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1. AML typical mutations (CEBPA, FLT3, NPM1) identify a high-risk chronic myelomonocytic leukemia independent of CPSS molecular

Author

Castaño-Díez, Sandra, López-Guerra, Mònica, Zugasti, Inés, Calvo, Xavier, Schulz, Felicitas Isabel, Avendaño, Alejandro, Mora, Elvira, Falantes, José, Azaceta, Gemma, Ibáñez, Mariam, Chen, Tzu, Notario, Cristina, Amer, Neus, Palomo, Laura, Pomares, Helena, Vila, Jordi, Bernal del Castillo, Teresa, Jiménez-Vicente, Carlos, Esteban, Daniel, Guijarro, Francesca, Álamo, José, Cortés-Bullich, Albert, Torrecillas-Mayayo, Víctor, Triguero, Ana, Mont-de Torres, Lucía, Carcelero, Ester, Cardús, Aina, Germing, Ulrich, Betz, Beate, Rozman, Maria, Arenillas, Leonor, Zamora, Lurdes, Díez-Campelo, María, Xicoy, Blanca, Esteve, Jordi, and Díaz-Beyá, Marina

Published
2025
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2. Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome

Author

Guijarro, Francesca, López-Guerra, Monica, Morata, Jordi, Bataller, Alex, Paz, Sara, Cornet-Masana, Josep Maria, Banús-Mulet, Antònia, Cuesta-Casanovas, Laia, Carbó, Josep Maria, Castaño-Díez, Sandra, Jiménez-Vicente, Carlos, Cortés-Bullich, Albert, Triguero, Ana, Martínez-Roca, Alexandra, Esteban, Daniel, Gómez-Hernando, Marta, Álamo Moreno, José Ramón, López-Oreja, Irene, Garrote, Marta, Risueño, Ruth M., Tonda, Raúl, Gut, Ivo, Colomer, Dolors, Díaz-Beya, Marina, and Esteve, Jordi

Published
2023
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3. At-Home Care Program for Acute Myeloid Leukemia Induction Phase in Patients Treated with Venetoclax-Based Low-Intensity Regimens.

Author

Martínez-Roca, Alexandra, Jiménez-Vicente, Carlos, Merchán, Beatriz, Castaño-Diez, Sandra, Zugasti, Inés, Brillembourg, Helena, Bataller, Álex, Guijarro, Francesca, Cortés-Bullich, Albert, Trigueros, Ana, Pérez-Valencia, Amanda Isabel, Gallego, Cristina, Ballestar, Nuria, Rodríguez-Lobato, Luis Gerardo, Carcelero, Esther, Díaz-Beyá, Marina, Esteve, Jordi, and Fernández-Avilés, Francesc

Subjects
THERAPEUTIC use of antineoplastic agents, PATIENT education, FEBRILE neutropenia, PATIENT safety, RESEARCH funding, PATIENT readmissions, EVALUATION of medical care, RETROSPECTIVE studies, DESCRIPTIVE statistics, CANCER chemotherapy, MEDICAL records, ACQUISITION of data, MYELOID leukemia, ADVERSE health care events, DATA analysis software, COMPARATIVE studies, EVALUATION
Abstract

Simple Summary: Venetoclax combined with azacitidine (VenAza) in patients with acute myeloid leukemia (AML) presents a high incidence of cytopenias and infections during initial treatment cycles, making early management challenging. To address this, our center implemented an At-Home (AH) program during the VenAza induction phase, focusing on therapy administration, patient and caregiver education, and adverse events (AEs) management. From March 2019 to May 2022, 75 patients with newly diagnosed or relapsed/refractory AML were treated with VenAza, with the experiment comparing outcomes between a hospital-based (inpatient) cohort of 24 patients initially admitted for treatment administration and an AH cohort (n = 44). Although most patients experienced grade 3–4 cytopenia (96.9%), the incidence of serious infections and other AEs was similar between groups. The AH cohort had a significantly lower hospital readmission rate after ramp-up (29.5% vs. 84.6%, p = 0.0001) and shorter hospital stays (8 vs. 13 days, p = 0.28). AH management proved to be safe and effective, optimizing resource use and improving patient and caregiver well-being. Background: Even though venetoclax in combination with azacitidine (VenAza) is considered a low-intensity regimen, its patients present a high incidence of cytopenia and infections during the first courses, making the initial management a challenging phase. Methods: This difficulty in our center led to the establishment of an At-Home (AH) program for ramp-up and follow-up patients during the VenAza combination induction phase focused on therapy administration, patient and caregiver education, and management of adverse events (AEs). A total of 70 patients with newly diagnosed acute myeloid leukemia (ND-AML) or relapsed/refractory AML (R/R AML) were treated with VenAza from March 2019 to May 2022. We compared outcomes between patients managed with a hospital-based (inpatient) approach and those managed through the AH program. Results: Despite most patients experiencing grade 3–4 cytopenias (96.9%), the incidence of serious infections and other AEs was comparable between both groups, with no significant difference in febrile neutropenia (42.3% vs. 27.8%, p = 0.38). Overall, the AH cohort demonstrated a significantly lower hospital readmission rate after ramp-up (29.5% vs. 84.6%, p = 0.001). Moreover, the inpatient cohort's admission days were longer than in the AH cohort (13 vs. 8, p = 0.28). Conclusions: AH management was feasible and safe, leading to better resource use, enhanced patient comfort, and improved treatment compliance. The potential of AH programs for managing low-intensity chemotherapy regimens can reduce hospital admissions and subsequently improve patient and caregiver well-being. [ABSTRACT FROM AUTHOR]

