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1. COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant

Author: Martínez López, Joaquín, Cruz, Javier de la, Gil Manso, Rodrigo, Hernández Rivas, José Ángel, Bastos Oteiro, Mariana, Arroyo Barea, Andrés, Calbacho Robles, María, García Suárez, Julio, Martínez López, Joaquín, Cruz, Javier de la, Gil Manso, Rodrigo, Hernández Rivas, José Ángel, Bastos Oteiro, Mariana, Arroyo Barea, Andrés, Calbacho Robles, María, and García Suárez, Julio
Abstract: This HEMATO-MADRID COVID-19 study assessed COVID-19 outcomes in 1818 hematologic cancer patients from February 2020 to October 2022 across different phases, including the Omicron period. Severe cases were more common in patients over 70 years with comorbidities or chronic lymphocytic leukemia. However, during the Omicron period, rates of severe illness reduced notably, especially among vaccinated individuals. Hospitalization, intensive care admissions, and overall mortality decreased in the Omicron phase compared to pre-Omicron, yet mortality rates in hospitalized patients remained high. Older age consistently correlated with higher mortality risk in both phases. Factors like prior stem cell transplantation, vaccination, and specific treatments were linked to improved survival rates among hematologic cancer patients facing COVID-19., A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64–2.87), with >1 comorbidity (2.44, 1.85–3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19–2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2–0.37) or BA.4/BA.5 (0.13, 0.08–0.19) periods and among patients vaccinated with one or two (0.51, 0.34–0.75) or three or four (0.22, 0.16–0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03–3.25) and Omicron (3.19, 95% CI 1.59–6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients., Depto. de Medicina, Fac. de Medicina, TRUE, pub, Descuento UCM
Published: 2024

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

Author: Arellano-Orden, Elena [0000-0003-0581-8947], Salmanton-García, Jon, Marchesi, Francesco, Farina, Francesca, Weinbergerová, Barbora, Itri, Federico, Dávila-Valls, Julio, Martín-Pérez, Sonia, Glenthøj, Andreas, Hersby, Ditte Stampe, Gomes da Silva, Maria, Nunes Rodrigues, Raquel, López-García, Alberto, Córdoba, Raúl, Bilgin, Yavuz M., Falces-Romero, Iker, El-Ashwah, Shaimaa, Emarah, Ziad, Besson, Caroline, Kohn, Milena, Van Doesum, Jaap, Ammatuna, Emanuele, Marchetti, Monia, Labrador, Jorge, Zambrotta, Giovanni Paolo Maria, Verga, Luisa, Jaksic, Ozren, Nucci, Marcio, Piukovics, Klára, Cabirta-Touzón, Alba, Jiménez, Moraima, Arellano-Orden, Elena, Espigado, Ildefonso, Blennow, Ola, Nordlander, Anna, Meers, Stef, van Praet, Jens, Aiello, Tommaso Francesco, Garcia-Vidal, Carolina, Fracchiolla, Nicola, Sciumè, Mariarita, Seval, Guldane Cengiz, Žák, Pavel, Buquicchio, Caterina, Tascini, Carlo, Gräfe, Stefanie K., Schönlein, Martin, Adžić-Vukičević, Tatjana, Bonuomo, Valentina, Cattaneo, Chiara, Nizamuddin, Summiya, Čerňan, Martin, Plantefeve, Gaëtan, Prin, Romane, Szotkovski, Tomas, Collins, Graham P., Dargenio, Michelina, Petzer, Verena, Wolf, Dominik, Čolović, Natasha, Prezioso, Lucia, Valković, Toni, Passamonti, Francesco, Méndez, Gustavo-Adolfo, Sili, Uluhan, Vena, Antonio, Bavastro, Martina, Limongelli, Alessandro, Duarte, Rafael F., Ledoux, Marie-Pierre, Cvetanoski, Milche, Stojanoski, Zlate, Machado, Marina, Batinić, Josip, Magliano, Gabriele, Biernat, Monika M., Pantić, Nikola, Poulsen, Christian Bjørn, Cuccaro, Annarosa, Del Principe, Maria Ilaria, Kulasekararaj, Austin, Ormazabal-Vélez, Irati, Busca, Alessandro, Demirkan, Fatih, Ijaz, Marriyam, Klimko, Nikolai, Stoma, Igor, Khostelidi, Sofya, Fernández, Noemí, Omrani, Ali S, Bergantim, Rui, De Jonge, Nick, Fouquet, Guillemette, Navrátil, Milan, Abu-Zeinah, Ghaith, Samarkos, Michail, Maertens, Johan, De Ramón, Cristina, Guidetti, Anna, Magyari, Ferenc, González-López, Tomás José, Lahmer, Tobias, Finizio, Olimpia, Ali, Natasha, Pinczés, László Imre, Lavilla-Rubira, Esperanza, Romano, Alessandra, Merelli, Maria, Delia, Mario, Calbacho, Maria, Meletiadis, Joseph, Antić, Darko, Hernández-Rivas, José-Ángel, Marques de Almeida, Joyce, Al-Khabori, Murtadha, Hoenigl, Martin, Tisi, Maria Chiara, Khanna, Nina, Barać, Aleksandra, Eisa, Noha, Di Blasi, Roberta, Liévin, Raphaël, Miranda-Castillo, Carolina, Bahr, Nathan C., Lamure, Sylvain, Papa, Mario Virgilio, Yahya, Ayel, Aujayeb, Avinash, Novák, Jan, Erben, Nurettin, Fernández-Galán, María, Ribera-Santa Susana, José-María, Rinaldi, Ikhwan, Fazzi, Rita, Piedimonte, Monica, Duléry, Rémy, Gonzaga, Yung, Soto-Silva, Andrés, Sapienza, Giuseppe, Serris, Alexandra, Drgoňa, Ľuboš, Groh, Ana, Serrano, Laura, Gavriilaki, Eleni, Tragiannidis, Athanasios, Prattes, Juergen, Coppola, Nicola, Otašević, Vladimir, Mladenović, Miloš, Mitrović, Mirjana, Mišković, Bojana, Jindra, Pavel, Zompi, Sofia, Sacchi, Maria Vittoria, Krekeler, Carolin, Infante, Maria Stefania, García-Bordallo, Daniel, Çolak, Gökçe Melis, Mayer, Jiří, Nygaard, Marietta, Hanáková, Michaela, Ráčil, Zdeněk, Bonanni, Matteo, Koehler, Philipp, Rahimli, Laman, Cornely, Oliver A., Pagano, Livio, Arellano-Orden, Elena [0000-0003-0581-8947], Salmanton-García, Jon, Marchesi, Francesco, Farina, Francesca, Weinbergerová, Barbora, Itri, Federico, Dávila-Valls, Julio, Martín-Pérez, Sonia, Glenthøj, Andreas, Hersby, Ditte Stampe, Gomes da Silva, Maria, Nunes Rodrigues, Raquel, López-García, Alberto, Córdoba, Raúl, Bilgin, Yavuz M., Falces-Romero, Iker, El-Ashwah, Shaimaa, Emarah, Ziad, Besson, Caroline, Kohn, Milena, Van Doesum, Jaap, Ammatuna, Emanuele, Marchetti, Monia, Labrador, Jorge, Zambrotta, Giovanni Paolo Maria, Verga, Luisa, Jaksic, Ozren, Nucci, Marcio, Piukovics, Klára, Cabirta-Touzón, Alba, Jiménez, Moraima, Arellano-Orden, Elena, Espigado, Ildefonso, Blennow, Ola, Nordlander, Anna, Meers, Stef, van Praet, Jens, Aiello, Tommaso Francesco, Garcia-Vidal, Carolina, Fracchiolla, Nicola, Sciumè, Mariarita, Seval, Guldane Cengiz, Žák, Pavel, Buquicchio, Caterina, Tascini, Carlo, Gräfe, Stefanie K., Schönlein, Martin, Adžić-Vukičević, Tatjana, Bonuomo, Valentina, Cattaneo, Chiara, Nizamuddin, Summiya, Čerňan, Martin, Plantefeve, Gaëtan, Prin, Romane, Szotkovski, Tomas, Collins, Graham P., Dargenio, Michelina, Petzer, Verena, Wolf, Dominik, Čolović, Natasha, Prezioso, Lucia, Valković, Toni, Passamonti, Francesco, Méndez, Gustavo-Adolfo, Sili, Uluhan, Vena, Antonio, Bavastro, Martina, Limongelli, Alessandro, Duarte, Rafael F., Ledoux, Marie-Pierre, Cvetanoski, Milche, Stojanoski, Zlate, Machado, Marina, Batinić, Josip, Magliano, Gabriele, Biernat, Monika M., Pantić, Nikola, Poulsen, Christian Bjørn, Cuccaro, Annarosa, Del Principe, Maria Ilaria, Kulasekararaj, Austin, Ormazabal-Vélez, Irati, Busca, Alessandro, Demirkan, Fatih, Ijaz, Marriyam, Klimko, Nikolai, Stoma, Igor, Khostelidi, Sofya, Fernández, Noemí, Omrani, Ali S, Bergantim, Rui, De Jonge, Nick, Fouquet, Guillemette, Navrátil, Milan, Abu-Zeinah, Ghaith, Samarkos, Michail, Maertens, Johan, De Ramón, Cristina, Guidetti, Anna, Magyari, Ferenc, González-López, Tomás José, Lahmer, Tobias, Finizio, Olimpia, Ali, Natasha, Pinczés, László Imre, Lavilla-Rubira, Esperanza, Romano, Alessandra, Merelli, Maria, Delia, Mario, Calbacho, Maria, Meletiadis, Joseph, Antić, Darko, Hernández-Rivas, José-Ángel, Marques de Almeida, Joyce, Al-Khabori, Murtadha, Hoenigl, Martin, Tisi, Maria Chiara, Khanna, Nina, Barać, Aleksandra, Eisa, Noha, Di Blasi, Roberta, Liévin, Raphaël, Miranda-Castillo, Carolina, Bahr, Nathan C., Lamure, Sylvain, Papa, Mario Virgilio, Yahya, Ayel, Aujayeb, Avinash, Novák, Jan, Erben, Nurettin, Fernández-Galán, María, Ribera-Santa Susana, José-María, Rinaldi, Ikhwan, Fazzi, Rita, Piedimonte, Monica, Duléry, Rémy, Gonzaga, Yung, Soto-Silva, Andrés, Sapienza, Giuseppe, Serris, Alexandra, Drgoňa, Ľuboš, Groh, Ana, Serrano, Laura, Gavriilaki, Eleni, Tragiannidis, Athanasios, Prattes, Juergen, Coppola, Nicola, Otašević, Vladimir, Mladenović, Miloš, Mitrović, Mirjana, Mišković, Bojana, Jindra, Pavel, Zompi, Sofia, Sacchi, Maria Vittoria, Krekeler, Carolin, Infante, Maria Stefania, García-Bordallo, Daniel, Çolak, Gökçe Melis, Mayer, Jiří, Nygaard, Marietta, Hanáková, Michaela, Ráčil, Zdeněk, Bonanni, Matteo, Koehler, Philipp, Rahimli, Laman, Cornely, Oliver A., and Pagano, Livio
Abstract: 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.
Published: 2024

3. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients

Author: Weissmann, S., Roller, A., Jeromin, S., Hernández, M., Abáigar, M., Hernández Rivas, José Ángel, Grossmann, V., Haferlach, C., Kern, W., Haferlach, T., Schnittger, S., Kohlmann, A., Weissmann, S., Roller, A., Jeromin, S., Hernández, M., Abáigar, M., Hernández Rivas, José Ángel, Grossmann, V., Haferlach, C., Kern, W., Haferlach, T., Schnittger, S., and Kohlmann, A.
Abstract: Depto. de Bioquímica y Biología Molecular, Fac. de Farmacia, FALSE, pub
Published: 2024

4. SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

Author: Piñana, José Luis [0000-0001-8533-2562], Montoro, Juan [0000-0003-0024-8068], Sanz-Linares, Gabriela [0000-0001-7960-7988], García-Gutiérrez, Valentín [0000-0003-4752-0815], Hernández-Rivas, José Ángel [0000-0003-4550-757X], Piñana, José Luis, López-Corral, L., Martino, Rodrigo, Montoro, Juan, Vázquez-López, Lourdes, Pérez, Ariadna, Martin-Martin, Gabriel, Facal-Malvar, Ana, Ferrer, Elena, Pascual, M. Jesús, Sanz-Linares, Gabriela, Gago, Beatriz, Sánchez-Salinas, Andres, Villalón, Lucía, Conesa-Garcia, Venancio, Olave, María-Teresa, López-Jiménez, Javier, Marcos-Corrales, Sara, García-Blázquez, Sara, García-Gutiérrez, Valentín, Hernández-Rivas, José Ángel, Saus, Ana, Espigado, Ildefonso, Alonso, Carmen, Hernani, Rafael, Solano, Carlos, Ferrer-Lores, Blanca, Guerreiro, Manuel, Ruiz-García, María Montserrat, Muñoz-Bellido, Juan Luis, Navarro, David, Cedillo, Ángel, Sureda, Anna, Piñana, José Luis [0000-0001-8533-2562], Montoro, Juan [0000-0003-0024-8068], Sanz-Linares, Gabriela [0000-0001-7960-7988], García-Gutiérrez, Valentín [0000-0003-4752-0815], Hernández-Rivas, José Ángel [0000-0003-4550-757X], Piñana, José Luis, López-Corral, L., Martino, Rodrigo, Montoro, Juan, Vázquez-López, Lourdes, Pérez, Ariadna, Martin-Martin, Gabriel, Facal-Malvar, Ana, Ferrer, Elena, Pascual, M. Jesús, Sanz-Linares, Gabriela, Gago, Beatriz, Sánchez-Salinas, Andres, Villalón, Lucía, Conesa-Garcia, Venancio, Olave, María-Teresa, López-Jiménez, Javier, Marcos-Corrales, Sara, García-Blázquez, Sara, García-Gutiérrez, Valentín, Hernández-Rivas, José Ángel, Saus, Ana, Espigado, Ildefonso, Alonso, Carmen, Hernani, Rafael, Solano, Carlos, Ferrer-Lores, Blanca, Guerreiro, Manuel, Ruiz-García, María Montserrat, Muñoz-Bellido, Juan Luis, Navarro, David, Cedillo, Ángel, and Sureda, Anna
Abstract: This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3–6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109/ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16–0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27–0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15–0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02–0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02–0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.
Published: 2022

