RESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.
Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2 , Linfoma de Células B Grandes Difuso , Mutación , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Femenino , Persona de Mediana Edad , Masculino , México/epidemiología , Anciano , Adulto , Proteína Potenciadora del Homólogo Zeste 2/genética , Anciano de 80 o más Años , Estudios Prospectivos , Receptor Notch1/genética , Proteína de Unión a CREB/genética , Proteína p53 Supresora de Tumor/genética , Proteínas de Neoplasias/genética , Adulto Joven , Pronóstico , Adolescente , Proteínas de Unión al ADNRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. MIC-A and MIC-B are the natural ligands for NKG2D, a receptor expressed in NK cells. MIC-A soluble isoforms (sMICA) have been described in different malignancies. OBJECTIVES: To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. MATERIALS AND METHODS: sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. RESULTS: Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. CONCLUSIONS: Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.
Asunto(s)
Centro Germinal , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/sangre , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , Centro Germinal/patología , Centro Germinal/metabolismo , Adulto , Subgrupos Linfocitarios/metabolismo , Subgrupos Linfocitarios/inmunología , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Estadificación de Neoplasias , Inmunofenotipificación , Biomarcadores de TumorRESUMEN
PURPOSE: Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL. METHODS: Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression. RESULTS: The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL. CONCLUSION: This study's findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.
Asunto(s)
Linfoma de Células B Grandes Difuso , Síndrome Metabólico , Rituximab , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Síndrome Metabólico/complicaciones , Pronóstico , Anciano , Rituximab/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más Años , Doxorrubicina/uso terapéutico , Factores de Riesgo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Supervivencia sin Progresión , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Tasa de Supervivencia , Estadificación de Neoplasias , Adulto Joven , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVES: Even though frequent, it is not known how HIV infection and treatment impact in the consolidation by radiotherapy of non-Hodgkin diffuse large B-cell lymphomas (DBCL). This article aim to assess that difference that HIV makes on radiation treatment. PATIENTS AND METHODS: A retrospective cohort of all DBCL patients treated with chemotherapy and consolidative radiotherapy at a single institution between 2010 and 2018 was assessed. All patients had biopsy-proven lymphoma and were included if radiation was part of the treatment and had at least 6 months of follow-up or were followed until death. RESULTS: Three-hundred fifty-nine (359) patients were selected, with a median age at diagnosis of 57.7 years (13-90 years). Twenty-eight patients (7.8%) were HIV positive. Median follow-up was 48.0 months. Female patients were 51.3% and most had a good performance in the ECOG scale (78.8% are ECOG 0-1). Median overall survival was not reached, but mean OS was 50.1 months with 86 deaths. Median progression-free survival was 48.7 months. HIV infection had no impact on OS (p = 0.580) or PFS (p = 0.347) among patients treated with RT. HIV positive patients were more frequently staged only with CT (p > 0.05) with no impact on PFS (p = 0.191). No HIV positive patient received rituximab due to local policy restrictions and HIV positive patients were more prone to receive CHOP-like chemotherapy (p < 0.05), specially ones with etoposide (CHOEP). CHOP was associated with better survival (p = 0.015) in the overall population and in the HIV negative population (p = 0.002), but not in the HIV positive population (p = 0.982). RT toxicities were not overall more frequent in the HIV positive population (p = 0.567), except for fatigue (p < 0.05) and hematological toxicities (p = 0.022). CONCLUSION: HIV status did not influence on survival when patients were treated with consolidative radiotherapy. HIV infection was a bias on our sample for staging methods and chemotherapy regimens choices. For HIV positive patients there was an increase in fatigue and hematological toxicities of any grade with radiation.