Published
2024
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4. 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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5. 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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6. Whole Exome Sequencing of Intermediate-Risk Acute Myeloid Leukemia without Recurrent Genetic Abnormalities Offers Deeper Insights into New Diagnostic Classifications.

Author

Guijarro, Francesca, Castaño-Díez, Sandra, Jiménez-Vicente, Carlos, Garrote, Marta, Álamo, José Ramón, Gómez-Hernando, Marta, López-Oreja, Irene, Morata, Jordi, López-Guerra, Mònica, López, Cristina, Beà, Sílvia, Costa, Dolors, Colomer, Dolors, Díaz-Beyá, Marina, Rozman, Maria, and Esteve, Jordi

Subjects
ACUTE myeloid leukemia, MYELODYSPLASTIC syndromes, CYTOGENETICS, HETEROZYGOSITY, DYSPLASIA, BIOLOGY
Abstract

Two new diagnostic classifications of acute myeloid leukemia (AML) were published in 2022 to update current knowledge on disease biology. In previous 2017-edition categories of AML with myelodysplasia-related changes, AML was not otherwise specified, but AML with mutated RUNX1 experienced profound changes. We performed whole exome sequencing on a cohort of 69 patients with cytogenetic intermediate-risk AML that belonged to these diagnostic categories to correlate their mutational pattern and copy-number alterations with their new diagnostic distribution. Our results show that 45% of patients changed their diagnostic category, being AML myelodysplasia-related the most enlarged, mainly due to a high frequency of myelodysplasia-related mutations (58% of patients). These showed a good correlation with multilineage dysplasia and/or myelodysplastic syndrome history, but at the same time, 21% of de novo patients without dysplasia also presented them. RUNX1 was the most frequently mutated gene, with a high co-occurrence rate with other myelodysplasia-related mutations. We found a high prevalence of copy-neutral loss of heterozygosity, frequently inducing a homozygous state in particular mutated genes. Mild differences in current classifications explain the diagnostic disparity in 10% of patients, claiming a forthcoming unified classification. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature

Author

Castaño-Díez, Sandra, primary, Guijarro, Francesca, additional, López-Guerra, Mònica, additional, Pérez-Valencia, Amanda Isabel, additional, Gómez-Núñez, Marta, additional, Colomer, Dolors, additional, Díaz-Beyá, Marina, additional, Esteve, Jordi, additional, and Rozman, María, additional

Published
2024
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8. Evaluation of European LeukemiaNet 2022 risk classification in patients undergoing allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: Identification of a very poor prognosis genetic group.

Author

Jiménez‐Vicente, Carlos, Charry, Paola, Castaño‐Diez, Sandra, Guijarro, Francesca, López‐Guerra, Mònica, Pérez‐Valencia, Amanda Isabel, Martinez‐Roca, Alexandra, Cortés‐Bullich, Albert, Munárriz, Daniel, Solano, Maria Teresa, Rosiñol, Laura, Carreras, Enric, Urbano‐Ispizua, Álvaro, Fernández‐Avilés, Francesc, Martinez, Carmen, Suárez‐Lledó, María, Díaz‐Beyá, Marina, Rovira, Montserrat, Salas, María Queralt, and Esteve, Jordi

Subjects
HEMATOPOIETIC stem cell transplantation, ACUTE myeloid leukemia, ALLOIMMUNITY, GRAFT versus host reaction, CELL transplantation
Abstract