5. The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

Author: Visentin, Andrea, Chatzikonstantinou, Thomas, Scarfò, Lydia, Kapetanakis, Anargyros, Demosthenous, Christos, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Allsup, David, Cabrero, Alejandro Alonso, Andres, Martin, Antic, Darko, Baile, Mónica, Baliakas, Panagiotis, Besikli‐Dimou, Sotiria, Bron, Dominique, Chatzileontiadou, Sofia, Cordoba, Raul, Correa, Juan‐Gonzalo, Cuéllar‐García, Carolina, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Delgado, Julio, Dimou, Maria, Donaldson, David, Catherwood, Mark, Doubek, Michael, Efstathopoulou, Maria, Eichhorst, Barbara, Elashwah, Salma, Enrico, Alicia, Espinet, Blanca, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Frederiksen, Henrik, Fürstenau, Moritz, García‐Marco, José A., García‐Serra, Rocío, Collado, Rosa, Gentile, Massimo, Gimeno, Eva, Glenthøj, Andreas, da Silva, Maria Gomes, Hakobyan, Yervand K., Herishanu, Yair, Hernández‐Rivas, José Ángel, Herold, Tobias, Innocenti, Idanna, Itchaki, Gilad, Visentin, Andrea, Chatzikonstantinou, Thomas, Scarfò, Lydia, Kapetanakis, Anargyros, Demosthenous, Christos, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Allsup, David, Cabrero, Alejandro Alonso, Andres, Martin, Antic, Darko, Baile, Mónica, Baliakas, Panagiotis, Besikli‐Dimou, Sotiria, Bron, Dominique, Chatzileontiadou, Sofia, Cordoba, Raul, Correa, Juan‐Gonzalo, Cuéllar‐García, Carolina, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Delgado, Julio, Dimou, Maria, Donaldson, David, Catherwood, Mark, Doubek, Michael, Efstathopoulou, Maria, Eichhorst, Barbara, Elashwah, Salma, Enrico, Alicia, Espinet, Blanca, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Frederiksen, Henrik, Fürstenau, Moritz, García‐Marco, José A., García‐Serra, Rocío, Collado, Rosa, Gentile, Massimo, Gimeno, Eva, Glenthøj, Andreas, da Silva, Maria Gomes, Hakobyan, Yervand K., Herishanu, Yair, Hernández‐Rivas, José Ángel, Herold, Tobias, Innocenti, Idanna, and Itchaki, Gilad
Published: 2023
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6. COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Author: Martínez López, Joaquín, De la Cruz, Javier, Gil Manso, Rodrigo, Alegre Amor, Adrián, Ortiz, Javier, Llamas, Pilar, Martínez Díez, Yolanda, Hernández Rivas, José Ángel, González Gascón y Marín, Isabel, Benavente Cuesta, Celina, Estival Monteliu, Pablo, Jiménez Yuste, Víctor, Canales Albendea, Miguel Ángel, Bastos Oreiro, Mariana Beatriz, Kwon, Mi, Valenciano, Susana, Callejas Charavia, Marta, López Jiménez, Javier, Herrera Puente, Pilar, Duarte, Rafael, Núñez Martín Buitrago, Lucía, Sánchez Godoy, Pedro, Jacome Yerovi, Cristina, Martínez Barranco, Pilar, García Roa, María, Escolano Escobar, Cristian, Matilla García, Arturo, Rosado Sierra, Belén, Aláez Usón, María Concepción, Quiroz Cervantes, Keina, Martínez Chamorro, Carmen, Pérez Oteyza, Jaime, Martos Martinez, Rafael, Herráez, Regina, González Santillana, Clara, Del Campo, Juan Francisco, Alonso, Arancha, Fuente, Adolfo de la, Pascual, Adriana, Bustelos Rodriguez, Rosalía, Sebrango, Ana, Ruiz Mediavilla, Elena, Marcheco-Pupo, Eriel Alexis, Grande, Carlos, Cedillo, Ángel, Lumbreras Bermejo, Carlos Juan, Arroyo Barea, Andrés, Casas Rojo, Jose Manuel, Calbacho Robles, Maria, Diez Martín, José Luis, García Suárez, Julio, Martínez López, Joaquín, De la Cruz, Javier, Gil Manso, Rodrigo, Alegre Amor, Adrián, Ortiz, Javier, Llamas, Pilar, Martínez Díez, Yolanda, Hernández Rivas, José Ángel, González Gascón y Marín, Isabel, Benavente Cuesta, Celina, Estival Monteliu, Pablo, Jiménez Yuste, Víctor, Canales Albendea, Miguel Ángel, Bastos Oreiro, Mariana Beatriz, Kwon, Mi, Valenciano, Susana, Callejas Charavia, Marta, López Jiménez, Javier, Herrera Puente, Pilar, Duarte, Rafael, Núñez Martín Buitrago, Lucía, Sánchez Godoy, Pedro, Jacome Yerovi, Cristina, Martínez Barranco, Pilar, García Roa, María, Escolano Escobar, Cristian, Matilla García, Arturo, Rosado Sierra, Belén, Aláez Usón, María Concepción, Quiroz Cervantes, Keina, Martínez Chamorro, Carmen, Pérez Oteyza, Jaime, Martos Martinez, Rafael, Herráez, Regina, González Santillana, Clara, Del Campo, Juan Francisco, Alonso, Arancha, Fuente, Adolfo de la, Pascual, Adriana, Bustelos Rodriguez, Rosalía, Sebrango, Ana, Ruiz Mediavilla, Elena, Marcheco-Pupo, Eriel Alexis, Grande, Carlos, Cedillo, Ángel, Lumbreras Bermejo, Carlos Juan, Arroyo Barea, Andrés, Casas Rojo, Jose Manuel, Calbacho Robles, Maria, Diez Martín, José Luis, and García Suárez, Julio
Abstract: Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis., Fundación Madrileña de Hematología y Hemoterapia, Fundación Leucemia y Linfoma, Asociación Madrileña de Hematología y Hemoterapia, Depto. de Medicina, Fac. de Medicina, TRUE, pub
Published: 2023

7. The Five “Ws” of Frailty Assessment and Chronic Lymphocytic Leukemia: Who, What, Where, Why, and When

Author: González Gascón y Marín, Isabel, Ballesteros Andrés, Mónica, Martínez Flores, Sara, Rodríguez Vicente, Ana Eugenia, Pérez Carretero, Claudia, Quijada Álamo, Miguel, Rodríguez Sánchez, Alberto, Hernández Rivas, José Ángel, González Gascón y Marín, Isabel, Ballesteros Andrés, Mónica, Martínez Flores, Sara, Rodríguez Vicente, Ana Eugenia, Pérez Carretero, Claudia, Quijada Álamo, Miguel, Rodríguez Sánchez, Alberto, and Hernández Rivas, José Ángel
Abstract: Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person’s overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws., Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Mutua Madrileña, Red Temática de Investigación Cooperativa en Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Fundación Española de Hematología y Hemoterapia, Depto. de Medicina, Fac. de Medicina, TRUE, pub, Descuento UCM
Published: 2023

8. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

Author: Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Cordoba, Raul, Arellano, Elena, Gräfe, Stefanie K., Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martin-perez, Sonia, Rodrigues, Raquel Nunes, Rahimli, Laman, Pagano, Livio, Cornely, Oliver A., Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Cordoba, Raul, Arellano, Elena, Gräfe, Stefanie K., Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martin-perez, Sonia, Rodrigues, Raquel Nunes, Rahimli, Laman, Pagano, Livio, and Cornely, Oliver A.
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 o, 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 m
Published: 2023

9. SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination

Author: Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis, Martino, Rodrigo, Vazquez, Lourdes, López-Corral, L., Pérez, Ariadna, Chorão, Pedro, Avendaño-Pita, Alejandro, Pascual, María Jesús, Sánchez-Salinas, Andrés, Sanz-Linares, Gabriela, Olave, María T., Arroyo, Ignacio, Tormo, Mar, Villalon, Lucia, Conesa-García, Venancio, Gago, Beatriz, Terol, María José, Villalba, Marta, García-Gutiérrez, Valentín, Cabero, Almudena, Hernández-Rivas, José Ángel, Ferrer, Elena, García-Cadenas, Irene, Teruel, Anabel, Navarro, David, Cedillo, Ángel, Sureda, Anna, Solano, Carlos, Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis, Martino, Rodrigo, Vazquez, Lourdes, López-Corral, L., Pérez, Ariadna, Chorão, Pedro, Avendaño-Pita, Alejandro, Pascual, María Jesús, Sánchez-Salinas, Andrés, Sanz-Linares, Gabriela, Olave, María T., Arroyo, Ignacio, Tormo, Mar, Villalon, Lucia, Conesa-García, Venancio, Gago, Beatriz, Terol, María José, Villalba, Marta, García-Gutiérrez, Valentín, Cabero, Almudena, Hernández-Rivas, José Ángel, Ferrer, Elena, García-Cadenas, Irene, Teruel, Anabel, Navarro, David, Cedillo, Ángel, Sureda, Anna, and Solano, Carlos
Abstract: The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.
Published: 2023

10. Remdesivir or Nirmatrelvir/Ritonavir Therapy for Omicron SARS-CoV-2 Infection in Hematological Patients and Cell Therapy Recipients

Author: Piñana, José Luis, Heras, Inmaculada, Aiello, Tommaso Francesco, García-Cadenas, Irene, Vázquez, Lourdes, López Jiménez, Javier, Chorão, Pedro, Aroca, Cristina, García-Vidal, Carolina, Arroyo, Ignacio, Soler-Espejo, Eva, López-Corral, L., Avendaño, Alejandro, Arrufat, Anna, García-Gutierrez, V., Arellano, Elena, Hernández-Medina, Lorena, González-Santillana, Clara, Morell, Julia, Hernández-Rivas, José Ángel, Rodriguez-Galvez, Paula, Mico-Cerdá, Mireia, Guerreiro, Manuel, Campos, Diana, Navarro, David, Cedillo, Ángel, Martino, Rodrigo, Solano, Carlos, Piñana, José Luis, Heras, Inmaculada, Aiello, Tommaso Francesco, García-Cadenas, Irene, Vázquez, Lourdes, López Jiménez, Javier, Chorão, Pedro, Aroca, Cristina, García-Vidal, Carolina, Arroyo, Ignacio, Soler-Espejo, Eva, López-Corral, L., Avendaño, Alejandro, Arrufat, Anna, García-Gutierrez, V., Arellano, Elena, Hernández-Medina, Lorena, González-Santillana, Clara, Morell, Julia, Hernández-Rivas, José Ángel, Rodriguez-Galvez, Paula, Mico-Cerdá, Mireia, Guerreiro, Manuel, Campos, Diana, Navarro, David, Cedillo, Ángel, Martino, Rodrigo, and Solano, Carlos
Abstract: Background: Scarce data exist that analyze the outcomes of hematological patients with SARS-CoV-2 infection during the Omicron variant period who received treatment with remdesivir or nirmatrelvir/ritonavir. Methods: This study aims to address this issue by using a retrospective observational registry, created by the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group, spanning from 27 December 2021 to 30 April 2023. Results: This study included 466 patients, 243 (52%) who were treated with remdesivir and 223 (48%) with nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir was primarily used for mild cases, resulting in a lower COVID-19-related mortality rate (1.3%), while remdesivir was preferred for moderate to severe cases (40%), exhibiting a higher mortality rate (9%). A multivariate analysis in the remdesivir cohort showed that male gender (odds ratio (OR) 0.35, p = 0.042) correlated with a lower mortality risk, while corticosteroid use (OR 9.4, p < 0.001) and co-infection (OR 2.8, p = 0.047) were linked to a higher mortality risk. Prolonged virus shedding was common, with 52% of patients shedding the virus for more than 25 days. In patients treated with remdesivir, factors associated with prolonged shedding included B-cell malignancy as well as underlying disease, severe disease, a later onset of and shorter duration of remdesivir treatment and a higher baseline viral load. Nirmatrelvir/ritonavir demonstrated a comparable safety profile to remdesivir, despite a higher risk of drug interactions. Conclusions: Nirmatrelvir/ritonavir proved to be a safe and effective option for treating mild cases in the outpatient setting, while remdesivir was preferred for severe cases, where corticosteroids and co-infection significantly predicted worse outcomes. Despite antiviral therapy, prolonged shedding remains a matter of concern.
Published: 2023

11. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Author: Gilead Sciences, Salmanton-García, Jon, Marchesi, Francesco, Silva, Maria Gomes da, Farina, Francesca, Dávila-Valls, Julio, Bilgin, Yavuz M., Glenthøj, Andreas, Falces-Romero, Iker, Doesum, Jaap van, Labrador, Jorge, Buquicchio, Caterina, El-Ashwah, Shaimaa, Petzer, Verena, Van Praet, Jens, Schönlein, Martin, Dargenio, Michelina, Méndez, Gustavo-Adolfo, Meers, Stef, Itri, Federico, Giordano, Antonio, Pinczés, László Imre, Espigado, Ildefonso, Stojanoski, Zlate, López-García, Alberto, Prezioso, Lucia, Jaksic, Ozren, Vena, Antonio, Fracchiolla, Nicola S., González-López, Tomás José, Čolović, Natasa, Delia, Mario, Weinbergerová, Barbora, Marchetti, Monia, Marqués de Almeida, Joyce, Finizio, Olimpia, Besson, Caroline, Biernat, Monika M., Valković, Toni, Lahmer, Tobias, Cuccaro, Annarosa, Ormazabal-Vélez, Irati, Batinić, Josip, Fernández, Noemí, Jonge, Nick de, Tascini, Carlo, Anastasopoulou, Amalia N., Duléry, Rémy, Príncipe, María Ilaria del, Plantefeve, Gaëtan, Papa, Mario Virgilio, Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Córdoba, Raúl, Arellano-Orden, Elena, Gräfe, Stefanie, Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martín-Pérez, Sonia, Nunes-Rodrigues, Raquel, Rahimli, Laman, Pagano, Livio, Cornely, Oliver A., EPICOVIDEHA registry, Gilead Sciences, Salmanton-García, Jon, Marchesi, Francesco, Silva, Maria Gomes da, Farina, Francesca, Dávila-Valls, Julio, Bilgin, Yavuz M., Glenthøj, Andreas, Falces-Romero, Iker, Doesum, Jaap van, Labrador, Jorge, Buquicchio, Caterina, El-Ashwah, Shaimaa, Petzer, Verena, Van Praet, Jens, Schönlein, Martin, Dargenio, Michelina, Méndez, Gustavo-Adolfo, Meers, Stef, Itri, Federico, Giordano, Antonio, Pinczés, László Imre, Espigado, Ildefonso, Stojanoski, Zlate, López-García, Alberto, Prezioso, Lucia, Jaksic, Ozren, Vena, Antonio, Fracchiolla, Nicola S., González-López, Tomás José, Čolović, Natasa, Delia, Mario, Weinbergerová, Barbora, Marchetti, Monia, Marqués de Almeida, Joyce, Finizio, Olimpia, Besson, Caroline, Biernat, Monika M., Valković, Toni, Lahmer, Tobias, Cuccaro, Annarosa, Ormazabal-Vélez, Irati, Batinić, Josip, Fernández, Noemí, Jonge, Nick de, Tascini, Carlo, Anastasopoulou, Amalia N., Duléry, Rémy, Príncipe, María Ilaria del, Plantefeve, Gaëtan, Papa, Mario Virgilio, Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Córdoba, Raúl, Arellano-Orden, Elena, Gräfe, Stefanie, Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martín-Pérez, Sonia, Nunes-Rodrigues, Raquel, Rahimli, Laman, Pagano, Livio, Cornely, Oliver A., and EPICOVIDEHA registry
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 mortality difference in patients after nirmatrelvir/ritonavir administration., [Interpretation] Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir.
Published: 2023

12. 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: Gilead Sciences, Salmanton-García, Jon, Marchesi, Francesco, Koehler, Philipp, Weinbergerová, Barbora, Čolović, Natasa, Falces-Romero, Iker, Buquicchio, Caterina, Farina, Francesca, Praet, Jens van, Biernat, Monika M., Itri, Federico, Prezioso, Lucia, Tascini, Carlo, Vena, Antonio, Romano, Alessandra, Delia, Mario, Dávila-Valls, Julio, Martín-Pérez, Sonia, Lavilla-Rubira, Esperanza, Adžić-vukičević, Tatjana, García-Bordallo, Daniel, López-García, Alberto, Criscuolo, Mariana, Petzer, Verena, Fracchiolla, Nicola S., Espigado, Ildefonso, Sili, Uluhan, Meers, Stef, Erben, Nurettin, Cattaneo, Chiara, Tragiannidis, Athanasios, Gavriilaki, Eleni, Schönlein, Martin, Mitrovic, Mirjana, Pantic, Nikola, Merelli, Maria, Labrador, Jorge, Hernández-Rivas, José Ángel, Glenthøj, Andreas, Fouquet, Guillemette, Príncipe, María Ilaria del, Dargenio, Michelina, Calbacho, María, Besson, Caroline, Kohn, Milena, Gräfe, Stefanie, Hersby, Ditte Stampe, Arellano-Orden, Elena, Çolak, Gökçe Melis, Wolf, Dominik, Marchetti, Monia, Nordlander, Anna, Blennow, Ola, Córdoba, Raúl, Mišković, Bojana, Mladenović, Miloš, Bavastro, Martina, Limongelli, Alessandro, Rahimli, Laman, Pagano, Livio, Cornely, Oliver A., Gilead Sciences, Salmanton-García, Jon, Marchesi, Francesco, Koehler, Philipp, Weinbergerová, Barbora, Čolović, Natasa, Falces-Romero, Iker, Buquicchio, Caterina, Farina, Francesca, Praet, Jens van, Biernat, Monika M., Itri, Federico, Prezioso, Lucia, Tascini, Carlo, Vena, Antonio, Romano, Alessandra, Delia, Mario, Dávila-Valls, Julio, Martín-Pérez, Sonia, Lavilla-Rubira, Esperanza, Adžić-vukičević, Tatjana, García-Bordallo, Daniel, López-García, Alberto, Criscuolo, Mariana, Petzer, Verena, Fracchiolla, Nicola S., Espigado, Ildefonso, Sili, Uluhan, Meers, Stef, Erben, Nurettin, Cattaneo, Chiara, Tragiannidis, Athanasios, Gavriilaki, Eleni, Schönlein, Martin, Mitrovic, Mirjana, Pantic, Nikola, Merelli, Maria, Labrador, Jorge, Hernández-Rivas, José Ángel, Glenthøj, Andreas, Fouquet, Guillemette, Príncipe, María Ilaria del, Dargenio, Michelina, Calbacho, María, Besson, Caroline, Kohn, Milena, Gräfe, Stefanie, Hersby, Ditte Stampe, Arellano-Orden, Elena, Çolak, Gökçe Melis, Wolf, Dominik, Marchetti, Monia, Nordlander, Anna, Blennow, Ola, Córdoba, Raúl, Mišković, Bojana, Mladenović, Miloš, Bavastro, Martina, Limongelli, Alessandro, Rahimli, Laman, Pagano, Livio, and Cornely, Oliver A.
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 vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death., [Conclusions] Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.
Published: 2023

13. The Five “Ws” of Frailty Assessment and Chronic Lymphocytic Leukemia: Who, What, Where, Why, and When

Author: Instituto de Salud Carlos III, European Commission, Junta de Castilla y León, Fundación Mutua Madrileña, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Sociedad Española de Hematología y Hemoterapia, González-Gascón y Marín, Isabel, Ballesteros-Andrés, Mónica, Martínez-Flores, Sara, Rodríguez-Vicente, Ana Eugenia, Pérez-Carretero, Claudia, Quijada-Álamo, Miguel, Rodríguez-Sánchez, Alberto, Hernández-Rivas, José Ángel, Instituto de Salud Carlos III, European Commission, Junta de Castilla y León, Fundación Mutua Madrileña, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Sociedad Española de Hematología y Hemoterapia, González-Gascón y Marín, Isabel, Ballesteros-Andrés, Mónica, Martínez-Flores, Sara, Rodríguez-Vicente, Ana Eugenia, Pérez-Carretero, Claudia, Quijada-Álamo, Miguel, Rodríguez-Sánchez, Alberto, and Hernández-Rivas, José Ángel
Abstract: Chronic lymphocytic leukemia (CLL) is a disease of the elderly, but chronological age does not accurately discriminate frailty status at the inter-individual level. Frailty describes a person’s overall resilience. Since CLL is a stressful situation, it is relevant to assess the patient´s degree of frailty, especially before starting antineoplastic treatment. We are in the era of targeted therapies, which have helped to control the disease more effectively and avoid the toxicity of chemo (immuno) therapy. However, these drugs are not free of side effects and other aspects arise that should not be neglected, such as interactions, previous comorbidities, or adherence to treatment, since most of these medications are taken continuously. The challenge we face is to balance the risk of toxicity and efficacy in a personalized way and without forgetting that the most frequent cause of death in CLL is related to the disease. For this purpose, comprehensive geriatric assessment (GA) provides us with the opportunity to evaluate multiple domains that may affect tolerance to treatment and that could be improved with appropriate interventions. In this review, we will analyze the state of the art of GA in CLL through the five Ws.
Published: 2023

14. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Author: AbbVie Pharmaceuticals, European Commission, Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, López-García, Alberto, Marquet, Juan, Martín-Rodríguez, Lucía, Maynadié, Marc, Tadmor, Tamar, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fátima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Tomic, Kristina, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, María, Papajík, Tomás, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Tse, Eric, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martín, Smirnova, Svetlana, Vassilakopoulos, Theodoros, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Al-Shemari, Salem, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Aurran-Schleinitz, Thérèse, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Bacchiarri, Francesca, Panagiotidis, Panagiotis, Popov, Viola María, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine S., Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Bellido, Mar, Ghia, Paolo, Stamatopoulos, Kostas, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofía, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, María, Donaldson, David, Santos, Gimena Dos, Dreta, Bárbara, Efstathopoulou, María, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón y Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Kamel, Laribi, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, María, Konstantinou, Eliana, Koren-Michowitz, Maya, Kotsianidis, Ioannis, AbbVie Pharmaceuticals, European Commission, Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, López-García, Alberto, Marquet, Juan, Martín-Rodríguez, Lucía, Maynadié, Marc, Tadmor, Tamar, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fátima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Tomic, Kristina, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, María, Papajík, Tomás, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Tse, Eric, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martín, Smirnova, Svetlana, Vassilakopoulos, Theodoros, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Al-Shemari, Salem, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Aurran-Schleinitz, Thérèse, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Bacchiarri, Francesca, Panagiotidis, Panagiotis, Popov, Viola María, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine S., Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Bellido, Mar, Ghia, Paolo, Stamatopoulos, Kostas, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofía, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, María, Donaldson, David, Santos, Gimena Dos, Dreta, Bárbara, Efstathopoulou, María, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón y Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Kamel, Laribi, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, María, Konstantinou, Eliana, Koren-Michowitz, Maya, and Kotsianidis, Ioannis
Abstract: [Background]: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work., [Methods]: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022., [Findings]: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs). The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49–2.11; p < 0.001/OR = 1.89; 95% CI = 1.6–2.24; p < 0.001). CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36–2.41; p < 0.001/OR = 2.11; 95% CI = 1.12–3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08–0.33; p < 0.001). Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001)., [Interpretation]: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS.
Published: 2023

15. Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post–CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey

Author: Doesum, Jaap van, Salmanton-García, Jon, Marchesi, Francesco, Blasi, Roberta di, Falces-Romero, Iker, Cabirta, Alba, Farina, Francesca, Besson, Caroline, Weinbergerová, Barbora, Praet, Jens van, Schönlein, Martin, López-García, Alberto, Lamure, Sylvain, Guidetti, Anna, Ramón, Cristina de, Batinić, Josip, Gavriilaki, Eleni, Tragiannidis, Athanasios, Tisi, Maria Chiara, Plantefeve, Gaëtan, Petzer, Verena, Ormazabal-Vélez, Irati, Marques de Almedia, Joyce, Marchetti, Monia, Maertens, Johan, Machado, Marina, Kulasekararaj, Austin G., Hernández-Rivas, José Ángel, Gomes Da Silva, María, Fernández, Noemí, Espigado, Ildefonso, Drgona, Lubos, Dragonetti, Giulia, Metafuni, Elisabetta, Calbacho, María, Blennow, Ola, Wolf, Dominik, Anrooij, Bjorn van, Nunes-Rodrigues, Raquel, Nordlander, Anna, Martín-González, Juan-Alberto, Lievin, Raphaël, Jiménez, Moraima, Gräfe, Stefanie, García-Sanz, Ramón, Córdoba, Raúl, Rahimli, Laman, Meerten, Tom van, Cornely, Oliver A., Pagano, Livio, Doesum, Jaap van, Salmanton-García, Jon, Marchesi, Francesco, Blasi, Roberta di, Falces-Romero, Iker, Cabirta, Alba, Farina, Francesca, Besson, Caroline, Weinbergerová, Barbora, Praet, Jens van, Schönlein, Martin, López-García, Alberto, Lamure, Sylvain, Guidetti, Anna, Ramón, Cristina de, Batinić, Josip, Gavriilaki, Eleni, Tragiannidis, Athanasios, Tisi, Maria Chiara, Plantefeve, Gaëtan, Petzer, Verena, Ormazabal-Vélez, Irati, Marques de Almedia, Joyce, Marchetti, Monia, Maertens, Johan, Machado, Marina, Kulasekararaj, Austin G., Hernández-Rivas, José Ángel, Gomes Da Silva, María, Fernández, Noemí, Espigado, Ildefonso, Drgona, Lubos, Dragonetti, Giulia, Metafuni, Elisabetta, Calbacho, María, Blennow, Ola, Wolf, Dominik, Anrooij, Bjorn van, Nunes-Rodrigues, Raquel, Nordlander, Anna, Martín-González, Juan-Alberto, Lievin, Raphaël, Jiménez, Moraima, Gräfe, Stefanie, García-Sanz, Ramón, Córdoba, Raúl, Rahimli, Laman, Meerten, Tom van, Cornely, Oliver A., and Pagano, Livio
Abstract: Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.
Published: 2023

