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1. Author Correction: 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, Jimenez-Ubieto, Ana, Carreño-Tarragona, Gonzalo, Linares, 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, del Mar Herráez, María, Riaza, Rosalía, Magro, Elena, Steegman, Juan Luis, Wang, Chongwu, de Toledo, Paula, García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, and Martínez-López, Joaquín

Published
2024
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2. Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study

Author

Salamero, Olga, Molero, Antonieta, Pérez-Simón, José Antonio, Arnan, Montserrat, Coll, Rosa, Garcia-Avila, Sara, Acuña-Cruz, Evelyn, Cano, Isabel, Somervaille, Tim C P, Gutierrez, Sonia, Arévalo, María Isabel, Xaus, Jordi, Buesa, Carlos, Limón, Ana, Faller, Douglas V, Bosch, Francesc, and Montesinos, Pau

Published
2024
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3. Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort

Author

Oñate, Guadalupe, Pratcorona, Marta, Garrido, Ana, Artigas-Baleri, Alicia, Bataller, Alex, Tormo, Mar, Arnan, Montserrat, Vives, Susana, Coll, Rosa, Salamero, Olga, Vall-Llovera, Ferran, Sampol, Antònia, Garcia, Antoni, Cervera, Marta, Avila, Sara Garcia, Bargay, Joan, Ortín, Xavier, Nomdedéu, Josep F., Esteve, Jordi, and Sierra, Jorge

Published
2023
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5. Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group.

Author

Oñate, Guadalupe, Garrido, Ana, Arnan, Montserrat, Pomares, Helena, Alonso, Ester, Tormo, Mar, Diaz-Beya, Marina, Vives, Susana, Zamora, Lurdes, Sampol, Antonia, Coll, Rosa, Salamero, Olga, Cervera, Marta, Garcia, Antoni, Vall-Llovera, Ferran, Garcia-Avila, Sara, Bargay, Joan, Ortin, Xavier, Iranzo, Eva, and Guijarro, Francisca

Subjects
ACUTE myeloid leukemia, YOUNG adults, OLDER people, SURVIVAL rate, KARYOTYPES
Abstract

Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults (≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs. 73%; p = 0.03 and 4-yr OS 53% vs. 33%; p < 0.001). Remission and survival outcomes varied among different genetic subsets. An especially adverse genetic group included complex, monosomal karyotype, TP53 alterations (deleted/mutated), and MECOMr. Transplant feasibility in this very adverse risk group was low, and OS and EFS at 4 years were 14% and 12%, in contrast to 70% and 57% in the favorable group and 38% and 32% in all other patients. We integrated clinical and genetic data into the Intensive Chemotherapy Score for AML (ICSA) with 6-risk categories with significantly different remission rates and OS, validated in another cohort of 581 AML patients from a previous CETLAM protocol. In summary, we identified groups of fit patients that benefit differently from an intensive approach which may be helpful in future treatment decisions. [ABSTRACT FROM AUTHOR]

Published
2025
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6. Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups.

Author

Vives, Susana, Quintela, David, Morgades, Mireia, Cano-Ferri, Isabel, Serrano, Alfons, Acuña-Cruz, Evelyn, Cervera, Marta, Díaz-Beyá, Marina, Vidriales, Belén, Raposo-Puglia, José Ángel, Arnan, Montserrat, Garrido, Ana, Balerdi, Amaia, Cabello, Ana Isabel, Herrera-Puente, Pilar, Serrano, Josefina, Coll, Rosa, Tormo, Mar, López-Marín, Javier, and García-Ávila, Sara

Subjects
FEBRILE neutropenia, DRUG toxicity, DRUG side effects, SALVAGE therapy, PROTEIN-tyrosine kinase inhibitors, RETROSPECTIVE studies, DESCRIPTIVE statistics, DISEASE remission, MULTIVARIATE analysis, LIVER diseases, DRUG efficacy, MEDICAL records, ACQUISITION of data, GENETIC mutation, PROGRESSION-free survival, OVERALL survival, EVALUATION
Abstract

Simple Summary: Relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) is associated with a poor prognosis. Mutations in the FLT3 gene provide a target for therapeutic intervention. Two FLT3 inhibitors, gilteritinib and quizartinib, when used as single agents, have demonstrated efficacy in this context. The aim of our retrospective study was to compare the outcomes of 50 patients diagnosed with FLT3-mutated AML treated with gilteritinib or quizartinib monotherapy, with results from phase 3 clinical trials and with other real-world studies. Despite differences among the cohorts, our findings confirm that gilteritinib and quizartinib monotherapy represent effective and tolerable treatment options for patients with relapsed/refractory FLT3-mutated AML in real-world settings, with response and toxicity rates consistent with those reported in prior studies. Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population. [ABSTRACT FROM AUTHOR]

Published
2024
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7. European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

Author

Bataller, Alex, Garrido, Ana, Guijarro, Francesca, Oñate, Guadalupe, Diaz-Beyá, Marina, Arnan, Montserrat, Tormo, Mar, Vives, Susana, de Llano, María Paz Queipo, Coll, Rosa, Gallardo, David, Vall-Llovera, Ferran, Escoda, Lourdes, Garcia-Guiñon, Antonio, Salamero, Olga, Sampol, Antònia, Merchan, Brayan M., Bargay, Joan, Castaño-Díez, Sandra, Esteban, Daniel, Oliver-Caldés, Aina, Rivero, Andrea, Mozas, Pablo, López-Guerra, Mònica, Pratcorona, Marta, Zamora, Lurdes, Costa, Dolors, Rozman, Maria, Nomdedéu, Josep F., Colomer, Dolors, Brunet, Salut, Sierra, Jorge, and Esteve, Jordi

Published
2022
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9. 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, Jimenez-Ubieto, Ana, Carreño-Tarragona, Gonzalo, Linares, 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, del Mar Herráez, María, Riaza, Rosalía, Magro, Elena, Steegman, Juan Luis, Wang, Chongwu, de Toledo, Paula, García-Gutiérrez, Valentín, Ayala, Rosa, Ribera, Josep-Maria, Barrio, Santiago, and Martínez-López, Joaquín

Published
2022
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10. Post thawing viable CD34+ Cells dose is a better predictor of clinical outcome in lymphoma patients undergoing autologous stem cell transplantation