Summary: European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo‐HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia‐free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse‐plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2‐year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo‐HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Characteristics and long‐term outcome in a large series of chronic myelomonocytic leukaemia patients including 104 formerly referred to as oligomonocytic

Author

Castaño‐Díez, Sandra, primary, Pomares, Helena, additional, Esteban, Daniel, additional, Guijarro, Francesca, additional, Jiménez‐Vicente, Carlos, additional, Zugasti, Inés, additional, Álamo, José Ramón, additional, Mayayo, Víctor Torrecillas, additional, López‐Guerra, Mònica, additional, de la Fuente, Cristina, additional, Charry, Paola, additional, Cortés‐Bullich, Albert, additional, Bataller, Álex, additional, Maluquer, Clara, additional, Colomer, Dolors, additional, Rozman, María, additional, Arnan, Montserrat, additional, Xicoy, Blanca, additional, Esteve, Jordi, additional, and Díaz‐Beyá, Marina, additional

Published
2023
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11. Machine Learning Improves Risk Stratification in Myelodysplastic Neoplasms: An Analysis of the Spanish Group of Myelodysplastic Syndromes

Author

Mosquera Orgueira, Adrian, primary, Perez Encinas, Manuel Mateo, additional, Diaz Varela, Nicolas A, additional, Mora, Elvira, additional, Díaz-Beyá, Marina, additional, Montoro, María Julia, additional, Pomares, Helena, additional, Ramos, Fernando, additional, Tormo, Mar, additional, Jerez, Andres, additional, Nomdedeu, Josep F, additional, De Miguel Sanchez, Carlos, additional, Leonor, Arenillas, additional, Cárcel, Paula, additional, Cedena Romero, Maria Teresa, additional, Xicoy, Blanca, additional, Rivero, Eugenia, additional, del Orbe Barreto, Rafael Andres, additional, Diez-Campelo, Maria, additional, Benlloch, Luis E., additional, Crucitti, Davide, additional, and Valcárcel, David, additional

Published
2023
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12. P714: DISSECTING THE CLINICAL HETEROGENEITY OF ISOLATED TRISOMY 8 MYELODYSPLASTIC SYNDROMES THROUGH MUTATIONAL PROFILE

Author

María Toribio Castelló, Sofía, primary, Castaño, Sandra, additional, Villaverde-Ramiro, Angela, additional, Such, Esperanza, additional, Arnan, Montserrat, additional, Solé, Francesc, additional, Díaz Beyá, Marina, additional, Díez-Campelo, María, additional, del Rey, Mónica, additional, González, Teresa, additional, and Hernández Rivas, Jesus, additional

Published
2023
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13. Characteristics and long‐term outcome in a large series of chronic myelomonocytic leukaemia patients including 104 formerly referred to as oligomonocytic.

Author

Castaño‐Díez, Sandra, Pomares, Helena, Esteban, Daniel, Guijarro, Francesca, Jiménez‐Vicente, Carlos, Zugasti, Inés, Álamo, José Ramón, Mayayo, Víctor Torrecillas, López‐Guerra, Mònica, de la Fuente, Cristina, Charry, Paola, Cortés‐Bullich, Albert, Bataller, Álex, Maluquer, Clara, Colomer, Dolors, Rozman, María, Arnan, Montserrat, Xicoy, Blanca, Esteve, Jordi, and Díaz‐Beyá, Marina

Subjects
CHRONIC leukemia, PROGNOSIS, MULTIVARIATE analysis
Abstract

Summary: Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut‐off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)‐CMML. Five‐year survival was longer for OM‐CMML than for other patients (p < 0.001). Multivariate analysis identified OM‐CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5‐year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM‐CMML. Our results support the inclusion of OM‐CMML in the CMML category as a subtype with superior outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Mutational Profile Enables the Identification of a High-Risk Subgroup in Myelodysplastic Syndromes with Isolated Trisomy 8

Author

Toribio-Castelló, Sofía, primary, Castaño, Sandra, additional, Villaverde-Ramiro, Ángela, additional, Such, Esperanza, additional, Arnán, Montserrat, additional, Solé, Francesc, additional, Díaz-Beyá, Marina, additional, Díez-Campelo, María, additional, del Rey, Mónica, additional, González, Teresa, additional, and Hernández-Rivas, Jesús María, additional

