http://hdl.handle.net/10171/17106 2013-05-18T16:30:52Z http://hdl.handle.net/10171/23495 Title: TAK1 mRNA Expression in the Tumor Tissue of Locally Advanced Head and Neck Cancer Patients Author(s) : Honorato, B. (Beatriz); Alcalde, J. (Juan); Martinez-Monge, R. (Rafael); Garcia-Foncillas, J. (Jesús); Zabalegui, N. (Natalia) Abstract: Resistance to radio and chemotherapy is one of the major drawbacks in the progression of head and neck squamous cell cancer (HNSCC) patients, evidencing the importance of finding optimum molecular prognosis markers to develop personalized treatment schedules. TGF-β effector TAK1 activity has been related to a greater aggressiveness in several types of cancer (Kondo et al. 1998; Edlund et al. 2003; Kaur et al. 2005) and, although there has been described no significant implication of TAK1 in HNSCC development, we have further examined the role of its mRNA expression as a marker of prognosis in HNSCC. Fifty-nine advanced HNSCC patients were recruited for the study. The tumor expression of TAK1 mRNA was analyzed with RT-PCR using Taqman technology and its relationship with the clinical outcome of the patients studied. TAK1 mRNA expression was lower in patients that relapsed than in those that did not, but the difference was only significant between the patients that showed response to treatment (p < 0.001). ROC curve analyses pointed a 0.5 expression ratio TAK1/B2M value as an optimum cut-off point for relapse and response. Our data suggest the TAK1 mRNA analysis by Taqman RT-PCR can predict the risk of relapse in HNSCC patients. 2007-12-31T23:00:00Z http://hdl.handle.net/10171/22732 Title: Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy Author(s) : Zarate, R. (Ruth); Arias, F. (F.); Bandres, E. (E.); Cubedo, E. (Elena); Malumbres, R. (Raquel); Garcia-Foncillas, J. (Jesús) Abstract: AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys /Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients. 2005-12-31T23:00:00Z http://hdl.handle.net/10171/21674 Title: Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes Author(s) : Sarobe, P. (Pablo); Huarte, E. (Eduardo); Lasarte, J.J. (Juan José); Lopez-Diaz-de-Cerio, A. (Ascensión); García, N. (Nicolás); Borras-Cuesta, F. (Francisco); Prieto, J. (Jesús) Abstract: BACKGROUND/AIMS: Identification of epitopes recognized by cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) proteins is of importance because they can be used for vaccination, treatment of infection or monitoring of immune responses. Our purpose was to characterize new CTL epitopes in HCV structural proteins. METHODS: Peptides were synthesized and tested in HLA-A2 binding assays. Binder peptides were used to stimulate peripheral blood mononuclear cells from HCV+ patients and controls, and activity measured in chromium release and ELISPOT assays. RESULTS: Twenty binder peptides were found, and stimulation of HCV+ patient cells with nine peptides showing high binding ability led to the growth of CD8+ CTL recognizing peptide E2(614-622) in association with HLA-A2. Peptide E2(614-622) was recognized by 30% of HLA-A2+ patients with chronic HCV infection, but no responses were observed in control groups. Five peptides derived from region E2(614-622) from 26 different viral isolates bound to HLA-A2 molecules, and all of them but one, containing Phe at position 622, were recognized by E2(614-622) specific CTL. CONCLUSIONS: These results show that peptide E2(614-622) belongs to a highly conserved region of HCV E2, and might be a good candidate to induce anti-HCV CTL responses in HLA-A2+ subjects. 2000-12-31T23:00:00Z http://hdl.handle.net/10171/21650 Title: T(h)1 but not T(h)0 cell help is efficient to induce cytotoxic T lymphocytes by immunization with short synthetic peptides Author(s) : Lopez-Diaz-de-Cerio, A. (Ascensión); Casares, N. (Noelia); Lasarte, J.J. (Juan José); Sarobe, P. (Pablo); Perez-Mediavilla, L.A. (Luis Alberto); Ruiz, M. (Marta); Prieto, J. (Jesús); Borras-Cuesta, F. (Francisco) Abstract: Immunization of BALB/c mice with peptide HVSGHRMAWDMMMNWA, encompassing residues 121-135 from hepatitis C virus E1 protein, induced CD4(+) T(h)1 cells as well as a long-lasting CD8(+) cytotoxic T lymphocyte (CTL) response in vivo when the peptide was administered s.c. with or without incomplete Freund's adjuvant. Using truncated peptides from this sequence it was shown that the determinant recognized by cytotoxic T cells was encompassed by residues SGHRMAWDM. Deletion