Author

Fernandez-Sojo, Jesus, Cid, Joan, Azqueta, Carmen, Valdivia, Elena, Martorell, Lluis, Codinach, Margarita, Marsal, Julia, Mussetti, Alberto, Esquirol, Albert, Trabazo, Maria, Benitez, Maria Isabel, Ferra, Christelle, Fox, Maria Laura, Linares, Mónica, Alonso, Eva, García-Rey, Enric, García-Muñoz, Nadia, Medina, Laura, Castillo-Flores, Nerea, Vall-Llovera, Ferran, Garcia, Antoni, Pinacho, Asuncion, Talarn, Carme, Arroba, Jose Garcia, Coll, Rosa, Santos, Mireia, Valero, Oliver, Carreras, Enric, Lozano, Miquel, and Querol, Sergio

Published
2022
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11. Frequency, Clinical Characteristics and Outcome of Adults With Acute Lymphoblastic Leukemia and COVID 19 Infection in the First vs. Second Pandemic Wave in Spain

Author

Ribera, Josep-Maria, Morgades, Mireia, Coll, Rosa, Barba, Pere, López-Lorenzo, Jose-Luis, Montesinos, Pau, Foncillas, María-Angeles, Cabrero, Mónica, Gómez-Centurión, Ignacio, Morales, María-Dolores, Varela, María-Rosario, Herrera, Pilar, García-Cadenas, Irene, Calbacho, María, Torrent, Anna, Maluquer, Clara, Calabuig, Marisa, Garcia-Guiñon, Antoni, Bautista, Guiomar, Llorente, Laura, Gil, Cristina, Artola, María-Teresa, González-Campos, José, Fernández-Moreno, Ainhoa, Bárez, Abelardo, Giménez-Pérez, Teresa, Bergua, Juan, Sánchez-Sánchez, María-José, Mateos, María-Carmen, and Piñana, José-Luis

Published
2021
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12. Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

Author

Genescà, Eulàlia, Morgades, Mireia, González-Gil, Celia, Fuster-Tormo, Francisco, Haferlach, Claudia, Meggendorfer, Manja, Montesinos, Pau, Barba, Pere, Gil, Cristina, Coll, Rosa, Moreno, María-José, Martínez-Carballeira, Daniel, García-Cadenas, Irene, Vives, Susana, Ribera, Jordi, González-Campos, José, Díaz-Beya, Marina, Mercadal, Santiago, Artola, María-Teresa, Cladera, Antonia, Tormo, Mar, Bermúdez, Arancha, Vall-llovera, Ferran, Martínez-Sánchez, Pilar, Amigo, María-Luz, Monsalvo, Silvia, Novo, Andrés, Cervera, Marta, García-Guiñon, Antonio, Ciudad, Juana, Cervera, José, Hernández-Rivas, Jesús-María, Granada, Isabel, Haferlach, Torsten, Orfao, Alberto, Solé, Francesc, and Ribera, Josep-Maria

Published
2021
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13. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

Author

Ribera, Josep-Maria, Morgades, Mireia, Ciudad, Juana, Montesinos, Pau, Esteve, Jordi, Genescà, Eulàlia, Barba, Pere, Ribera, Jordi, García-Cadenas, Irene, Moreno, María José, Martínez-Carballeira, Daniel, Torrent, Anna, Martínez-Sánchez, Pilar, Monsalvo, Silvia, Gil, Cristina, Tormo, Mar, Artola, María Teresa, Cervera, Marta, González-Campos, José, Rodríguez, Carlos, Bermúdez, Arancha, Novo, Andrés, Soria, Beatriz, Coll, Rosa, Amigo, María-Luz, López-Martínez, Aurelio, Fernández-Martín, Rosa, Serrano, Josefina, Mercadal, Santiago, Cladera, Antònia, Giménez-Conca, Alberto, Peñarrubia, María-Jesús, Abella, Eugènia, Vall-llovera, Ferran, Hernández-Rivas, Jesús-María, Garcia-Guiñon, Antoni, Bergua, Juan-Miguel, de Rueda, Beatriz, Sánchez-Sánchez, María-José, Serrano, Alfons, Calbacho, María, Alonso, Natalia, Méndez-Sánchez, Jose-Ángel, García-Boyero, Raimundo, Olivares, Matxalen, Barrena, Susana, Zamora, Lurdes, Granada, Isabel, Lhermitte, Ludovic, Feliu, Evarist, and Orfao, Alberto

Published
2021
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15. Impact of Antibacterial Prophylaxis on Morbidity-Mortality of Patients with Myeloid Neoplasms Treated with Non-Intensive Venetoclax Combinations

Author

Garrido Paniagua, Sara, primary, Novoa Jáuregui, Sandra, additional, Molero Yordi, Antonieta, additional, Vall-llovera Calmet, Ferran, additional, Valencia Becerra, Laura Camila, additional, Escolano Escobar, Cristian, additional, Arnaiz Martín, Irene, additional, Ocampo Martínez, Raquel, additional, Masana Flores, Elena, additional, González-Santillana, Clara Isabel, additional, Pacheco Reyes, Alfredo, additional, Capellán García, Raquel, additional, Aceituno Caneiro, Marta, additional, Coll, Rosa, additional, Albasanz-Puig, Adaia, additional, Ruiz Camps, Isabel, additional, Alonso-Martínez, Carla, additional, Pérez-González, Ana, additional, Sola Soto, Maria, additional, Fox, Maria Laura, additional, Valcarcel, David, additional, and Salamero, Olga, additional

Published
2023
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16. Impact of Center-related Characteristics and Macroeconomic Factors on the Outcome of Adult Patients With Acute Lymphoblastic Leukemia Treated With Pediatric-inspired Protocols

