Martinez-Lopez J.,Hospital Universitario 12 Of Octubre |
Lahuerta J.J.,Hospital Universitario 12 Of Octubre |
Pepin F.,Sequenta |
Gonzalez M.,Hospital Universitario Of Salamanca Ibsal |
And 20 more authors.
Blood | Year: 2014
We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma(MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allelespecific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD- by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P <.0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD1.When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10-3 27 months, MRD 10-3 to 10-5 48 months, and MRD <10 -5 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD1. In complete response patients, the TTP remained significantly longer for MRD- compared with MRD+ patients (131 vs 35 months; P 5 .0009). © 2014 by The American Society of Hematology.
San Roman J.A.,Institute Ciencias Del Corazon |
Sanchez P.L.,Hospital Universitario Of Salamanca Ibsal |
Sanchez P.L.,Hospital General Universitario Gregorio Maranon |
Villa A.,Hospital General Universitario Gregorio Maranon |
And 14 more authors.
Journal of the American College of Cardiology | Year: 2015
Background Stem cell-based therapy has emerged as a potential therapy in acute myocardial infarction (AMI). Although various approaches have been studied, intracoronary injection of bone marrow autologous mononuclear cells (BMMC) and the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize endogenous cells have attracted the most attention. Objectives This study compares, for the first time, the efficacy of BMMC injection, G-CSF mobilization, and the combination of both with standard treatment. Methods On Day 1 after primary percutaneous coronary intervention, 120 patients were randomized to a 1) intracoronary BMMC injection; 2) mobilization with G-CSF; 3) both (BMMC injection plus G-CSF); or 4) conventional treatment (control group). G-CSF, 10 μg/kg/day subcutaneously, was started Day 1 and maintained for 5 days. BMMC injection was performed on Days 3 to 5. Our primary endpoint was absolute change in 12-month left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV) relative to baseline measured by cardiac magnetic resonance. Results The mean change in LVEF between baseline and follow-up for all patients was 4 ± 6% (p = 0.006). Change in LVEF and LVESV over time did not differ significantly among the 4 groups. Patients actively treated with any stem cell approach showed similar changes in LVEF and LVESV versus control subjects, with a small but significant reduction in infarct area (p = 0.038). Conclusions In our study, 3 different bone marrow-derived stem cell approaches in AMI did not result in improvement of LVEF or volumes compared with standard AMI care (Trial of Hematopoietic Stem Cells in Acute Myocardial Infarction [TECAM]; NCT00984178) © 2015 American College of Cardiology Foundation.
Mateos M.-V.,Hospital Universitario Of Salamanca Ibsal |
Ocio E.M.,Hospital Universitario Of Salamanca Ibsal |
Paiva B.,University of Navarra |
Rosinol L.,Hospital Clinic I Provincial Of Barcelona |
And 5 more authors.
Blood Reviews | Year: 2015
Multiple myeloma is the second most frequent haematological disease. The introduction of high-dose melphalan followed by autologous haematopoietic cell transplant (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want to definitively cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response, while ensuring quality of life. The treatment should be individualized on the basis of host and disease features and better monitoring of the response upon use of high-sensitivity techniques for evaluating residual disease.For young patients, HDT/ASCT is a standard of care for treatment and its efficacy has been enhanced and challenged by the new drugs. For elderly patients, treatment options were limited to alkylators, but new upfront treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) combined or not with alkylators have significantly improved outcomes.Extended treatment for young and elderly patients improves the quality and duration of clinical responses; however, the optimal scheme, appropriate doses and duration of long-term therapy have not yet been fully determined.This review summarises the progress in the treatment of patients with newly diagnosed multiple myeloma, addressing critical questions such as the optimal induction, early versus late ASCT, consolidation and/or maintenance for young patients, and how we can choose the best option for non-transplant-eligible patients. © 2015 Elsevier Ltd.
PubMed | Hospital Clinic Of Barcelona, Hospital General Universitario Of Elche, Hospital Universitario 12 Of Octubre, Hospital Universitario Marques Of Valdecilla and 17 more.
Type: | Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico | Year: 2016
To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology.A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement.Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival.High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.