of residues from the N-terminus or the C-terminus of the wild-type peptide abrogated its helper character. When Val122 of the wild peptide was replaced by Ala, the ability to induce a cytotoxic response was lost concomitantly with the loss of the T(h)1 pattern of cytokine production. Interestingly, the Ala-modified peptide, when co-immunized with a peptide encompassing residues 323-329 from ovalbumin (OVA), which is able to induce a T(h)1 response in BALB/c mice, restored the capacity of the modified peptide to induce CTL. However, co-immunization of the Ala-modified peptide with a peptide encompassing residues 106-118 from sperm whale myoglobin, which induces a T(h)0 cytokine profile in BALB/c mice, was much less efficient than the OVA peptide to restore CTL induction. These results demonstrate that CTL induction with a short synthetic peptide requires that this peptide contains domains recognized by T(c) cells as well as by T(h)1 cells. For those peptides that do not contain this type of T(h) domain, competent T cell help can be provided by co-immunization with a distinct peptide that is able to stimulate a T(h)1 response. 1998-12-31T23:00:00Z http://hdl.handle.net/10171/21489 Title: Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide Author(s) : Lasarte, J.J. (Juan José); Corrales, F.J. (Fernando José); Casares, N. (Noelia); Lopez-Diaz-de-Cerio, A. (Ascensión); Qian, C. (Cheng); Xie, X. (Xiaoming); Borras-Cuesta, F. (Francisco); Prieto, J. (Jesús) Abstract: Joint immunization with two recombinant adenoviruses, one expressing hepatitis C virus (HCV) core and E1 proteins and another expressing IL-12 (RAdIL-12), strongly potentiates cellular immune response against HCV Ags in BALB/c mice when RAdIL-12 was used at doses of 1 x 105-1 x 107 plaque-forming units. However, cellular immunity against HCV Ags was abolished when higher doses (1 x 108 plaque-forming units) of RAdIL-12 were used. This immunosuppressive effect was associated with marked elevation of IFN-gamma and nitric oxide in the serum and increased cell apoptosis in the spleen. Administration of N-nitro-L -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, to mice that received high doses of RAdIL-12 was lethal, whereas no apparent systemic toxicity by L -NAME was observed in those immunized with lower doses of the adenovirus. Interestingly, in mice immunized with recombinant adenovirus expressing core and E1 proteins of HCV in combination with RAdIL-12 at low doses (1 x 107 plaque-forming units), L -NAME inhibited T cell proliferation and CTL activity in response to HCV Ags and also production of Abs against adenoviral proteins. In conclusion, gene transfer of IL-12 can increase or abolish cell immunity against an Ag depending of the dose of the vector expressing the cytokine. IL-12 stimulates the synthesis of NO which is needed for the immunostimulating effects of IL-12, but apoptosis of T cells and immunosuppression ensues when IFN-gamma and NO are generated at very high concentrations. 1998-12-31T23:00:00Z http://hdl.handle.net/10171/20620 Title: Abnormal priming of CD4(+) T cells by dendritic cells expressing hepatitis C virus core and E1 proteins Author(s) : Sarobe, P. (Pablo); Lasarte, J.J. (Juan José); Casares, N. (Noelia); Lopez-Diaz-de-Cerio, A. (Ascensión); Baixeras, E. (Elena); Labarga, P. (Pablo); García, N. (Nicolás); Borras-Cuesta, F. (Francisco); Prieto, J. (Jesús) Abstract: Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4(+) T cells responding to HCV core in patients with chronic HCV infection. However, CD4(+) response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens. 2001-12-31T23:00:00Z http://hdl.handle.net/10171/20615 Title: Vaccination with an adenoviral vector encoding hepatitis C virus (HCV) NS3 protein protects against infection with HCV-recombinant vaccinia virus Author(s) : Arribillaga, L. (Laura); Lopez-Diaz-de-Cerio, A. (Ascensión); Sarobe, P. (Pablo); Casares, N. (Noelia); Gorraiz, M. (Marta); Vales, A. (África); Bruña-Romero, O. (Oscar); Borras-Cuesta, F. (Francisco); Paranhos-Baccala, G. (Glaucia); Prieto, J. (Jesús); Ruiz, J. (Juan); Lasarte, J.J. (Juan José) Abstract: Cellular immune response plays an important role in the clearance of hepatitis C virus (HCV). Thus, development of efficient ways to induce anti-viral cellular immune responses is an important step toward prevention and/or treatment of HCV infection. With this aim, we have constructed a replication-deficient