Author

Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Barba, Pere, Morgades, Mireia, Montesinos, Pau, Gonzalez-Campos, Jose, Torrent, Anna, Gil, Cristina, Bernal, Teresa, Tormo, Mar, Mercadal, Santiago, Novoa, Sandra, García-Cadenas, Irene, Queipo de Llano, M. Paz, Cervera, Marta, Coll, Rosa, Bermudez, Arancha, Amigo, María Luz, Monsalvo, Silvia, Esteve, Jordi, García-Boyero, Raimundo, Novo, Andres, Hernández, Jesús M., Cladera, Antonia, Martínez-Sánchez, Pilar, Serrano, Josefina, Artola, María Teresa, Soria, Beatriz, Abella, Eugènia, Vall-Llovera, Ferran, Bergua, Juan, Herrera, Pilar, Barrios, Daniel, Ribera, Josep-Maria, Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Barba, Pere, Morgades, Mireia, Montesinos, Pau, Gonzalez-Campos, Jose, Torrent, Anna, Gil, Cristina, Bernal, Teresa, Tormo, Mar, Mercadal, Santiago, Novoa, Sandra, García-Cadenas, Irene, Queipo de Llano, M. Paz, Cervera, Marta, Coll, Rosa, Bermudez, Arancha, Amigo, María Luz, Monsalvo, Silvia, Esteve, Jordi, García-Boyero, Raimundo, Novo, Andres, Hernández, Jesús M., Cladera, Antonia, Martínez-Sánchez, Pilar, Serrano, Josefina, Artola, María Teresa, Soria, Beatriz, Abella, Eugènia, Vall-Llovera, Ferran, Bergua, Juan, Herrera, Pilar, Barrios, Daniel, and Ribera, Josep-Maria

Abstract

Diagnosis and treatment of hematological cancers is usually provided in many healthcare facilities including large but also middle size centers.1 Providing cancer care in local institutions might be advantageous for patients and caregivers in terms of financial burden and quality of life. However, it might carry potential risks derived of the limited experience of smaller centers and differences in accessibility to complex therapies including allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor (CAR) T-cells. These risks might be especially relevant in infrequent cancers as adult acute lymphoblastic leukemia (ALL).

Published
2023

17. LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

Author

Instituto de Salud Carlos III, European Commission, Cruz, David, Rodríguez-Romanos, Rocío, González-Bartulos, Marta, García-Cadenas, Irene, Cámara, Rafael de la, Heras, Inmaculada, Buño, Ismael, Santos, Nazly, Lloveras, Natàlia, Velarde, Pilar, Tuset, Esperanza, Martínez, Carmen, González, Marcos, Sanz, Guillermo F., Ferrá, Christelle, Sampol, Antonia, Coll, Rosa, Pérez-Simón, José A., López-Jiménez, Javier, Jurado, Manuel, Gallardo, David, GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH), Instituto de Salud Carlos III, European Commission, Cruz, David, Rodríguez-Romanos, Rocío, González-Bartulos, Marta, García-Cadenas, Irene, Cámara, Rafael de la, Heras, Inmaculada, Buño, Ismael, Santos, Nazly, Lloveras, Natàlia, Velarde, Pilar, Tuset, Esperanza, Martínez, Carmen, González, Marcos, Sanz, Guillermo F., Ferrá, Christelle, Sampol, Antonia, Coll, Rosa, Pérez-Simón, José A., López-Jiménez, Javier, Jurado, Manuel, Gallardo, David, and GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)

Abstract

Introduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule., Methods: To determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors., Results: We detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS., Discussion: We conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted.

Published
2023

18. Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials

Author

Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Generalitat de Catalunya, La Caixa, González-Gil, Celia, Morgades, Mireia, Lopes, Thaysa, Fuster‐Tormo, Francisco, García-Chica, Jesús, Zhao, Ran, Montesinos, Pau, Torrent, Anna, Díaz-Beya, Marina, Coll, Rosa, Hermosín, Lourdes, Mercadal, Santiago, González-Campos, José A., Zamora, Lurdes, Artola, Teresa, Vall-Llovera, Ferran, Tormo, Mar, Gil-Cortés, Cristina, Barba, Pere, Novo, Andrés, Ribera, Jordi, Bernal, Teresa, López de Ugarriza, Paula, Queipo de Llano, María‐Paz, Martínez-Sánchez, Pilar, Giménez, Alicia, González-Martínez, Teresa, Cladera, Antonia, Cervera, José, Fernández-Martín, Rosa, Ardaiz, María Ángeles, Vidal, María Jesús, Baena, Ángela, López-Bigas, Nuria, Bigas, Anna, Maciejewski, Jaroslaw, Orfao, Alberto, Ribera, Josep-Maria, Genescà, Eulàlia, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Generalitat de Catalunya, La Caixa, González-Gil, Celia, Morgades, Mireia, Lopes, Thaysa, Fuster‐Tormo, Francisco, García-Chica, Jesús, Zhao, Ran, Montesinos, Pau, Torrent, Anna, Díaz-Beya, Marina, Coll, Rosa, Hermosín, Lourdes, Mercadal, Santiago, González-Campos, José A., Zamora, Lurdes, Artola, Teresa, Vall-Llovera, Ferran, Tormo, Mar, Gil-Cortés, Cristina, Barba, Pere, Novo, Andrés, Ribera, Jordi, Bernal, Teresa, López de Ugarriza, Paula, Queipo de Llano, María‐Paz, Martínez-Sánchez, Pilar, Giménez, Alicia, González-Martínez, Teresa, Cladera, Antonia, Cervera, José, Fernández-Martín, Rosa, Ardaiz, María Ángeles, Vidal, María Jesús, Baena, Ángela, López-Bigas, Nuria, Bigas, Anna, Maciejewski, Jaroslaw, Orfao, Alberto, Ribera, Josep-Maria, and Genescà, Eulàlia

Abstract

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

Published
2023

19. Evaluation of the outcomes of newly diagnosed patients with high-risk myelodysplastic syndrome according to the initial therapeutical strategies chosen in usual clinical practice

Author

Montoro, Maria Julia, Pomares, Helena, Coll, Rosa, Bernal del Castillo, Teresa, Tormo, Mar, Jiménez, Ana, Brunet, Salut, Casaño, Javier, Oiartzabal, Itziar, Díez-Campelo, María, Ramos, Fernando, Romero, Rafael, Salido-Fiérrez, Eduardo, Pedro Olive, Carme, Bargay, Joan, Muñoz-Novas, Carolina, López, Rocío, Rafel, Montserrat, Valcárcel, David, and ERASME study group

Subjects
Real-world evidence, Treatment, High-risk, Clinical practice, Myelodysplastic syndrome
Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases without a care standard and show variability in treatment outcomes. This Spanish, observational, prospective study ERASME (CEL-SMD-2012-01) assessed the evolution of newly diagnosed and treatment-naïve high-risk MDS patients (according to IPPS-R). 204 patients were included: median age 73.0 years, 54.4% males, 69.6% 0-1 ECOG, and 94.6% with comorbidities. Active treatment was the most common strategy (52.0%) vs. stem cell transplantation (25.5%) and supportive care/watchful-waiting (22.5%). Overall (median) event-free survival was 7.9 months (9.1, 8.3, and 5.3); progression-free survival: 10.1 months (12.9, 12.8, and 4.3); and overall survival: 13.8 months (15.4, 14.9; 8.4), respectively, with significant differences among groups. Adverse events (AEs) of ≥3 grade were reported in 72.6% of patients; serious AEs reported in 60.6%. 33.1% of patients died due to AEs. Three patients developed second primary malignant neoplasms (median: 8.2 months). Our study showed better outcomes in patients receiving active therapy early after diagnosis.

