Medina, N, Damm, A, Goulas, Y, Wieneke, S, Hueni, A, Malenovsky, Z, Alonso, L, Pacheco-Labrador, J, Cendrero-Mateo, M, Tomelleri, E, Burkart, A, Cogliati, S, Rascher, U, Arthur, A, Aasen H., Van Wittenberghe S., Medina N. S., Damm A., Goulas Y., Wieneke S., Hueni A., Malenovsky Z., Alonso L., Pacheco-Labrador J., Cendrero-Mateo M. P., Tomelleri E., Burkart A., Cogliati S., Rascher U., and Arthur A. M.

Abstract

Imaging and non-imaging spectroscopy employed in the field and from aircraft is frequently used to assess biochemical, structural, and functional plant traits, as well as their dynamics in an environmental matrix. With the increasing availability of high-resolution spectroradiometers, it has become feasible to measure fine spectral features, such as those needed to estimate sun-induced chlorophyll fluorescence (F), which is a signal related to the photosynthetic process of plants. The measurement of F requires highly accurate and precise radiance measurements in combination with very sophisticated measurement protocols. Additionally, because F has a highly dynamic nature (compared with other vegetation information derived from spectral data) and low signal intensity, several environmental, physiological, and experimental aspects have to be considered during signal acquisition and are key for its reliable interpretation. The European Cooperation in Science and Technology (COST) Action ES1309 OPTIMISE has produced three articles addressing the main challenges in the field of F measurements. In this paper, which is the second of three, we review approaches that are available to measure F from the leaf to the canopy scale using ground-based and airborne platforms. We put specific emphasis on instrumental aspects, measurement setups, protocols, quality checks, and data processing strategies. Furthermore, we review existing techniques that account for atmospheric influences on F retrieval, address spatial scaling effects, and assess quality checks and the metadata and ancillary data required to reliably interpret retrieved F signals.

Published
2019

34. Sun-induced chlorophyll fluorescence III: Benchmarking retrieval methods and sensor characteristics for proximal sensing

Author

Cendrero-Mateo, M, Wieneke, S, Damm, A, Alonso, L, Pinto, F, Moreno, J, Guanter, L, Celesti, M, Rossini, M, Sabater, N, Cogliati, S, Julitta, T, Rascher, U, Goulas, Y, Aasen, H, Pacheco-Labrador, J, Arthur, A, Cendrero-Mateo M. P., Wieneke S., Damm A., Alonso L., Pinto F., Moreno J., Guanter L., Celesti M., Rossini M., Sabater N., Cogliati S., Julitta T., Rascher U., Goulas Y., Aasen H., Pacheco-Labrador J., Arthur A. M., Cendrero-Mateo, M, Wieneke, S, Damm, A, Alonso, L, Pinto, F, Moreno, J, Guanter, L, Celesti, M, Rossini, M, Sabater, N, Cogliati, S, Julitta, T, Rascher, U, Goulas, Y, Aasen, H, Pacheco-Labrador, J, Arthur, A, Cendrero-Mateo M. P., Wieneke S., Damm A., Alonso L., Pinto F., Moreno J., Guanter L., Celesti M., Rossini M., Sabater N., Cogliati S., Julitta T., Rascher U., Goulas Y., Aasen H., Pacheco-Labrador J., and Arthur A. M.

Abstract

The interest of the scientific community on the remote observation of sun-induced chlorophyll fluorescence (SIF) has increased in the recent years. In this context, hyperspectral ground measurements play a crucial role in the calibration and validation of future satellite missions. For this reason, the European cooperation in science and technology (COST) Action ES1309 OPTIMISE has compiled three papers on instrument characterization, measurement setups and protocols, and retrieval methods (current paper). This study is divided in two sections; first, we evaluated the uncertainties in SIF retrieval methods (e.g., Fraunhofer line depth (FLD) approaches and spectral fitting method (SFM)) for a combination of of-the-shelf commercial spectrometers. Secondly, we evaluated how an erroneous implementation of the retrieval methods increases the uncertainty in the estimated SIF values. Results show that the SFM approach applied to high-resolution spectra provided the most reliable SIF retrieval with a relative error (RE) ≤ 6% and < 5% for F 687 and F 760 , respectively. Furthermore, although the SFM was the least affected by an inaccurate definition of the absorption spectral window (RE = 5%) and/or interpolation strategy (RE = 15-30%), we observed a sensitivity of the SIF retrieval for the simulated training data underlying the SFM model implementation.

