58 results on '"Peñarrubia MJ"'
Search Results
2. Poster: ABCL-181: Updated Results of a Phase 2 Study from GELTAMO Investigating the Combination of Ibrutinib with R-GEMOX in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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Búa, Beatriz Rey, primary, Ubieto, A Jiménez, additional, Blanco, JJ Sánchez, additional, Abrisqueta, P, additional, Gutiérrez, A, additional, Páyez, A Ramírez, additional, Giné, E, additional, Etxetxipia, I Zeberio, additional, Terol, MJ, additional, Cruz, F de la, additional, Andreu, R, additional, Ramirez, MJ, additional, Fuente, A de la, additional, Viguria, MC, additional, Peñarrubia, MJ, additional, Grande, C, additional, Barrigón, MD Caballero, additional, and García-Sancho, A Martín, additional
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- 2021
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3. Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia
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Ribera JM, Morgades M, Montesinos P, Martino R, Barba P, Soria B, Bermúdez A, Moreno MJ, González-Campos J, Vives S, Gil C, Abella E, Guàrdia R, Martínez-Carballeira D, Martínez-Sánchez P, Amigo ML, Mercadal S, Serrano A, López-Martínez A, Vall-Llovera F, Sánchez-Sánchez MJ, Peñarrubia MJ, Calbacho M, Méndez JA, Bergua J, Cladera A, Tormo M, García-Belmonte D, Feliu E, Ciudad J, Orfao A, and PETHEMA Group, S
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Adult acute lymphoblastic leukemia ,efficacy ,Escherichia coli asparaginase ,pegylated ,toxicity ,native - Abstract
Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.
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- 2018
4. Bam Regimen Followed By High-Dose Therapy and Autologous Stem Cell Transplantation As First-Line Treatment Of Primary Central Nervous System Lymphoma: A Multicenter Study From Spanish Group GEL-TAMO
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López-Parra, M, primary, Martín, A, additional, Grande, C, additional, Bobillo, S, additional, Rojas, S M, additional, Sancho, JM, additional, Alonso, N, additional, González-Barca, E, additional, Escoda, L, additional, Fernández-Abellán, P, additional, Álvarez-Carmona, A, additional, Montalbán, C, additional, Moraleda, JM, additional, Pardal, E, additional, Peñarrubia, MJ, additional, Pérez-Ceballos, E, additional, González-Sierra, P, additional, Pérez-Oteyza, J, additional, Ramírez, MJ, additional, Salar, A, additional, Sánchez-Godoy, P, additional, Graus, F, additional, Caballero, M.D., additional, and López-Guillermo, A, additional
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- 2013
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5. Subacute Thyroiditis Associated with Interferon-α 2a Therapy
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Peñarrubia Mj, Mónica Marazuela, A. Arranz, and B. González‐Fernández
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,General Medicine ,medicine.disease ,Biochemistry ,Gastroenterology ,Endocrinology ,Internal medicine ,medicine ,business ,Interferon Alpha 2a ,Subacute thyroiditis - Published
- 1995
6. Ibrutinib in Combination with R-GemOx in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma of Nongerminal Center B-cell-like Type: Phase II Clinical Trial of the Spanish GELTAMO Group.
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Rey-Búa B, Grande C, Sánchez Blanco JJ, Abrisqueta P, Gutiérrez A, Ramírez Páyer Á, Giné E, Zeberio Etxetxipia I, Terol MJ, de la Cruz Vicente F, Andreu R, Ramirez MJ, de la Fuente A, Viguria MC, Peñarrubia MJ, Jiménez-Ubieto A, Montes-Moreno S, López-Guillermo A, Caballero MD, and Martín García-Sancho A
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- Humans, Male, Female, Aged, Middle Aged, Adult, Aged, 80 and over, Deoxycytidine analogs & derivatives, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Gemcitabine, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Drug Resistance, Neoplasm, Rituximab administration & dosage, Rituximab adverse effects, Oxaliplatin administration & dosage, Oxaliplatin adverse effects, Treatment Outcome, Spain epidemiology, Pyrimidines administration & dosage, Pyrimidines adverse effects, Pyrimidines therapeutic use, Adenine analogs & derivatives, Adenine administration & dosage, Piperidines administration & dosage, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects
- Abstract
Purpose: This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL)., Patients and Methods: The IBDCL trial (NCT02692248) included patients with histologic diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem-cell transplantation. Patients received an induction treatment consisting of six or eight cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate after four cycles., Results: Sixty-four patients were included, 72% of them refractory to the last regimen. The overall response rate and complete remission rate after the fourth cycle were 53% [95% confidence interval (CI), 41-65] and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance, and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year progression-free survival and overall survival were 18% (95% CI, 8-28) and 26% (95% CI, 14-37), respectively. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (44%), neutropenia (30%), and anemia (14%). Grade ≥3 infectious and cardiovascular treatment-related adverse events were reported in 6 (9%) and 1 (2%) patient, respectively., Conclusions: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL., (©2024 American Association for Cancer Research.)
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- 2024
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7. Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.
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Alcoceba M, Stewart JP, García-Álvarez M, Díaz LG, Jiménez C, Medina A, Chillón MC, Gazdova J, Blanco O, Díaz FJ, Peñarrubia MJ, Fernández S, Montes C, Cabero A, Caballero MD, García-Sanz R, González M, González D, Tamayo P, Gutiérrez NC, García-Sancho AM, and Sarasquete ME
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- Humans, Female, Male, Middle Aged, Aged, Adult, Liquid Biopsy methods, Aged, 80 and over, Positron Emission Tomography Computed Tomography, Rituximab therapeutic use, Rituximab administration & dosage, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Biomarkers, Tumor blood, Vincristine therapeutic use, Vincristine administration & dosage, Prognosis, Doxorubicin therapeutic use, Doxorubicin administration & dosage, High-Throughput Nucleotide Sequencing, Prednisone therapeutic use, Prednisone administration & dosage, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse blood, Lymphoma, Large B-Cell, Diffuse mortality, Lymphoma, Large B-Cell, Diffuse pathology, Neoplasm, Residual diagnosis, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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8. New therapies for relapsed or refractory aggressive B-cell lymphoma increase survival: Analysis from the RELINF registry of the GELTAMO group.
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Bastos-Oreiro M, Abrisqueta P, Gutierrez A, Jiménez Ubieto A, Poza M, Fernanez-Caldas P, LLacer MJ, Gonzalez de Villambrosia S, Córdoba R, López A, Ceballos E, Navarro B, Muntañola A, Donato E, Diez-Baeza E, Escoda L, Luzardo H, Peñarrubia MJ, García Belmonte D, Pardal E, Lozada C, and Martín García-Sancho A
- Abstract
Competing Interests: The authors declare no conflict of interest.
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- 2024
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9. Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis.
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Marín-Quílez A, Di Buduo CA, Díaz-Ajenjo L, Abbonante V, Vuelta E, Soprano PM, Miguel-García C, Santos-Mínguez S, Serramito-Gómez I, Ruiz-Sala P, Peñarrubia MJ, Pardal E, Hernández-Rivas JM, González-Porras JR, García-Tuñón I, Benito R, Rivera J, Balduini A, and Bastida JM
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- Humans, Blood Platelets metabolism, Galactose metabolism, Glycosylation, Integrin beta1 metabolism, Megakaryocytes metabolism, Thrombopoiesis genetics, Uridine Diphosphate metabolism, Thrombocytopenia genetics, Thrombocytopenia metabolism, UDPglucose 4-Epimerase genetics, UDPglucose 4-Epimerase metabolism
- Abstract
Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed 4 variants that affect GALE, 3 of those previously unreported (Pedigree A, p.Lys78ValfsX32 and p.Thr150Met; Pedigree B, p.Val128Met; and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease in N-acetyl-lactosamine (LacNAc), showing a hypoglycosylation pattern, reduced surface expression of gylcoprotein Ibα-IX-V (GPIbα-IX-V) complex and mature β1 integrin, and increased apoptosis. In vitro studies performed with patients-derived megakaryocytes showed normal ploidy and maturation but decreased proplatelet formation because of the impaired glycosylation of the GPIbα and β1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand factor were also shown. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasizes the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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10. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.
