José Rodríguez

Hospital Universitari Son Espases, Palma, Balearic Islands, Spain

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Publications (29)129.56 Total impact

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    ABSTRACT: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2(+) patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2(-) patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2(+) and COX-2(-) patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 12/2014; · 4.59 Impact Factor
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    ABSTRACT: PURPOSE: Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated nuclear factor κB (NF-κB) activity has been associated with several lymphoproliferative diseases, but its importance in T cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase, NIK, in this pathway and its role as a potential molecular target in T cell lymphomas. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T cell lymphoma cell lines and observed its effect on downstream targets and cell viability. RESULTS: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than IKK knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and a reduced expression of several prosurvival and antiapoptotic factors. CONCLUSIONS: The results of the present study indicate that NIK could be promising therapeutic target in these aggressive malignancies.
    Clinical Cancer Research 03/2013; · 7.84 Impact Factor
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    ABSTRACT: Cyclooxygenase 2 (COX-2) is an inflammatory enzyme involved in the pathogenesis and prognosis of several malignancies. In the present study, we investigated the prognostic value of COX-2 expression in a large (N = 242), uniformly treated Hodgkin lymphoma (HL) population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analysis was done, including comparing the most recognized clinical variables: the early- and advanced-stage subgroups. COX-2 was expressed on Reed-Sternberg cells in 37% of patients. There were no differences in the distribution of clinical variables according to COX-2 expression. With a median follow-up time of 58 months, PFS at 5 years was 60% and 79% for COX-2(+) and COX-2(-) patients, respectively (P = .003). The overall survival was 73% and 91%, respectively (P < .001). The major impact on prognosis was observed in the early AA stage (I-II) group. In fact, in these low-risk groups the expression of COX-2 defined a group with significantly worse progression-free and overall survival. In conclusion, COX-2 was expressed on Reed-Sternberg cells in one-third of HL patients and was a major independent, unfavorable prognostic factor in early-stage HL. We conclude that COX-2 may be a major prognostic variable in HL and a potential therapeutic target.
    Blood 04/2012; 119(25):6072-9. · 9.78 Impact Factor
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    ABSTRACT: Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib. Dose-response and cellular growth assays indicate that erlotinib reduces cell proliferation in all tested cell lines without inducing cytotoxic effects. Flow cytometric analyses confirm that EGFR inhibition does not induce apoptosis in glioma cells, leading to cell cycle arrest in G(1). Interestingly, erlotinib also prevents spontaneous multicellular tumour spheroid growth in U87MG cells and cooperates with sub-optimal doses of temozolomide (TMZ) to reduce multicellular tumour spheroid growth. This cooperation appears to be schedule-dependent, since pre-treatment with erlotinib protects against TMZ-induced cytotoxicity whereas concomitant treatment results in a cooperative effect. Cell cycle arrest in erlotinib-treated cells is associated with an inhibition of ERK and Akt signaling, resulting in cyclin D1 downregulation, an increase in p27(kip1) levels and pRB hypophosphorylation. Interestingly, EGFR inhibition also perturbs Rho GTPase signaling and cellular morphology, leading to Rho/ROCK-dependent formation of actin stress fibres and the inhibition of glioma cell motility and invasion.
    PLoS ONE 01/2012; 7(6):e38770. · 3.53 Impact Factor
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    ABSTRACT: The International Prognostic Score (IPS) is the most widely used system to date for identifying risk groups for the outcome of patients with advanced Hodgkin lymphoma, although important limitations have been recognized. We analyzed the value of the IPS in a series of 311 patients with advanced classical Hodgkin lymphoma (cHL) (Ann Arbor stage III, IV or stage II with B symptoms and/or bulky masses) treated with first-line chemotherapy including adriamycin (adriamycin, bleomycin, vinblastine, dacarbazine [ABVD] or equivalent variants). In univariate and multivariate analyses, stage IV disease and age ≥ 45 years were the only factors with independent predictive significance for overall survival (OS) (p = 0.002 and p < 0.001, respectively). Stage IV was still significant for freedom from progression (FFP) (p = 0.001) and age ≥ 45 years was borderline significant (p = 0.058). IPS separates prognostic groups, as in the original publication, but this is mainly due to the high statistical significance of stage IV and age ≥ 45 years. Moreover, the combination of these two factors enables a simpler system to be constructed that separates groups with different FFP and OS. In conclusion, in our series, stage IV and age ≥ 45 years are the key prognostic factors for the outcome of advanced cHL.