Published
2023

20. LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

Author

Cruz, David, primary, Rodríguez-Romanos, Rocío, additional, González-Bartulos, Marta, additional, García-Cadenas, Irene, additional, de la Cámara, Rafael, additional, Heras, Inmaculada, additional, Buño, Ismael, additional, Santos, Nazly, additional, Lloveras, Natàlia, additional, Velarde, Pilar, additional, Tuset, Esperanza, additional, Martínez, Carmen, additional, González, Marcos, additional, Sanz, Guillermo F., additional, Ferrá, Christelle, additional, Sampol, Antonia, additional, Coll, Rosa, additional, Pérez-Simón, Jose A., additional, López-Jiménez, Javier, additional, Jurado, Manuel, additional, and Gallardo, David, additional

Published
2023
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21. Iadademstat Combination with Azacitidine Is a Safe and Effective Treatment in First Line Acute Myeloid Leukemia. Final Results of the Alice Trial

Author

Salamero, Olga, primary, Somervaille, Tim C.P, additional, Molero, Antonieta, additional, Acuña-Cruz, Evelyn, additional, Perez-Simon, Jose A., additional, Coll, Rosa, additional, Arnan, Montserrat, additional, Merchan, Brayan, additional, Perez, Ana, additional, Cano, Isabel, additional, Rodríguez-Veiga, Rebeca, additional, Arevalo, Mabel, additional, Gutierrez, Sonia, additional, Buesa, Carlos, additional, Faller, Douglas V, additional, Bosch, Francesc, additional, and Montesinos, Pau, additional

Published
2022
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22. Evaluation of Lenalidomide (LEN) Vs Placebo in Non-Transfusion Dependent Low Risk Del(5q) MDS Patients. Final Results of Sintra-REV Phase III International Multicenter Clinical Trial

Author

López Cadenas, Félix, primary, Lumbreras, Eva, additional, González, Teresa, additional, Xicoy, Blanca, additional, Sánchez-García, Joaquín, additional, Coll, Rosa, additional, Slama, Bohrane, additional, Hernández-Rivas, José Ángel, additional, Thepot, Sylvain, additional, Bernal, Teresa, additional, Guerci-Bresler, Agnès, additional, Sanz, Guillermo, additional, Bargay, Joan, additional, Amigo, Maria Luz, additional, De Paz Arias, Raquel, additional, Preudhomme, Claude, additional, Giagounidis, Aristoteles, additional, Platzbecker, Uwe, additional, Wickenhauser, Stefan, additional, Goetze, Katharina S., additional, Arar, Ali, additional, Hernández Rivas, Jesús M, additional, Toribio Castelló, Sofía M, additional, Fenaux, Pierre, additional, Del Cañizo, Consuelo, additional, and Diez-Campelo, Maria, additional

Published
2022
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23. RAS Mutations in Adult Acute Myeloid Leukemia (AML). Frequency, Mutational Spectrum, and Identification of a Comutation Bias for KRASK117 (TET2/ASXL1)

Author

Artigas-Baleri, Alícia, primary, Castellet, Helena, additional, Pratcorona, Marta, additional, Zamora, Lurdes, additional, Lopez-Guerra, Monica, additional, Tazón, Bárbara, additional, Vives, Susana, additional, Tormo, Mar, additional, Arnan, Montserrat, additional, Garcia-Guiñon, Antoni, additional, Coll., Rosa, additional, Sampol, Antonia, additional, Bargay, Joan, additional, Vall-Llovera, Ferran, additional, Salamero, Olga, additional, Lopez-Cadenas, Felix, additional, Garrido Díaz, Ana, additional, Esteve, Jordi, additional, Sierra, Jorge, additional, and Nomdedeu, Josep F, additional

Published
2022
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24. Real-Life Experience of Use of Venetoclax in Patients with Relapsed/Refractory Acute Myeloid Leukemia. a Single Center Experience

Author

Pomares, Helena, primary, Jasson, Villarreal Hernandez, additional, Vives, Susana, additional, Cervera, Marta, additional, Coll, Rosa, additional, Zamora, Lurdes, additional, Maluquer, Clara, additional, Ibarra, Gladys, additional, Ribes Amoros, Julia, additional, Gener-Ricós, Georgina, additional, Galiano, Mercedes, additional, Sureda, Anna, additional, and Arnan Sangerman, Montserrat, additional

Published
2022
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25. Long-Term Evolution of Somatic Mutations in Patients with Del(5q) MDS Early Treated with Lenalidomide in the Sintra-Rev Clinical Trial: Safe and Effecitive Approach?

Author

Toribio Castelló, Sofía M, primary, Lopez-Cadenas, Felix, additional, Preudhomme, Claude, additional, Villaverde Ramiro, Angela, additional, Fenwarth, Laurène, additional, Lumbreras, Eva, additional, González, Teresa, additional, Del Rey, Mónica, additional, Xicoy, Blanca, additional, Renneville, Aline, additional, Sánchez-Garcia, Joaquín, additional, Coll, Rosa, additional, Slama, Bohrane, additional, Hernández-Rivas, José Ángel, additional, Thepot, Sylvain, additional, Bernal, Teresa, additional, Guerci-Bresler, Agnès, additional, Götze, Katharina, additional, Hernández-Rivas, Jesús María, additional, Fenaux, Pierre, additional, Del Cañizo, Consuelo, additional, and Diez-Campelo, Maria, additional

Published
2022
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26. Genomics improves risk stratifi cation of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials

Author

González-Gil, Celia, primary, Morgades, Mireia, additional, Lopes, Thaysa, additional, Fuster-Tormo, Francisco, additional, García-Chica, Jesús, additional, Zhao, Ran, additional, Montesinos, Pau, additional, Torrent, Anna, additional, Diaz-Beya, Marina, additional, Coll, Rosa, additional, Hermosín, Lourdes, additional, Mercadal, Santiago, additional, González-Campos, José, additional, Zamora, Lurdes, additional, Artola, Teresa, additional, Vall-Llovera, Ferran, additional, Tormo, Mar, additional, Gil-Cortés, Cristina, additional, Barba, Pere, additional, Novo, Andrés, additional, Ribera, Jordi, additional, Bernal, Teresa, additional, De Ugarriza, Paula López, additional, Queipo, María-Paz, additional, Martínez-Sánchez, Pilar, additional, Giménez, Alicia, additional, González-Martínez, Teresa, additional, Cladera, Antonia, additional, Cervera, José, additional, Fernández-Martín, Rosa, additional, Ardaiz, María Ángeles, additional, Vidal, María Jesús, additional, Baena, Ángela, additional, López-Bigas, Nuria, additional, Bigas, Anna, additional, Maciejewski, Jaroslaw, additional, Orfao, Alberto, additional, Ribera, Josep Maria, additional, and Genescà, Eulalia, additional

Published
2022
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28. Donor CTLA-4 Genotype Influences Clinical Outcome after T Cell-Depleted Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Identical Sibling Donors

Author

Bosch-Vizcaya, Anna, Pérez-García, Arianne, Brunet, Salut, Solano, Carlos, Buño, Ismael, Guillem, Vicent, Martínez-Laperche, Carolina, Sanz, Guillermo, Barrenetxea, Cristina, Martínez, Carmen, Tuset, Esperanza, Lloveras, Natàlia, Coll, Rosa, Guardia, Ramon, González, Yolanda, Roncero, Josep M., Bustins, Anna, Gardella, Santiago, Fernández, Cristalina, Buch, Joan, and Gallardo, David

Published
2012
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29. 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

30. Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols

Author

Generalitat de Catalunya, Fundación la Caixa, Ribera, Jordi, Granada, Isabel, Morgades, Mireia, González, Teresa, Ciudad, Juana, Such, Esperanza, Calasanz, Mª Jose, Mercadal, Santiago, Coll, Rosa, González-Campos, José A., Tormo, Mar, García-Cadenas, Irene, Gil, Cristina, Cervera, Marta, Barba, Pere, Costa, Dolors, Ayala Bueno, Rosa, Bermúdez, Arantxa, Orfao, Alberto, Ribera, Josep-Maria, Generalitat de Catalunya, Fundación la Caixa, Ribera, Jordi, Granada, Isabel, Morgades, Mireia, González, Teresa, Ciudad, Juana, Such, Esperanza, Calasanz, Mª Jose, Mercadal, Santiago, Coll, Rosa, González-Campos, José A., Tormo, Mar, García-Cadenas, Irene, Gil, Cristina, Cervera, Marta, Barba, Pere, Costa, Dolors, Ayala Bueno, Rosa, Bermúdez, Arantxa, Orfao, Alberto, and Ribera, Josep-Maria

Abstract

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).

Published
2022

31. Detection of Kinase Domain Mutations in BCR-ABL1 Leukemia by Ultra-deep Sequencing of Genomic DNA

Author

Sánchez, Ricardo, primary, Dorado, Sara, additional, Ruíz-Heredia, Yanira, additional, Martin, Alejandro, additional, Rosa-Rosa, Juan Manuel, additional, Ribera, Jordi, additional, García, Olga, additional, Jimenez-Ubieto, Ana, additional, Carreño-Tarragona, Gonzalo, additional, Linares, María, additional, Rufián, Laura, additional, Juárez, Alexandra, additional, Carrillo, Jaime, additional, Espino, María José, additional, Cáceres, Mercedes, additional, Expósito, Sara, additional, Cuevas, Beatriz, additional, Vanegas, Raúl, additional, Casado, Luis Felipe, additional, Torrent, Anna, additional, Zamora, Lurdes, additional, Mercadal, Santiago, additional, Coll, Rosa, additional, Cervera, Marta, additional, Morgades, Mireia, additional, Hernández-Rivas, José Ángel, additional, Bravo, Pilar, additional, Serí, Cristina, additional, Anguita, Eduardo, additional, Barragán, Eva, additional, Sargas, Claudia, additional, Ferrer, Francisca, additional, Sánchez-Calero, Jorge, additional, Sevilla, Julián, additional, Ruíz, Elena, additional, Villalón, Lucía, additional, Herráez, María Mar, additional, Riaza, Rosalía, additional, Magro, Elena, additional, Steegman, Juan Luis, additional, Wang, Chongwu, additional, de Toledo, Paula, additional, García-Gutiérrez, Valentín, additional, Ayala, Rosa, additional, Ribera, Josep Maria, additional, Barrio, Santiago, additional, and Martínez-López, Joaquín, additional

Published
2022
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34. Genomics Improves Risk Stratification of Adults with T-Cell Acute Lymphoblastic Leukemia Patients Enrolled in Measurable Residual Disease-Oriented Trials

Author

González-Gil, Celia, primary, Morgades, Mireia, additional, Lopes, Thaysa, additional, Fuster-Tormo, Francisco, additional, García-Chica, Jesús, additional, Zhao, Ran, additional, Montesinos, Pau, additional, Torrent, Anna, additional, Diaz-Beya, Marina, additional, Coll, Rosa, additional, Hermosín, Lourdes, additional, Mercadal, Santiago, additional, González-Campos, José, additional, Zamora, Lurdes, additional, Artola, Teresa, additional, Vall-Llovera, Ferran, additional, Tormo, Mar, additional, Gil-Cortés, Cristina, additional, Barba, Pere, additional, Novo, Andrés, additional, Ribera, Jordi, additional, Bernal, Teresa, additional, Ugarriza, Paula López, additional, Queipo, María-Paz, additional, Martínez-Sánchez, Pilar, additional, Giménez, Alicia, additional, González-Martínez, Teresa, additional, Cladera, Antonia, additional, Cervera, José, additional, Fernández-Martín, Rosa, additional, Ardaiz, María Ángeles, additional, Vidal, María Jesús, additional, Baena, Ángela, additional, López-Bigas, Nuria, additional, Bigas, Anna, additional, Maciejewski, Jaroslaw, additional, Orfao, Alberto, additional, Ribera, Josep Maria, additional, and Genescà, Eulalia, additional

Published
2022
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35. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases

Author

Palomo, Laura, Xicoy, Blanca, Garcia, Olga, Mallo, Mar, Ademà, Vera, Cabezón, Marta, Arnan, Montse, Pomares, Helena, Larrayoz, María José, Calasanz, María José, Maciejewski, Jaroslaw P., Huang, Dayong, Shih, Lee-Yung, Ogawa, Seishi, Cervera, Jose, Such, Esperanza, Coll, Rosa, Grau, Javier, Solé, Francesc, and Zamora, Lurdes

Published
2016
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36. 5′‐nucleotidase, cytosolic II genotype, and clinical outcome in patients with acute myeloid leukemia with intermediate‐risk cytogenetics.