Published
2023
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15. Venetoclax with hypomethylating agents might lead to eradication of measurable residual disease (MRD) persisting after intensive chemotherapy in acute myeloid leukemia (AML) patients with mutated NPM1 and rearranged CBF

Author

Jiménez-Vicente, Carlos, Martínez-Roca, Alexandra, Pomares, Helena, Castaño-Diez, Sandra, Guijarro, Francesca, López-Guerra, Mònica, Bataller, Alex, Esteban, Daniel, Cortés-Bullich, Albert, Pérez-Valencia, Amanda Isabel, Guardia-Torrelles, Ares, Zugasti, Inés, Rovira, Montserrat, Fernández-Avilés, Francesc, Colomer, Dolors, Arnan, Montserrat, Díaz-Beyá, Marina, and Esteve, Jordi

Published
2023
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16. Supervised Machine Learning Improves Risk Stratification in Newly Diagnosed Myelodysplastic Syndromes: An Analysis of the Spanish Group of Myelodysplastic Syndromes

Author

Mosquera Orgueira, Adrian, primary, Perez Encinas, Manuel, additional, Diaz Varela, Nicolas A, additional, Mora, Elvira, additional, Díaz-Beyá, Marina, additional, Montoro, María Julia, additional, Pomares, Helena, additional, Ramos, Fernando, additional, Tormo, Mar, additional, Jerez, Andres, additional, Nomdedeu, Josep F, additional, De Miguel Sanchez, Carlos, additional, Leonor, Arenillas, additional, Cárcel, Paula, additional, Cedena Romero, Maria Teresa, additional, Xicoy, Blanca, additional, Rivero, Eugenia, additional, del Orbe Barreto, Rafael Andres, additional, Diez-Campelo, Maria, additional, Benlloch, Luis E., additional, Crucitti, Davide, additional, and Valcárcel, David, additional

Published
2022
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17. Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD

Author

Vilorio-Marqués, Laura, Castañón Fernández, Christelle, Mora, Elvira, Gutiérrez, Lorena, Rey Bua, Beatriz, Jiménez Lorenzo, Maria José, Díaz-Beyá, Marina, Vara Pampliega, Miriam, Molero, Antonieta, Sánchez-García, Joaquín, Calabuig, Marisa, Cedena, María Teresa, Chen-Liang, Tzu, Díaz Santa, Johana Alejandra, Padilla, Irene, Hernández, Francisca, Díez, Rosana, Asensi, Pedro, Xicoy, Blanca, Sanz, Guillermo, Valcárcel, David, Diez-Campelo, María, Bernal, Teresa, Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Vilorio-Marqués L, Castañón Fernández C] Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain. [Mora E] Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Gutiérrez L] Hematology Department, Hospital Universitario de Canarias, La Laguna, Spain. [Rey Bua B] Hematology Department, Hospital Clínico Universitario, Salamanca, Spain. [Jiménez Lorenzo MJ] Hematology Department, Hospital Germans Trias i Pujol, Institut Català d’Oncologia-Josep Carreras, Leukemia Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. [Molero A, Valcárcel D] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
hypomethylating agent, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Hematology, acute myeloid leukemia, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], infection, myelodysplastic syndrome, Medicaments antineoplàstics - Efectes secundaris, neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES], Leucèmia mieloide aguda - Tractament, Avaluació de resultats (Assistència sanitària), Other subheadings::Other subheadings::/adverse effects [Other subheadings], treatment outcome, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
Abstract

The authors declared the following potential conflict of interest with respect to the research, authorship, and/or publication of this article: T.B. has received support for attending meetings and/or travel from Jazz Pharmaceutical, honoraria from Jazz Pharmaceutical, BMS, and Pfizer. D.V. has received honoraria from Celgene/BMS, Amgen, Novartis, Jazz Pharmaceuticals, and Pfizer and support for attending meetings and/or travel from Amgen, BMS/Celgene, and Jazz. M.D.-C. reports honoraria and membership on entity's Board of directors or advisory committees from Novartis, BMS, and Takeda. Dr G.S. has received personal fees from AbbVie, Amgen, and Astellas and has received research funding from Celgene/BMS Janssen-Cilag, Novartis, Roche, and Takeda. Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated. Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting. Design: Observational study. Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection. Results: The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26-1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3-8] versu 8 [5-16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09-1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14-3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30-2.24], p < 0.001), and platelet count 20% (HR = 1.57 [95% CI = 1.19-2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35-2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51-0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996-0.998], p = 0.016) protected from it. Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.