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Ribera JM, Morgades M, Ciudad J, Montesinos P, Esteve J, Genescà E, Barba P, Ribera J, García-Cadenas I, Moreno MJ, Martínez-Carballeira D, Torrent A, Martínez-Sánchez P, Monsalvo S, Gil C, Tormo M, Artola MT, Cervera M, González-Campos J, Rodríguez C, Bermúdez A, Novo A, Soria B, Coll R, Amigo ML, López-Martínez A, Fernández-Martín R, Serrano J, Mercadal S, Cladera A, Giménez-Conca A, Peñarrubia MJ, Abella E, Vall-Llovera F, Hernández-Rivas JM, Garcia-Guiñon A, Bergua JM, de Rueda B, Sánchez-Sánchez MJ, Serrano A, Calbacho M, Alonso N, Méndez-Sánchez JÁ, García-Boyero R, Olivares M, Barrena S, Zamora L, Granada I, Lhermitte L, Feliu E, and Orfao A
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- Adolescent, Adult, Consolidation Chemotherapy, Female, Hematopoietic Stem Cell Transplantation, Humans, Induction Chemotherapy, Maintenance Chemotherapy, Male, Middle Aged, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Prognosis, Transplantation, Homologous, Treatment Outcome, Young Adult, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812., (© 2021 by The American Society of Hematology.)
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- 2021
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11. R-COMP versus R-CHOP as first-line therapy for diffuse large B-cell lymphoma in patients ≥60 years: Results of a randomized phase 2 study from the Spanish GELTAMO group.
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Sancho JM, Fernández-Alvarez R, Gual-Capllonch F, González-García E, Grande C, Gutiérrez N, Peñarrubia MJ, Batlle-López A, González-Barca E, Guinea JM, Gimeno E, Peñalver FJ, Fuertes M, Bastos M, Hernández-Rivas JÁ, Moraleda JM, García O, Sorigué M, and Martin A
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- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Prednisone administration & dosage, Prospective Studies, Retrospective Studies, Rituximab administration & dosage, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy, Ventricular Function, Left drug effects
- Abstract
The use of non-pegylated liposomal doxorubicin (Myocet
® ) in diffuse large B-cell lymphoma (DLBCL) has been investigated in retrospective and single-arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R-CHOP or investigational R-COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVEF along follow-up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R-CHOP arm vs. 7% in R-COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R-CHOP compared with R-COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R-CHOP patients (nine episodes, four grade ≥3) and in four R-COMP patients (five episodes, all grade 1-2). No significant differences in efficacy were observed. In conclusion, R-COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R-CHOP. However, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)- Published
- 2021
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12. Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.
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García-Azorín D, Martínez-Pías E, Trigo J, Hernández-Pérez I, Valle-Peñacoba G, Talavera B, Simón-Campo P, de Lera M, Chavarría-Miranda A, López-Sanz C, Gutiérrez-Sánchez M, Martínez-Velasco E, Pedraza M, Sierra Á, Gómez-Vicente B, Guerrero Á, Ezpeleta D, Peñarrubia MJ, Gómez-Herreras JI, Bustamante-Munguira E, Abad-Molina C, Orduña-Domingo A, Ruiz-Martin G, Jiménez-Cuenca MI, Juarros S, Del Pozo-Vegas C, Dueñas-Gutierrez C, de Paula JMP, Cantón-Álvarez B, Vicente JM, and Arenillas JF
- Abstract
Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND., (Copyright © 2020 García-Azorín, Martínez-Pías, Trigo, Hernández-Pérez, Valle-Peñacoba, Talavera, Simón-Campo, de Lera, Chavarría-Miranda, López-Sanz, Gutiérrez-Sánchez, Martínez-Velasco, Pedraza, Sierra, Gómez-Vicente, Guerrero, Ezpeleta, Peñarrubia, Gómez-Herreras, Bustamante-Munguira, Abad-Molina, Orduña-Domingo, Ruiz-Martin, Jiménez-Cuenca, Juarros, del Pozo-Vegas, Dueñas-Gutierrez, de Paula, Cantón-Álvarez, Vicente and Arenillas.)
- Published
- 2020
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13. Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma.
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Alegre A, de la Rubia J, Sureda Balari A, Encinas Rodríguez C, Suárez A, Blanchard MJ, Bargay Lleonart J, Rodríguez-Otero P, Insunza A, Palomera L, Peñarrubia MJ, Ríos-Tamayo R, Casado Montero LF, González MS, Potamianou A, Couturier C, Pei H, Hevia H, Milionis I, Gaudig M, and Mateos MV
- Abstract
Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had ≥3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17) months, with a median number of 12 (range: 1-25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatment-emergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma. European Clinical Trials Database number: 2015-002993-19., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)
- Published
- 2020
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14. Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia.
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González-López TJ, Sánchez-González B, Jarque I, Bernat S, Fernández-Fuertes F, Caparrós I, Soto I, Fernández-Rodríguez A, Bolaños E, Pérez-Rus G, Pascual C, Hernández-Rivas JA, López-Ansoar E, Gómez-Nuñez M, Martínez-Robles V, Olivera P, Yera Cobo M, Peñarrubia MJ, Fernández-Miñano C, de Cabo E, Martínez Badas MP, Perdomo G, and García-Frade LJ
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- Age Factors, Aged, Aged, 80 and over, Benzoates administration & dosage, Benzoates adverse effects, Biomarkers, Combined Modality Therapy, Comorbidity, Drug Therapy, Combination, Female, Humans, Hydrazines administration & dosage, Hydrazines adverse effects, Male, Prognosis, Purpura, Thrombocytopenic, Idiopathic blood, Purpura, Thrombocytopenic, Idiopathic diagnosis, Pyrazoles administration & dosage, Pyrazoles adverse effects, Retrospective Studies, Treatment Outcome, Benzoates therapeutic use, Hydrazines therapeutic use, Purpura, Thrombocytopenic, Idiopathic drug therapy, Pyrazoles therapeutic use
- Abstract
Background: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65-year-old population., Methods: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated., Results: Median age of our cohort was 76 (interquartile range, IQR, 70-81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8-21) days. Median time on response was 320 (IQR, 147-526) days. Sixty-three adverse events (AEs), mainly grade 1-2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self-limited pulmonary embolisms in secondary ITP were the only thrombotic events observed., Conclusion: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD-ITP were poor. A relatively high number of deaths were observed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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15. Polymorphisms in Receptors Involved in Opsonic and Nonopsonic Phagocytosis, and Correlation with Risk of Infection in Oncohematology Patients.
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Herrero-Sánchez MC, Angomás EB, de Ramón C, Tellería JJ, Corchete LA, Alonso S, Ramos MDC, Peñarrubia MJ, Márquez S, Fernández N, García Frade LJ, and Sánchez Crespo M
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- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents therapeutic use, Aspergillosis immunology, Candidiasis immunology, Child, Child, Preschool, Female, Hematologic Neoplasms immunology, Humans, Male, Middle Aged, Opportunistic Infections microbiology, Opportunistic Infections virology, Polymorphism, Genetic, Retrospective Studies, Risk Factors, Young Adult, C-Reactive Protein genetics, Hematologic Neoplasms complications, Lectins, C-Type genetics, Opportunistic Infections immunology, Phagocytosis, Serum Amyloid P-Component genetics
- Abstract
High-risk hematological malignancies are a privileged setting for infection by opportunistic microbes, with invasive mycosis being one of the most serious complications. Recently, genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and nonopsonic clearance of microbes, pentraxin-3 (PTX3) and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered for a group of 198 patients with high-risk hematological malignancies. Polymorphisms for the pentraxin-3 gene ( PTX3 ) showed a significant association with the risk of fungal infection by Candida spp. and, especially, by Aspergillus spp. This link remained even for patients undergoing antifungal prophylaxis, thus demonstrating the clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did not show any definite correlation with the risk of invasive mycosis, nor did they influence the expression of Dectin-1 isoforms generated by alternative splicing. The PTX3 mRNA expression level was significantly lower in samples from healthy volunteers who showed these polymorphisms, although no differences were observed in the extents of induction elicited by bacterial lipopolysaccharide and heat-killed Candida albicans , thus suggesting that the expression of PTX3 at the start of infection may influence the clinical outcome. PTX3 mRNA expression can be a good biomarker to establish proper antifungal prophylaxis in immunodepressed patients., (Copyright © 2018 American Society for Microbiology.)
- Published
- 2018
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16. A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group.
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Pardal E, Díez Baeza E, Salas Q, García T, Sancho JM, Monzón E, Moraleda JM, Córdoba R, de la Cruz F, Queizán JA, Rodríguez MJ, Navarro B, Hernández JA, Díez R, Vahi M, Viguria MC, Canales M, Peñarrubia MJ, González-López TJ, Montes-Moreno S, González-Barca E, Caballero D, and Martín A
- Subjects
- Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Disease Management, Doxorubicin therapeutic use, Humans, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse mortality, Prednisone therapeutic use, Prognosis, Retrospective Studies, Rituximab, Spain, Survival Analysis, Vincristine therapeutic use, Lymphoma, Large B-Cell, Diffuse diagnosis
- Abstract
The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1-2) R-IPI, and treatment with R-CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R-CHOP-like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0-1 vs. 2-3 risk factors (age > 85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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17. Efficacy and safety of eltrombopag in persistent and newly diagnosed ITP in clinical practice.