Published
2019

35. Nitrogen and phosphorus effect on sun-induced fluorescence and gross primary productivity in mediterranean grassland

Author

Martini, D, Pacheco-Labrador, J, Perez-Priego, O, van der Tol, C, El-Madany, T, Julitta, T, Rossini, M, Reichstein, M, Christiansen, R, Rascher, U, Moreno, G, Pilar Martin, M, Yang, P, Carrara, A, Guan, J, Gonzalez-Cascon, R, Migliavacca, M, Martini D., Pacheco-Labrador J., Perez-Priego O., van der Tol C., El-Madany T. S., Julitta T., Rossini M., Reichstein M., Christiansen R., Rascher U., Moreno G., Pilar Martin M., Yang P., Carrara A., Guan J., Gonzalez-Cascon R., Migliavacca M., Martini, D, Pacheco-Labrador, J, Perez-Priego, O, van der Tol, C, El-Madany, T, Julitta, T, Rossini, M, Reichstein, M, Christiansen, R, Rascher, U, Moreno, G, Pilar Martin, M, Yang, P, Carrara, A, Guan, J, Gonzalez-Cascon, R, Migliavacca, M, Martini D., Pacheco-Labrador J., Perez-Priego O., van der Tol C., El-Madany T. S., Julitta T., Rossini M., Reichstein M., Christiansen R., Rascher U., Moreno G., Pilar Martin M., Yang P., Carrara A., Guan J., Gonzalez-Cascon R., and Migliavacca M.

Abstract

Sun-Induced fluorescence at 760 nm (F760) is increasingly being used to predict gross primary production (GPP) through light use efficiency (LUE) modeling, even though the mechanistic processes that link the two are not well understood. We analyzed the effect of nitrogen (N) and phosphorous (P) availability on the processes that link GPP and F760 in a Mediterranean grassland manipulated with nutrient addition. To do so, we used a combination of process-based modeling with Soil-Canopy Observation of Photosynthesis and Energy (SCOPE), and statistical analyses such as path modeling. With this study, we uncover the mechanisms that link the fertilization-driven changes in canopy nitrogen concentration (N%) to the observed changes in F760 and GPP. N addition changed plant community structure and increased canopy chlorophyll content, which jointly led to changes in photosynthetic active radiation (APAR), ultimately affecting both GPP and F760. Changes in the abundance of graminoids, (%graminoids) driven by N addition led to changes in structural properties of the canopy such as leaf angle distribution, that ultimately influenced observed F760 by controlling the escape probability of F760 (Fesc). In particular, we found a change in GPP-F760 relationship between the first and the second year of the experiment that was largely driven by the effect of plant type composition on Fesc, whose best predictor is %graminoids. The P addition led to a statistically significant increase on light use efficiency of fluorescence emission (LUEf), in particular in plots also with N addition, consistent with leaf level studies. The N addition induced changes in the biophysical properties of the canopy that led to a trade-off between surface temperature (Ts), which decreased, and F760 at leaf scale (F760leaf,fw), which increased. We found that Ts is an important predictor of the light use efficiency of photosynthesis, indicating the importance of Ts in LUE modeling approaches to predict GPP

Published
2019

36. Multiple-constraint inversion of SCOPE. Evaluating the potential of GPP and SIF for the retrieval of plant functional traits

Author

Pacheco-Labrador, J, Perez-Priego, O, El-Madany, T, Julitta, T, Rossini, M, Guan, J, Moreno, G, Carvalhais, N, Martin, M, Gonzalez-Cascon, R, Kolle, O, Reischtein, M, van der Tol, C, Carrara, A, Martini, D, Hammer, T, Moossen, H, Migliavacca, M, Pacheco-Labrador J., Perez-Priego O., El-Madany T. S., Julitta T., Rossini M., Guan J., Moreno G., Carvalhais N., Martin M. P., Gonzalez-Cascon R., Kolle O., Reischtein M., van der Tol C., Carrara A., Martini D., Hammer T. W., Moossen H., Migliavacca M., Pacheco-Labrador, J, Perez-Priego, O, El-Madany, T, Julitta, T, Rossini, M, Guan, J, Moreno, G, Carvalhais, N, Martin, M, Gonzalez-Cascon, R, Kolle, O, Reischtein, M, van der Tol, C, Carrara, A, Martini, D, Hammer, T, Moossen, H, Migliavacca, M, Pacheco-Labrador J., Perez-Priego O., El-Madany T. S., Julitta T., Rossini M., Guan J., Moreno G., Carvalhais N., Martin M. P., Gonzalez-Cascon R., Kolle O., Reischtein M., van der Tol C., Carrara A., Martini D., Hammer T. W., Moossen H., and Migliavacca M.

