RESUMEN
Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células T Periférico/terapia , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Linfoma de Células T Periférico/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trasplante Autólogo , Adulto JovenRESUMEN
BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
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Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Quimioterapia de Inducción , Análisis de Intención de Tratar , Linfoma de Células del Manto/mortalidad , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Inducción de Remisión , Rituximab , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of (90)Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of (90)Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. PATIENTS AND METHODS: Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point. RESULTS: With a median follow-up of 32 months (range, 29-60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively. CONCLUSIONS: For chemosensitive advanced high-risk B-cell lymphoma, the addition of (90)Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov: NCT00607854.
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Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Busulfano/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped , Humanos , Linfoma de Células B/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Terapia Recuperativa , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Vidarabina/uso terapéuticoRESUMEN
BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.
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Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/radioterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/administración & dosificación , Carmustina/efectos adversos , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Folicular/patología , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Podofilotoxina/administración & dosificación , Podofilotoxina/efectos adversos , Inducción de Remisión , Rituximab , Trasplante de Células Madre , Trasplante Autólogo , Irradiación Corporal Total , Adulto JovenRESUMEN
BACKGROUND: Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL). METHODS: Patients received oral lenalidomide 25 mg on days 1-21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR). RESULTS: Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7-5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0-NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively. CONCLUSION: Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
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Antineoplásicos/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Lenalidomida , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Tasa de Supervivencia , Talidomida/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hepatitis B/epidemiología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Trasplante de Células Madre/efectos adversos , Activación Viral , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , ADN Viral/genética , Femenino , Genotipo , Hepatitis B/mortalidad , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Rituximab , Resultado del TratamientoRESUMEN
INTRODUCTION: An observation of limbic encephalitis associated with Hodgkin's disease is compared with rare cases of the literature. The clinical presentation was relapsing episodes of febrile cognitive disorders with confusion and meningitis, curable after treatment of Hodgkin's disease. Recent concepts on limbic encephalitis are discussed. CASE REPORT: A seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease. The treatment of Hodgkin's disease led to perfect recovery of cognitive function, so that the patient could drive his car. CONCLUSION: Lymphoproliferative disease, such as Hodgkin's disease, is a possible diagnosis in patients with limbic encephalitis. A dysimmune process underlying Hodgkin's disease might be operating in this association.
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Confusión/etiología , Confusión/psicología , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/psicología , Encefalitis Límbica/etiología , Encefalitis Límbica/psicología , Meningitis/etiología , Meningitis/psicología , Anciano , Autoanticuerpos/análisis , Autoanticuerpos/aislamiento & purificación , Electroencefalografía , Fiebre/etiología , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Recuperación de la Función , Recurrencia , Tomografía Computarizada por Rayos XRESUMEN
CAR-T cells are genetically modified human lymphocytes and gene therapy medicinal products. They are developed to treat cancers that express a membrane antigen targeted by the CAR. The FDA approved the two first-in-class medicinal products in 2017 and EMA in August 2018; both are autologous CAR-T cells targeting CD19 that is expressed at the surface of normal B-cells throughout their differentiation, and on B-cell lymphoid malignancies. Clinical efficacy was demonstrated for B-cell acute lymphoblastic leukemias, non-Hodgkin's lymphoma and chronic lymphocytic leukemia, although the marketing authorizations are less liberal in terms of indications. Manufacturing of these personalized treatments necessitates that a novel organization and supply chain be set in place, to ensure product preservation, patient safety and compliance with complex regulatory requirements. Side effects are commensurate with clinical efficacy and can be life-threatening: proper management imposes tight coordination between various specialists, particularly between hematologists and intensive care practitioners. High pricing for these treatments is part of a long-term trend for increasing costs of innovations in hematology and oncology; it questions the ability of healthcare systems to sustain their reimbursement.
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Inmunoterapia Adoptiva , Neoplasias/terapia , Receptores Quiméricos de Antígenos/inmunología , Antígenos CD19/inmunología , Humanos , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunologíaRESUMEN
The ubiquitous herpesvirus Epstein-Barr virus (EBV) is linked to the development of several malignancies, including nasopharyngeal carcinoma (UCNT) and Hodgkin lymphoma (HL). Despite the well-known oncogenic properties of the EBV latent membrane protein 1 (LMP-1), the different oncogenic pathways involved in the pathogenesis of each disease remain unclear. This study reported, for the first time, the case of a patient with sequential development of UCNT and HL. Polymerase chain reaction was used to determine the LMP-1 gene sequence and demonstrate that the two tumours contained different clonal viral genomes, suggesting a central and specific role of EBV infection.