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González-López TJ, Fernández-Fuertes F, Hernández-Rivas JA, Sánchez-González B, Martínez-Robles V, Alvarez-Román MT, Pérez-Rus G, Pascual C, Bernat S, Arrieta-Cerdán E, Aguilar C, Bárez A, Peñarrubia MJ, Olivera P, Fernández-Rodríguez A, de Cabo E, García-Frade LJ, and González-Porras JR
- Subjects
- Aged, Benzoates adverse effects, Chronic Disease, Follow-Up Studies, Humans, Hydrazines adverse effects, Middle Aged, Pyrazoles adverse effects, Benzoates administration & dosage, Hydrazines administration & dosage, Purpura, Thrombocytopenic, Idiopathic drug therapy, Pyrazoles administration & dosage
- Abstract
Eltrombopag is safe and effective in primary chronic ITP. However, lack of clinical trials avoids a clear demonstration of its utility in newly diagnosed and persistent ITP. Our aim here is to report Spanish results for this type of patients. We retrospectively evaluated 220 adult primary ITP patients. According to standard definition, patients were allocated to newly diagnosed (n = 30), persistent (n = 30), and chronic (n = 160) ITP. Groups were homogenous regarding most relevant parameters. 180 (90%) of 220 patients achieved a platelet response (R) with 167 (75.9%) complete responses (CR) after a 15-month follow-up. No statistical significant differences among groups but a trend towards a greater efficacy in newly diagnosed ITP were observed (93.3% of responses with 86.7% of CR). Efficacy in persistent ITP (83.3% of responses with 80.0% of CR) and chronic ITP (79.4% of responses with 73.1% of CR) was similar. 70 patients (31.8%) experienced adverse events. 15 of them were grade 3-4. Most common adverse effects were headache and hepatobiliary laboratory abnormalities (HBLAs). One persistent ITP had a venous thrombosis and one chronic ITP had grade II myelofibrosis. We consider Eltrombopag use for the early stage ITP as effective and safe as it is in chronic ITP.
- Published
- 2017
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18. The number of tumor infiltrating T-cell subsets in lymph nodes from patients with Hodgkin lymphoma is associated with the outcome after first line ABVD therapy<sup/>.
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Alonso-Álvarez S, Vidriales MB, Caballero MD, Blanco O, Puig N, Martin A, Peñarrubia MJ, Zato E, Galende J, Bárez A, Alcoceba M, Orfão A, González M, and García-Sanz R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Bleomycin adverse effects, Bleomycin therapeutic use, CD4-CD8 Ratio, Child, Dacarbazine adverse effects, Dacarbazine therapeutic use, Doxorubicin adverse effects, Doxorubicin therapeutic use, Female, Hodgkin Disease drug therapy, Hodgkin Disease pathology, Humans, Immunophenotyping, Kaplan-Meier Estimate, Lymph Nodes metabolism, Lymph Nodes pathology, Lymphocytes, Tumor-Infiltrating metabolism, Lymphocytes, Tumor-Infiltrating pathology, Male, Middle Aged, Neoplasm Staging, Phenotype, Prognosis, ROC Curve, T-Lymphocyte Subsets metabolism, T-Lymphocyte Subsets pathology, Treatment Outcome, Vinblastine adverse effects, Vinblastine therapeutic use, Young Adult, Hodgkin Disease immunology, Hodgkin Disease mortality, Lymph Nodes immunology, Lymphocyte Count, Lymphocytes, Tumor-Infiltrating immunology, T-Lymphocyte Subsets immunology
- Abstract
Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0.7%, and CD4
+ T-cell predominance. The amount of CD19+ B cells, and NK cells did not show association with disease features. However, high numbers of CD8+ and CD4+ cells were associated with better and poorer outcomes, respectively. Patients with ≥15% cytotoxic CD8+ cells among the total cell population had a longer 10-year freedom from treatment failure (FFTF) (93% vs. 73%, p=.04). In turn, cases with ≥75% of CD4+ infiltrating cells showed a significantly decreased FFTF (73% vs. 96%, p=.021). Consequently, CD4/CD8 ratio ≥5 associated with a poorer 10-year FFTF (69.5% vs. 94%, p=.02). This deleterious effect was particularly prominent in advanced disease (n = 58, p=.01). In multivariate analysis, a CD4/CD8 ratio ≥5 was the only independent variable to predict for treatment failure (HR = 4.5, 95% confidence interval, 1.2-16.8). In conclusion, our study shows that high CD4+ and low CD8+ T-cells infiltrates of tumor specimens associate with poor prognosis in HL patients, and CD4/CD8 ratio might be potentially useful for tailoring therapy.- Published
- 2017
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19. HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis.
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García-Álvarez M, Alcoceba M, López-Parra M, Puig N, Antón A, Balanzategui A, Prieto-Conde I, Jiménez C, Sarasquete ME, Chillón MC, Gutiérrez ML, Corral R, Alonso JM, Queizán JA, Vidán J, Pardal E, Peñarrubia MJ, Bastida JM, García-Sanz R, Marín L, and González M
- Subjects
- Adult, Aged, Aged, 80 and over, B-Lymphocytes pathology, Chromosomes, Human, Pair 6 genetics, Female, Humans, Lymphocyte Count, Lymphocytosis blood, Male, Middle Aged, Prognosis, Genes, Immunoglobulin Heavy Chain, Histocompatibility Antigens Class I genetics, Lymphocytosis genetics, Mutation
- Abstract
Introduction: Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL., Aims: We evaluated the role of HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) in hiMBL/CLL susceptibility, hiMBL progression to CLL, and treatment requirement in a large series of 263 patients diagnosed in our center with hiMBL (n = 156) or Binet A CLL (n = 107)., Results: No consistent association between HLA specificities and hiMBL or CLL susceptibility was found. With a median follow-up of 7.7 years, 48/156 hiMBLs (33%) evolved to asymptomatic CLLs, while 16 hiMBLs (10%) and 44 CLLs (41%) required treatment. No HLA specificities were found to be significantly associated with hiMBL progression or treatment in the whole cohort. However, within antigen-experienced immunoglobulin heavy-chain (IGHV)-mutated hiMBLs, which represents the highest proportion of hiMBL cases (81%), the presence of HLA-DQB1*03 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB1*02 specificity was associated with a lesser requirement for 15-year treatment (10% vs. 36%, P = 0.012)., Conclusion: In conclusion, our results suggest a role for HLA in IGHV-mutated hiMBL prognosis, and are consistent with the growing evidence of the influence of 6p21 on predisposition to CLL. Larger non-biased series are required to enable definitive conclusions to be drawn.
- Published
- 2017
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20. Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice.
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González-López TJ, Alvarez-Román MT, Pascual C, Sánchez-González B, Fernández-Fuentes F, Jarque I, Pérez-Rus G, Pérez-Crespo S, Bernat S, Hernández-Rivas JA, Andrade MM, Cortés M, Gómez-Nuñez M, Olivera P, Martínez-Robles V, Fernández-Rodríguez A, Fuertes-Palacio MA, Fernández-Miñano C, de Cabo E, Fisac R, Aguilar C, Bárez A, Peñarrubia MJ, García-Frade LJ, and González-Porras JR
- Subjects
- Aged, Benzoates administration & dosage, Benzoates adverse effects, Chronic Disease, Female, Humans, Hydrazines administration & dosage, Hydrazines adverse effects, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Purpura, Thrombocytopenic, Idiopathic diagnosis, Purpura, Thrombocytopenic, Idiopathic immunology, Pyrazoles administration & dosage, Pyrazoles adverse effects, Retreatment, Retrospective Studies, Spain, Treatment Outcome, Benzoates therapeutic use, Hydrazines therapeutic use, Purpura, Thrombocytopenic, Idiopathic drug therapy, Pyrazoles therapeutic use
- Abstract
Background: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting., Methods: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated., Results: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2., Conclusion: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
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21. Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months.
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Casado LF, García-Gutiérrez JV, Massagué I, Giraldo P, Pérez-Encinas M, de Paz R, Martínez-López J, Bautista G, Osorio S, Requena MJ, Palomera L, Peñarrubia MJ, Calle C, Hernández-Rivas JÁ, Burgaleta C, Maestro B, García-Ormeña N, and Steegmann JL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Drug Substitution, Female, Gene Expression Regulation, Neoplastic, Humans, Imatinib Mesylate administration & dosage, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Protein Kinase Inhibitors administration & dosage, Retreatment, Retrospective Studies, Time Factors, Transcription, Genetic, Treatment Failure, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl genetics, Genes, abl, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use
- Abstract
Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2015
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22. Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.