recombinant adenovirus expressing HCV NS3 protein (RAdNS3). The efficacy of RAdNS3 was tested in vivo by measuring the protection against infection with a recombinant vaccinia virus expressing HCV-polyprotein (vHCV1-3011). Immunisation with 10(9)pfu of RAdNS3 induced anti-NS3 humoral, T helper and T cytotoxic responses. We identified eight epitopes recognised by IFN-gamma producing cells, five of them exhibiting lytic activity. Moreover, we show that RAdNS3 immunised mice were protected against challenge with vHCV1-3011 and that this protection was mediated by CD8(+) cells. In conclusion, our results suggest that adenoviral vectors encoding NS3 might be useful for the induction of prophylactic and/or therapeutic anti-HCV immunity. 2001-12-31T23:00:00Z http://hdl.handle.net/10171/20609 Title: A recombinant adenovirus encoding hepatitis C virus core and E1 proteins protects mice against cytokine-induced liver damage Author(s) : Lasarte, J.J. (Juan José); Sarobe, P. (Pablo); Boya, P. (Patricia); Casares, N. (Noelia); Arribillaga, L. (Laura); Lopez-Diaz-de-Cerio, A. (Ascensión); Gorraiz, M. (Marta); Borras-Cuesta, F. (Francisco); Prieto, J. (Jesús) Abstract: Hepatitis C virus (HCV) infection has a strong tendency to evolve to chronicity despite up-regulation of proapoptotic cytokines in the inflamed liver. The mechanisms responsible for persistent viral replication in this inflammatory environment are obscure. It is conceivable that viral replication would be facilitated if the infected hepatocytes are rendered resistant to cytokine-induced cytotoxicity. In this study, we investigated if an adenovirus encoding HCV core and E1 (RAdCE1) could reduce liver cell injury in different in vivo models of cytokine-mediated hepatotoxicity in mice. We show that RAdCE1 markedly attenuates hepatocellular apoptosis and the increase in serum transaminase levels after concanavalin A (con A) challenge. This protective effect is accompanied by an inhibition of nuclear translocation of nuclear factor kappaB (NF-kappaB); reduced expression of inducible nitric oxide synthase (iNOS); decreased hepatic messenger RNA levels of chemokines macrophage inflammatory protein 2 (MIP-2), monocyte chemoattractant protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10); and abrogation of liver leukocyte infiltration. RAdCE1 also causes a reduction in serum transaminase levels and inhibits hepatocellular apoptosis in mice given tumor necrosis factor (TNF)-alpha plus D-galactosamine. In conclusion, HCV structural antigens can protect liver cells against the proapoptotic effects of proinflammatory cytokines. The antiapoptotic status of infected liver cells may represent a mechanism favoring viral persistence. Our findings also suggest that, in chronic hepatitis C, the burden of hepatocellular damage mainly affects noninfected liver cells. 2002-12-31T23:00:00Z http://hdl.handle.net/10171/20437 Title: Engineering Th determinants for efficient priming of humoral and cytotoxic T cell responses Author(s) : Lopez-Diaz-de-Cerio, A. (Ascensión); Lasarte, J.J. (Juan José); Casares, N. (Noelia); Sarobe, P. (Pablo); Ruiz, M. (Marta); Prieto, J. (Jesús); Borras-Cuesta, F. (Francisco) Abstract: To engineer T(h) determinants (THd) to prime help for humoral or cytotoxic T cell responses, we modified ovalbumin [OVA(323-337)] and myoglobin [MYO(106-118)] eliciting T(h)1 and T(h)0 cytokine profiles respectively. Residues along the sequence of both THd were replaced with amino acids representative of different families. Replacements at positions P-1 and P5 pointing to the TCR in both THd afforded higher levels of IFN-gamma and IL-4 production. Peptides eliciting different proportions of IFN-gamma and IL-4 were co-immunized with a peptide hapten or a T cytotoxic determinant (TCd) respectively. OVA(323-337)- and MYO(106-118)-derived peptides afforded the best THd for the induction of cytotoxic T lymphocyte (CTL) and anti-hapten antibodies respectively. IFN-gamma and IL-4, primed by MYO(106-118)-derived peptides, correlated significantly with antibody production against the hapten (P < 0.05 for IFN-gamma and P < 0.05 for IL-4). Interestingly, two peptides derived from OVA(323-337), 323G and 327G, which induced the clearest T(h)2 cytokine profiles, were not the most efficient to prime cell help for the induction of anti-hapten antibodies. For CTL induction, OVA(323-337)-derived peptides, inducing a T(h)1-like profile, required a lower dose (5 nmol) than T(h)0 peptides (50 nmol). The dose of 50 nmol was detrimental for T(h)1-like peptides. Interestingly, IFN-gamma primed by the THd correlated significantly with that induced by the TCd (P < 0.01). 