Abstract

The most recent efforts to provide remote sensing (RS) estimates of plant function rely on the combination of Radiative Transfer Models (RTM) and Soil-Vegetation-Atmosphere Transfer (SVAT) models, such as the Soil-Canopy Observation Photosynthesis and Energy fluxes (SCOPE) model. In this work we used ground spectroradiometric and chamber-based CO2 flux measurements in a nutrient manipulated Mediterranean grassland in order to: 1) develop a multiple-constraint inversion approach of SCOPE able to retrieve vegetation biochemical, structural as well as key functional traits, such as chlorophyll concentration (Cab), leaf area index (LAI), maximum carboxylation rate (Vcmax) and the Ball-Berry sensitivity parameter (m); and 2) compare the potential of the of gross primary production (GPP) and sun-induced fluorescence (SIF), together with up-welling Thermal Infrared (TIR) radiance and optical reflectance factors (RF), to estimate such parameters. The performance of the proposed inversion method as well as of the different sets of constraints was assessed with contemporary measurements of water and heat fluxes and leaf nitrogen content, using pattern-oriented model evaluation. The multiple-constraint inversion approach proposed together with the combination of optical RF and diel GPP and TIR data provided reliable estimates of parameters, and improved predicted water and heat fluxes. The addition of SIF to this scheme slightly improved the estimation of m. Parameter estimates were coherent with the variability imposed by the fertilization and the seasonality of the grassland. Results revealed that fertilization had an impact on Vcmax, while no significant differences were found for m. The combination of RF, SIF and diel TIR data weakly constrained functional traits. Approaches not including GPP failed to estimate LAI; however GPP overestimated Cab in the dry period. These problems might be related to the presence of high fractions of senescent leaves in the grassland. The pr

Published
2019

37. IMPACT OF DISEASE TREATMENT ON THE OUTCOME OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WITH COVID‐19: A MULTICENTER STUDY ON BEHALF OF GELLC

Author

Muntañola, A., primary, Mirás, F., additional, Hernández‐Rivas, J. A., additional, Baile, M., additional, Osorio, S., additional, Terol, Ma J., additional, Gimeno, E., additional, Alonso, R., additional, Baltasar, P., additional, López‐García, A., additional, Labrador, J., additional, López‐Jiménez, J., additional, Hernández‐Rodríguez, I., additional, Alfayate, A., additional, Oliveira, A. C, additional, Gómez‐Roncero, Ma I., additional, Vidal, Ma J., additional, Bárez, A., additional, López‐Rubio, M., additional, Riaza, R., additional, Correa, J., additional, Hernández‐Sánchez, E., additional, Romero, P., additional, Yáñez, L., additional, Andreu, R., additional, Santiago, R., additional, Zabalza, A., additional, Torres, A., additional, Seri, C., additional, Ramírez‐Payer, A., additional, García‐Malo, Ma D., additional, García‐Pintos, M., additional, Mateos Mazón, J. J., additional, Rodríguez‐Fernández, A., additional, Ma Vale, A., additional, Ríos, E., additional, Loscertales, J., additional, Do Nascimiento, J., additional, Pérez‐Fernández, I., additional, José Lis, Ma, additional, Pérez, S., additional, Ruiz, Ma E., additional, Villalón, L., additional, Velasquez, C. A., additional, Campoy, F., additional, Muiña, B., additional, Soler, J. A., additional, Sánchez, Ma J., additional, Cuesta, A., additional, Pimentel, A., additional, Sánchez‐Ramírez, M., additional, Ruiz‐Camps, I., additional, Villacampa, G., additional, Bosch, F., additional, and Abrisqueta, P., additional

Published
2021
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38. Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial

Author

Simoes C, Paiva B, Martinez-Cuadron D, Bergua J, Vives S, Algarra L, Tormo M, Martinez P, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, Gil C, Lopez J, Vidriales M, Labrador J, Falantes J, Sayas M, Ayala R, Martinez-Lopez J, Villar S, Calasanz M, Prosper F, San-Miguel J, Sanz M, Montesinos P, and Programa Estudio Terapeutica Hemop

Abstract

The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase 3 FLUGAZA clinical trial, which randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine (FLUGA) vs 5-azacitidine. After consolidation, patients continued treatment if MRD was >= 0.01% or stopped if MRD was