16. One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients

Author: Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis, Vázquez, Lourdes, Calabuig, Marisa, López-Corral, L., Martín-Martín, Gabriel, Villalón, Lucía, Sanz-Linares, Gabriela, Conesa-Garcia, Venancio, Sánchez-Salinas, Andrés, Gago, Beatriz, Facal, Ana, Risco-Gálvez, Irene, Olave, María T., Espigado, Ildefonso, López Jiménez, Javier, Hernández-Rivas, José Ángel, Avendaño, Alejandro, Arroyo, Ignacio, Ferrer, Elena, García-Cadenas, Irene, González-Santillana, Clara, Roldán-Pérez, Alicia, Ferrer, Blanca, Guerreiro, Manuel, Suarez-Lledó, María, Camara, Ángela, Campos-Beltrán, Diana, Navarro, David, Cedillo, Ángel, Sureda, Anna, Solano, Carlos, Martino, Rodrigo, Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis, Vázquez, Lourdes, Calabuig, Marisa, López-Corral, L., Martín-Martín, Gabriel, Villalón, Lucía, Sanz-Linares, Gabriela, Conesa-Garcia, Venancio, Sánchez-Salinas, Andrés, Gago, Beatriz, Facal, Ana, Risco-Gálvez, Irene, Olave, María T., Espigado, Ildefonso, López Jiménez, Javier, Hernández-Rivas, José Ángel, Avendaño, Alejandro, Arroyo, Ignacio, Ferrer, Elena, García-Cadenas, Irene, González-Santillana, Clara, Roldán-Pérez, Alicia, Ferrer, Blanca, Guerreiro, Manuel, Suarez-Lledó, María, Camara, Ángela, Campos-Beltrán, Diana, Navarro, David, Cedillo, Ángel, Sureda, Anna, Solano, Carlos, and Martino, Rodrigo
Abstract: The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3–6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7–391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16–20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.
Published: 2023

17. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

Author: Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Cordoba, Raul, Arellano, Elena, Gräfe, Stefanie K., Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martin-perez, Sonia, Rodrigues, Raquel Nunes, Rahimli, Laman, Pagano, Livio, Cornely, Oliver A., Nucci, Marcio, Jiménez, Moraima, Aujayeb, Avinash, Hernández-Rivas, José Ángel, Merelli, Maria, Cattaneo, Chiara, Blennow, Ola, Nordlander, Anna, Cabirta, Alba, Varricchio, Gina, Sacchi, Maria Vittoria, Cordoba, Raul, Arellano, Elena, Gräfe, Stefanie K., Wolf, Dominik, Emarah, Ziad, Ammatuna, Emanuele, Hersby, Ditte Stampe, Martin-perez, Sonia, Rodrigues, Raquel Nunes, Rahimli, Laman, Pagano, Livio, and Cornely, Oliver A.
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 o, 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 m
Published: 2023

18. Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

Author: Sánchez, Ricardo, Dorado, Sara, Ruíz-Heredia, Yanira, Martín-Muñoz, Alejandro, Rosa-Rosa, Juan Manuel, Ribera, Jordi, García, Olga, Jiménez-Ubieto, Ana, Carreño-Tarragona, Gonzalo, Linares Gómez, María, Rufián, Laura, Juárez, Alexandra, Carrillo, Jaime, Espino, María José, Cáceres, Mercedes, Expósito, Sara, Cuevas, Beatriz, Vanegas, Raúl, Casado, Luis Felipe, Torrent, Anna, Zamora, Lurdes, Mercadal, Santiago, Coll, Rosa, Cervera, Marta, Morgades, Mireia, Hernández-Rivas, José Ángel, Bravo, Pilar, Serí, Cristina, Anguita, Eduardo, Barragán, Eva, Sargas, Claudia, Ferrer-Marín, Francisca, Sánchez-Calero, Jorge, Sevilla, Julián, Ruíz, Elena, Villalón, Lucía, Herráez, María del Mar, Riaza, Rosalía, Magro, Elena, Steegman, Juan Luis, Wang, Chongwu, Toledo, Paula de, García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, Martínez López, Joaquín, Sánchez, Ricardo, Dorado, Sara, Ruíz-Heredia, Yanira, Martín-Muñoz, Alejandro, Rosa-Rosa, Juan Manuel, Ribera, Jordi, García, Olga, Jiménez-Ubieto, Ana, Carreño-Tarragona, Gonzalo, Linares Gómez, María, Rufián, Laura, Juárez, Alexandra, Carrillo, Jaime, Espino, María José, Cáceres, Mercedes, Expósito, Sara, Cuevas, Beatriz, Vanegas, Raúl, Casado, Luis Felipe, Torrent, Anna, Zamora, Lurdes, Mercadal, Santiago, Coll, Rosa, Cervera, Marta, Morgades, Mireia, Hernández-Rivas, José Ángel, Bravo, Pilar, Serí, Cristina, Anguita, Eduardo, Barragán, Eva, Sargas, Claudia, Ferrer-Marín, Francisca, Sánchez-Calero, Jorge, Sevilla, Julián, Ruíz, Elena, Villalón, Lucía, Herráez, María del Mar, Riaza, Rosalía, Magro, Elena, Steegman, Juan Luis, Wang, Chongwu, Toledo, Paula de, García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, and Martínez López, Joaquín
Abstract: The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease., NCBI, Depto. de Bioquímica y Biología Molecular, Fac. de Farmacia, TRUE, pub
Published: 2022

19. Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients

Author: Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, Bosch, Francesc, Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, and Bosch, Francesc
Abstract: In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
Published: 2022

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

Author: Pagano, Livio, Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Blennow, Ola, Gomes da Silva, Maria, Glenthøj, Andreas, van Doesum, Jaap, Bilgin, Yavuz M, López-García, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, van Praet, Jens, Jaksic, Ozren, Valković, Toni, Falces-Romero, Iker, Martín-Pérez, Sonia, Jiménez, Moraima, Dávila-Valls, Julio, Schönlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Imre Pinczés, László, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-Vélez, Irati, Fracchiolla, Nicola, Samarkos, Michail, Méndez, Gustavo-Adolfo, Hernández-Rivas, José-Ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, di Blasi, Roberta, Marques de Almedia, Joyce, Dargenio, Michelina, Biernat, Monika M, Sciumè, Mariarita, de Ramón, Cristina, de Jonge, Nick, Batinić, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández, Noemí, Zambrotta, Giovanni, Sacchi, Maria Vittoria, Guidetti, Anna, Demirkan, Fatih, Prezioso, Lucia, Ráčil, Zdeněk, Nucci, Marcio, Mladenović, Miloš, Liévin, Raphaël, Hanáková, Michaela, Gräfe, Stefanie, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adžić-Vukičević, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, Cornely, Oliver A, Pagano, Livio, Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Blennow, Ola, Gomes da Silva, Maria, Glenthøj, Andreas, van Doesum, Jaap, Bilgin, Yavuz M, López-García, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, van Praet, Jens, Jaksic, Ozren, Valković, Toni, Falces-Romero, Iker, Martín-Pérez, Sonia, Jiménez, Moraima, Dávila-Valls, Julio, Schönlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Imre Pinczés, László, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-Vélez, Irati, Fracchiolla, Nicola, Samarkos, Michail, Méndez, Gustavo-Adolfo, Hernández-Rivas, José-Ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, di Blasi, Roberta, Marques de Almedia, Joyce, Dargenio, Michelina, Biernat, Monika M, Sciumè, Mariarita, de Ramón, Cristina, de Jonge, Nick, Batinić, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández, Noemí, Zambrotta, Giovanni, Sacchi, Maria Vittoria, Guidetti, Anna, Demirkan, Fatih, Prezioso, Lucia, Ráčil, Zdeněk, Nucci, Marcio, Mladenović, Miloš, Liévin, Raphaël, Hanáková, Michaela, Gräfe, Stefanie, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adžić-Vukičević, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, and Cornely, Oliver A
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

21. Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients

Author: Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, Bosch, Francesc, Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, and Bosch, Francesc
Abstract: In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
Published: 2022

22. Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients

Author: Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, Bosch, Francesc, Universidad de Sevilla. Departamento de Medicina, Piñana, José L., Vázquez, Lourdes, Martino, Rodrigo, García Gutiérrez, Valentín, Pérez Simón, José Antonio, Hernández Rivas, José Ángel, and Bosch, Francesc
Abstract: In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
Published: 2022

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

Author: Gilead Sciences, Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Doesum, Jaap van, López-García, Alberto, Farina, Francesca, Jakšić, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, Jonge, Nick de, Glenthøj, Andrea, Ramón, Cristina de, Biernat, Monika, Fracchiolla, Nicola S., Aujayeb, Avinash, Praet, Jens van, Schönlein, Martin, Méndez, Gustavo-Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Córdoba, Raúl, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, Kort, Elizabeth De, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, García-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Yi Ann Chai, Louis, Shan Kho, Chi, Bonanni, Matteo, Lievin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., Pagano, Livio, Gilead Sciences, Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Doesum, Jaap van, López-García, Alberto, Farina, Francesca, Jakšić, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, Jonge, Nick de, Glenthøj, Andrea, Ramón, Cristina de, Biernat, Monika, Fracchiolla, Nicola S., Aujayeb, Avinash, Praet, Jens van, Schönlein, Martin, Méndez, Gustavo-Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Córdoba, Raúl, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, Kort, Elizabeth De, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, García-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Yi Ann Chai, Louis, Shan Kho, Chi, Bonanni, Matteo, Lievin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., and Pagano, Livio
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused high mortality in patients with hematological malignancies (HM).1 The newly emerged omicron variants of SARS-CoV-2 harbor multiple novel spike protein mutations that raise concerns about vaccine efficiency and antiviral efficacy of the available therapeutic monoclonal antibodies.2 The first published clinical data in immunocompetent patients have found that infection with omicron variants is associated with reduced vaccine efficiency compared to the delta variants, but decreased hospital admission and mortality.3, 4 Preliminary, prepublished, data from a large case–control study have shown that the vaccine effect against omicron in immunocompromised patients, including HM patients, is even more reduced, but data regarding clinical outcomes are lacking.5 The aim of this study was to describe risk factors, antiviral treatment and outcomes of SARS-CoV-2 omicron variant infection in 593 HM patients included in the EPICOVIDEHA registry.
Published: 2022

24. Circulating tumor and immune cells for minimally invasive risk stratification of smoldering multiple myeloma

Author: Termini, Rosalinda, Žihala, David, Terpos, Evangelos, Pérez-Montaña, Albert, Jelínek, Tomáš, Raab, Marc S., Weinhold, Niels, Mai, Elias K., Grab, Anna Luise, Corre, Jill, Vergez, Francois, Sacco, Antonio, Chiarini, Marco, Giustini, Viviana, Tucci, Alessandra, Rodríguez, Sara, Moreno, Cristina, Perez, Cristina, Maia, Catarina, Martín-Sánchez, Esperanza, Guerrero, Camilla, Botta, Cirino, Garcés, Juan José, López, Aitziber, Tamariz-Amador, Luis-Esteban, Prósper, Felipe, Bargay, Joan, Cabezudo, María-Elena, Ocio, Enrique M., Hajek, Roman, Martínez-López, Joaquín, Solano, Fernando, Iglesias, Rebeca, Paiva, Artur, Geraldes, Catarina, Vitoria, Helena, Gómez, Clara, Arriba, Felipe de, Ludwig, Heinz, Garcia-Guiñon, Antonio, Casanova, María, Cabañas, Valentin, Sirvent, Maialen, Oriol, Albert, Rubia, Javier de la, Hernández-Rivas, José Ángel, Palomera, Luis, Sarasa, María, Ríos, Pablo, Puig, Noemi, Mateos, Maria Victoria, Flores-Montero, Juan, Orfao, Alberto, Goldschmidt, Hartmut, Avet-Loiseau, Hervé, Roccaro, Aldo M., San-Miguel, Jesús, Paiva, Bruno, Termini, Rosalinda, Žihala, David, Terpos, Evangelos, Pérez-Montaña, Albert, Jelínek, Tomáš, Raab, Marc S., Weinhold, Niels, Mai, Elias K., Grab, Anna Luise, Corre, Jill, Vergez, Francois, Sacco, Antonio, Chiarini, Marco, Giustini, Viviana, Tucci, Alessandra, Rodríguez, Sara, Moreno, Cristina, Perez, Cristina, Maia, Catarina, Martín-Sánchez, Esperanza, Guerrero, Camilla, Botta, Cirino, Garcés, Juan José, López, Aitziber, Tamariz-Amador, Luis-Esteban, Prósper, Felipe, Bargay, Joan, Cabezudo, María-Elena, Ocio, Enrique M., Hajek, Roman, Martínez-López, Joaquín, Solano, Fernando, Iglesias, Rebeca, Paiva, Artur, Geraldes, Catarina, Vitoria, Helena, Gómez, Clara, Arriba, Felipe de, Ludwig, Heinz, Garcia-Guiñon, Antonio, Casanova, María, Cabañas, Valentin, Sirvent, Maialen, Oriol, Albert, Rubia, Javier de la, Hernández-Rivas, José Ángel, Palomera, Luis, Sarasa, María, Ríos, Pablo, Puig, Noemi, Mateos, Maria Victoria, Flores-Montero, Juan, Orfao, Alberto, Goldschmidt, Hartmut, Avet-Loiseau, Hervé, Roccaro, Aldo M., San-Miguel, Jesús, and Paiva, Bruno
Abstract: [Purpose]: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model. [Experimental Design]: We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment. [Results]: Patients with >0.015% versus ≤0.015% CTCs at baseline had a median time-to-progression of 17 months versus not reached (HR, 4.9; P < 0.001). Presence of >20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2 g/dL M-protein, and >0.015% CTCs. The 20/2/20 and 20/2/0.015 models yielded similar risk stratification (C-index of 0.76 and 0.78). The combination of the 20/2/0.015 model with an immune risk score based on the percentages of SLAN+ and SLAN− nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells, allowed patient’ stratification into low, intermediate-low, intermediate-high, and high-risk disease with 0%, 20%, 39%, and 73% rates of progression at 2 years. [Conclusions]: This study showed that CTCs outperform BM PCs for assessing tumor burden. Additional analysis in larger series are needed to define a consensus cutoff of CTCs for minimally invasive stratification of SMM.
Published: 2022