2002-12-31T23:00:00Z http://hdl.handle.net/10171/20412 Title: Immunization with a tumor-associated CTL epitope plus a tumor-related or unrelated Th1 helper peptide elicits protective CTL immunity Author(s) : Casares, N. (Noelia); Lasarte, J.J. (Juan José); Lopez-Diaz-de-Cerio, A. (Ascensión); Sarobe, P. (Pablo); Ruiz, M. (Marta); Melero, I. (Ignacio); Prieto, J. (Jesús); Borras-Cuesta, F. (Francisco) Abstract: Immunization with cytotoxic T cell epitope SPSYVYHQF (AH1), derived from MuLV gp70 envelope protein expressed by CT26 tumor cells, does not protect BALB/c mice against challenge with CT26 tumor cells. By contrast, immunization with AH1 plus T helper peptides OVA(323-337) or SWM(106-118) eliciting Th1 and Th0 profiles, protected 83% and 33% of mice, respectively. Interestingly, immunization with AH1 plus both helper peptides reverted the efficacy to 33%. We identified the endogenous T helper peptide p(320-333) from gp70 which elicits a Th1 profile and is naturally processed. As for OVA(323-337), immunization with p(320-333) alone did not protect against tumor challenge. However, p(320-333) plus AH1 protected 89% of mice at day 10 after vaccination. Only 20% of mice vaccinated with AH1 + OVA(323-337) or AH1 + p(320-333) were protected when challenged 80 days after immunization. Treatment with OVA(323-337) or with p(320-333) around established tumors delayed tumor growth. Our results show that tumor-related as well as tumor-unrelated but strong Th1 peptides may be useful for inducing CTL responses in tumor immunotherapy. 2000-12-31T23:00:00Z http://hdl.handle.net/10171/20411 Title: CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination Author(s) : Casares, N. (Noelia); Arribillaga, L. (Laura); Sarobe, P. (Pablo); Dotor, J. (Javier); Lopez-Diaz-de-Cerio, A. (Ascensión); Melero, I. (Ignacio); Lasarte, J.J. (Juan José) Abstract: CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+) cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25(+) T reg cells is restored over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25(+) T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25(+) T reg on the induction of long-lasting cellular immune responses. 2002-12-31T23:00:00Z http://hdl.handle.net/10171/20331 Title: In situ localization of anion exchanger-2 in the human kidney Author(s) : Castillo, J. (José E.); Martinez-Anso, E. (Eduardo); Malumbres, R. (Raquel); Alava, E. (Enrique) de; Garcia, C. (Carmen); Medina, J.F. (Juan Francisco); Prieto, J. (Jesús) Abstract: Na+-independent anion exchangers (AE) are a family of membrane carriers that mediate the electroneutral exchange of Cl- for HCO3- ions across plasma membranes. They are involved in intracellular pH and cell volume regulation as well as in transepithelial acid-base transport. While anion exchanger-1 (AE1) has been localized previously in the human kidney, thus far there has been no definite report on anion exchanger-2 (AE2) in this human tissue. Accordingly, immunohistochemistry was carried out on surgical specimens of the human kidney (fixed in formalin and embedded in paraffin), using a specific AE2 monoclonal antibody. Strong immunostaining was observed at the basolateral membrane of cells of thick ascending limbs and distal convoluted tubules, colocalizing with the basal membranous labyrinth of cellular interdigitations, typical of these segments. In fact, AE2 staining was attenuated at the macula densa, where basal infoldings are scarce. Additionally, in situ hybridization experiments on formalin-fixed tissue demonstrated the presence of AE2 mRNA in the same segments of the distal nephron. On the other hand, control immunohistochemistry with a monoclonal antibody against AE1 gave the expected immunoreactivity at the basal pole of the type A intercalated cells of connecting tubules and cortical collecting ducts, and in erythrocytes. Our results indicate that, depending on the nephron segment and corresponding cell types, AE1 and AE2 proteins are differentially involved in the Na+-independent exchange of Cl- for HCO3- at the basolateral membrane of polarized kidney epithelial cells. 