    Leukemia & lymphoma 12/2011; 53(5):812-9. · 2.61 Impact Factor
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    ABSTRACT: The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of haematopoietic cell fate that controls proliferation and apoptosis, among other processes. Despite the central role of FOXO3 as a tumour suppressor and phosphatidylinositol 3-kinase (PI3K)/AKT effector, little is known about its involvement in mantle cell lymphoma (MCL) biology. This study investigated the expression and activity of FOXO3 in MCL cell lines and in primary cultures. We analysed the expression of key FOXO regulators and targets, and studied the effect of modulators of FOXO function on cell viability and apoptosis. FOXO3 was constitutively inactivated in MCL cell lines, and showed cytoplasmic localization in patient-derived cells. PI3K and AKT, but not mammalian target of rapamycin (mTOR), inhibitors induced FOXO3 nuclear translocation and activation in correlation with their impact on MCL proliferation and survival. Moreover, FOXO3-defective cells were resistant to PI3K/AKT inhibitors. Reactivation of FOXO function with a nuclear export inhibitor had a profound effect on cell viability, consistent with FOXO3 nuclear accumulation. Interestingly, inhibition of FOXO3 nuclear export enhanced the effect of doxorubicin. Taken together, our results confirm that FOXO3 is a relevant regulator of proliferation and apoptosis in MCL, and suggest that reactivation of FOXO3 function might be a useful therapeutic strategy in MCL patients.
    British Journal of Haematology 11/2011; 156(3):334-45. · 4.94 Impact Factor
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    ABSTRACT: Mantle cell lymphoma has been considered an incurable disease with current chemotherapy regimens. Recent intense chemoimmunotherapy induction regimens with or without consolidation with autologous stem cell transplantation procedures are showing a potential for cure in a sizable fraction of patients. Similarly, in the salvage setting, preliminary experience with non-myeloablative allogeneic transplant may cure some patients even after multiple therapeutic failures. However, the recent knowledge of the three basic biologic derangements that are integrated in the disease may change the therapeutic approach of the disease in the near future. In fact, new drugs that target more specifically the major molecular alterations of the disease are being progressively incorporated into the therapeutic armamentarium of the disease. In the near future, more individualized approaches that will take into account not only risk factors present at diagnosis but also biomarkers representative of the molecular alterations present in the disease are foreseen. In this review, we are going to discuss the current therapeutic approaches and the main new drugs that target more specifically the major molecular pathways alterations of the disease.
    European Journal Of Haematology 11/2010; 85(5):371-86. · 2.55 Impact Factor
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    ABSTRACT: Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease. Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022). This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).
    Blood 08/2010; 116(8):e12-7. · 9.78 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphomas (DLBCLs) are the most common type of non-Hodgkin lymphomas. With chemotherapy and progenitor stem cell transplantation, about 60% of patients with DLBCL are long-term survivors. The International Prognostic Index identifies patients with different outcomes. However, biologic characteristics also may help to discriminate different treatments groups. DNA copy number changes identified by array comparative genomic hybridization (array-CGH) were studied in 40 patients who had DLBCL with a poor prognosis and who were treated uniformly with dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and intensification before high-dose chemotherapy with autologous stem cell transplantation. In total, 722 copy number changes were observed (median, 5 copy number changes per patient; range, 0-75 copy number changes per patient), with a predominance of gains. Gains on 2p16 were present only in patients who failed to achieve a complete response after escalated CHOP therapy (P < .05). In univariate analysis, gains on 2p16 and losses on 17p13 (the tumor protein p53 gene TP53 gene) were associated with a poor response to the therapy. Furthermore, age >60 years and losses on 10q23.31 (the phosphatase and tensin homolog gene PTEN) or on 17p13 were associated with short survival. In multivariate analysis, only advanced age and losses on 10q23.31 retained an adverse prognostic impact. Array-CGH identified multiple regions with common copy number changes, some of which were associated with outcome in patients with DLBCL.