Published
2022

18. Poster: MDS-472 STAG2 and SRSF2 Mutations Might Define Prognosis of MDS Patients With Isolated Trisomy 8

Author

Toribio-Castelló, Sofía, primary, Castaño-Díez, Sandra, additional, Villaverde-Ramiro, Ángela, additional, López-Cadenas, Félix, additional, Díaz-Beyá, Marina, additional, Rodríguez-Iglesias, Irene, additional, González-Briones, Sara, additional, Hernández-Rivas, Jesús María, additional, González, Teresa, additional, Rey, Mónica Del, additional, and Díez-Campelo, María, additional

Published
2022
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19. Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Author

Castaño-Díez, Sandra, primary, López-Guerra, Mónica, additional, Bosch-Castañeda, Cristina, additional, Bataller, Alex, additional, Charry, Paola, additional, Esteban, Daniel, additional, Guijarro, Francesca, additional, Jiménez-Vicente, Carlos, additional, Castillo-Girón, Carlos, additional, Cortes, Albert, additional, Martínez-Roca, Alexandra, additional, Triguero, Ana, additional, Álamo, José Ramón, additional, Beà, Silvia, additional, Costa, Dolors, additional, Colomer, Dolors, additional, Rozman, María, additional, Esteve, Jordi, additional, and Díaz-Beyá, Marina, additional

Published
2022
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20. AML-468 Midostaurin Plus Intensive Chemotherapy in FLT3-Mutated AML: “Real-Life” Data Versus the RATIFY Study

Author

Bobes, Alejandro, Tormo, Mar, Diaz-Beya, Marina, Beneit, Paola, Botella, Carmen, Fernández Moreno, Ainhoa, Mayol, Antonia Sampol, Sangerman, Montserrat Arnan, Bermejo, Ana Yeguas, de la Luz Amigo, Maria, Labrador, Jorge, García Guinon, Antoni, Garrido, Ana, Serrano, Josefina, Polo, Susana Vives, García Fortes, Maria, José Sayas, Maria, Bergua, Juan Miguel, Olave, María Teresa, Vall-Llovera, Ferran, Bargay, Juan, Sanchez, María Pereiro, García Boyero, Raimundo, Diaz-Lopez, Antonio, and de la Fuente, Adolfo

Published
2024
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21. Midostaurin Plus Intensive Chemotherapy in FLT3-Mutated AML: “Real-Life” Data Versus the RATIFY Study

Author

Bobes, Alejandro, Tormo, Mar, Diaz-Beya, Marina, Beneit, Paola, Botella, Carmen, Fernández Moreno, Ainhoa, Sampol Mayol, Antonia, Arnan Sangerman, Montserrat, Yeguas Bermejo, Ana, de la Luz Amigo, Maria, Labrador, Jorge, García Guinon, Antoni, Garrido, Ana, Serrano, Josefina, Vives Polo, Susana, García Fortes, Maria, José Sayas, Maria, Miguel Bergua, Juan, Teresa Olave, María, Vall-Llovera, Ferran, Bargay, Juan, Pereiro Sanchez, María, García Boyero, Raimundo, Diaz-Lopez, Antonio, and de la Fuente, Adolfo

Published
2024
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23. A Systems Biology- and Machine Learning-Based Study to Unravel Potential Therapeutic Mechanisms of Midostaurin as a Multitarget Therapy on FLT3-Mutated AML

Author

Díaz-Beyá, Marina, primary, García-Fortes, María, additional, Valls, Raquel, additional, Artigas, Laura, additional, Gómez-Casares, Mª Teresa, additional, Montesinos, Pau, additional, Sánchez-Guijo, Fermín, additional, Coma, Mireia, additional, Vendranes, Meritxell, additional, and Martínez-López, Joaquín, additional

Published
2022
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24. Results of ARI ‐0001 CART19 cell therapy in patients with relapsed/refractory CD19 ‐positive acute lymphoblastic leukemia with isolated extramedullary disease

Author

Ortiz‐Maldonado, Valentín, primary, Alonso‐Saladrigues, Anna, additional, Español‐Rego, Marta, additional, Martínez‐Cibrián, Nuria, additional, Faura, Anna, additional, Magnano, Laura, additional, Català, Albert, additional, Benítez‐Ribas, Daniel, additional, Giné, Eva, additional, Díaz‐Beyá, Marina, additional, Correa, Juan Gonzalo, additional, Rovira, Montserrat, additional, Montoro‐Lorite, Mercedes, additional, Martínez‐Roca, Alexandra, additional, Rodríguez‐Lobato, Luis Gerardo, additional, Cabezón, Raquel, additional, Cid, Joan, additional, Lozano, Miquel, additional, Garcia‐Rey, Enric, additional, Conde, Nuria, additional, Pedrals, Georgina, additional, Rozman, María, additional, Torrebadell, Montserrat, additional, Setoain, Xavier, additional, Rodríguez, Sonia, additional, Esteve, Jordi, additional, Pascal, Mariona, additional, Urbano‐Ispizua, Álvaro, additional, Juan, Manel, additional, Delgado, Julio, additional, and Rives, Susana, additional