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

Author: Gilead Sciences, Infante, María-Stefania, Salmanton-García, Jon, Ana Fernández-Cruz, Marchesi, Francesco, Jakšić, Ozren, Weinbergerová, Barbora, Duarte, Rafael F., Itri, Federico, Valković, Toni, Szotkovski, Tomas, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andrea, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Cengiz Seval, Guldane, Machado, Marina, Córdoba, Raúl, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin G., Falces-Romero, Iker, Cattaneo, Chiara, Doesum, Jaap van, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriel, Ledoux, Marie-Pierre, Ramón, Cristina de, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Gomes Da Silva, María, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila, Julio, Praet, Jens van, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenovic, Milos, Hanakova, Michaela, Zambrotta, Giovanni, Jonge, Nick de, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, María, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, Pagano, Livio, Gilead Sciences, Infante, María-Stefania, Salmanton-García, Jon, Ana Fernández-Cruz, Marchesi, Francesco, Jakšić, Ozren, Weinbergerová, Barbora, Duarte, Rafael F., Itri, Federico, Valković, Toni, Szotkovski, Tomas, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andrea, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Cengiz Seval, Guldane, Machado, Marina, Córdoba, Raúl, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin G., Falces-Romero, Iker, Cattaneo, Chiara, Doesum, Jaap van, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriel, Ledoux, Marie-Pierre, Ramón, Cristina de, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Gomes Da Silva, María, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila, Julio, Praet, Jens van, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenovic, Milos, Hanakova, Michaela, Zambrotta, Giovanni, Jonge, Nick de, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, María, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, and Pagano, Livio
Abstract: Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.
Published: 2022

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

Author: Gilead Sciences, Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, María, Glenthøj, Andrea, Doesum, Jaap van, Bilgin, Yavuz M., López-García, Alberto, Itri, Federico, Nunes-Rodrigues, Raquel, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Praet, Jens van, Jakšić, Ozren, Valković, Toni, Falces-Romero, Iker, Martín-Pérez, Sonia, Jiménez, Moraima, Dávila, Julio, Schönlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-Vélez, Irati, Fracchiolla, Nicola S., Samarkos, Michail, Méndez, Gustavo-Adolfo, Hernández-Rivas, José Ángel, Espigado, Ildefonso, Čerňan, Martin, Petzer, Verena, Lamure, Sylvain, Blasi, Roberta di, Marques de Almedia, Joyce, Dargenio, Michelina, Biernat, Monika, Sciumè, Mariarita, Ramón, Cristina de, Jonge, Nick de, Batinić, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández, Noemí, Zambrotta, Giovanni, Sacchi, Maria Vittoria, Guidetti, Anna, Demirkan, Fatih, Prezioso, Lucia, Ráčil, Zdeněk, Nucci, Marcio, Mladenovic, Milos, Lievin, Raphaël, Hanakova, Michaela, Gräfe, Stefanie, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adžić-Vukičević, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, Cornely, Oliver A., Gilead Sciences, Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, María, Glenthøj, Andrea, Doesum, Jaap van, Bilgin, Yavuz M., López-García, Alberto, Itri, Federico, Nunes-Rodrigues, Raquel, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Praet, Jens van, Jakšić, Ozren, Valković, Toni, Falces-Romero, Iker, Martín-Pérez, Sonia, Jiménez, Moraima, Dávila, Julio, Schönlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-Vélez, Irati, Fracchiolla, Nicola S., Samarkos, Michail, Méndez, Gustavo-Adolfo, Hernández-Rivas, José Ángel, Espigado, Ildefonso, Čerňan, Martin, Petzer, Verena, Lamure, Sylvain, Blasi, Roberta di, Marques de Almedia, Joyce, Dargenio, Michelina, Biernat, Monika, Sciumè, Mariarita, Ramón, Cristina de, Jonge, Nick de, Batinić, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández, Noemí, Zambrotta, Giovanni, Sacchi, Maria Vittoria, Guidetti, Anna, Demirkan, Fatih, Prezioso, Lucia, Ráčil, Zdeněk, Nucci, Marcio, Mladenovic, Milos, Lievin, Raphaël, Hanakova, Michaela, Gräfe, Stefanie, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adžić-Vukičević, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, and Cornely, Oliver A.
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

27. Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

Author: Fundación CRIS contra el Cáncer, Sánchez, R., Dorado, S., Ruíz-Heredia, Y., Martín-Muñóz, A., Rosa-Rosa, J.M., Ribera, J., García, O., Jiménez-Ubieto, A., Carreño-Tarragona, G., Linares, Manuel, Rufián, L., Juárez, A., Carrillo, J., Espino, M.J., Cáceres, M., Expósito, Sara, Cuevas, B., Vanegas, R., Casado, Luis Felipe, Torrent, Anna, Zamora, Lurdes, Mercadal, Santiago, Coll, Rosa, Cervera, M., Morgades, Mireia, Hernández-Rivas, José Ángel, Bravo, Pilar, Seri, Cristina, Anguita, Eduardo, Barragán, Eva, Sargas, Claudia, Ferrer-Marín, F., Sánchez-Calero, J., Sevilla, Julián, Ruiz, Elena, Villalón, Lucía, del Mar Herráez, M., Riaza, R., Magro, Elena, Steegmann, Juan Luis, Wang, C., de Toledo, P., García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, Martínez-López, Joaquín, Fundación CRIS contra el Cáncer, Sánchez, R., Dorado, S., Ruíz-Heredia, Y., Martín-Muñóz, A., Rosa-Rosa, J.M., Ribera, J., García, O., Jiménez-Ubieto, A., Carreño-Tarragona, G., Linares, Manuel, Rufián, L., Juárez, A., Carrillo, J., Espino, M.J., Cáceres, M., Expósito, Sara, Cuevas, B., Vanegas, R., Casado, Luis Felipe, Torrent, Anna, Zamora, Lurdes, Mercadal, Santiago, Coll, Rosa, Cervera, M., Morgades, Mireia, Hernández-Rivas, José Ángel, Bravo, Pilar, Seri, Cristina, Anguita, Eduardo, Barragán, Eva, Sargas, Claudia, Ferrer-Marín, F., Sánchez-Calero, J., Sevilla, Julián, Ruiz, Elena, Villalón, Lucía, del Mar Herráez, M., Riaza, R., Magro, Elena, Steegmann, Juan Luis, Wang, C., de Toledo, P., García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, and Martínez-López, Joaquín
Abstract: The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.
Published: 2022

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

Author: Infante, Maria Stefania, Salmanton-García, Jon, Fernández-Cruz, Ana, Marchesi, Francesco, Jaksic, Ozren, Weinbergerová, Barbora, Besson, Caroline, Duarte, Rafael F, Itri, Federico, Valković, Toni, Szotkovski, Tomáš, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andreas, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Seval, Guldane Cengiz, Machado, Marina, Cordoba, Raul, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin, Falces-Romero, Iker, Cattaneo, Chiara, Van Doesum, Jaap, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriele, Ledoux, Marie-Pierre, de Ramon, Cristina, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Da Silva, Maria Gomes, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila-Vals, Julio, Van Praet, Jens, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenović, Miloš, Hanakova, Michaela, Zambrotta, Giovanni Paolo Maria, De Jonge, Nick, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, Maria, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, Pagano, Livio, Infante, Maria Stefania, Salmanton-García, Jon, Fernández-Cruz, Ana, Marchesi, Francesco, Jaksic, Ozren, Weinbergerová, Barbora, Besson, Caroline, Duarte, Rafael F, Itri, Federico, Valković, Toni, Szotkovski, Tomáš, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andreas, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Seval, Guldane Cengiz, Machado, Marina, Cordoba, Raul, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin, Falces-Romero, Iker, Cattaneo, Chiara, Van Doesum, Jaap, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriele, Ledoux, Marie-Pierre, de Ramon, Cristina, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Da Silva, Maria Gomes, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila-Vals, Julio, Van Praet, Jens, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenović, Miloš, Hanakova, Michaela, Zambrotta, Giovanni Paolo Maria, De Jonge, Nick, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, Maria, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, and Pagano, Livio
Abstract: Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.
Published: 2022

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

Author: Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Van Doesum, Jaap, López-García, Alberto, Farina, Francesca, Jaksic, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, De Jonge, Nick, Glenthøj, Andreas, De Ramón, Cristina, Biernat, Monika M., Fracchiolla, Nicola, Aujayeb, Avinash, Van Praet, Jens, Schönlein, Martin, Méndez, Gustavo Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Cordoba, Raul, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, De Kort, Elizabeth, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, Garcia-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Chai, Louis Yi Ann, Kho, Chi Shan, Bonanni, Matteo, Liévin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., Pagano, Livio, Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Van Doesum, Jaap, López-García, Alberto, Farina, Francesca, Jaksic, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, De Jonge, Nick, Glenthøj, Andreas, De Ramón, Cristina, Biernat, Monika M., Fracchiolla, Nicola, Aujayeb, Avinash, Van Praet, Jens, Schönlein, Martin, Méndez, Gustavo Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Cordoba, Raul, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, De Kort, Elizabeth, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, Garcia-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Chai, Louis Yi Ann, Kho, Chi Shan, Bonanni, Matteo, Liévin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., and Pagano, Livio
Published: 2022

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

Author: Pagano, Livio, Salmanton-garcía, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, Maria, Glenthøj, Andreas, Van Doesum, Jaap A., Bilgin, Yavuz M, Lopez-garcia, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Van Praet, Jens, Jaksic, Ozren, Valkovic, Toni, Falces-romero, Iker, Martin-perez, Sonia, Jiménez, Moraima, Davila-valls, Julio, Schonlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-velez, Irati, Fracchiolla, Nicola Stefano, Samarkos, Michail, Mendez, Gustavo-adolfo, Hernández-rivas, José-ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, Di Blasi, Roberta, Marques De Almeida, Joyce, Dargenio, Michelina, Biernat, Monika Maria, Sciumè, Mariarita, De Ramón, Cristina, De Jonge, Nick Alexander, Batinic, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández Escalada, Noemi, Zambrotta, Giovanni Paolo Maria, Sacchi, Maria Vittoria, Guidetti, Anna, Demirken, Fatih, Prezioso, Lucia, Racil, Zdenek, Nucci, Marcio, Mladenovic, Miloš, Lievin, Raphaël, Hanakova, Michaela, Grafe, Stefanie K, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adzic-vukicevic, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, Cornely, Oliver A., Pagano, Livio, Salmanton-garcía, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, Maria, Glenthøj, Andreas, Van Doesum, Jaap A., Bilgin, Yavuz M, Lopez-garcia, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Van Praet, Jens, Jaksic, Ozren, Valkovic, Toni, Falces-romero, Iker, Martin-perez, Sonia, Jiménez, Moraima, Davila-valls, Julio, Schonlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-velez, Irati, Fracchiolla, Nicola Stefano, Samarkos, Michail, Mendez, Gustavo-adolfo, Hernández-rivas, José-ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, Di Blasi, Roberta, Marques De Almeida, Joyce, Dargenio, Michelina, Biernat, Monika Maria, Sciumè, Mariarita, De Ramón, Cristina, De Jonge, Nick Alexander, Batinic, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández Escalada, Noemi, Zambrotta, Giovanni Paolo Maria, Sacchi, Maria Vittoria, Guidetti, Anna, Demirken, Fatih, Prezioso, Lucia, Racil, Zdenek, Nucci, Marcio, Mladenovic, Miloš, Lievin, Raphaël, Hanakova, Michaela, Grafe, Stefanie K, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adzic-vukicevic, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, and Cornely, Oliver A.
Abstract: Limited data have been published on the epidemiology and outcomes of breakthrough COVID-19 in patients with hematological malignancy (HM) after anti-SARS-CoV-2 vaccination. Adult HM who received at least one dose of anti-SARS-CoV-2 vaccine and diagnosed with breakthrough COVID-19 between January 2021 and March 2022 and registered in EPICOVIDEHA were included in this analysis. A total of 1548 cases were included, mainly with lymphoid malignancies (1181 cases, 76%). After viral genome sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received at least two vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received specific treatment for COVID-19. After 30-days follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was of 7.9%, comparable to that reported for the other variants. The 30-day mortality rate was significantly lower than in the pre-vaccine era (31%). In the univariable analysis, older age (p<0.001), active HM (p<0.001), severe and critical COVID-19 (p=0.007 and p<0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p<0.001). In the multivariable model, older age, active disease, critical COVID-19 and at least 2-3 comorbidities were correlated with a higher mortality, whereas the administration of monoclonal antibodies, alone (p<0.001) or combined with antivirals (p=0.009), was observed protective. While mortality is significantly lower than in the pre-vaccination 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 (www.clinicaltrials.gov; National Clinical Trials identifier NCT04733729) is an international open web-based regi
Published: 2022