Published
2021

39. Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial

Author

Jimenez-Cortegana C, Palazon-Carrion N, Garcia-Sancho A, Nogales-Fernandez E, Carnicero-Gonzalez F, Rios-Herranz E, de la Cruz-Vicente F, Rodriguez-Garcia G, Fernandez-Alvarez R, Dominguez A, Casanova-Espinosa M, Martinez-Banaclocha N, Guma-Padro J, Gomez-Codina J, Labrador J, Salar-Silvestre A, Rodriguez-Abreu D, Galvez-Carvajal L, Provencio M, Sanchez-Beato M, Guirado-Risueno M, Espejo-Garcia P, Lejeune M, Alvaro T, Sanchez-Margalet V, de la Cruz-Merino L, Spanish Lymphoma Oncology Grp GOTE, and Spanish Grp Immunobiotherapy Canc

Subjects
tumor, biomarkers, immunotherapy, Cellular, immunomodulation, myeloid-derived suppressor cells, immunity
Abstract

Background The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. Methods Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. Results In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. Conclusions In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

Published
2021

40. Evolving treatment patterns and outcomes in older patients (>= 60 years) with AML: changing everything to change nothing?

Author

Martinez-Cuadron D, Serrano J, Gil C, Tormo M, Martinez-Sanchez P, Perez-Simon J, Garcia-Boyero R, Rodriguez-Medina C, Lopez-Pavia M, Benavente C, Bergua J, Lavilla-Rubira E, Amigo M, Herrera P, Alonso-Dominguez J, Bernal T, Colorado M, Sayas M, Algarra L, Vidriales M, Rodriguez-Macias G, Vives S, Perez-Encinas M, Lopez A, Noriega V, Garcia-Fortes M, Ramos F, Rodriguez-Gutierrez J, Costilla-Barriga L, Labrador J, Boluda B, Rodriguez-Veiga R, Martinez-Lopez J, Sanz M, and Montesinos P

Abstract

There are no studies analyzing how therapeutic changes impact on outcomes of older AML patients. This study analyzes patient ' s and disease characteristics, treatment patterns, and outcomes of 3637 AML patients aged >= 60 years reported to the PETHEMA registry. Study periods were 1999-2006 (before hypomethylating agents-HMAs availability) vs 2007-2013, and treatments were intensive chemotherapy (IC), non-intensive, clinical trial (CT), and supportive care only (SC). Median age was 72 (range, 60-99), 57% male, median ECOG 1 (range, 0-4), secondary AML 914 (30%), with adverse-risk genetic in 720 (32%). Treatment differed between study periods (1999-2006 vs 2007-2013): IC 58% vs 32%, non-intensive 1 vs 23%, CT 0 vs 2%, SC 27 vs 28% (p < 0.001). Median OS was 4.7 months (1-year OS 29% and 5-years 7%, without differences between periods), 1.2 for SC, 7.8 for non-intensive, 8.6 for IC, and 10.4 for CT (p < 0.001). OS improved in the 2007-2013 period for IC patients (10.3 vs 7.5 months,p = 0.004), but worsened for SC patients (1.2 vs 1.6 months,p = 0.03). Our real-life study shows that, despite evolving treatment for elderly patients during the last decade, OS has remained unchanged. Epidemiologic registries will critically assess whether novel therapies lead to noteworthy advances in the near future (#NCT02606825).

Published
2021

41. Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: Translational results from the R2-GDP-GOTEL trial

Author

Universitat Rovira i Virgili, Jiménez-Cortegana C; Palazón-Carrión N; Martin Garcia-Sancho A; Nogales-Fernandez E; Carnicero-González F; Ríos-Herranz E; De La Cruz-Vicente F; Rodríguez-Garciá G; Fernández-Álvarez R; Rueda Dominguez A; Casanova-Espinosa M; Martínez-Banaclocha N; Gumà-Padrò J; Gómez-Codina J; Labrador J; Salar-Silvestre A; Rodriguez-Abreu D; Galvez-Carvajal L; Provencio M; Sánchez-Beato M; Guirado-Risueño M; Espejo-Garciá P; Lejeune M; Álvaro T; Sánchez-Margalet V; De La Cruz-Merino L, Universitat Rovira i Virgili, and Jiménez-Cortegana C; Palazón-Carrión N; Martin Garcia-Sancho A; Nogales-Fernandez E; Carnicero-González F; Ríos-Herranz E; De La Cruz-Vicente F; Rodríguez-Garciá G; Fernández-Álvarez R; Rueda Dominguez A; Casanova-Espinosa M; Martínez-Banaclocha N; Gumà-Padrò J; Gómez-Codina J; Labrador J; Salar-Silvestre A; Rodriguez-Abreu D; Galvez-Carvajal L; Provencio M; Sánchez-Beato M; Guirado-Risueño M; Espejo-Garciá P; Lejeune M; Álvaro T; Sánchez-Margalet V; De La Cruz-Merino L