Author

Díaz‐Santa, Johana, Rodríguez‐Romanos, Rocío, Coll, Rosa, Osca, Gemma, Pratcorona, Marta, González‐Bártulos, Marta, Garrido, Ana, Angona, Anna, Talarn, Carme, Tormo, Mar, Arnan, Montserrat, Vives, Susanna, Salamero, Olga, Tuset, Esperanza, Lloveras, Natàlia, Díez, Isabel, Zamora, Lurdes, Bargay, Joan, Sampol, Antonia, and Cruz, David

Subjects
ACUTE myeloid leukemia, CYTOGENETICS, TREATMENT effectiveness, CYTIDINE deaminase, GENOTYPES
Abstract

Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5′‐nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate‐risk cytogenetic AML patients receiving cytarabine‐based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p:.003; HR 2.16, 95% CI 1.29–3.61) and lower disease‐free survival (DFS) (p:.002; HR 2.45, 95% CI 1.41–4.27), associated to a higher relapse incidence (p:.010; HR 2.23, 95% CI 1.21–4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT‐3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Iadademstat in Combination with Azacitidine Generates Robust and Long Lasting Responses in AML Patients (ALICE Trial)

Author

Salamero, Olga, primary, Somervaille, Tim C.P, additional, Molero, Antonieta, additional, Acuña-Cruz, Evelyn, additional, Pérez-Simón, Jose, additional, Coll, Rosa, additional, Arnan Sangerman, Montserrat, additional, Merchan, Brayan, additional, Perez, Ana, additional, Cano, Isabel, additional, Rodríguez-Veiga, Rebeca, additional, Gutierrez, Sonia, additional, Buesa, Carlos, additional, Bosch, Francesc, additional, and Montesinos, Pau, additional

Published
2021
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38. Venetoclax Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia

Author

Villarreal Hernandez, Jasson, primary, Condom, Maria, additional, Pomares, Helena, additional, Vives, Susana, additional, Coll, Rosa, additional, Cervera, Marta, additional, Maluquer, Clara, additional, Ibarra Fernandez, Gladys, additional, Torrents, Albert, additional, Galiano, Mercedes, additional, Sureda, Anna, additional, and Arnan Sangerman, Montserrat, additional

Published
2021
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39. Genomic Data Improves Prognostic Stratification in Adult T-Cell Acute Lymphoblastic Leukemia Patients Enrolled in Measurable Residual Disease-Oriented Trials

Author

González-Gil, Celia, primary, Morgades, Mireia, additional, Fuster-Tormo, Francisco, additional, García-Chica, Jesus, additional, Montesinos, Pau, additional, Torrent, Anna, additional, Diaz-Beyá, Marina, additional, Coll, Rosa, additional, Ribera, Jordi, additional, Zhao, Ran, additional, Hermosin, Maria Lourdes, additional, Mercadal, Santiago, additional, González-Campos, José, additional, Artola, M Teresa, additional, Vall-Llovera, Ferran, additional, Tormo, Mar, additional, Gil, Cristina, additional, Barba, Pere, additional, Novo, Andrés, additional, Bernal del Castillo, Teresa, additional, Queipo De Llano, Maria, additional, Martínez, Pilar, additional, González, Teresa, additional, Cladera, Antonia, additional, Serrano, Alfons, additional, Fernández-Martín, Rosa, additional, Ardaiz, Maria C., additional, Vidal, Maria Jesus, additional, Baena, Ángela, additional, Lopez-Bigas, Nuria, additional, Bigas, Anna, additional, Maciejewski, Jaroslaw P., additional, Orfao, Alberto, additional, Ribera, Josep-Maria, additional, and Genescà, Eulàlia, additional

Published
2021
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40. ALL-154: t(1;19)(q23;p13) TCF3-PBX1 May Not Be an Intermediate-Risk Subtype in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Patients Treated With MRD-Oriented Protocols from the PETHEMA Group

Author

Ribera, Jordi, primary, Morgades, Mireia, additional, Granada, Isabel, additional, Torrent, Anna, additional, Zamora, Lurdes, additional, González, Teresa, additional, Ciudad, Juana, additional, Barrena, Susana, additional, Such, Esperanza, additional, Avetisyan, Gayane, additional, Calasanz, Maria José, additional, Genescà, Eulàlia, additional, González-Gil, Celia, additional, Fuster-Tormo, Francisco, additional, Mercadal, Santiago, additional, Maluquer, Clara, additional, Coll, Rosa, additional, González-Campos, José, additional, Tormo, Mar, additional, García-Cadenas, Irene, additional, Nomdedeu, Josep, additional, Gil, Cristina, additional, Cervera, Marta, additional, Escoda, Lourdes, additional, Montesinos, Pau, additional, Barba, Pere, additional, Esteve, Jordi, additional, Díaz-Beyá, Marina, additional, Martínez-Sánchez, Pilar, additional, Martínez-López, Joaquín, additional, Novo, Andrés, additional, Queipo, M Paz, additional, Bermúdez, Arancha, additional, Bergua, Juan, additional, Olave, M Teresa, additional, De Rueda, Beatriz, additional, Artola, M Teresa, additional, Hernández-Rivas, Jesús M, additional, Orfao, Alberto, additional, and Ribera, Josep M, additional

Published
2021
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41. Poster: ALL-154: t(1;19)(q23;p13) TCF3-PBX1 May Not Be an Intermediate-Risk Subtype in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Patients Treated With MRD-Oriented Protocols from the PETHEMA Group