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González-López TJ, Pascual C, Álvarez-Román MT, Fernández-Fuertes F, Sánchez-González B, Caparrós I, Jarque I, Mingot-Castellano ME, Hernández-Rivas JA, Martín-Salces M, Solán L, Beneit P, Jiménez R, Bernat S, Andrade MM, Cortés M, Cortti MJ, Pérez-Crespo S, Gómez-Núñez M, Olivera PE, Pérez-Rus G, Martínez-Robles V, Alonso R, Fernández-Rodríguez A, Arratibel MC, Perera M, Fernández-Miñano C, Fuertes-Palacio MA, Vázquez-Paganini JA, Gutierrez-Jomarrón I, Valcarce I, de Cabo E, Sainz A, Fisac R, Aguilar C, Paz Martínez-Badas M, Peñarrubia MJ, Calbacho M, de Cos C, González-Silva M, Coria E, Alonso A, Casaus A, Luaña A, Galán P, Fernández-Canal C, Garcia-Frade J, and González-Porras JR
- Subjects
- Adult, Aged, Blood Platelets drug effects, Blood Platelets pathology, Chronic Disease, Drug Administration Schedule, Drug Monitoring, Female, Follow-Up Studies, Humans, Male, Middle Aged, Platelet Count, Purpura, Thrombocytopenic, Idiopathic pathology, Purpura, Thrombocytopenic, Idiopathic surgery, Receptors, Thrombopoietin agonists, Receptors, Thrombopoietin genetics, Receptors, Thrombopoietin metabolism, Recurrence, Remission Induction, Retrospective Studies, Splenectomy, Treatment Outcome, Benzoates administration & dosage, Erythropoiesis drug effects, Hematinics administration & dosage, Hydrazines administration & dosage, Purpura, Thrombocytopenic, Idiopathic drug therapy, Pyrazoles administration & dosage
- Abstract
Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2015
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23. Genomic analysis of clonal eosinophils by CGH arrays reveals new genetic regions involved in chronic eosinophilia.
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Arefi M, Robledo C, Peñarrubia MJ, García de Coca A, Cordero M, Hernández-Rivas JM, and García JL
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Chromosomes, Human, Pair 11 chemistry, Chromosomes, Human, Pair 19 chemistry, Chromosomes, Human, Pair 20 chemistry, Chromosomes, Human, Pair 8 chemistry, Chronic Disease, Clone Cells, Comparative Genomic Hybridization, Eosinophilia diagnosis, Eosinophilia pathology, Eosinophils pathology, Female, Fusion Proteins, bcr-abl genetics, Genomic Instability, Hematologic Neoplasms diagnosis, Hematologic Neoplasms pathology, Humans, Male, Middle Aged, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders pathology, Receptor, Platelet-Derived Growth Factor alpha genetics, Chromosome Aberrations, Eosinophilia genetics, Eosinophils metabolism, Genome, Hematologic Neoplasms genetics, Myeloproliferative Disorders genetics
- Abstract
To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization (aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph- (MPN-Ph-), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases. Genomic imbalances were found in 76% of all MPN patients. Losses on 20q were the most frequent genetic abnormality in MPNs (32%), affected the three types of MPN studied. This study also found losses at 11q13.3 in 26% of patients with MPN-Ph- and in 19p13.11 in two of the three patients with an MPN associated with a PDGFRA rearrangement. In addition, 29% of patients with CML had losses on 8q24. In summary, aCGH revealed clonality in eosinophils in most MPNs, suggesting that it could be a useful technique for defining clonality in these diseases. The presence of genetic losses in new regions could provide new insights into the knowledge of these MPN associated with eosinophilia., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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24. Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?
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García-Gutiérrez V, Puerta JM, Maestro B, Casado Montero LF, Muriel A, Molina Hurtado JR, Perez-Encinas M, Moreno Romero MV, Suñol PB, Sola Garcia R, De Paz R, Ramirez Sanchez MJ, Osorio S, Mata Vazquez MI, Martinez López J, Sastre JL, Portero Mde L, Bautista G, Duran Nieto MS, Giraldo P, Jimenez Jambrina M, Burgaleta C, Ruiz Aredondo J, Peñarrubia MJ, Requena MJ, Fernández Valle Mdel C, Calle C, Paz Coll A, Hernández-Rivas JÁ, Franco Osorio R, Cano P, Tallón Pérez D, Fernández de la Mata M, Garrido PL, and Steegmann JL
- Subjects
- Benzamides pharmacology, Clinical Trials, Phase III as Topic, Disease-Free Survival, Drug Resistance, Neoplasm, Fusion Proteins, bcr-abl antagonists & inhibitors, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Multicenter Studies as Topic, Piperazines pharmacology, Protein Kinase Inhibitors administration & dosage, Pyrimidines pharmacology, Randomized Controlled Trials as Topic, Survival Analysis, Treatment Outcome, Benzamides therapeutic use, Biomarkers, Tumor blood, Drug Substitution, Fusion Proteins, bcr-abl blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Watchful Waiting
- Abstract
In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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25. Incidence and clinical characteristics of myeloproliferative neoplasms displaying a PDGFRB rearrangement.
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Arefi M, García JL, Peñarrubia MJ, Queizán JA, Hermosín L, López-Corral L, Megido M, Giraldo P, de las Heras N, Vanegas RJ, Gutiérrez NC, and Hernández-Rivas JM
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Benzamides, Bone Marrow Neoplasms drug therapy, Female, Follow-Up Studies, Humans, Imatinib Mesylate, In Situ Hybridization, Fluorescence, Incidence, Male, Middle Aged, Myeloproliferative Disorders drug therapy, Piperazines administration & dosage, Piperazines therapeutic use, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors therapeutic use, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Treatment Outcome, Bone Marrow Neoplasms epidemiology, Bone Marrow Neoplasms genetics, Myeloproliferative Disorders epidemiology, Myeloproliferative Disorders genetics, Receptor, Platelet-Derived Growth Factor beta genetics, Translocation, Genetic
- Abstract
Objectives: The myeloproliferative neoplasms displaying a PDGFRB rearrangement are rare diseases derived from a haematopoietic stem cell. The goals of the study were to assess the incidence of these disorders and to define the clinical and biological characteristics as well as the response to the imatinib therapy., Methods: A total of 556 patients with myeloproliferative neoplasms were studied by means of molecular cytogenetics., Results: The incidence of myeloproliferative neoplasms (MPN) with PDGFRB rearrangement was low (10 cases, 1.8% of all MPN). Most of the patients showed moderate anaemia (median Hb was 10.0 gr/dL; range from 7.5 to 13 g/dL), leukocytosis (median white blood cells was 21.7 × 10(9) /L with a range from 4 to 43 × 10(9) /L) and eosinophilia (median circulating eosinophils was 2.4 × 10(9) /L with a range of 1.1-5.7 × 10(9) /L) with a median of bone marrow infiltration cells displaying PDGFRB rearrangement of 55% (range, 37-85%). In three cases, a t(5;12) was observed while two patients showed rearrangements of 17q21 region. In two cases, a del(5)(q31) was observed. Most of the patients responded to standard dosage of imatinib, and the response was maintained in the time in those patients with a follow-up higher than 9 years., Conclusions: The incidence of patients with PDGFRB rearrangement is low. These patients showed leukocytosis with eosinophilia and anaemia. The efficacy of imatinib therapy in patients showing PDGFRB rearrangement is high. For this reason, in all patients with MPN without any other molecular aberration, PDGFRB rearrangement should be ascertained., (© 2012 John Wiley & Sons A/S.)
- Published
- 2012
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26. Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic Acid and anthracycline-based chemotherapy.
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Montesinos P, González JD, González J, Rayón C, de Lisa E, Amigo ML, Ossenkoppele GJ, Peñarrubia MJ, Pérez-Encinas M, Bergua J, Debén G, Sayas MJ, de la Serna J, Ribera JM, Bueno J, Milone G, Rivas C, Brunet S, Löwenberg B, and Sanz M
- Subjects
- Adult, Aged, Anthracyclines administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Marrow Neoplasms epidemiology, Female, Humans, Incidence, Male, Middle Aged, Neoplasms, Second Primary epidemiology, Prognosis, Prospective Studies, Risk Factors, Treatment Outcome, Tretinoin administration & dosage, Anthracyclines adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow Neoplasms chemically induced, Leukemia, Promyelocytic, Acute drug therapy, Neoplasms, Second Primary chemically induced, Tretinoin adverse effects
- Abstract
Purpose: We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR)., Patients and Methods: From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy., Results: Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months., Conclusion: t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.