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Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Primarias Secundarias/genética , Proteínas de la Matriz Viral/genética , Adulto , Enfermedad de Hodgkin/virología , Humanos , Masculino , Neoplasias Nasofaríngeas/virología , Neoplasias Primarias Secundarias/virología , Técnicas de Amplificación de Ácido Nucleico , Reacción en Cadena de la PolimerasaRESUMEN
The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLA-identical sibling donor ('donor' group), while 13 patients had no donor ('no-donor' group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the 'donor' group could actually proceed to RIC allo-SCT. With a median follow-up of 36 (range, 21-60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11-55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7-48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56-98%; P=0.0003) among the nontransplanted patients. In an 'intention-to-treat' analysis, the Kaplan-Meier estimate of PFS was significantly higher in the 'donor' group as compared to the 'no-donor' group (P=0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15-0.82; P=0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.
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Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia/terapia , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre , Trasplante HomólogoRESUMEN
Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.
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Aminoglicósidos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/sangre , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Antineoplásicos/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Gemtuzumab , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/sangre , Recurrencia , Inducción de Remisión , Lectina 3 Similar a Ig de Unión al Ácido SiálicoRESUMEN
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common leukaemia in the Western world. Recent advancement in the aetiology, pathophysiology and the development of new therapeutics tools have significantly modified the current management of CLL. CURRENT KNOWLEDGE AND KEY POINTS: The cellular origin of CLL is still unknown. The current main hypothesis will be first briefly described. This review will then focus on the newly defined prognostic factors and the development and use of new drugs for the treatment of CLL. To describe the modern and practical management of CLL, we will compare classical and new prognostic markers. Then, we will discuss the various therapeutic options including chemotherapy and immunotherapy (monoclonal antibodies, allogenic transplantation), and define their current respective indications. FUTURE PROSPECTS AND PROJECTS: These new diagnostic and prognostic markers will allow the characterization of new prognostic subgroups of patients. This will lead to a targeted and individualized therapeutic approach. We will present the first results of clinical trials and the on-going studies conducted in this disease.
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Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Humanos , Incidencia , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.
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Perfilación de la Expresión Génica , Ganglios Linfáticos/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Humanos , Linfoma de Células T/clasificación , Linfoma de Células T/diagnóstico , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly high-dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (>1.5 times from baseline values; n=5), hypotension and pain (n=1), and violent chest pain and arrhythmia (n=1). The overall frequency of infusion-related reactions was 29% (n=6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.
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Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Micosis/prevención & control , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Anfotericina B/efectos adversos , Antifúngicos/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Micosis/etiología , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
We investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. At 100 days, the cumulative incidence of grades 2-3 and grades 3-4 acute GVHD was 23% and 4%, respectively. The chronic GVHD (cGVHD) cumulative incidence was 16%, with one patient experiencing severe cGVHD. The 3-year OS, PFS, relapse rates and 1-year non-relapse mortality (NRM) were 63%, 59%, 21% and 20%, respectively. Uncontrolled disease status and high hematopoietic cell transplantation comorbidity index (HCT-CI) were associated with lower OS, whereas PBSC was an independent protective factor. Uncontrolled disease and HCT-CI >2 was predictive for NRM. Finally, disease status other than CR was predictive of relapse. In conclusion, haplo-HSCT is a valid treatment in advanced HL, offering excellent rates of survival and acceptable toxicities.
Asunto(s)
Ciclofosfamida/uso terapéutico , Enfermedad de Hodgkin/terapia , Trasplante Haploidéntico/métodos , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad de Hodgkin/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica , Pronóstico , Análisis de Supervivencia , Trasplante Haploidéntico/mortalidad , Adulto JovenRESUMEN
Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively. BEAM, Z-BEAM and R-BEAM groups were well balanced for age, time from diagnosis to ASCT and disease status at ASCT. The cumulative incidences of relapse (IR) at 2 years were 34, 34 and 32% for Z-BEAM, R-BEAM and BEAM, respectively. By multivariate analysis, there were no significant differences with Z-BEAM or R-BEAM compared with BEAM for IR, non-relapse mortality, event-free survival or overall survival. With the caveat that the limitations of registry analyses have to be taken into account, this study does not support adding radioimmunotherapy or R to BEAM in ASCT for relapsed FL. However, we cannot rule out the existence a particular subset of patients who could benefit from Z-BEAM conditioning that cannot be identified in our series, and this should be tested in a randomized trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma Folicular/terapia , Radioinmunoterapia/métodos , Adulto , Anciano , Carmustina/uso terapéutico , Estudios de Casos y Controles , Terapia Combinada/métodos , Citarabina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Linfoma Folicular/mortalidad , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab/uso terapéutico , Análisis de Supervivencia , Trasplante Autólogo , Adulto JovenRESUMEN
PURPOSE: To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. RESULTS: Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. CONCLUSION: Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rituximab , Terapia Recuperativa , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.