    Cancer 06/2009; 115(16):3728-37. · 5.20 Impact Factor
  • Antonio Gutiérrez, Jose Rodríguez
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    ABSTRACT: Peripheral T-cell lymphoma constitutes a heterogeneous group, with a low incidence and no standard frontline therapy. The current study evaluates the use of frontline autologous stem cell transplantation in 83 peripheral T-cell lymphomas included in the first and largest prospective trial. Results indicate that the procedure is feasible, with a low treatment-related mortality, and is associated with a better outcome than obtained with conventional chemotherapy. A general problem in this and other prospective trials is that approximately 30% of cases do not receive transplantation owing to disease progression. Thus, new approaches aimed at increasing the number of chemosensitive patients should be found, some of which are discussed in this article. For chemoresistant or relapsing patients, promising results have been reported using allogeneic stem cell transplantation or adding new agents.
    Expert Review of Hematology 06/2009; 2(3):255-60. · 2.38 Impact Factor
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    ABSTRACT: The aim of the project was to identify biological variables in high-clinical-risk patients with diffuse large B-cell lymphoma (DLBCL), treated with risk-adapted therapies. The study was performed in a series of high-clinical-risk patients with DLBCL treated with MegaCHOP or MegaCHOP + IFE followed by autologous stem-cell transplantation (ASCT). An initial reduced set of diagnostic tumoral samples was studied by gene expression profiling and gene-set-enrichment analysis. A set of potential biomarkers extracted from this study was then explored in tissue microarrays containing paraffin-diagnostic tissue from 50 patients. The statistical analysis identified 17 immunohistochemical markers associated with the clinical endpoints. A subsequent multivariate analysis identified FoxP3+ T-reg cells as an independent predictor of failure-free survival. Bcl6 expression, CG/ABC subclasses and IPI were found not to predict survival in this series. The increased presence of regulatory T-cells as a marker of adverse outcome highlights specific components of the tumoral microenvironment in the pathogenesis and treatment response prediction for high-clinical-risk patients with DLBCL.
    Leukemia & lymphoma 05/2009; 50(4):571-81. · 2.61 Impact Factor
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    ABSTRACT: Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols. The hallmark genetic alteration of MCL is the t(11;14)(q13;32) chromosomal translocation that leads to the overexpression of cyclin D1. Recently, new molecular alterations of major importance in the pathogenic mechanisms of this disease have been discovered, and have revealed the biological heterogeneity of MCL. The first section of our review discusses our current understanding of the molecular biology of this entity according to recent information from comparative genomic hybridization (CGH) and expression profiling studies, which are leading to the identification of several druggable targets. In the second section we revise new therapeutic strategies based on new drug families that target key molecular pathways of major relevance in this malignancy. We analyze emerging agents that are already producing significant results in different models of human cancers, including MCL. Based on the current knowledge and recent studies, we suggest that the encouraging results described here should provide a rationale platform for the design of new treatments that may overcome the resistance of this aggressive lymphoma to conventional therapy and improve patient prognosis.
    Blood reviews 05/2009; 23(5):205-16. · 7.19 Impact Factor
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    ABSTRACT: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.