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- 2010
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27. Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients.
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Chillón MC, Santamaría C, García-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M, Marín L, Caballero MD, Vidriales MB, Ramos F, Bernal T, Díaz-Mediavilla J, García de Coca A, Peñarrubia MJ, Queizán JA, Giraldo P, San Miguel JF, and González M
- Subjects
- Adult, Biomarkers, Tumor genetics, Cohort Studies, Female, Follow-Up Studies, Humans, Leukemia, Promyelocytic, Acute metabolism, Male, Middle Aged, Point Mutation genetics, Risk Factors, Young Adult, Gene Expression Regulation, Neoplastic, Leukemia, Promyelocytic, Acute diagnosis, Leukemia, Promyelocytic, Acute genetics, Oncogene Proteins, Fusion antagonists & inhibitors, Oncogene Proteins, Fusion genetics, Tandem Repeat Sequences genetics, fms-Like Tyrosine Kinase 3 genetics
- Abstract
Background: Internal tandem duplications of the FLT3 gene (FLT3-ITDs) are frequent in patients with acute promyelocytic leukemia (APL), however its clinical impact remains controversial., Design and Methods: We analyzed the prognostic significance of FLT3-ITD mutant level and size, as well as FLT3-D835 point mutations, PML-RARalpha expression and other predictive factors in 129 APL patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86) PETHEMA trials., Results: FLT3-ITDs and D835 mutations were detected in 21% and 9% of patients, respectively. Patients with increased ITD mutant/wild-type ratio or longer ITD size displayed shorter 5-year relapse-free survival (RFS) (P=0.048 and P<0.0001, respectively). However, patients with D835 mutations did not show differences in RFS or overall survival (OS). Moreover, patients with initial normalized copy number (NCN) of PML-RARalpha transcripts less than the 25(th) percentile had adverse clinical features and shorter 5-year RFS (P<0.0001) and OS (P=0.004) compared to patients with higher NCN. Patients with low NCN showed increased incidence of ITDs (P=0.001), with higher ratios (P<0.0001) and/or longer sizes (P=0.007). Multivariate analysis showed that long FLT3-ITD (P=0.001), low PML-RARalpha levels (P=0.004) and elevated WBC counts (>10x10(9)/L) (P=0.018) were independent predictors for shorter RFS. We identified a subgroup of patients with high WBC, long FLT3-ITD and low NCN of transcripts that showed an extremely bad prognosis (5-year RFS 23.4%, P<0.0001)., Conclusions: In conclusion, FLT3-ITD size and PML-RARalpha transcript levels at diagnosis could contribute to improve the risk stratification in APL.
- Published
- 2010
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28. High FOXO3a expression is associated with a poorer prognosis in AML with normal cytogenetics.
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Santamaría CM, Chillón MC, García-Sanz R, Pérez C, Caballero MD, Ramos F, de Coca AG, Alonso JM, Giraldo P, Bernal T, Queizán JA, Rodriguez JN, Fernández-Abellán P, Bárez A, Peñarrubia MJ, Vidriales MB, Balanzategui A, Sarasquete ME, Alcoceba M, Díaz-Mediavilla J, San Miguel JF, and Gonzalez M
- Subjects
- Adolescent, Adult, Aged, Female, Forkhead Box Protein O3, Humans, Leukemia, Myeloid, Acute enzymology, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Phosphatidylinositol 3-Kinases metabolism, Prognosis, Proto-Oncogene Proteins c-akt metabolism, Survival Analysis, Young Adult, Forkhead Transcription Factors genetics, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute genetics
- Abstract
The PI3/AKT pathway is up-regulated in acute myeloid leukemia (AML), but its prognostic relevance in cytogenetically normal AML (CN-AML) is unclear. We evaluated RNA levels of AKT and two downstream substrates (FOXO3a-p27) in 110 de novo CN-AML, included in the Spanish PETHEMA therapeutic protocols. Patients with high FOXO3a gene expression displayed shorter OS (p=0.015) and RFS (p=0.048) than low FOXO3a expressers. Features selected in the multivariate analysis as having an independent prognostic value for a shorter survival were WBC>50x10(9)/L, age >65 years and high FOXO3a expression. We concluded that FOXO3a assessment could contribute to improve the molecular-based risk stratification in CN-AML.
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- 2009
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29. Influence of MBL-2 mutations in the infection risk of patients with follicular lymphoma treated with rituximab, fludarabine, and cyclophosphamide.
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Martínez-López J, Rivero A, Rapado I, Montalbán C, Paz-Carreira J, Canales M, Martínez R, Sánchez-Godoy P, Fernández de Sevilla A, Peñalver FJ, Gonzalez M, Prieto E, Salar A, Burgaleta C, Queizán JA, Peñarrubia MJ, Monteagudo MD, Cabrera C, De la Serna J, and Tomás JF
- Subjects
- Adult, Aged, Alleles, Anti-Infective Agents therapeutic use, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clinical Trials, Phase II as Topic statistics & numerical data, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Early Termination of Clinical Trials, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Haplotypes genetics, Humans, Infections etiology, Infections genetics, Lymphoma, Follicular drug therapy, Lymphoma, Follicular epidemiology, Lymphopenia chemically induced, Lymphopenia complications, Male, Middle Aged, Multicenter Studies as Topic, Neutropenia chemically induced, Neutropenia complications, Prospective Studies, Risk, Rituximab, Spain epidemiology, Vidarabine administration & dosage, Vidarabine adverse effects, Vidarabine analogs & derivatives, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Infections epidemiology, Lymphoma, Follicular genetics, Mannose-Binding Lectin genetics
- Abstract
The employment of current treatments based on chemotherapy and immunotherapy leads to inmunosuppression. The presence of mutations or polymorphisms in genes related to immune system might involve an additional disadvantage. The aim of the present study was to analyze mannose-binding lectin (MBL-2 gene) mutations and their association with severe infections and event-free survival in patients diagnosed with follicular lymphoma, treated uniformly, in the clinical trial LNHF-03. The results of this trial showed impressive clinical efficacy but was complicated with 80 documented infectious episodes. Patients were classified into two genotypic groups, AA and AO/OO, based on their haplotypic inheritance. Neither the number of infectious episodes nor differences in event-free survival was found as a function of MBL-2 groups. Other factors, including the lymphoma malignancy and the immune alterations associated with the disease, should be considered responsible for this observation.
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- 2009
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30. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia.
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Santamaría CM, Chillón MC, García-Sanz R, Pérez C, Caballero MD, Ramos F, de Coca AG, Alonso JM, Giraldo P, Bernal T, Queizán JA, Rodriguez JN, Fernández-Abellán P, Bárez A, Peñarrubia MJ, Balanzategui A, Vidriales MB, Sarasquete ME, Alcoceba M, Díaz-Mediavilla J, San Miguel JF, and Gonzalez M
- Subjects
- Adult, Aged, Antigens, Neoplasm genetics, Cytogenetic Analysis, DNA-Binding Proteins genetics, Disease-Free Survival, Female, Gene Expression, Genetic Markers, Humans, Leukemia, Myeloid, Acute mortality, MDS1 and EVI1 Complex Locus Protein, Male, Middle Aged, Mutation, Nucleophosmin, Prognosis, Proto-Oncogenes genetics, Risk Factors, Spain epidemiology, Survival Rate, Trans-Activators genetics, Transcription Factors genetics, Transcriptional Regulator ERG, Biomarkers, Tumor genetics, Leukemia, Myeloid, Acute genetics, Models, Genetic
- Abstract
We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM, and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo cytogenetically normal acute myeloblastic leukemias. In the multivariate analysis, high ERG or EVI1 and low PRAME expressions were associated with a shorter relapse-free survival (RFS) and overall survival (OS). A 0 to 3 score was given by assigning a value of 0 to favorable parameters (low ERG, low EVI1, and high PRAME) and 1 to adverse parameters. This model distinguished 4 subsets of patients with different OS (2-year OS of 79%, 65%, 46%, and 27%; P = .001) and RFS (2-year RFS of 92%, 65%, 49%, and 43%; P = .005). Furthermore, this score identified patients with different OS (P = .001) and RFS (P = .013), even within the FLT3/NPM1 intermediate-risk/high-risk subgroups. Here we propose a new molecular score for cytogenetically normal acute myeloblastic leukemias, which could improve patient risk-stratification.
- Published
- 2009
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31. Hematologic and cytogenetic response to lenalidomide in de novo acute myeloid leukemia with chromosome 5q deletion.