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

Author: Infante, Maria Stefania, Salmanton-García, Jon, Fernández-Cruz, Ana, Marchesi, Francesco, Jaksic, Ozren, Weinbergerová, Barbora, Besson, Caroline, Duarte, Rafael F, Itri, Federico, Valković, Toni, Szotkovski, Tomáš, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andreas, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Seval, Guldane Cengiz, Machado, Marina, Cordoba, Raul, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin, Falces-Romero, Iker, Cattaneo, Chiara, Van Doesum, Jaap, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriele, Ledoux, Marie-Pierre, de Ramon, Cristina, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Da Silva, Maria Gomes, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila-Vals, Julio, Van Praet, Jens, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenović, Miloš, Hanakova, Michaela, Zambrotta, Giovanni Paolo Maria, De Jonge, Nick, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, Maria, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, Pagano, Livio, Infante, Maria Stefania, Salmanton-García, Jon, Fernández-Cruz, Ana, Marchesi, Francesco, Jaksic, Ozren, Weinbergerová, Barbora, Besson, Caroline, Duarte, Rafael F, Itri, Federico, Valković, Toni, Szotkovski, Tomáš, Busca, Alessandro, Guidetti, Anna, Glenthøj, Andreas, Collins, Graham P., Bonuomo, Valentina, Sili, Uluhan, Seval, Guldane Cengiz, Machado, Marina, Cordoba, Raul, Blennow, Ola, Abu-Zeinah, Ghaith, Lamure, Sylvain, Kulasekararaj, Austin, Falces-Romero, Iker, Cattaneo, Chiara, Van Doesum, Jaap, Piukovics, Klára, Omrani, Ali S., Magliano, Gabriele, Ledoux, Marie-Pierre, de Ramon, Cristina, Cabirta, Alba, Verga, Luisa, López-García, Alberto, Da Silva, Maria Gomes, Stojanoski, Zlate, Meers, Stef, Lahmer, Tobias, Martín-Pérez, Sonia, Dávila-Vals, Julio, Van Praet, Jens, Samarkos, Michail, Bilgin, Yavuz M., Karlsson, Linda Katharina, Batinić, Josip, Nordlander, Anna, Schönlein, Martin, Hoenigl, Martin, Ráčil, Zdeněk, Mladenović, Miloš, Hanakova, Michaela, Zambrotta, Giovanni Paolo Maria, De Jonge, Nick, Adžić-Vukičević, Tatjana, Nunes-Rodrigues, Raquel, Prezioso, Lucia, Navrátil, Milan, Marchetti, Monia, Cuccaro, Annarosa, Calbacho, Maria, Giordano, Antonio, Cornely, Oliver A., Hernández-Rivas, José Ángel, and Pagano, Livio
Abstract: Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.
Published: 2022

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

Author: Pagano, Livio, Salmanton-garcía, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, Maria, Glenthøj, Andreas, Van Doesum, Jaap A., Bilgin, Yavuz M, Lopez-garcia, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Van Praet, Jens, Jaksic, Ozren, Valkovic, Toni, Falces-romero, Iker, Martin-perez, Sonia, Jiménez, Moraima, Davila-valls, Julio, Schonlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-velez, Irati, Fracchiolla, Nicola Stefano, Samarkos, Michail, Mendez, Gustavo-adolfo, Hernández-rivas, José-ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, Di Blasi, Roberta, Marques De Almeida, Joyce, Dargenio, Michelina, Biernat, Monika Maria, Sciumè, Mariarita, De Ramón, Cristina, De Jonge, Nick Alexander, Batinic, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández Escalada, Noemi, Zambrotta, Giovanni Paolo Maria, Sacchi, Maria Vittoria, Guidetti, Anna, Demirken, Fatih, Prezioso, Lucia, Racil, Zdenek, Nucci, Marcio, Mladenovic, Miloš, Lievin, Raphaël, Hanakova, Michaela, Grafe, Stefanie K, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adzic-vukicevic, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, Cornely, Oliver A., Pagano, Livio, Salmanton-garcía, Jon, Marchesi, Francesco, Blennow, Ola, Gomes Da Silva, Maria, Glenthøj, Andreas, Van Doesum, Jaap A., Bilgin, Yavuz M, Lopez-garcia, Alberto, Itri, Federico, Nunes Rodrigues, Raquel, Weinbergerová, Barbora, Farina, Francesca, Dragonetti, Giulia, Berg Venemyr, Caroline, Van Praet, Jens, Jaksic, Ozren, Valkovic, Toni, Falces-romero, Iker, Martin-perez, Sonia, Jiménez, Moraima, Davila-valls, Julio, Schonlein, Martin, Ammatuna, Emanuele, Meers, Stef, Delia, Mario, Stojanoski, Zlate, Nordlander, Anna, Lahmer, Tobias, Pinczés, László Imre, Buquicchio, Caterina, Piukovics, Klára, Ormazabal-velez, Irati, Fracchiolla, Nicola Stefano, Samarkos, Michail, Mendez, Gustavo-adolfo, Hernández-rivas, José-ángel, Espigado, Ildefonso, Cernan, Martin, Petzer, Verena, Lamure, Sylvain, Di Blasi, Roberta, Marques De Almeida, Joyce, Dargenio, Michelina, Biernat, Monika Maria, Sciumè, Mariarita, De Ramón, Cristina, De Jonge, Nick Alexander, Batinic, Josip, Aujayeb, Avinash, Marchetti, Monia, Fouquet, Guillemette, Fernández Escalada, Noemi, Zambrotta, Giovanni Paolo Maria, Sacchi, Maria Vittoria, Guidetti, Anna, Demirken, Fatih, Prezioso, Lucia, Racil, Zdenek, Nucci, Marcio, Mladenovic, Miloš, Lievin, Raphaël, Hanakova, Michaela, Grafe, Stefanie K, Sili, Uluhan, Machado, Marina, Cattaneo, Chiara, Adzic-vukicevic, Tatjana, Verga, Luisa, Labrador, Jorge, Rahimli, Laman, Bonanni, Matteo, Passamonti, Francesco, Pagliuca, Antonio, Corradini, Paolo, Hoenigl, Martin, Koehler, Philipp, Busca, Alessandro, and Cornely, Oliver A.
Abstract: Limited data have been published on the epidemiology and outcomes of breakthrough COVID-19 in patients with hematological malignancy (HM) after anti-SARS-CoV-2 vaccination. Adult HM who received at least one dose of anti-SARS-CoV-2 vaccine and diagnosed with breakthrough COVID-19 between January 2021 and March 2022 and registered in EPICOVIDEHA were included in this analysis. A total of 1548 cases were included, mainly with lymphoid malignancies (1181 cases, 76%). After viral genome sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received at least two vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received specific treatment for COVID-19. After 30-days follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was of 7.9%, comparable to that reported for the other variants. The 30-day mortality rate was significantly lower than in the pre-vaccine era (31%). In the univariable analysis, older age (p<0.001), active HM (p<0.001), severe and critical COVID-19 (p=0.007 and p<0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p<0.001). In the multivariable model, older age, active disease, critical COVID-19 and at least 2-3 comorbidities were correlated with a higher mortality, whereas the administration of monoclonal antibodies, alone (p<0.001) or combined with antivirals (p=0.009), was observed protective. While mortality is significantly lower than in the pre-vaccination 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 (www.clinicaltrials.gov; National Clinical Trials identifier NCT04733729) is an international open web-based regi
Published: 2022

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

Author: Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Van Doesum, Jaap, López-García, Alberto, Farina, Francesca, Jaksic, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, De Jonge, Nick, Glenthøj, Andreas, De Ramón, Cristina, Biernat, Monika M., Fracchiolla, Nicola, Aujayeb, Avinash, Van Praet, Jens, Schönlein, Martin, Méndez, Gustavo Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Cordoba, Raul, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, De Kort, Elizabeth, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, Garcia-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Chai, Louis Yi Ann, Kho, Chi Shan, Bonanni, Matteo, Liévin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., Pagano, Livio, Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Van Doesum, Jaap, López-García, Alberto, Farina, Francesca, Jaksic, Ozren, Pinczés, László Imre, Bilgin, Yavuz M., Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobias, Fernández, Noemí, Hernández-Rivas, José Ángel, Petzer, Verena, De Jonge, Nick, Glenthøj, Andreas, De Ramón, Cristina, Biernat, Monika M., Fracchiolla, Nicola, Aujayeb, Avinash, Van Praet, Jens, Schönlein, Martin, Méndez, Gustavo Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Cordoba, Raul, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, De Kort, Elizabeth, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, Garcia-Vidal, Carolina, Dargenio, Michelina, Danion, François, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Chai, Louis Yi Ann, Kho, Chi Shan, Bonanni, Matteo, Liévin, Raphaël, Marchesi, Francesco, Cornely, Oliver A., and Pagano, Livio
Published: 2022

34. COVID-19 in vaccinated adult patients with hematological malignancies:preliminary results from EPICOVIDEHA

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M., Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andreas, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María Josefa, Hernández-Rivas, José Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver A., Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M., Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andreas, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María Josefa, Hernández-Rivas, José Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, and Cornely, Oliver A.
Published: 2022

35. Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients

Author: Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis [0000-0001-8533-2562], Piñana, José Luis, Rodríguez-Belenguer, Pablo, Caballero, Dolores, Martino, Rodrigo, López-Corral, L., Terol, María José, Vázquez-López, Lourdes, Calabuig, Marisa, Sanz-Linares, Gabriela, Marín-Jimenez, Francisca, Alonso, Carmen, Montoro, Juan, Ferrer, Elena, Facal-Malvar, Ana, Pascual, M. Jesús, Rodríguez-Fernández, Alicia, Olave, María-Teresa, Cascales-Hernández, Almudena, Gago, Beatriz, Hernández-Rivas, José Ángel, Villalón, Lucía, Corona, Magdalena, Roldán-Pérez, Alicia, Ribes-Amoros, Julia, González-Santillana, Clara, García-Sanz, Ramón, Navarro, David, Serrano-López, Antonio J., Cedillo, Ángel, Soria-Olivas, Emilio, Sureda, Anna, Solano, Carlos, Vanderbilt University, Sociedad Española de Hematología y Hemoterapia, Piñana, José Luis [0000-0001-8533-2562], Piñana, José Luis, Rodríguez-Belenguer, Pablo, Caballero, Dolores, Martino, Rodrigo, López-Corral, L., Terol, María José, Vázquez-López, Lourdes, Calabuig, Marisa, Sanz-Linares, Gabriela, Marín-Jimenez, Francisca, Alonso, Carmen, Montoro, Juan, Ferrer, Elena, Facal-Malvar, Ana, Pascual, M. Jesús, Rodríguez-Fernández, Alicia, Olave, María-Teresa, Cascales-Hernández, Almudena, Gago, Beatriz, Hernández-Rivas, José Ángel, Villalón, Lucía, Corona, Magdalena, Roldán-Pérez, Alicia, Ribes-Amoros, Julia, González-Santillana, Clara, García-Sanz, Ramón, Navarro, David, Serrano-López, Antonio J., Cedillo, Ángel, Soria-Olivas, Emilio, Sureda, Anna, and Solano, Carlos
Abstract: Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.
Published: 2022

36. TRAF3 alterations are frequent in del-3′IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features

Author: Universidad de Salamanca, Fundacion de la Sociedad Española de Hematología y Hemoterapia, Centro de Investigación Biomédica en Red Cáncer (España), Red Temática de Investigación Cooperativa en Cáncer (España), Fundación Memoria de D. Samuel Solorzano Barruso, Junta de Castilla y León, Instituto de Salud Carlos III, Pérez-Carretero, Claudia, Hernández-Sánchez, María, González, Teresa, Quijada-Álamo, Miguel, Martín-Izquierdo, Marta, Santos-Mínguez, Sandra, Miguel, Cristina, Vidal, María Jesús, García de Coca, Alfonso, Galende, Josefina, Pardal, Emilia, Aguilar, Carlos, Vargas-Pabón, Manuel, Dávila, Julio, Gascón-Y-Marín, Isabel, Hernández-Rivas, José Ángel, Benito, Rocío, Hernández, Jesús M., Rodríguez-Vicente, Ana Eugenia, Universidad de Salamanca, Fundacion de la Sociedad Española de Hematología y Hemoterapia, Centro de Investigación Biomédica en Red Cáncer (España), Red Temática de Investigación Cooperativa en Cáncer (España), Fundación Memoria de D. Samuel Solorzano Barruso, Junta de Castilla y León, Instituto de Salud Carlos III, Pérez-Carretero, Claudia, Hernández-Sánchez, María, González, Teresa, Quijada-Álamo, Miguel, Martín-Izquierdo, Marta, Santos-Mínguez, Sandra, Miguel, Cristina, Vidal, María Jesús, García de Coca, Alfonso, Galende, Josefina, Pardal, Emilia, Aguilar, Carlos, Vargas-Pabón, Manuel, Dávila, Julio, Gascón-Y-Marín, Isabel, Hernández-Rivas, José Ángel, Benito, Rocío, Hernández, Jesús M., and Rodríguez-Vicente, Ana Eugenia
Abstract: Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3′IGH (del-3′IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3′IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3′IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3′IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3′IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3′IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.
Published: 2022