    PLoS ONE 01/2009; 4(12):e8173. · 3.53 Impact Factor
  • José Rodríguez, Antonio Gutiérrez, Miguel Piris
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    ABSTRACT: Primary mediastinal B-cell lymphoma (PMBCL) is a recognised subtype of diffuse large B-cell lymphoma according to the WHO classification that represents approximately 5% of aggressive lymphomas, and 2% of all cases of lymphomas. It presents with unique clinical, morphologic and immunophenotypic characteristics that define the disease. Retrospective studies have found that PMBCL patients have excellent survival rates with a distinct plateau and a trend to better outcome if treated with dose-intensified chemotherapy with MACOPB or VACOPB. In spite of the multiple molecular data known, generated on the pathogenesis of this tumour, treatment is still essentially based on a combination of chemo and immunotherapy. We take this opportunity for reviewing the recent biologic data provided by gene expression profiling of the tumour, for discussing new potential therapeutic targets.
    Leukemia & lymphoma 05/2008; 49(6):1050-61. · 2.61 Impact Factor
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    ABSTRACT: The role of high-dose therapy and autologous stem-cell transplantation (HDT/ASCT) in the up-front treatment of poor-risk aggressive lymphoma is still unknown. We conducted a prospective multi-centre trial with dose-escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT according to early response assessed by CT and gallium scan (Ga67S). Eighty-six patients with newly diagnosed and Ga-67 avid aggressive B-cell lymphoma received MegaCHOP for three courses and were evaluated for response by CT and Ga67S. Patients with CT response and negative Ga67S received another MegaCHOP cycle followed by BEAM and ASCT. Those patients with positive Ga67S or without CT response received salvage treatment with two courses of ifosfamide and etoposide (IFE) followed, whenever response had been achieved, by BEAM and ASCT. Response rate before HDT/ASCT was 85% and, with 34 months of median follow-up, progression-free survival (PFS), overall survival (OS) and treatment-related mortality were 56%, 64% and 7%, respectively. For transplanted patients (81% of the whole series), PFS and OS were 67% and 74%, respectively. No different outcomes were observed between patients achieving an early negative Ga67S response treated with MegaCHOP and BEAM/ASCT and patients with mid-treatment positive Ga67S who received IFE prior BEAM/ASCT. This response-adapted strategy including early treatment modifications prior HDT/ASCT have yielded encouraging PFS and OS in patients with poor-risk B aggressive non-Hodgkin's lymphoma.
    European Journal Of Haematology 04/2008; 80(3):227-35. · 2.55 Impact Factor
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    ABSTRACT: Given the excellent results obtained with present new induction regimens in PMBL, the role of frontline ASCT is controversial. We present 71 patients with PMBL receiving induction chemotherapy, followed by ASCT as frontline therapy from the GEL-TAMO registry. Most patients presented with high-risk clinical features. At transplant, 49% of patients were in CR, 32% in PR and 18% failed induction therapy; 53% received radiotherapy. After the transplant 75% of patients achieved CR. With a median follow-up of 52.5 months, the OS, PFS and DFS at 4 years from diagnosis were, respectively, 84%, 81% and 81% for the first CR patients and 49%, 42% and 82% for the induction failure (PR and refractory) patients. Disease progression was the main cause of death (79%). By multivariate survival analysis the tumour score, refractory disease at transplant and radiotherapy were independent variables associated with OS and PFS. Our experience, with a prolonged follow-up, shows that patients with PMBL presenting at diagnosis with high-risk features or PR response to induction therapy have an encouraging survival with frontline ASCT. However, patients who received the transplant after failing the induction regimen have a very poor prognosis and should be tested with other innovative approaches. Finally, only a randomized trial could prove the value of ASCT as frontline therapy and also must be considered that addition to Rituximab to induction treatments could make ASCT unnecessary.
    Hematological Oncology 04/2008; 26(3):171-8. · 2.04 Impact Factor
  • Jose Rodriguez, Antonio Gutierrez
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    ABSTRACT: Rituximab is a mouse/human chimeric IgG1kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B-lymphocytes. The mechanisms of action of rituximab involve complement-dependent cytotoxicity (CDC), complement-dependent cellular cytotoxicity (CDCC), antibody dependent cellular cytotoxicity (ADCC) and induction of apoptosis. Pharmacokinetic issues, tumor and molecular related factors mediate resistance to rituximab. Optimizing rituximab treatment requires a therapeutic project that might ideally be individualized and that includes enhancing of ADCC and CDC mechanisms, acting over apoptosis-regulating proteins and using synergistic conventional chemotherapeutic agents. Pharmacokinetic favourable schedules in specific diseases alone or associated to chemotherapeutic agents are not well known, therefore studies focusing on these issues are warranted. New information regarding targeting the lymphoma microenvironment and rituximab effects is the focus of current research.