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Peñarrubia MJ, Silvestre LA, Conde J, Cantalapiedra A, and Garcia Frade LJ
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- Aged, Female, Humans, Lenalidomide, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute genetics, Thalidomide therapeutic use, Treatment Outcome, Antineoplastic Agents therapeutic use, Chromosome Deletion, Chromosomes, Human, Pair 5, Leukemia, Myeloid, Acute drug therapy, Thalidomide analogs & derivatives
- Published
- 2009
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32. The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia.
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Santamaría C, Chillón MC, García-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M, Ramos F, Bernal T, Queizán JA, Peñarrubia MJ, Giraldo P, San Miguel JF, and Gonzalez M
- Subjects
- Antigens, Neoplasm genetics, Biomarkers, Tumor analysis, Bone Marrow pathology, Case-Control Studies, Disease-Free Survival, Follow-Up Studies, Humans, Leukemia, Promyelocytic, Acute mortality, Leukemia, Promyelocytic, Acute pathology, Leukocyte Count, Polymerase Chain Reaction, Prognosis, Treatment Outcome, Antigens, Neoplasm analysis, Leukemia, Promyelocytic, Acute diagnosis
- Abstract
Background: The gene for preferentially expressed antigen of melanoma (PRAME) has been shown to be over-expressed in acute promyelocytic leukemia, but its actual incidence and clinical impact are still unknown., Design and Methods: We studied PRAME expression at diagnosis using real-time quantitative polymerase chain reaction in 125 patients with acute promyelocytic leukemia enrolled in the Spanish PETHEMA-96 (n=45) and PETHEMA-99 (n=80) clinical trials. In addition, PRAME expression was evaluated as a marker of disease activity in 225 follow-up samples from 67 patients with acute promyelocytic leukemia., Results: At diagnosis, PRAME expression in patients with acute promyelocytic leukemia was significantly higher (p<0.001) than in patients with non-M3 acute myeloid leukemia (n=213) and in healthy controls (n=10). Furthermore, patients with acute promyelocytic leukemia with high PRAME expression had a favorable outcome. Thus, the 5-year relapse-free survival was better in patients with >100-fold PRAME expression (86% vs. 74%; p=0.03), and this cut-off established two sub-groups with different relapse-free survival rates among patients with a white cell count <10(9)/L (5-year relapse-free survival 94% vs. 80%, p=0.01). This effect was similar in patients with a white cell count >10(9)/L, although differences were not statistically significant. In multivariate analysis, white cell count >10(9)/L (p<0.001), bone marrow blasts >90% (p=0.001), and PRAME expression <100-fold (p=0.009) were associated with short relapse-free survival. Samples at remission showed PRAME levels similar to those in normal controls while samples at relapse over-expressed PRAME again. Furthermore, 12/13 samples collected within the 6-month period preceding relapse showed a >10-fold increase in PRAME expression levels., Conclusions: Low PRAME expression defines a subgroup of patients with acute promyelocytic leukemia with a short relapse-free survival. This marker could be useful as a secondary marker for monitoring patients with acute promyelocytic leukemia.
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- 2008
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33. [Jejunal mucormycosis in a patient with Hodgkin's lymphoma].
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Madrigal B, Arenal JJ, Torres A, Peñarrubia MJ, Vara A, Ruiz M, Hernández A, and Enríquez P
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- Humans, Male, Middle Aged, Hodgkin Disease complications, Jejunal Diseases complications, Jejunal Diseases microbiology, Mucormycosis complications
- Abstract
We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.
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- 2008
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34. Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients.
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Carreras E, Rosiñol L, Terol MJ, Alegre A, de Arriba F, García-Laraña J, Bello JL, García R, León A, Martínez R, Peñarrubia MJ, Poderós C, Ribas P, Ribera JM, San Miguel J, Bladé J, and Lahuerta JJ
- Subjects
- Adult, Aged, Busulfan administration & dosage, Dose-Response Relationship, Drug, Female, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease prevention & control, Humans, Male, Melphalan adverse effects, Middle Aged, Myeloablative Agonists adverse effects, Peripheral Blood Stem Cell Transplantation adverse effects, Spain, Transplantation Conditioning methods, Transplantation, Autologous adverse effects, Busulfan adverse effects, Hepatic Veno-Occlusive Disease chemically induced, Melphalan administration & dosage, Multiple Myeloma therapy, Myeloablative Agonists administration & dosage, Transplantation Conditioning adverse effects
- Abstract
Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with the first procedure. After 2 years of the trial, a number of episodes resembling classical VOD but with a late onset were recognized. Consequently, the protocol was modified, and Bu/MEL was replaced by melphalan 200 mg/m(2) (MEL-200). Three years later, after a total of 734 patients had undergone first autologous SCT, the incidence and characteristics of VOD episodes were analyzed in the whole series. Nineteen cases of VOD (8%) were observed among the first 240 patients receiving Bu/MEL, whereas only 2 (0.4%) were observed among the 494 patients treated with MEL-200 (P < .0001). VOD manifestations in the Bu/MEL group appeared at a median of 29 days (range, 3-57 days) after ASCT. Mortality directly attributable to VOD was 2% in the Bu/MEL group and 0.2% in the MEL-200 group (P = .026). This high incidence of severe VOD probably had a multifactorial origin (busulfan followed by melphalan and previous use of BCNU). This observation should be kept in mind when designing future trials for the treatment of MM.
- Published
- 2007
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35. Is intracranial pressure monitoring in the epidural space reliable? Fact and fiction.
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Poca MA, Sahuquillo J, Topczewski T, Peñarrubia MJ, and Muns A
- Subjects
- Aged, Aged, 80 and over, Electrodes, Implanted, Female, Humans, Lumbosacral Region, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Epidural Space physiopathology, Intracranial Hypertension physiopathology, Intracranial Pressure physiology, Monitoring, Physiologic methods, Subarachnoid Space physiopathology, Subdural Space physiopathology
- Abstract
Object: Epidural pressures have been reported as being systematically higher than ventricular fluid pressures. These discrepancies have been attributed both to the characteristics of the sensor and to the particular anatomy of the epidural space. To determine which of these two possible causes better explains higher epidural readings, the authors compared pressure values obtained during simultaneous epidural and lumbar pressure monitoring in 53 patients and during simultaneous subdural and lumbar pressure monitoring in 22 patients. The same nonfluid coupled sensor device was used in all compartments., Methods: All 75 patients had normal craniospinal communication. Simultaneous intracranial and lumbar readings were performed every 30 seconds. The epidural-lumbar and subdural-lumbar pressure values were compared using correlation analysis and the Bland-Altman method. The median differences in initial epidural-lumbar and subdural-lumbar pressure values were 11 mm Hg (interquartile range 2-24 mm Hg) and 0 mm Hg (interquartile range -2 to 1 mm Hg), respectively. The correlation coefficients of the mean epidural-lumbar and subdural-lumbar intracranial pressure (ICP) values were p = 0.48 (p < 0.001) and p = 0.88 (p < 0.001), respectively. Using the Bland-Altman analysis, epidural-lumbar methods showed a mean difference of -20.93 mm Hg; epidural pressure values were systematically higher than lumbar values, and these discrepancies were greater with higher ICP values. Subdural-lumbar methods showed a mean difference of 0.35 mm Hg and both were equally valid with all mean ICP values., Conclusions: Epidural ICP monitoring produces artifactually high values. These values are not related to the type of sensor used but to the specific characteristics of the epidural intracranial space.
- Published
- 2007
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36. Oral anticoagulant treatment: risk factors involved in 500 intracranial hemorrhages.
- Author
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Cantalapiedra A, Gutierrez O, Tortosa JI, Yañez M, Dueñas M, Fernandez Fontecha E, Peñarrubia MJ, and García-Frade LJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Hemorrhage mortality, Female, Humans, International Normalized Ratio, Male, Middle Aged, Retrospective Studies, Risk Factors, Spain epidemiology, Cerebral Hemorrhage chemically induced, Platelet Aggregation Inhibitors adverse effects
- Abstract
Intracranial bleeding is the most severe complication caused by anticoagulant or antiplatelet treatment. The increasing use of this therapy, especially in older people, makes the balance between clinical benefit and bleeding risk an important consideration. A retrospective study of all consecutive 500 intracranial hemorrhages in the West Valladolid area, approximately 220,000 people, during the period 1998 to 2004, was performed. In relation to mortality, predisposing conditions were included, such as age, antithrombotic treatment, arterial hypertension, cancer, blood diseases, vascular malformations, and traumatisms. The incidence of intracranial hemorrhage was 310 per 100,000 per year with a mortality of 30%. Higher mortality was found in antiplatelet-treated patients (44.9%) than in anticoagulated patients (31.1%). This may be related to a different mean age of 78 vs. 71 years. Arterial hypertension was the most frequent risk factor (45.1% in nontreated patients, 60% anticoagulated, and 75.5% antiplatelet). The relative risk of intracranial bleeding in anticoagulated patients was 11.2 (p < 0.001) with an incidence of 0.03% and a median of 14 months since treatment began. The median INR was 3.3. In 40% of the patients the previous five controls were in range. Strict consideration of indications criteria joined to a better control of risk factors may avoid intracranial bleeding episodes.