Abstract

Background The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. Methods Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. Results In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. Conclusions In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for ove

Published
2021

45. Photosynthesis-sun induced fluorescence relationship in a Mediterranean grassland

Author

Martini, D, Pacheco-Labrador, J, Perez-Priego, O, Van Der Tol, C, El Madany, T, Julitta, T, Rossini, M, Gitelson, A, Reichstein, M, Migliavacca, M, Martini D., Pacheco-Labrador J., Perez-Priego O., Van Der Tol C., El Madany T., Julitta T., Rossini M., Gitelson A., Reichstein M., Migliavacca M., Martini, D, Pacheco-Labrador, J, Perez-Priego, O, Van Der Tol, C, El Madany, T, Julitta, T, Rossini, M, Gitelson, A, Reichstein, M, Migliavacca, M, Martini D., Pacheco-Labrador J., Perez-Priego O., Van Der Tol C., El Madany T., Julitta T., Rossini M., Gitelson A., Reichstein M., and Migliavacca M.

Abstract

Sun induced fluorescence at 760 nm (F 760 ) has shown to provide a valid approach to quantify gross primary production (GPP) at various scales, however the relationship between GPP and F 760 is influenced by the escape probability of fluorescence (Fesc), a variable which is not still fully understood. Combining radiative transfer modelling approaches, by means of the SCOPE model, and a data driven methodology based on variable selection methods we identify the predictors of Fesc, focusing on the effect of functional and structural traits. We show that Fesc is mainly predicted by structural variables such as fraction of grasses and near infrared reflectance. Building on the analysis of the predictor of Fesc, LUE p and LUE f we present a semi-empirical model formulation based only on optical data that significantly improves the GPP prediction.

Published
2018

46. Assessing the use of multiple constraints and ancillary data to support scope model inversion in a experimental grassland

Author

Pacheco-Labrador, J, Carvalhais, N, Perez-Priego, O, El-Madany, T, Rossini, M, Julitta, T, Moreno, G, Gonzalez-Cascon, R, Pilar Martin, M, Reichstein, M, Carrara, A, Guanter, L, Migliavacca, M, Pacheco-Labrador J., Carvalhais N., Perez-Priego O., El-Madany T. S., Rossini M., Julitta T., Moreno G., Gonzalez-Cascon R., Pilar Martin M., Reichstein M., Carrara A., Guanter L., Migliavacca M., Pacheco-Labrador, J, Carvalhais, N, Perez-Priego, O, El-Madany, T, Rossini, M, Julitta, T, Moreno, G, Gonzalez-Cascon, R, Pilar Martin, M, Reichstein, M, Carrara, A, Guanter, L, Migliavacca, M, Pacheco-Labrador J., Carvalhais N., Perez-Priego O., El-Madany T. S., Rossini M., Julitta T., Moreno G., Gonzalez-Cascon R., Pilar Martin M., Reichstein M., Carrara A., Guanter L., and Migliavacca M.

Abstract

The SCOPE model embeds the state of art for coupling soil vegetation atmosphere transfer (SVAT) and radiative transfer models (RTM). For that reason the FLuorescence EXplorer (FLEX) mission selected this model to derive vegetation properties through inversion. However inverse problem is often ill-posed, providing equally likely solutions and hence inflating the uncertainty of the retrieved parameters. In this work we test the use of different priors based on ancillary measurements and literature to support multiple-constrain inversion of SCOPE. Results show that prior information on the relationships between variables such as leaf chlorophyll content (Cab), leaf carotenoids content (Cca), leaf water content (Cw) and/or maximum carboxylation rate (Vcmax) reduce inversion uncertainties and overfitting, and should be sampled/estimated together with optical data.