Author

Ribera, Jordi, primary, Morgades, Mireia, additional, Granada, Isabel, additional, Torrent, Anna, additional, Zamora, Lurdes, additional, González, Teresa, additional, Ciudad, Juana, additional, Barrena, Susana, additional, Such, Esperanza, additional, Avetisyan, Gayane, additional, Calasanz, Maria José, additional, Genescà, Eulàlia, additional, González-Gil, Celia, additional, Fuster-Tormo, Francisco, additional, Mercadal, Santiago, additional, Maluquer, Clara, additional, Coll, Rosa, additional, González-Campos, José, additional, Tormo, Mar, additional, García-Cadenas, Irene, additional, Nomdedeu, Josep, additional, Gil, Cristina, additional, Cervera, Marta, additional, Escoda, Lourdes, additional, Montesinos, Pau, additional, Barba, Pere, additional, Esteve, Jordi, additional, Díaz-Beyá, Marina, additional, Martínez-Sánchez, Pilar, additional, Martínez-López, Joaquín, additional, Novo, Andrés, additional, Queipo, M Paz, additional, Bermúdez, Arancha, additional, Bergua, Juan, additional, Olave, M Teresa, additional, De Rueda, Beatriz, additional, Artola, M Teresa, additional, Hernández-Rivas, Jesús M, additional, Orfao, Alberto, additional, and Ribera, Josep M, additional

Published
2021
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42. Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

Author

Oñate, Guadalupe, Bataller, Alex, Garrido, Ana, Hoyos Colell, Montserrat, Arnan, Montserrat, Vives Polo, Susana, Coll, Rosa, Tormo, Mar, Sampol, Antònia, Escoda, Lourdes, Salamero, Olga, Garcia, Antoni, Bargay, Joan, Aljarilla, Alba, Nomdedeu, Josep, Esteve Reyner, Jordi, Sierra, Jorge, Pratcorona, Marta, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Oñate G, Garrido A, Hoyos M] Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. [Bataller A] Hospital Clínic, Barcelona, Spain. [Arnan M] Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Barcelona, Spain. [Vives S] ICO, Hospital Germans Trias i Pujol, Jose Carreras Leukemia Research Institute, Badalona, Spain. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, NPM1, Neoplasm, Residual, Leucèmia mieloide, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Leucèmia mieloide aguda - Prognosi, Intensive chemotherapy, medicine.disease_cause, Allelic ratio, Gastroenterology, DNA Methyltransferase 3A, neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES], fluids and secretions, hemic and lymphatic diseases, Internal medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Medicine, Mutational status, In patient, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Mutation, Otros calificadores::Otros calificadores::/genética [Otros calificadores], business.industry, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES], Nuclear Proteins, hemic and immune systems, Hematology, Prognosis, Acute Myeloid Leukemia with Mutated NPM1, Enzymes, body regions, Leukemia, Myeloid, Acute, Anomalies cromosòmiques, Myeloid leukemia, Leucèmia mieloide aguda - Aspectes genètics, embryonic structures, High ratio, Enzims, business, Nucleophosmin
Abstract

Prognostic impact; Mutation; Acute myeloid leukemia Impacte pronòstic; Mutació; Leucèmia mieloide aguda Impacto pronóstico; Mutación; Leucemia mieloide aguda The negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3high; ≥0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3Amut) has been suggested to negatively influence prognosis in AML-NPM1, we analyzed the impact of DNMT3Amut in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3Amut status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3high) was independent of DNMT3Amut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3Amut was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3Amut patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD−; P = .027 and P = .001, respectively). Finally, DNMT3Amut patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3Amut did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention. This work was supported in part by the Biomedical Research Institute (IIB Sant-Pau) and the José Carreras Leukemia Research Institute as well as grants from the Catalan Government (PERIS SLT002/16/0043 and AGAUR 2017 SGR 139) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (PI17/01246, PI20/01621 and CM20/00061).

Published
2021

43. Role of Allogeneic Stem Cell Transplantation in Preventing Relapse in Adult BCR::ABL1-like Acute Lymphoblastic Leukemia

Author

Ribera, Jordi, Morgades, Mireia, Granada, Isabel, González, Teresa, Sánchez, Ricardo, Ayala, Rosa, Such, Esperanza, Avetisyan, Gayane, Barrera, Susana, Soriano, Beatriz, Torrent, Anna, Gil, Cristina, Botella, Carmen, Maluquer Artigal, Clara, Barba, Pere, Montesinos, Pau, González-Campos, José, Martínez-Sánchez, Pilar, Coll, Rosa, Esteve, Jordi, Benito Sanchez, Maria Rocio, Lopes, Thaysa, González Gil, Celia, Genescà, Eulàlia, Martínez-López, Joaquin, Hernández-Rivas, Jesús María, Orfao, Alberto, and Ribera, Josep-Maria

Published
2023
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45. Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials

Author

Fundación la Caixa, Instituto de Salud Carlos III, Generalitat de Catalunya, Ribera, Josep-Maria, Morgades, Mireia, Genescà, Eulàlia, Cerello Chapchap, Eduardo, Montesinos, Pau, Acuña‐Cruz, Evelyn, Gil, Cristina, García‐Cadenas, Irene, Barba, Pere, González‐Campos, José, Queipo de Llano, María‐Paz, Torrent, Anna, Ribera, Jordi, Granada, Isabel, Bernal, T., Díaz‐Beyá, Marina, Amigo, María Luz, Coll, Rosa, Tormo, Mar, Vall‐Llovera, Ferran, Gómez‐Centurión, Ignacio, Sánchez‐Sánchez, María‐José, Soria, Beatriz, Cladera, Antonia, Artola, María Teresa, Garcia‐Guiñon, Antonio, Giménez-Conca, Alberto, Amador, María‐Lourdes, Martínez‐Sanchez, Pilar, Algarra, Jesús Lorenzo, Vidal, María Jesús, Alonso, Natalia, Maluquer, Clara, Llorente, Laura, García‐Boyero, Raimundo, Ciudad, Juana, Feliu, Evarist, Orfao, Alberto, Fundación la Caixa, Instituto de Salud Carlos III, Generalitat de Catalunya, Ribera, Josep-Maria, Morgades, Mireia, Genescà, Eulàlia, Cerello Chapchap, Eduardo, Montesinos, Pau, Acuña‐Cruz, Evelyn, Gil, Cristina, García‐Cadenas, Irene, Barba, Pere, González‐Campos, José, Queipo de Llano, María‐Paz, Torrent, Anna, Ribera, Jordi, Granada, Isabel, Bernal, T., Díaz‐Beyá, Marina, Amigo, María Luz, Coll, Rosa, Tormo, Mar, Vall‐Llovera, Ferran, Gómez‐Centurión, Ignacio, Sánchez‐Sánchez, María‐José, Soria, Beatriz, Cladera, Antonia, Artola, María Teresa, Garcia‐Guiñon, Antonio, Giménez-Conca, Alberto, Amador, María‐Lourdes, Martínez‐Sanchez, Pilar, Algarra, Jesús Lorenzo, Vidal, María Jesús, Alonso, Natalia, Maluquer, Clara, Llorente, Laura, García‐Boyero, Raimundo, Ciudad, Juana, Feliu, Evarist, and Orfao, Alberto

Abstract

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.