Published
2022
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25. Real-World Data on Chronic Myelomonocytic Leukemia : Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Author

Castaño-Díez, Sandra, López-Guerra, Mónica, Bosch-Castañeda, Cristina, Bataller, Alex, Charry, Paola, Esteban, Daniel, Guijarro, Francesca, Jiménez-Vicente, Carlos, Castillo-Girón, Carlos, Cortes, Albert, Martínez-Roca, Alexandra, Triguero, Ana, Álamo, José Ramón, Bea, Sílvia, Costa, Dolors, Colomer, Dolors, Rozman, María, Esteve Reyner, Jordi, Díaz-Beyá, Marina, and Universitat Autònoma de Barcelona

Subjects
chronic myelomonocytic leukemia, CMML, AML transformation, clonal evolution, prognosis, treatment, hypomethylating agents, targeted therapy, gene mutations, survival, Cancer Research, Leukemia, Oncology, Leucèmia, Molecular genetics, Genètica molecular
Abstract

This research was supported by grants from resident award Contractes Clínic de Recerca Emili Letang-Josep Font 2021, granted by Hospital Clínic de Barcelona; and it was funded by Instituto de Salud Carlos III (ISCIII) through the project "FIS PI19/01476" and co-funded by the European Union. Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy

Published
2022

26. Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndromes (MDS)

Author

Tentori, Cristina Astrid, Gregorio, Caterina, Robin, Marie, Gagelmann, Nico, Gurnari, Carmelo, Ball, Somedeb, Caballero Berrocal, Juan Carlos, Lanino, Luca, D'Amico, Saverio, Spreafico, Marta, Maggioni, Giulia, Travaglino, Erica, Sauta, Elisabetta, Meggendorfer, Manja, Zhao, Lin-Pierre, Bernardi, Massimo, Di Grazia, Carmen, Vago, Luca, Rivoli, Giulia, Borin, Lorenza Maria, Chiusolo, Patrizia, Giaccone, Luisa, Voso, Maria Teresa, Bewersdorf, Jan Philipp, Nibourel, Olivier, Díaz-Beyá, Marina, Jerez, Andres, Hernandez, Francisca Maria, Velázquez Kennedy, Kyra, Xicoy, Blanca, Ubezio, Marta, Campagna, Alessia, Russo, Antonio, Todisco, Gabriele, Mannina, Daniele, Bramanti, Stefania, Zampini, Matteo, Riva, Elena, Bicchieri, Marilena, Asti, Gianluca, Viviani, Filippo, Buizza, Alessandro, Tinterri, Benedetta, Bacigalupo, Andrea, Rambaldi, Alessandro, Passamonti, Francesco, Ciceri, Fabio, Savevski, Victor, Santoro, Armando, Al Ali, Najla H, Sallman, David A, Sole, Francesc, Garcia-Manero, Guillermo, Germing, Ulrich, Kordasti, Shahram, Santini, Valeria, Sanz, Guillermo, Kern, Wolfgang, Kubasch, Anne Sophie, Platzbecker, Uwe, Diez-Campelo, Maria, Maciejewski, Jaroslaw P., Ades, Lionel, Fenaux, Pierre, Haferlach, Torsten, Zeidan, Amer M., Castellani, Gastone, Komrokji, Rami S., Ieva, Francesca, and Della Porta, Matteo Giovanni

Published
2023
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27. Chronic Myelomonocytic Leukemia (CMML) with AML Typical Mutations ( NPM1, FLT3 or CEBPA) Identify a High-Risk CMML Group Independent of Molecular-Cpss