    Reviews on Recent Clinical Trials 02/2008; 3(1):22-30.
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    ABSTRACT: The prognosis of old or immunocompromised patients with refractory or relapsing diffuse large-cell lymphoma (DLCL) is very poor as the current standard of salvage therapy with autologous stem cell transplantation (ASCT) is not feasible for most of them. New active regimens with an acceptable toxicity profile are needed. We aim to report the results of a phase II trial of the GEMOX-R regimen in DLCL. A total of 32 patients received GEMOX-R regimen in 2-wk intervals if feasible or every 3 wk for a planned six to eight courses. Median age of the population was 69 yr. Forty-one percent of the patients were primary refractory and 59% after relapsing. At GEMOX-R, 75% of patients had a stage III-IV and an adjusted International Prognostic Index > 1 was observed in 69%. The response rate was 43% with 34% complete response. Neutropenia and thrombopenia grade III-IV were observed in 43% of the patients and neurotoxicity grade III-IV in 7% of cases. Median follow-up for alive patients was 13 months and the median survival was 9.1 months. At 12 months, the overall survival and progression-free survival were 41% and 29%, respectively. GEMOX-R is a new salvage regimen for DLCL with high activity and relatively safe toxicity profile, which can be offered to elderly patients not candidates of ASCT consolidation. The high efficacy of the regimen in this unfavorable population and also in immunocompromised situations warrant further investigation of this regimen in all salvage situations of this type of lymphomas.
    European Journal Of Haematology 02/2008; 80(2):127-32. · 2.55 Impact Factor
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    ABSTRACT: Mantle cell lymphoma constitutes one of the lymphomas with poorest prognosis at relapse with limited effective salvage regimens due to advanced age. We present results of a new salvage regimen, rituximab, gemcitabine and oxaliplatin (GEMOX-R), in 14 patients with relapsing (n = 9) or refractory (n = 5) mantle cell lymphoma. The median number of cycles was 5.5 for a total of 72 cycles evaluated in the current study. The median age was 69.5 years with high-risk features. Patients received a mean number of prior treatment lines of 1.79. Sixty-four percent achieved CR (total response rate of 85%). With a median follow-up of 11 months, OS and PFS were 58% and 45% at 12 months. The major toxicity was thrombopenia grade III-IV (35%). Factors related with overall survival were ECOG performance status and a-IPI at GEMOX-R. We conclude that GEMOX-R displays an outstanding efficacy with an excellent toxicity profile in a pretreated elderly population.
    Leukemia and Lymphoma 12/2007; 48(11):2172-8. · 2.61 Impact Factor
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    ABSTRACT: Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis. Materials and We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray. We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68(+) cells. Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.
    Journal of Clinical Oncology 09/2007; 25(22):3321-9. · 18.04 Impact Factor

Publication Stats

387 Citations
129.56 Total Impact Points

Institutions

  • 2012
    • Hospital Universitari Son Espases
      Palma, Balearic Islands, Spain
  • 2011
    • IGTP Health Sciences Research Institute of the Germans Trias i Pujol Foundation
      Badalona, Catalonia, Spain
  • 2010
    • Hospital Universitario Severo Ochoa
      Madrid, Madrid, Spain
  • 2009
    • University of the Balearic Islands
      • Department of Biology
      Palma, Balearic Islands, Spain
  • 2008–2009
    • Hospital General Universitario Gregorio Marañón
      • Department of Medical Oncology
      Madrid, Madrid, Spain
    • University Hospital Vall d'Hebron
      Barcino, Catalonia, Spain
  • 2003–2009
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain
    • University of Valencia
      Valenza, Valencia, Spain