Published
2021

46. Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

Author

Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Generalitat de Catalunya, La Caixa, Genescà, Eulàlia, Morgades, Mireia, González-Gil, Celia, Fuster‐Tormo, Francisco, Haferlach, Claudia, Meggendorfer, Manja, Montesinos, Pau, Barba, Pere, Gil, Cristina, Coll, Rosa, Moreno, María José, Martínez-Carballeira, Daniel, García-Cadenas, Irene, Vives, Susana, Ribera, Jordi, González-Campos, José A., Díaz-Beya, Marina, Mercadal, Santiago, Artola, María Teresa, Cladera, Antonia, Tormo, Mar, Bermúdez, Arantxa, Vall‐Llovera, Ferran, Martínez-Sánchez, Pilar, Amigo, María Luz, Monsalvo, Silvia, Novo, Andrés, Cervera, Marta, Garcia-Guiñon, Antonio, Ciudad, Juana, Cervera, José, Hernández, Jesús M., Granada, Isabel, Haferlach T., Orfao, Alberto, Solé, Francesc, Ribera, Josep-Maria, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Generalitat de Catalunya, La Caixa, Genescà, Eulàlia, Morgades, Mireia, González-Gil, Celia, Fuster‐Tormo, Francisco, Haferlach, Claudia, Meggendorfer, Manja, Montesinos, Pau, Barba, Pere, Gil, Cristina, Coll, Rosa, Moreno, María José, Martínez-Carballeira, Daniel, García-Cadenas, Irene, Vives, Susana, Ribera, Jordi, González-Campos, José A., Díaz-Beya, Marina, Mercadal, Santiago, Artola, María Teresa, Cladera, Antonia, Tormo, Mar, Bermúdez, Arantxa, Vall‐Llovera, Ferran, Martínez-Sánchez, Pilar, Amigo, María Luz, Monsalvo, Silvia, Novo, Andrés, Cervera, Marta, Garcia-Guiñon, Antonio, Ciudad, Juana, Cervera, José, Hernández, Jesús M., Granada, Isabel, Haferlach T., Orfao, Alberto, Solé, Francesc, and Ribera, Josep-Maria

Abstract

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.

Published
2021

48. Validation of the European Leukemianet 2017 Prognostic Classification for Patients with De Novo Acute Myeloid Leukemia Treated with a Risk-Adapted Protocol (CETLAM 2012)

Author

Bataller, Alex, primary, Garrido, Ana, additional, Guijarro, Francesca, additional, Diaz-Beyá, Marina, additional, Oñate, Guadalupe, additional, Hoyos, Montserrat, additional, Arnan, Montserrat, additional, Tormo, Mar, additional, Vives, Susana, additional, Queipo De Llano, Maria Paz, additional, Salamero, Olga, additional, Coll, Rosa, additional, Gallardo, David, additional, Vall-Llovera, Ferran, additional, Escoda, Lourdes, additional, Sampol, Antonia, additional, Garcia-Guiñon, Antonio, additional, Merchan, Brayan, additional, Bargay, Joan, additional, Lopez-Guerra, Monica, additional, Pratcorona, Marta, additional, Zamora, Lurdes, additional, Brunet, Salut, additional, Nomdedeu, Josep F, additional, Sierra, Jorge, additional, and Esteve, Jordi, additional

Published
2020
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49. Phase 3 Study of Lenalidomide (LEN) Vs Placebo in Non-Transfusion Dependent (TD) Low Risk Del(5q) MDS Patients - Interim Analysis of the European Sintra-REV Trial

Author

López Cadenas, Félix, primary, Lumbreras, Eva, additional, Xicoy, Blanca, additional, Sánchez, Joaquín, additional, Coll, Rosa, additional, Slama, Bohrane, additional, Hernandez-Rivas, Jose Angel, additional, Thepot, Sylvain, additional, Bernal, Teresa, additional, Arrizabalaga, Beatriz, additional, Guerci-Bresler, Agnès, additional, Sanz, Guillermo F, additional, Bargay, Joan, additional, Amigo, Maria Luz, additional, de Paz, Raquel, additional, Nomdedeu, Benet, additional, Giagounidis, Aristoteles, additional, Platzbecker, Uwe, additional, Wickenhauser, Stefan, additional, Götze, Katharina S., additional, Arar, Ali, additional, Hernández Rivas, Jesus María, additional, Fenaux, Pierre, additional, Del Cañizo, Consuelo, additional, and Diez-Campelo, Maria, additional

Published
2020
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50. Frequency, Clinical Characteristics and Outcome of Adult Patients with Acute Lymphoblastic Leukemia (ALL) and COVID-19 in Spain: Results of a Survey from Pethema and Geth Groups

Author

Ribera, Josep-Maria, primary, Morgades, Mireia, additional, Coll, Rosa, additional, Lopez Lorenzo, Jose Luis, additional, Montesinos, Pau, additional, Varela, Rosario, additional, Cabrero, Mónica, additional, Gómez-Centurión, Ignacio, additional, Morales, M. Dolores, additional, Garcia-Guiñon, Antoni, additional, Bautista, Guiomar, additional, Herrera Puente, Pilar, additional, Llorente, Laura, additional, García-Cadenas, Irene, additional, Barba, Pere, additional, Calbacho, Maria, additional, Gil, Cristina, additional, Foncillas, Maria Angeles, additional, Artola, María Teresa, additional, De La Camara, Rafael, additional, and Piñana Sanchez, Jose Luis, additional

Published
2020
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