37. A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma

Author: Fundacion de la Sociedad Española de Hematología y Hemoterapia, Encinas, Cristina, Hernández-Rivas, José Ángel, Oriol, Albert, Rosiñol, Laura, Blanchard, María Jesús, Bellón, José María, García-Sanz, Ramón, Rubia, Javier de la, López de la Guía, Ana, Jiménez-Ubieto, Ana, Jarque, Isidro, Iñigo, Belén, Dourdil, Mª Victoria, Arriba, Felipe de, Cuéllar Pérez-Ávila, Clara, Gonzalez, Yolanda, Hernandez, Miguel T., Bargay, Joan, Granell, Miquel, Rodríguez-Otero, Paula, Silvent, Maialen, Cabrera, Carmen, Ríos, Rafael, Alegre, Adrián, Gironella, Mercedes, Gonzalez, Marta-Sonia, Sureda, Anna, Sampol, Antonia, Ocio, Enrique M., Krsnik, Isabel, García, Antonio, García-Mateo, Aránzazu, Soler, Joan Alfons, Martín, Jesús, Arguiñano, José M., Mateos, Maria Victoria, Bladé, Joan, San-Miguel, Jesús, Lahuerta, Juan José, Martínez-López, Joaquín, Fundacion de la Sociedad Española de Hematología y Hemoterapia, Encinas, Cristina, Hernández-Rivas, José Ángel, Oriol, Albert, Rosiñol, Laura, Blanchard, María Jesús, Bellón, José María, García-Sanz, Ramón, Rubia, Javier de la, López de la Guía, Ana, Jiménez-Ubieto, Ana, Jarque, Isidro, Iñigo, Belén, Dourdil, Mª Victoria, Arriba, Felipe de, Cuéllar Pérez-Ávila, Clara, Gonzalez, Yolanda, Hernandez, Miguel T., Bargay, Joan, Granell, Miquel, Rodríguez-Otero, Paula, Silvent, Maialen, Cabrera, Carmen, Ríos, Rafael, Alegre, Adrián, Gironella, Mercedes, Gonzalez, Marta-Sonia, Sureda, Anna, Sampol, Antonia, Ocio, Enrique M., Krsnik, Isabel, García, Antonio, García-Mateo, Aránzazu, Soler, Joan Alfons, Martín, Jesús, Arguiñano, José M., Mateos, Maria Victoria, Bladé, Joan, San-Miguel, Jesús, Lahuerta, Juan José, and Martínez-López, Joaquín
Abstract: Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.
Published: 2022

38. COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M, Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José-María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andrea, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás-José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María-Josefa, Hernández-Rivas, José-Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver A, Pagano, Livio (ORCID:0000-0001-8287-928X), Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M, Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José-María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andrea, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás-José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María-Josefa, Hernández-Rivas, José-Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver A, and Pagano, Livio (ORCID:0000-0001-8287-928X)
Abstract: no abstract
Published: 2022

39. COVID-19 in vaccinated adult patients with hematological malignancies:preliminary results from EPICOVIDEHA

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M., Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andreas, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María Josefa, Hernández-Rivas, José Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver A., Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, López-García, Alberto, Lamure, Sylvain, Itri, Federico, Gomes-Silva, Maria, Dragonetti, Giulia, Falces-Romero, Iker, van Doesum, Jaap, Sili, Uluhan, Labrador, Jorge, Calbacho, Maria, Bilgin, Yavuz M., Weinbergerová, Barbora, Serrano, Laura, Ribera-Santa Susana, José María, Malak, Sandra, Loureiro-Amigo, José, Glenthøj, Andreas, Córdoba-Mascuñano, Raúl, Nunes-Rodrigues, Raquel, González-López, Tomás José, Karlsson, Linda Katharina, Jiménez-Lorenzo, María Josefa, Hernández-Rivas, José Ángel, Jaksic, Ozren, Ráčil, Zdeněk, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, and Cornely, Oliver A.
Published: 2022

40. From Biomarkers to Models in the Changing Landscape of Chronic Lymphocytic Leukemia: Evolve or Become Extinct

Author: González Gascón y Marín, Isabel, Muñoz Novas, Carolina, Rodríguez Vicente, Ana-Eugenia, Quijada Álamo, Miguel, Hernández Sánchez, María, Pérez Carretero, Claudia, Ramos Ascanio, Victoria, Hernández Rivas, José Ángel, González Gascón y Marín, Isabel, Muñoz Novas, Carolina, Rodríguez Vicente, Ana-Eugenia, Quijada Álamo, Miguel, Hernández Sánchez, María, Pérez Carretero, Claudia, Ramos Ascanio, Victoria, and Hernández Rivas, José Ángel
Abstract: hronic lymphocytic leukemia (CLL) is an extremely heterogeneous disease. With the advent of oral targeted agents (Tas) the treatment of CLL has undergone a revolution, which has been accompanied by an improvement in patient’s survival and quality of life. This paradigm shift also affects the value of prognostic and predictive biomarkers and prognostic models, most of them inherited from the chemoimmunotherapy era but with a different behavior with Tas. This review discusses: (i) the role of the most relevant prognostic and predictive biomarkers in the setting of Tas; and (ii) the validity of classic and new scoring systems in the context of Tas. In addition, a critical point of view about predictive biomarkers with special emphasis on 11q deletion, novel resistance mutations, TP53 abnormalities, IGHV mutational status, complex karyotype and NOTCH1 mutations is stated. We also go over prognostic models in early stage CLL such as IPS-E. Finally, we provide an overview of the applicability of the CLL-IPI for patients treated with Tas, as well as the emergence of new models, generated with data from patients treated with Tas., Instituto de Salud Carlos III (ISCIII)/ FEDER, Junta de Castilla y León, Depto. de Medicina, Fac. de Medicina, TRUE, pub
Published: 2021

41. The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment

Author: Instituto de Salud Carlos III, Junta de Castilla y León, European Commission, Fundación Memoria de D. Samuel Solorzano Barruso, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Fundacion de la Sociedad Española de Hematología y Hemoterapia, Asociación Española Contra el Cáncer, Janssen Research and Development, Sociedad Española de Hematología y Hemoterapia, Pérez-Carretero, Claudia, González-Gascón y Marín, Isabel, Rodríguez-Vicente, Ana Eugenia, Quijada-Álamo, Miguel, Hernández-Rivas, José Ángel, Hernández-Sánchez, María, Hernández, Jesús M., Instituto de Salud Carlos III, Junta de Castilla y León, European Commission, Fundación Memoria de D. Samuel Solorzano Barruso, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Fundacion de la Sociedad Española de Hematología y Hemoterapia, Asociación Española Contra el Cáncer, Janssen Research and Development, Sociedad Española de Hematología y Hemoterapia, Pérez-Carretero, Claudia, González-Gascón y Marín, Isabel, Rodríguez-Vicente, Ana Eugenia, Quijada-Álamo, Miguel, Hernández-Rivas, José Ángel, Hernández-Sánchez, María, and Hernández, Jesús M.
Abstract: The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients.
Published: 2021

42. Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

Author: Fundación Memoria de D. Samuel Solorzano Barruso, Instituto de Salud Carlos III, Quijada-Álamo, Miguel, Pérez-Carretero, Claudia, Hernández-Sánchez, María, Rodríguez-Vicente, Ana Eugenia, Herrero, Ana B., Hernandez-Sánchez, Jesus M., Martín-Izquierdo, Marta, Santos-Mínguez, Sandra, Rey, Mónica del, González, Teresa, Rubio, Araceli, García de Coca, Alfonso, Dávila, Julio, Hernández-Rivas, José Ángel, Parker, H., Strefford, Jonathan C., Benito, Rocío, Ordóñez, José Luis, Fundación Memoria de D. Samuel Solorzano Barruso, Instituto de Salud Carlos III, Quijada-Álamo, Miguel, Pérez-Carretero, Claudia, Hernández-Sánchez, María, Rodríguez-Vicente, Ana Eugenia, Herrero, Ana B., Hernandez-Sánchez, Jesus M., Martín-Izquierdo, Marta, Santos-Mínguez, Sandra, Rey, Mónica del, González, Teresa, Rubio, Araceli, García de Coca, Alfonso, Dávila, Julio, Hernández-Rivas, José Ángel, Parker, H., Strefford, Jonathan C., Benito, Rocío, and Ordóñez, José Luis
Abstract: [Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established., [Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response., [Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition., [Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.
Published: 2021

43. From biomarkers to models in the changing landscape of chronic lymphocytic leukemia: Evolve or become extinct

Author: Instituto de Salud Carlos III, European Commission, Junta de Castilla y León, Fundación Memoria de D. Samuel Solorzano Barruso, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Fundacion de la Sociedad Española de Hematología y Hemoterapia, Asociación Española Contra el Cáncer, Janssen Research and Development, González-Gascón y Marín, Isabel, Muñoz-Novas, Carolina, Rodríguez-Vicente, Ana Eugenia, Quijada-Álamo, Miguel, Hernández-Sánchez, María, Pérez-Carretero, Claudia, Ramos-Ascanio, Victoria, Hernández-Rivas, José Ángel, Instituto de Salud Carlos III, European Commission, Junta de Castilla y León, Fundación Memoria de D. Samuel Solorzano Barruso, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Fundacion de la Sociedad Española de Hematología y Hemoterapia, Asociación Española Contra el Cáncer, Janssen Research and Development, González-Gascón y Marín, Isabel, Muñoz-Novas, Carolina, Rodríguez-Vicente, Ana Eugenia, Quijada-Álamo, Miguel, Hernández-Sánchez, María, Pérez-Carretero, Claudia, Ramos-Ascanio, Victoria, and Hernández-Rivas, José Ángel
Abstract: Chronic lymphocytic leukemia (CLL) is an extremely heterogeneous disease. With the advent of oral targeted agents (Tas) the treatment of CLL has undergone a revolution, which has been accompanied by an improvement in patient’s survival and quality of life. This paradigm shift also affects the value of prognostic and predictive biomarkers and prognostic models, most of them inherited from the chemoimmunotherapy era but with a different behavior with Tas. This review discusses: (i) the role of the most relevant prognostic and predictive biomarkers in the setting of Tas; and (ii) the validity of classic and new scoring systems in the context of Tas. In addition, a critical point of view about predictive biomarkers with special emphasis on 11q deletion, novel resistance mutations, TP53 abnormalities, IGHV mutational status, complex karyotype and NOTCH1 mutations is stated. We also go over prognostic models in early stage CLL such as IPS-E. Finally, we provide an overview of the applicability of the CLL-IPI for patients treated with Tas, as well as the emergence of new models, generated with data from patients treated with Tas.
Published: 2021

44. Chronic lymphocytic leukemia patients with <scp>IGH</scp> translocations are characterized by a distinct genetic landscape with prognostic implications

Author: Pérez‐Carretero, Claudia, Hernández Sánchez, María, González, Teresa, Quijada‐Álamo, Miguel, Martín‐Izquierdo, Marta, Vidal, María‐Jesús, García de Coca, Alfonso, Hernández Rivas, José Ángel, Aguilar, Carlos, Vargas‐Pabón, Manuel, Alonso, Sara, Sierra, Magdalena, Rubio‐Martínez, Araceli, Dávila, Julio, Díaz‐Valdés, José R., Queizán, José‐Antonio, Benito, Rocío, Rodríguez‐Vicente, Ana E., Hernández‐Rivas, Jesús‐María, Pérez‐Carretero, Claudia, Hernández Sánchez, María, González, Teresa, Quijada‐Álamo, Miguel, Martín‐Izquierdo, Marta, Vidal, María‐Jesús, García de Coca, Alfonso, Hernández Rivas, José Ángel, Aguilar, Carlos, Vargas‐Pabón, Manuel, Alonso, Sara, Sierra, Magdalena, Rubio‐Martínez, Araceli, Dávila, Julio, Díaz‐Valdés, José R., Queizán, José‐Antonio, Benito, Rocío, Rodríguez‐Vicente, Ana E., and Hernández‐Rivas, Jesús‐María
Abstract: Chromosome 14q32 rearrangements/translocations involving the immunoglobulinheavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). Theprognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement(IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profilewith recurrent mutations in BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genesrelated to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treat-ment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, NOTCH1, SF3B1, TP53, BIRC3 and BRAF werealso mutated. The presence of these mutations not only was an independent risk fac-tor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients(13q−/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status ofIGHby FISH analysis to refine the risk-stratification CLL model., Instituto de Salud Carlos III, 'El Fondo Social Europeo invierte en tu futuro, European Regional Development Fund, Spanish Fondo de Investigaciones Sanitarias, Depto. de Bioquímica y Biología Molecular, Fac. de Farmacia, FALSE, pub
Published: 2020

45. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia:a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author: Scarfò, Lydia, Chatzikonstantinou, Thomas, Rigolin, Gian Matteo, Quaresmini, Giulia, Motta, Marina, Vitale, Candida, Garcia-Marco, Jose Antonio, Hernández-Rivas, José Ángel, Mirás, Fatima, Baile, Mónica, Marquet, Juan, Niemann, Carsten U., Reda, Gianluigi, Munir, Talha, Gimeno, Eva, Marchetti, Monia, Quaglia, Francesca Maria, Varettoni, Marzia, Delgado, Julio, Iyengar, Sunil, Janssens, Ann, Marasca, Roberto, Ferrari, Angela, Cuéllar-García, Carolina, Itchaki, Gilad, Špaček, Martin, De Paoli, Lorenzo, Laurenti, Luca, Levin, Mark David, Lista, Enrico, Mauro, Francesca R., Šimkovič, Martin, Van Der Spek, Ellen, Vandenberghe, Elisabeth, Trentin, Livio, Wasik-Szczepanek, Ewa, Ruchlemer, Rosa, Bron, Dominique, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Farina, Lucia, Foglietta, Myriam, Gentile, Massimo, Herishanu, Yair, Herold, Tobias, Jaksic, Ozren, Kater, Arnon P., Kersting, Sabina, Malerba, Lara, Orsucci, Lorella, Popov, Viola Maria, Sportoletti, Paolo, Yassin, Mohamed, Pocali, Barbara, Barna, Gabor, Chiarenza, Annalisa, dos Santos, Gimena, Nikitin, Eugene, Andres, Martin, Dimou, Maria, Doubek, Michael, Enrico, Alicia, Hakobyan, Yervand, Kalashnikova, Olga, Ortiz Pareja, Macarena, Papaioannou, Maria, Rossi, Davide, Shah, Nimish, Shrestha, Amit, Stanca, Oana, Stavroyianni, Niki, Strugov, Vladimir, Tam, Constantine, Zdrenghea, Mihnea, Coscia, Marta, Stamatopoulos, Kostas, Rossi, Giuseppe, Rambaldi, Alessandro, Montserrat, Emili’, Foà, Robin, Cuneo, Antonio, Ghia, Paolo, Scarfò, Lydia, Chatzikonstantinou, Thomas, Rigolin, Gian Matteo, Quaresmini, Giulia, Motta, Marina, Vitale, Candida, Garcia-Marco, Jose Antonio, Hernández-Rivas, José Ángel, Mirás, Fatima, Baile, Mónica, Marquet, Juan, Niemann, Carsten U., Reda, Gianluigi, Munir, Talha, Gimeno, Eva, Marchetti, Monia, Quaglia, Francesca Maria, Varettoni, Marzia, Delgado, Julio, Iyengar, Sunil, Janssens, Ann, Marasca, Roberto, Ferrari, Angela, Cuéllar-García, Carolina, Itchaki, Gilad, Špaček, Martin, De Paoli, Lorenzo, Laurenti, Luca, Levin, Mark David, Lista, Enrico, Mauro, Francesca R., Šimkovič, Martin, Van Der Spek, Ellen, Vandenberghe, Elisabeth, Trentin, Livio, Wasik-Szczepanek, Ewa, Ruchlemer, Rosa, Bron, Dominique, De Paolis, Maria Rosaria, Del Poeta, Giovanni, Farina, Lucia, Foglietta, Myriam, Gentile, Massimo, Herishanu, Yair, Herold, Tobias, Jaksic, Ozren, Kater, Arnon P., Kersting, Sabina, Malerba, Lara, Orsucci, Lorella, Popov, Viola Maria, Sportoletti, Paolo, Yassin, Mohamed, Pocali, Barbara, Barna, Gabor, Chiarenza, Annalisa, dos Santos, Gimena, Nikitin, Eugene, Andres, Martin, Dimou, Maria, Doubek, Michael, Enrico, Alicia, Hakobyan, Yervand, Kalashnikova, Olga, Ortiz Pareja, Macarena, Papaioannou, Maria, Rossi, Davide, Shah, Nimish, Shrestha, Amit, Stanca, Oana, Stavroyianni, Niki, Strugov, Vladimir, Tam, Constantine, Zdrenghea, Mihnea, Coscia, Marta, Stamatopoulos, Kostas, Rossi, Giuseppe, Rambaldi, Alessandro, Montserrat, Emili’, Foà, Robin, Cuneo, Antonio, and Ghia, Paolo
Abstract: Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
Published: 2020

46. Clinical characteristics and outcome of SARS-CoV-2 infection in admitted patients with chronic lymphocytic leukemia from a single European country

Author: Abrisqueta, Pau [0000-0001-9625-7422], Muntañola, Ana, Villacampa, Guillermo, Hernández-Rivas, José Ángel, Alonso, Rosalía, Mirás, Fátima, Osorio, Santiago, Baile, Mónica, Baltasar, Patricia, López Jiménez, Javier, Hernández‑Rodríguez, Inés, Valencia, Susana, Alfayate, Ana, Gimeno, Eva, Bárez, Abelardo, Oliveira, Ana Carla, Riaza Grau, Rosalía, Romero, Pilar, Delgado, Julio, Yáñez, Lucrecia, Zabalza, Amaya, Torres, Ana, Gómez-Roncero, María Isabel, Crespo, Marta, Córdoba, Raúl, Mateos, Juan José, Pérez, Sonia, Andreu, Rafael, Labrador, Jorge, Ruiz, María Elena, Velasquez, César Andrés, Terol, María José, Santiago, Raquel, Vidal, María Jesús, Campoy García, Fiz, Villalón, Lucía, Muiña, Begoña, Soler, Joan Alfons, Seri, Cristina, Sánchez, María José, Cuesta, Amalia, Ramos, Rafael, Sánchez‑Montalvá, Sánchez‑Montalvá, Adrán, Ruiz‑Camps, Isabel, González, Marcos, Abrisqueta, Pau, Bosch, Francesc, Abrisqueta, Pau [0000-0001-9625-7422], Muntañola, Ana, Villacampa, Guillermo, Hernández-Rivas, José Ángel, Alonso, Rosalía, Mirás, Fátima, Osorio, Santiago, Baile, Mónica, Baltasar, Patricia, López Jiménez, Javier, Hernández‑Rodríguez, Inés, Valencia, Susana, Alfayate, Ana, Gimeno, Eva, Bárez, Abelardo, Oliveira, Ana Carla, Riaza Grau, Rosalía, Romero, Pilar, Delgado, Julio, Yáñez, Lucrecia, Zabalza, Amaya, Torres, Ana, Gómez-Roncero, María Isabel, Crespo, Marta, Córdoba, Raúl, Mateos, Juan José, Pérez, Sonia, Andreu, Rafael, Labrador, Jorge, Ruiz, María Elena, Velasquez, César Andrés, Terol, María José, Santiago, Raquel, Vidal, María Jesús, Campoy García, Fiz, Villalón, Lucía, Muiña, Begoña, Soler, Joan Alfons, Seri, Cristina, Sánchez, María José, Cuesta, Amalia, Ramos, Rafael, Sánchez‑Montalvá, Sánchez‑Montalvá, Adrán, Ruiz‑Camps, Isabel, González, Marcos, Abrisqueta, Pau, and Bosch, Francesc
Abstract: Spain has been one the most affected countries by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) pandemic [1, 2]. Patients with chronic lymphocytic leukemia (CLL) could be at risk of more severe COVID-19 clinical forms [3] since they often carry immune perturbations aggravated by treatments used for the disease itself [4]. Two major series on patients with COVID-19 and CLL encompassing different countries and health systems reported heterogeneous factors related to the outcome [5, 6]. Herein, we are presenting the largest series of CLL patients with proved COVID-19 from a single country and Health system.
Published: 2020

47. Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications

Author: Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Memoria de D. Samuel Solorzano Barruso, Asociación Española Contra el Cáncer, Sociedad Española de Hematología y Hemoterapia, European Commission, Pérez-Carretero, Claudia, Hernández-Sánchez, María, González, Teresa, Quijada-Álamo, Miguel, Martín-Izquierdo, Marta, Hernandez-Sánchez, Jesus M., Vidal-Manceñido, María Jesús, García de Coca, Alfonso, Aguilar, Carlos, Vargas, Manuel, Alonso, Sara, Sierra, Magdalena, Rubio, Araceli, Dávila, Julio, Díaz-Valdés, José R., Queizán, José-Antonio, Hernández-Rivas, José Ángel, Benito, Rocío, Rodríguez-Vicente, Ana Eugenia, Hernández, Jesús M., Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Memoria de D. Samuel Solorzano Barruso, Asociación Española Contra el Cáncer, Sociedad Española de Hematología y Hemoterapia, European Commission, Pérez-Carretero, Claudia, Hernández-Sánchez, María, González, Teresa, Quijada-Álamo, Miguel, Martín-Izquierdo, Marta, Hernandez-Sánchez, Jesus M., Vidal-Manceñido, María Jesús, García de Coca, Alfonso, Aguilar, Carlos, Vargas, Manuel, Alonso, Sara, Sierra, Magdalena, Rubio, Araceli, Dávila, Julio, Díaz-Valdés, José R., Queizán, José-Antonio, Hernández-Rivas, José Ángel, Benito, Rocío, Rodríguez-Vicente, Ana Eugenia, and Hernández, Jesús M.
Abstract: Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). The prognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next‐generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement (IGHR‐CLLs) and we demonstrate that IGHR‐CLLs have a distinct mutational profile with recurrent mutations in NOTCH1, IGLL5, POT1, BCL2, FBXW7, ZMYM3, MGA, BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7 mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non‐Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR‐CLLs had mutations in genes related to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treatment (TFT). Moreover, IGHR‐CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, being this prognosis particularly poor when NOTCH1, SF3B1, TP53, BIRC3 and BRAF were also mutated. The presence of these mutations not only was an independent risk factor within IGHR‐CLLs, but also refined the prognosis of low‐risk cytogenetic patients (13q−/normal FISH). Hence, our study demonstrates that IGHR‐CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status of IGH by FISH analysis to refine the risk‐stratification CLL model.
Published: 2020

48. Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

Author: Martínez-López, Joaquín [0000-0001-7908-0063], Mateos, Maria Victoria [0000-0003-2390-1218], Lahuerta, Juan José [0000-0002-3393-9570], San-Miguel, Jesús [0000-0002-9183-4857], Martínez-López, Joaquín, Mateos, Maria Victoria, Encinas, Cristina, Sureda, Anna, Hernández-Rivas, José Ángel, López de la Guía, Ana, Conde, Diego, Krsnik, Isabel, Prieto, Elena, Riaza Grau, Rosalía, Gironella, Mercedes, Blanchard, María Jesús, Caminos, Nerea, Fernández de Larrea, Carlos, Senin, María Alicia, Escalante, Fernando, Puerta, José Enrique de la, Gimenez, Eugenio, Martínez-Barranco, Pilar, Mateos, Juan José, Casado, Luis Felipe, Bladé, Joan, Lahuerta, Juan José, Cruz, Javier de la, San-Miguel, Jesús, Martínez-López, Joaquín [0000-0001-7908-0063], Mateos, Maria Victoria [0000-0003-2390-1218], Lahuerta, Juan José [0000-0002-3393-9570], San-Miguel, Jesús [0000-0002-9183-4857], Martínez-López, Joaquín, Mateos, Maria Victoria, Encinas, Cristina, Sureda, Anna, Hernández-Rivas, José Ángel, López de la Guía, Ana, Conde, Diego, Krsnik, Isabel, Prieto, Elena, Riaza Grau, Rosalía, Gironella, Mercedes, Blanchard, María Jesús, Caminos, Nerea, Fernández de Larrea, Carlos, Senin, María Alicia, Escalante, Fernando, Puerta, José Enrique de la, Gimenez, Eugenio, Martínez-Barranco, Pilar, Mateos, Juan José, Casado, Luis Felipe, Bladé, Joan, Lahuerta, Juan José, Cruz, Javier de la, and San-Miguel, Jesús
Abstract: There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.
Published: 2020

49. Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality

Author: Pethema Foundation, Martínez-López, Joaquín, Mateos, Maria Victoria, Encinas, Cristina, Sureda, Anna, Hernández-Rivas, José Ángel, López de la Guía, Ana, Conde, Diego, Krsnik, Isabel, Prieto, Elena, Riaza Grau, Rosalía, Gironella, Mercedes, Blanchard, María Jesús, Caminos, Nerea, Fernández de Larrea, Carlos, Senin, María Alicia, Escalante, Fernando, Puerta, José Enrique de la, Gimenez, Eugenio, Martínez-Barranco, Pilar, Mateos, Juan José, Casado, Luis Felipe, Bladé, Joan, Lahuerta, Juan José, Cruz, Javier de la, San-Miguel, Jesús, Pethema Foundation, Martínez-López, Joaquín, Mateos, Maria Victoria, Encinas, Cristina, Sureda, Anna, Hernández-Rivas, José Ángel, López de la Guía, Ana, Conde, Diego, Krsnik, Isabel, Prieto, Elena, Riaza Grau, Rosalía, Gironella, Mercedes, Blanchard, María Jesús, Caminos, Nerea, Fernández de Larrea, Carlos, Senin, María Alicia, Escalante, Fernando, Puerta, José Enrique de la, Gimenez, Eugenio, Martínez-Barranco, Pilar, Mateos, Juan José, Casado, Luis Felipe, Bladé, Joan, Lahuerta, Juan José, Cruz, Javier de la, and San-Miguel, Jesús
Abstract: There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.
Published: 2020

50. DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains

Author: Instituto de Salud Carlos III, European Commission, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Sociedad Española de Hematología y Hemoterapia, Junta de Castilla y León, Hernández-Sánchez, María, Rodríguez-Vicente, Ana Eugenia, González-Gascón y Marín, Isabel, Quijada-Álamo, Miguel, Hernandez-Sánchez, Jesus M., Martín-Izquierdo, Marta, Hernández-Rivas, José Ángel, Benito, Rocío, Hernández, Jesús M., Instituto de Salud Carlos III, European Commission, Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red Cáncer (España), Sociedad Española de Hematología y Hemoterapia, Junta de Castilla y León, Hernández-Sánchez, María, Rodríguez-Vicente, Ana Eugenia, González-Gascón y Marín, Isabel, Quijada-Álamo, Miguel, Hernandez-Sánchez, Jesus M., Martín-Izquierdo, Marta, Hernández-Rivas, José Ángel, Benito, Rocío, and Hernández, Jesús M.
Abstract: The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. The mutational status of 54 genes was evaluated using a custom-designed gene panel including recurrent mutated genes observed in CLL and widely associated with CLL pathogenesis. A total of 21 mutations were detected; TP53 (42.8%), ATM (28.5%), SF3B1 (28.5%), and BRAF (28.5%) were the most recurrently mutated genes. Of these mutations, 61.9% were detected in genes previously associated with a poor prognosis in CLL. Interestingly, five of the seven patients exhibited alterations in TP53 or ATM (deletion and/or mutation), genes involved in the DNA damage response (DDR), which could be related to a high genetic instability in this subgroup of patients. In conclusion, CLL patients with several chromosomal gains exhibit high genetic instability, with mutations in CLL driver genes and high-risk genetic alterations involving ATM and/or TP53 genes.
Published: 2019

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