Author

Castaño-Díez, Sandra, Zugasti, Ines, Calvo, Xavier, Schulz, Felicitas, Avendaño Pita, Alejandro, Mora, Elvira, Falantes, Jose Francisco, Azaceta, Gemma, Ibáñez, Mariam, Chen, Tzu, Notario, Cristina, Amer Salas, Neus, López-Guerra, Mònica, Jimenez-Vicente, Carlos, Esteban, Daniel, Guijarro, Francesca, Álamo Moreno, José Ramón, Cortés-Bullich, Albert, Munárriz, Daniel, Torrecillas-Mayayo, Víctor, Triguero, Ana, Tovar, Natalia, Martínez-Roca, Alexandra, Merchán Muñoz, Beatriz, Carcelero, Esther, Germing, Ulrich, Betz, Beate, Rozman, María, Arenillas, Leonor, Zamora, Lurdes, Diez-Campelo, Maria, Xicoy, Blanca, Esteve, Jordi, and Díaz-Beyá, Marina

Published
2023
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29. Venetoclax and Azacytidine Treatment for High Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia As a Bridge Therapy to Transplant. a GESMD Study

Author

Zugasti, Ines, Castaño-Díez, Sandra, Esteban, Daniel, Avendaño Pita, Alejandro, Pomares, Helena, Pérez González, Ana, Garcia-Avila, Sara, Padilla-Conejo, Irene, de la Fuente, Cristina, Martínez-Roca, Alexandra, Guijarro, Francesca, Álamo Moreno, José Ramón, Jimenez-Vicente, Carlos, Cortés-Bullich, Albert, Torrecillas, Victor, Guardia, Ares, Munárriz, Daniel, Carcelero, Esther, Suarez-Lledo, Maria, Salas, Maria Queralt, Lopez, Felix, Ramos, Fernando, Xicoy, Blanca, Valcarcel, David, Arnan Sangerman, Montserrat, Diez-Campelo, Maria, Martinez, Carmen, Rovira, Montserrat, Fernández-Avilés, Francesc, Esteve, Jordi, and Díaz-Beyá, Marina

Published
2023
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30. Evaluation of the Use of Post-Transplant Cyclophosphamide in Patients Diagnosed of Myelodysplastic Syndrome Who Undergo Allogenic Hematopoietic Cell Transplantation

Author

Tolosa-Ridao, Carles, Charry, Paola, Castaño-Díez, Sandra, Suarez-Lledo, Maria, Merchán Muñoz, Beatriz, Esteban, Daniel, Cortés-Bullich, Albert, Guijarro, Francesca, Solano, Maria Teresa, Martínez-Roca, Alexandra, Jimenez-Vicente, Carlos, Rosiñol, Laura, Carreras, Enric, Urbano-Ispizua, Alvaro, Fernández-Avilés, Francesc, Martinez, Carmen, Esteve, Jordi, Rovira, Montserrat, Díaz-Beyá, Marina, and Salas, Maria Queralt

Published
2023
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31. Validation of ELN 2022 Risk Classification in Patients Diagnosed with AML Undergoing Allogeneic Hematopoietic Cell Transplantation

Author

Jimenez-Vicente, Carlos, Charry, Paola, Suarez-Lledo, Maria, Merchán Muñoz, Beatriz, Castaño-Díez, Sandra, Perez-Valencia, Amanda Isabel, Martínez-Roca, Alexandra, Guijarro, Francesca, López-Guerra, Mònica, Cortés-Bullich, Albert, Esteban, Daniel, Guardia-Torrelles, Ares, Zugasti, Ines, Munárriz, Daniel, Rosiñol, Laura, Urbano-Ispizua, Alvaro, Fernández-Avilés, Francesc, Martinez, Carmen, Díaz-Beyá, Marina, Rovira, Montserrat, Salas, Maria Queralt, and Esteve, Jordi

Published
2023
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32. Allogeneic Hematopoietic Cell Transplantation with Sequential-Based Conditioning in Refractory / Relapsed Acute Myeloid Leukemia: Experience from a Single Institution

Author

Tolosa-Ridao, Carles, Charry, Paola, Suarez-Lledo, Maria, Esteban, Daniel, Díaz-Beyá, Marina, Cortés-Bullich, Albert, Merchán Muñoz, Beatriz, Martínez-Roca, Alexandra, Solano, Maria Teresa, Guijarro, Francesca, Castaño-Díez, Sandra, Jimenez-Vicente, Carlos, Nomdedeu, Meritxell, Cid, Joan, Lozano, Miquel, Pedraza, Alexandra, Rosiñol, Laura, Carreras, Enric, Urbano-Ispizua, Alvaro, Fernández-Avilés, Francesc, Martinez, Carmen, Esteve, Jordi, Rovira, Montserrat, and Salas, Maria Queralt