Published
2018

47. A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia

Author

Vives S, Martinez-Cuadron D, Bergua Burgues J, Algarra L, Tormo M, Martinez-Sanchez M, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, Lopez-Lorenzo J, Gil C, Vidriales B, Falantes J, Serrano A, Labrador J, Sayas M, Foncillas M, Amador Barciela M, Olave M, Colorado M, Gascon A, Fernandez M, Simiele A, Perez-Encinas M, Rodriguez-Veiga R, Garcia O, Martinez-Lopez J, Barragan E, Paiva B, Sanz M, Montesinos P, PETHEMA Group, Instituto de Salud Carlos III, and Celgene

Subjects
Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Azacitidine, acute myeloid leukemia, azacitidine, cytarabine, elderly patients, fludarabine, Filgrastim, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Fludarabine, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Aged, Chemotherapy, Acute myeloid leukemia, Venetoclax, business.industry, Remission Induction, Cytarabine, medicine.disease, Elderly patients, Regimen, Leukemia, Myeloid, Acute, Treatment Outcome, Oncology, chemistry, 030220 oncology & carcinogenesis, business, Progressive disease, Vidarabine, medicine.drug
Abstract

PETHEMA Group., [Background] Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA)., [Methods] Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. [Results] The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). [Conclusions] FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML., This study was supported by the Spanish Biomedical Research Centre in Cancer of the Carlos III Health Institute (CB16/12/00369) and by the Carlos III Health Institute/Subdirectorate General for Health Research (FIS No. PI16/01661). Celgene provided the azacitidine and financial support for this study.

Published
2020

49. MIDOSTAURIN IN DAILY PRACTICE VERSUS RATIFY RESULTS

Author

De la Fuente A, Diaz B, Beneit P, Fernandez A, Arnan M, Garrido A, Vives P, Garcia F, Sampol A, Labrador J, Garcia G, Gil C, Vall-LLovera F, Olave M, Ortin X, Salamero O, Cervera M, Garcia B, Serrano J, and Tormo M

Published
2020

50. Effects of varying solar-view geometry and canopy structure on solar-induced chlorophyll fluorescence and PRI

Author

Biriukova, K, Celesti, M, Evdokimov, A, Pacheco-Labrador, J, Julitta, T, Migliavacca, M, Giardino, C, Miglietta, F, Colombo, R, Panigada, C, Rossini, M, Biriukova, Khelvi, Celesti, Marco, Evdokimov, Anton, Pacheco-Labrador, Javier, Julitta, Tommaso, Migliavacca, Mirco, Giardino, Claudia, Miglietta, Franco, Colombo, Roberto, Panigada, Cinzia, Rossini, Micol, Biriukova, K, Celesti, M, Evdokimov, A, Pacheco-Labrador, J, Julitta, T, Migliavacca, M, Giardino, C, Miglietta, F, Colombo, R, Panigada, C, Rossini, M, Biriukova, Khelvi, Celesti, Marco, Evdokimov, Anton, Pacheco-Labrador, Javier, Julitta, Tommaso, Migliavacca, Mirco, Giardino, Claudia, Miglietta, Franco, Colombo, Roberto, Panigada, Cinzia, and Rossini, Micol

Abstract

The increasing amount of continuous time series of solar-induced fluorescence (SIF) and vegetation indices (e.g. Photochemical Reflectance Index, PRI) acquired with high temporal (sub-minute) frequencies is foreseen to allow tracking of the structural and physiological changes of vegetation in a variety of ecosystems. Coupled with observations of CO2, water, and energy fluxes from eddy covariance flux towers, these measurements can bring new insights into the remote monitoring of ecosystem functioning. However, continuously changing solar-view geometry imposes directional effects on diurnal cycles of the fluorescence radiance in the observation direction (F) and PRI, controlled by structural and biochemical vegetation properties. An improved understanding of these variations can potentially help to disentangle directional responses of vegetation from physiological ones in the continuous long-term optical measurements and, therefore, allow to deconvolve the physiological information relevant to ecosystem functioning. Moreover, this will also be useful for better interpreting and validating F and PRI satellite products (e.g., from the upcoming ESA FLEX mission). Many previous studies focused on the characterization of reflectance directionality, but only a handful of studies investigated directional effects on F and vegetation indices related to plant physiology. The aim of this study is to contribute to the understanding of red (F687) and far-red (F760) fluorescence and PRI anisotropy based on field spectroscopy data and simulations with the Soil-Canopy Observation of Photochemistry and Energy fluxes (SCOPE) model. We present an extensive dataset of multi-angular measurements of F and PRI collected at canopy level with a high-resolution instrument (FloX, JB Hyperspectral Devices UG, Germany) over different ecosystems: Mediterranean grassland, alfalfa, chickpea and rice. We found, that F760 and F687 directional responses of horizontally homogeneous canopies are charac

Published
2020

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