1999-12-31T23:00:00Z http://hdl.handle.net/10171/20027 Title: The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience Author(s) : Rodriguez, J. (J); Conde, E. (E.); Gutierrez, A. (Antonio); Arranz, R. (R.); Leon, A. (Angel); Marin, J. (Julián); Bendandi, M. (Maurizio); Albo, C. (Carmen); Caballero, M.D. (M.D.) Abstract: Abstract BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases. 2006-12-31T23:00:00Z http://hdl.handle.net/10171/20026 Title: Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group Author(s) : Rodriguez, J. (J); Conde, E. (E.); Gutierrez, A. (Antonio); Arranz, R. (R.); Leon, A. (Angel); Marin, J. (Julián); Bendandi, M. (Maurizio); Albo, C. (Carmen); Caballero, M.D. (M.D.); Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GEL-TAMO) Abstract: OBJECTIVE: Retrospective data shows that peripheral T-cell lymphoma (PTCL) patients sensitive to conventional chemotherapy for aggressive lymphomas may respond better if this treatment is consolidated with frontline autologous stem cell transplantation (ASCT). Here, we present data from a prospective phase II trial of high-dose chemotherapy and ASCT as a frontline consolidation therapy for aggressive nodal PTCL. METHODS: This study involved 26 gallium-scan-positive patients with high-risk nodal PTCL [excluding anaplastic lymphoma kinase (ALK) positive]. Patients received three courses of MegaCHOP before they were evaluated, and those that were gallium-scan-negative at this stage then received another course of MegaCHOP and ASCT. Patients who remained gallium-scan-positive received two courses of an IFE regimen (ifosfamide 10 g/m(2), etoposide 150 mg/m(2)/12 h on days 1-3) and if they at least achieved PR, they then received the transplant. RESULTS: Complete response (CR) was achieved by 12 patients (46%) after three courses of MegaCHOP and 12 patients received IFE as a salvage therapy. After the ASCT (n = 19), 89% of patients achieved CR. In contrast, six patients (23%) did not receive the transplant because of the progression of the disease (n = 5) or lethal toxicity (n = 1). One patient in first-line CR refused ASCT. After a median follow-up of 35 months, the overall survival (OS) and progression-free survival (PFS) at 3 yr was 73% and 53%, respectively. Moreover, the OS, PFS and disease-free survival (DFS) were 84%, 56% and 63%, respectively 2 yr after transplant in patients who received ASCT consolidation (n = 19). CONCLUSIONS: Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after three courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome. 2006-12-31T23:00:00Z http://hdl.handle.net/10171/20025 Title: The adjusted International Prognostic Index and beta-2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma Author(s) : Rodriguez, J. (J); Conde, E. (E.); Gutierrez, A. (Antonio); Lahuerta, J.J. (Juan J.); Arranz, R. (R.); Sureda, A. (Anna); Zuazu, J. (Javier); Fernandez-de-Sevilla, A. (A.); Bendandi, M. (Maurizio); Solano, C. (C.); Leon, A. (Angel); Varela, M.R. (María Rosario); Caballero, M.D. (M.D.); Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GEL-TAMO) Abstract: BACKGROUND AND OBJECTIVES: Preliminary data on the use of autologous stem cell transplantation (ASCT) as a salvage therapy for peripheral T-cell lymphoma (PTCL) indicate that the results are similar to those obtained in aggressive B-cell lymphomas. The aim of our study was to analyze outcomes of a large series of patients with PTCL with a prolonged follow-up who received ASCT as salvage therapy. DESIGN AND METHODS: Between 1990 and 2004, 123 patients in this situation were registered in the GELTAMO database. The median age at transplantation was 43.5 years; in 91% of patients the disease was chemosensitive. RESULTS: Seventy-three percent of the patients achieved complete remission, 11% partial remission and the procedure failed in 16%. At a median follow-up of 61 months, the 5-year overall and progression-free survival rates were 45% and 34%, respectively. The presence of more than one factor of the adjusted International Prognostic Index (a-IPI) and a high beta2-microglobulin at transplantation were identified as adverse prognostic factors for both overall and progression-free survival and allowed the population to be stratified into three distinct risk groups. INTERPRETATION AND CONCLUSIONS: Our data show that approximately one third of patients with PTCL in the salvage setting may enjoy prolonged survival following ASCT, provided they are transplanted in a chemosensitive disease state. The a-IPI and beta2-microglobulin level predict the outcome after ASCT in relapsing/refractory PTCL. 2006-12-31T23:00:00Z