Published
2023
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33. Molecular Classification of Chronic Myelomonocytic Leukemia: Results of the Analysis of an International Cohort of 2,471 Patients

Author

Lanino, Luca, Hunter, Anthony M., Sala, Claudia, Dall'Olio, Daniele, Dall'Olio, Lorenzo, Pleyer, Lisa, Xicoy, Blanca, Meggendorfer, Manja, Sauta, Elisabetta, Travaglino, Erica, Robin, Marie, Palomo, Laura, Quintela, David, Jerez, Andres, Cornejo, Elena, Garcia Martin, Paloma, Díaz-Beyá, Marina, Avendaño Pita, Alejandro, Roldan, Veronica, Fiallo Suarez, Dolly Viviana, Cerezo Velasco, Estefania, Calabuig, Marisa, Rivoli, Giulia, Bernardi, Massimo, Onida, Francesco, Borin, Lorenza Maria, Passamonti, Francesco, Campagna, Alessia, Ubezio, Marta, Russo, Antonio, Todisco, Gabriele, Maggioni, Giulia, Tentori, Cristina Astrid, Viviani, Filippo, Buizza, Alessandro, Asti, Gianluca, Zampini, Matteo, Santoro, Armando, Kern, Wolfgang, Platzbecker, Uwe, Sole, Francesc, Diez-Campelo, Maria, Consagra, Angela, Al Ali, Najla H, Sallman, David A, Fenaux, Pierre, Itzykson, Raphael, Fontenay, Michaela, Zeidan, Amer M., Komrokji, Rami S., Santini, Valeria, Haferlach, Torsten, Germing, Ulrich, D'Amico, Saverio, Castellani, Gastone, Solary, Eric, Padron, Eric, and Della Porta, Matteo Giovanni

Published
2023
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34. Chronic Myelomonocytic Leukemia (CMML) with AML Typical Mutations ( NPM1, FLT3or CEBPA) Identify a High-Risk CMML Group Independent of Molecular-Cpss

Author

Castaño-Díez, Sandra, Zugasti, Ines, Calvo, Xavier, Schulz, Felicitas, Avendaño Pita, Alejandro, Mora, Elvira, Falantes, Jose Francisco, Azaceta, Gemma, Ibáñez, Mariam, Chen, Tzu, Notario, Cristina, Amer Salas, Neus, López-Guerra, Mònica, Jimenez-Vicente, Carlos, Esteban, Daniel, Guijarro, Francesca, Álamo Moreno, José Ramón, Cortés-Bullich, Albert, Munárriz, Daniel, Torrecillas-Mayayo, Víctor, Triguero, Ana, Tovar, Natalia, Martínez-Roca, Alexandra, Merchán Muñoz, Beatriz, Carcelero, Esther, Germing, Ulrich, Betz, Beate, Rozman, María, Arenillas, Leonor, Zamora, Lurdes, Diez-Campelo, Maria, Xicoy, Blanca, Esteve, Jordi, and Díaz-Beyá, Marina

Abstract

CMML is rarely associated with AML typical mutations such as NPM1, FLT3, CEBPAand IDH1/2 (mutAML-CMML). It is unknown what its clinical meaning is and if its presence should change our management into an AML-type treatment. The aim was to describe the characteristics, prognosis and treatment of mutAML-CMML patients.

Published
2023
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35. Chronic myelomonocytic leukemia with NPM1 mutation or acute myeloid leukemia?

Author

Castaño-Díez S, Álamo JR, López-Guerra M, Gómez-Hernando M, Zugasti I, Jiménez-Vicente C, Guijarro F, López-Oreja I, Esteban D, Charry P, Torrecillas V, Mont-de Torres L, Cortés-Bullich A, Bataller Á, Guardia A, Munárriz D, Carcelero E, Riu G, Triguero A, Tovar N, Vela D, Beà S, Costa D, Colomer D, Rozman M, Esteve J, and Díaz-Beyá M

Abstract

The 2022 WHO revision and the ICC classification have recently modified the diagnostic criteria for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia. However, there is no consensus on whether CMML with NPM1 mutation (NPM1mut) should be diagnosed as AML. Nowadays, it is a subject of discussion because of its diagnostic and therapeutic implications. Therefore, we describe a case of a patient diagnosed with CMML NPM1mut and briefly review the literature to highlight the uncertainty about how to classify a CMML with NPM1 mutation. We emphasize the importance of a comprehensive molecular study, which is crucial to optimize the individualized treatment of patients, enabling them to access targeted therapies., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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