PubMed | Hospital Universitario Madrid Sanchinarro, Complejo Asistencial Universitario Of Leon, Hospital Clinico Universitario, Hospital Clinico San Carlos and 6 more.
Type: Journal Article | Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico | Year: 2016
Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.
PubMed | Hospital Universitario La Paz, Hospital Universitario Of Salamanca Ibsal, Lhospitalet Of Llobregat, Hospital del Mar and Hospital Universitario Marques Of Valdecilla
Type: Clinical Trial, Phase I | Journal: British journal of haematology | Year: 2016
Diffuse large B-cell lymphoma (DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15mg) given on days 1-14 of every 21-day cycle, in combination with R-ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10mg/d was identified as the MTD because, in the 15mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15mg cohorts, respectively) were evaluable. All toxicities occurring during LR-ESHAP cycles resolved appropriately and no grade 4-5 non-haematological toxicities were observed. The complete remission and overall response rates were 474% and 789%, respectively. With a median follow-up of 246 (174-382) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR-ESHAP regimen is feasible and yields encouraging outcomes.
Hurchla M.A.,University of Washington |
Garcia-Gomez A.,University of Salamanca |
Garcia-Gomez A.,Centro En Red Of Medicina Regenerativa Y Terapia Celular Of Castilla Y Leo N |
Garcia-Gomez A.,Hospital Universitario Of Salamanca Ibsal |
And 19 more authors.
Leukemia | Year: 2013
Proteasome inhibitors (PIs), namely bortezomib, have become a cornerstone therapy for multiple myeloma (MM), potently reducing tumor burden and inhibiting pathologic bone destruction. In clinical trials, carfilzomib, a next generation epoxyketone-based irreversible PI, has exhibited potent anti-myeloma efficacy and decreased side effects compared with bortezomib. Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. Interactions between myeloma cells and the bone marrow (BM) microenvironment augment the number and activity of bone-resorbing osteoclasts (OCs) while inhibiting bone-forming osteoblasts (OBs), resulting in increased tumor growth and osteolytic lesions. At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Finally, in mouse models of disseminated MM, the epoxyketone-based PIs decreased murine 5TGM1 and human RPMI-8226 tumor burden and prevented bone loss. These data demonstrate that, in addition to anti-myeloma properties, carfilzomib and oprozomib effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM. © 2013 Macmillan Publishers Limited All rights reserved.
PubMed | IIS Fundacion Jimenez Diaz, Hospital General Universitario Gregorio Maranon, Hospital Universitario Of Salamanca Ibsal, Hospital Virgen Of La Salud and 2 more.
Type: | Journal: International journal of cardiology | Year: 2016
The most common valve diseases are calcific aortic stenosis (AS) and aortic regurgitation (AR). The former is characterized by thickening of valve leaflets followed by progressive calcification, which produces progressive aortic valve (AV) narrowing, increased pressure afterload on the left ventricle (LV) and subsequent LV hypertrophy. On the other hand, AR is due to malcoaptation of the valve leaflets with resultant diastolic reflux of blood from aorta back to the LV producing volume and pressure overload and progressive LV dilatation. In order to isolate the molecular mechanisms taking place during AS, we have used an integrated -omic approach to compare plasma samples from AS and from AR patients used as controls. The final purpose of this work is to find molecular changes in response to the calcification of the AV, diminishing the effects of the AV dysfunction.Using two-dimensional difference gel electrophoresis (2D-DIGE) and gas chromatography coupled to mass spectrometry (GC-MS) in a cohort of 6 subjects, we have found differences in 24 protein spots and 19 metabolites, respectively. Among them, 7 proteins and 3 metabolites have been verificated by orthogonal techniques (SRM or turbidimetry): fibrinogen beta and gamma chain, vitronectin, apolipoprotein C-II, antithrombin III, haptoglobin, succinic acid, pyroglutamic acid and alanine. Classification according to their main function showed alterations related to coagulation, inflammation, oxidative stress, response to ischemia and lipid metabolism, defining 4 different molecular panels that characterize AS with high specificity and sensitivity.These results may facilitate management of these patients by making faster diagnostics of the disease and better understand these pathways for regulating its progression.