- Published
- 2006
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37. [Primary biliary cirrhosis, "sicca" síndrome and autoimmune hemolytic anemia].
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Cantalapiedra A, Peñarrubia MJ, Gutiérrez O, García-Pajares F, Núñez H, García-Frade J, and Caro-Patón A
- Subjects
- Female, Humans, Middle Aged, Anemia, Hemolytic, Autoimmune etiology, Liver Cirrhosis, Biliary complications, Liver Cirrhosis, Biliary diagnosis, Sjogren's Syndrome etiology
- Published
- 2005
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38. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction.
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Fernández-Avilés F, San Román JA, García-Frade J, Fernández ME, Peñarrubia MJ, de la Fuente L, Gómez-Bueno M, Cantalapiedra A, Fernández J, Gutierrez O, Sánchez PL, Hernández C, Sanz R, García-Sancho J, and Sánchez A
- Subjects
- Aged, Animals, Cardiac Catheterization, Cell Differentiation, Cold Temperature adverse effects, Combined Modality Therapy, Connexin 43 biosynthesis, Connexin 43 genetics, Coronary Restenosis prevention & control, Echocardiography, Stress, Female, Fibrinolytic Agents therapeutic use, Gene Expression Regulation, Heart physiology, Humans, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred BALB C, Middle Aged, Myocardial Infarction drug therapy, Myocardial Infarction pathology, Myocardial Reperfusion, Myocytes, Cardiac cytology, Organ Culture Techniques, Regeneration, Stents, Stroke Volume, Tenecteplase, Thrombolytic Therapy, Tissue Plasminogen Activator therapeutic use, Transplantation, Autologous, Bone Marrow Cells physiology, Myocardial Infarction therapy, Stem Cell Transplantation, Ventricular Remodeling physiology
- Abstract
Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability "in vitro" and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78+/-41x10(6) per patient) were intracoronarily transplanted 13.5+/-5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11+/-5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.
- Published
- 2004
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39. [Intracoronary stem cell transplantation in acute myocardial infarction].
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Avilés FF, San Román JA, García Frade J, Valdés M, Sánchez A, de la Fuente L, Peñarrubia MJ, Fernández ME, Tejedor P, Durán JM, Hernández C, Sanz R, and García Sancho J
- Subjects
- Aged, Coronary Vessels physiopathology, Feasibility Studies, Humans, Male, Myocardial Infarction diagnostic imaging, Myocardial Infarction physiopathology, Radiography, Treatment Outcome, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left physiopathology, Ventricular Function, Left physiology, Ventricular Remodeling physiology, Myocardial Infarction therapy, Stem Cell Transplantation methods, Ventricular Dysfunction, Left therapy
- Abstract
Introduction and Objectives: Experimental and clinical studies suggest that necrotic myocardium may have the capacity to regenerate. We have started a clinical study to demonstrate that the intracoronary implantation of stem cells is feasible and safe. The results in our first 5 patients are presented here., Patients and Method: We included patients with anterior acute myocardial infarction and isolated stenosis of the left anterior descending artery that was successfully repaired by primary or facilitated angioplasty. Patients received an intracoronary infusion of bone marrow-derived cells 10-15 days after the infarction. The follow-up protocol included low-dose dobutamine echocardiography, magnetic resonance studies and ECG Holter monitoring., Results: The procedure was carried out with no complications. No patient had a cardiac event during the first 6 months. One patient had a transient ischemic attack without sequelae. No arrhythmias were found. Left ventricular end-diastolic volume remained the same at 6 months (159+/-25 ml, 157+/-16 ml), left ventricular end-systolic volume decreased (77+/-22 ml, 65+/-16 ml), and the ejection fraction increased (53+/-7%, 58+/-8%) although no statistically significant differences were found. In the 3 patients in whom dobutamine echocardiography ruled out viability, we found a significant reduction in both volumes., Conclusions: Intracoronary bone marrow-derived cell transplantation after an acute myocardial infarction seems to be safe and feasible, and might lead to favorable remodeling.
- Published
- 2004
40. A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses.
- Author
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Peñarrubia MJ, Odriozola J, González C, Massagué I, Miguel A, González San Miguel JD, Pérez Encinas M, Lavilla E, Giraldo MP, Casado LF, Ferrer S, and Steegmann JL
- Subjects
- Adult, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents economics, Disease Progression, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Interferon-alpha adverse effects, Interferon-alpha economics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukocyte Count, Male, Middle Aged, Survival Analysis, Cytogenetic Analysis, Interferon-alpha administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
- Abstract
Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.
- Published
- 2003
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41. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study.
- Author
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Oriol A, Ribera JM, Esteve J, Sanz MA, Brunet S, Garcia-Boyero R, Fernández-Abellán P, Martí JM, Abella E, Sánchez-Delgado M, Peñarrubia MJ, Besalduch J, Moreno MJ, Borrego D, Feliu E, and Ortega JJ
- Subjects
- Adolescent, Adult, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols toxicity, Burkitt Lymphoma mortality, Female, Humans, Male, Middle Aged, Prognosis, Remission Induction, Survival Analysis, Treatment Outcome, Burkitt Lymphoma complications, Burkitt Lymphoma drug therapy, HIV Infections mortality
- Abstract
Background and Objectives: Short, intensive multiagent chemotherapy has resulted in significant progress in Burkitt's lymphoma and leukemia. A protocol was designed to treat all adult patients with mature B-cell lymphoma or leukemia with the aims of comparing the response to therapy and survival with regards to their HIV infection status., Design and Methods: Fifty-three adult patients with advanced stage Burkitt's lymphoma or Burkitt's leukemia were treated. Response to therapy, survival and toxicity were evaluated according to their HIV infection status., Results: The median age of the patients was 53 years (range 15-74). There were no differences in CR rates between HIV-negative (77%) and HIV-positive patients (71%). Only age > 60 years was associated with a lower CR rate (OR 0.18, 95%CI 0.04-0.81, p=0.026). The 2-year overall survival (OS) probability was 51% (95%CI, 38%-64%) for the 53 patients. The OS of HIV-negative and HIV-positive patients did not significantly differ. Only age > 60 years was associated with a shorter OS (OR 5.1, 95%CI 2.0-12.7, p=0.001). The 2-year disease free survival (DFS) for the 40 patients achieving CR was 60% (95%CI, 45%-75%). Age > 60 years was the only identified factor associated with a shorter DFS (OR 5.2, 95%CI 1.4-20, p=0.015)., Interpretation and Conclusions: This study confirms the effectiveness of intensive strategies in adult patients with advanced stage Burkitt's lymphoma or leukemia. It also shows the feasibility of these strategies in individuals with HIV infection with comparable results. Advanced age proved to be the main adverse prognostic factor for response to therapy and survival.
- Published
- 2003
42. Emphysematous gastritis and severe aplastic anemia.
- Author
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Gutierrez O, Cantalapiedra A, Tabuyo MI, Del Villar R, Peñarrubia MJ, Sales R, and García-Frade LJ
- Subjects
- Anemia, Aplastic drug therapy, Antilymphocyte Serum therapeutic use, Cholelithiasis complications, Cyclosporine therapeutic use, Emphysema diagnostic imaging, Female, Gastritis diagnostic imaging, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Immunosuppressive Agents therapeutic use, Meropenem, Methylprednisolone therapeutic use, Metronidazole therapeutic use, Middle Aged, T-Lymphocytes, Thienamycins therapeutic use, Tomography, X-Ray Computed, Anemia, Aplastic complications, Emphysema complications, Gastritis complications
- Abstract
Emphysematous gastritis is a life-threatening disease. It is characterized by the presence of gas within the wall of the stomach. The etiology includes firstly infections with gas-forming organisms; other predisposing causes are the ingestion of corrosive substances and alcohol abuse. Diagnosis is based on radiological techniques, mainly computed tomographic scan (CT). The election treatment is antibiotics and surgery. The evolution is generally fatal. We present the first known case reported, which is associated with aplastic anemia with immunosuppressive therapy, its evolution with medical treatment and a literature review.
- Published
- 2003
- Full Text
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43. Are myeloma patients with renal failure candidates for autologous stem cell transplantation?
- Author
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San Miguel JF, Lahuerta JJ, García-Sanz R, Alegre A, Bladé J, Martinez R, García-Laraña J, De La Rubia J, Sureda A, Vidal MJ, Escudero A, Pérez-Esquiza E, Conde E, García-Ruiz JC, Cabrera R, Caballero D, Moraleda JM, Leon A, Besalduch J, Hernandez MT, Rifon J, Hernandez F, Solano C, Palomera L, Parody R, Gonzalez JD, Mataix R, Maldonado J, Constela J, Carrera D, Bello JL, De Pablos JM, Pérez-Simón JA, Torres JP, Olanguren J, Prieto E, Acebede G, Peñarrubia MJ, Torres P, Díez-Martín JL, Rivas A, Sánchez JM, and Díaz-Mediavilla J
- Subjects
- Adult, Aged, Antineoplastic Agents, Alkylating therapeutic use, Female, Hematopoietic Stem Cell Mobilization, Humans, Immunoglobulin Heavy Chains blood, Immunoglobulin Light Chains blood, Male, Melphalan therapeutic use, Middle Aged, Multiple Myeloma blood, Multiple Myeloma complications, Multiple Myeloma immunology, Neoplasm Staging, Registries, Retrospective Studies, Spain, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation mortality, Kidney Failure, Chronic complications, Multiple Myeloma therapy
- Abstract
Introduction: Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival., Materials and Methods: From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function., Results and Conclusion: Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).
- Published
- 2000
- Full Text
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44. [Treatment with lymphoblastoid alpha interferon in patients with chronic myeloid leukemia refractory to recombinant interferon alpha 2].
- Author
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Steegmann JL, Granados E, Vázquez L, de la Cámara R, Peñarrubia MJ, Fernández-Contreras E, Quiroga JA, and Fernández Rañada JM
- Subjects
- Adult, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Recombinant Proteins, Antineoplastic Agents therapeutic use, Interferon Type I therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
The results of the treatment with lymphoblastoid alpha interferon (IFN-alpha N1) in 10 patients with chronic myeloid leukaemia who had poor response to previous recombinant alpha interferon (rIFN-alpha) are presented. Eight of these patients had not developed anti-alpha 2 interferon antibodies, and 2 had non-neutralising anti-IFN antibodies. Three of the 10 patients received benefit from IFN-alpha N1 treatment. Two of them, with no response to rIFN alpha 2, attained complete haematologic response wit IFN-alpha N1. Cytogenetic responses although minimal, were achieved as well. The third patient, after receiving rIFN-alpha for 3 years with no response, had partial cytogenetic response after 4 months of treatment with IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN alpha 2 without anti-IFn alpha 2 neutralising antibodies may be useful in a minority of patients, although the frequency of cytogenetic responses is low.
- Published
- 1998
45. Interferon-alpha lymphoblastoid in chronic myeloid leukemia patients unresponsive to recombinant IFN alpha 2.
- Author
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Steegmann JL, Granados E, and Peñarrubia MJ
- Subjects
- Humans, Recombinant Proteins, Retrospective Studies, Treatment Outcome, Antineoplastic Agents therapeutic use, Interferon Type I therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Published
- 1997
46. Magnetic resonance imaging features of chloroma of the shoulder.
- Author
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Gómez N, Ocón E, Friera A, Peñarrubia MJ, and Acevedo A
- Subjects
- Aged, Biopsy, Bone Neoplasms complications, Female, Humans, Immunohistochemistry, Leukemia, Myeloid complications, Thrombocytosis complications, Thrombocytosis diagnosis, Bone Neoplasms diagnosis, Leukemia, Myeloid diagnosis, Magnetic Resonance Imaging, Shoulder Joint pathology
- Abstract
A patient with a history of essential thrombocytosis presented with diffuse skeletal pain and restricted motion of the left shoulder. Magnetic resonance imaging (MRI) of the left glenohumeral joint showed a soft tissue mass that displaced the rotator cuff. Biopsy of the mass revealed chloroma. MRI is the method that best characterizes this lesion.
- Published
- 1997
- Full Text
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47. Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-alpha).
- Author
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Steegmann JL, Requena MJ, Casado LF, Pico M, Peñarrubia MJ, Ferro MT, Resino M, and Fernandez-Rañada JM
- Subjects
- Bone Marrow Examination, Cell Division, Follow-Up Studies, Humans, Interferon alpha-2, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Neoplasm, Residual, RNA, Messenger genetics, Recombinant Proteins, Remission Induction, Sensitivity and Specificity, Blotting, Southern, DNA, Neoplasm analysis, Fusion Proteins, bcr-abl genetics, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Karyotyping, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Philadelphia Chromosome
- Abstract
Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.
- Published
- 1996
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48. [Imipenem combined with teicoplanin or vancomycin in the initial empirical treatment of febrile neutropenia. Analysis of the primary response and of a global sequential strategy in 126 episodes].
- Author
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Figuera A, Tomás JF, Hernández L, Jiménez ML, Peñarrubia MJ, del Rey MC, Arranz R, Cámara R, López-Lorenzo JL, and Fernández-Rañada JM
- Subjects
- Adolescent, Adult, Aged, Female, Fever microbiology, Humans, Infections complications, Male, Middle Aged, Neutropenia microbiology, Prospective Studies, Anti-Bacterial Agents administration & dosage, Drug Therapy, Combination administration & dosage, Imipenem administration & dosage, Infections drug therapy, Neutropenia drug therapy, Teicoplanin administration & dosage, Thienamycins administration & dosage, Vancomycin administration & dosage
- Abstract
The results of empiric antibiotic therapy in 126 episodes of febrile neutropenia in patients with hematologic neoplasms postchemotherapy and bone marrow transplantation are presented. The main objective of this work was the study of the initial control of infection comparing two glycopeptidic antibiotics: vancomycin and teicoplanin combined with imipenem in first line of empiric therapy. The secondary objective was to analyze the overall control of infection during the complete episode of neutropenia using a sequential empiric antibiotic therapy course which included the addition of amikacin followed by intravenous amphotericin B when fever persisted or recurred without microbiological documentation. Both initial courses (no guidelines), imipenem + vancomycin (arm A) and imipenem + teicoplanin (arm B) resulted in a similar percentage of response at 72 hours, both in episodes of fever of unknown origin (FUO) (55% and 68%, respectively; p = NS) and in those microbiologically documented (54% and 34.5%, p = NS); 58% and 79% of these episodes, respectively, were caused by gram-positive organisms. About 60% of patients in both arm ultimately required the empiric addition of amikacin, with or without amphotericin B, because of persistence or recurrence of fever; the percentage of overall responses in both arm did not differ significantly, both in FUO (70% and 86%, p = NS) and in microbiologically documented episodes (71% and 45%, p = NS). The overall infectious mortality for the whole group was 1.58%. In conclusion, no significant differences were observed in the clinical response or in toxicity between the combination of imipenem with any of the two glycopeptides: vancomycin or teicoplanin, for the initial empiric therapy of febrile neutropenia. The sequential empiric use of amikacin followed by amphotericin B assured an adequate overall control of infection in a group of patients with prolonged severe neutropenia.
- Published
- 1996
49. [Allogeneic bone marrow transplantation in chronic myeloid leukemia. The clinical results and risk factors in 70 patients].
- Author
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Tomás JF, Peñarrubia MJ, García JA, Figuera A, Gómez-García de Soria V, Steegmann JL, Arranz R, Cámara R, Gabriel R, and Vázquez L
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Prognosis, Recurrence, Remission Induction, Risk Factors, Spain epidemiology, Transplantation, Homologous, Treatment Outcome, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Bone Marrow Transplantation statistics & numerical data, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Background: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed., Methods: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk., Results: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%)., Conclusions: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.
- Published
- 1995
50. Hypertriglyceridemia may be severe in CML patients treated with interferon-alpha.
- Author
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Peñarrubia MJ, Steegmann JL, Lavilla E, Casado F, Requena MJ, Picó M, Arranz R, and Fernández-Rañada JM
- Subjects
- Adolescent, Adult, Apolipoprotein A-I metabolism, Apolipoproteins B blood, Cholesterol, HDL blood, Humans, Interferon alpha-2, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Middle Aged, Recombinant Proteins, Hypertriglyceridemia etiology, Interferon-alpha adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
We analyzed serum triglyceride (TG) levels in 22 chronic myeloid leukemia (CML) patients treated with interferon-alpha (IFN-alpha). Hypertriglyceridemia was present in one-half of patients at diagnosis, and IFN-alpha treatment was associated with a further increase in 90% of the total group of patients. This increase was maximal during the first months of therapy. Four patients (18%) reached levels higher than 1,000 mg/dl. This is the first report describing this secondary effect in CML patients treated with IFN-alpha.
- Published
- 1995
- Full Text
- View/download PDF
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