Asunto(s)
Infecciones por VIH/complicaciones , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Radioterapia/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Femenino , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Radioterapia/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Patients with diagnosis of diffuse large B-cell lymphoma, who relapse after stem cell transplant (SCT) or are no candidates to SCT, have a poor prognosis and no current treatment is available. Thus, we conduct a rotatory chemotherapy schedule that employed low doses of chemotherapy agents to assess efficacy and toxicity in this setting of patients; the end point was the improved outcome. METHODS: Retrospectively we revised an analysis of 461 patients who were treated with a low-doses regimen of cytotoxic agents, who were treated in a single institution, all patients has been treated with at least two salvage regimens, including SCT, > 18 years, performance status < 3, and that were informed about the possibility of severe toxicities,, were considered candidates to the study. They received a weekly rotatory scheme including low doses of cytotoxic agents during 2 years. RESULTS: Overall response rate was achieved in 314 patients (68%, 95% Confidence interval (CI) 59-76%) and complete response was achieved in 151 cases (32%, 95% CI 25-38%); actuarial curves at 10 years show that progression-free survival was 58% (95% CI 51-66%) and OS was 50% (95% CI 43-57%). Dose reduction was not necessary; toxicity was minimal and well controlled. No death related to acute or late toxicities has been observed. CONCLUSION: Low doses of cytotoxic agents for continuous, prolonged periods, with minimal drug-free intervals, represent a novel, active, and easily tolerated approach to management of patients with DLBCL in a terminal phase and improved outcome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citotoxinas/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The purpose of this study was to assess the influence of single-nucleotide polymorphisms (SNPs) on cytokine genes in the development of diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients and 221 controls were investigated. Among them, 97 patients treated with R-CHOP were subdivided into two groups: (i) complete remission of the disease and (ii) patients who progressed to death, relapsed, or had disease progression. The SNPs investigated by PCR-SSP were TNF -308G>A (rs1800629), IFNG +874A>T (rs2430561), IL6 -174G>C (rs1800795), IL10 -1082A>G (rs1800896), IL10 -819C>T (rs1800871), IL10 -592C>A (rs1800872), and TGFB1 codon10T>C (rs1982073) and codon25G>C (rs1800471). In general, the genotypes that have been associated in the literature with lower production or intermediate production of IL-10 and higher production of IFN-γ were associated with the protection of the development of the disease, possibly favoring the Th1 immune response and diminishing the capacity of cell proliferation. However, patients receiving R-CHOP treatment presented unfavorable prognoses in the presence of genotypes related to the intermediate production of IL-10 and high production of TGF-ß1, indicating that cytokines may be related to the response to treatment and action mechanisms of Rituximab.
Asunto(s)
Predisposición Genética a la Enfermedad , Haplotipos , Interferón gamma/genética , Interleucina-10/genética , Linfoma de Células B Grandes Difuso/genética , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica , Estudios de Casos y Controles , Ciclofosfamida , Doxorrubicina , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Prednisona , Pronóstico , Rituximab , Resultado del Tratamiento , VincristinaRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma, NOS (DLBCL NOS) is the commonest extranodal non-Hodgkin lymphoma diagnosed in the oral and maxillofacial region. However, few studies are currently available and its prognostic determinants remain undefined. PURPOSE: To analyse the available data on oral DLBCL NOS and to describe its clinicopathological features, identifying potential prognostic factors. METHODS: An electronic systematic search was performed using multiple databases with a specific search strategy in April 2018. All reports describing DLBCL NOS involving the oral cavity and jaw bones with sufficient clinicopathological information were assessed. RESULTS: Sixty-three publications were included in the study, comprising 122 cases. Oral DLBCL NOS was found predominantly in elderly males (61.5%), and most often presented as an asymptomatic swelling of the gingiva. Patients commonly were HIV-negative (36.1%), with few reports describing EBV-positive cases (four cases/3.3%). Only eight cases presented B symptoms and most cases were classified as stage I or II (48.4%). CHOP therapy was the main treatment option (24.5%) and the overall 5-year survival rate achieved 83%. Males and advanced Ann Arbor stage patients presented significantly lower survival rates in the univariate analysis, but no significance was found in the multivariate model. CONCLUSION: Oral DLBCL NOS is an aggressive malignancy, but with a high survival rate.
Asunto(s)
Linfoma de Células B Grandes Difuso , Neoplasias de la Boca , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Mandíbula , Maxilar , Boca , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Pronóstico , Factores Sexuales , Tasa de SupervivenciaRESUMEN
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a haematologic malignancy with poor prognosis when treated with chemotherapy. We evaluated response and survival benefits of chemoimmunotherapy in EBV-positive DLBCL patients. A total of 117 DLBCL patients were included in our retrospective analysis; 33 were EBV-positive (17 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and 16 with CHOP), and 84 were EBV-negative (all treated with R-CHOP). The outcomes of interest were complete response (CR) and overall survival (OS) in EBV-positive DLBCL patients (R-CHOP versus CHOP) and in DLBCL patients treated with R-CHOP (EBV-positive vs EBV-negative). There were no differences in the clinical characteristics between EBV-positive and EBV-negative DLBCL patients. Among EBV-positive DLBCL patients, R-CHOP was associated with higher odds of CR (OR 3.14, 95% CI 0.75-13.2; P = .10) and better OS (hazard ratio 0.30, 95% confidence interval [CI] 0.09-0.94; P = .04). There were no differences in CR rate (OR 0.52, 95% CI 0.18-1.56; P = .25) or OS (hazard ratio 0.93, 95% CI 0.32-2.67; P = .89) between EBV-positive and EBV-negative DLBCL patients treated with R-CHOP. Based on our study, the addition of rituximab to CHOP is associated with improved response and survival in EBV-positive DLBCL patients. Epstein-Barr virus status does not seem to affect response or survival in DLBCL patients treated with R-CHOP.
Asunto(s)
Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/patología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/patología , Linfocitos T Citotóxicos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Citocinas/análisis , Infecciones por Virus de Epstein-Barr/mortalidad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Adulto JovenAsunto(s)
Gutatión-S-Transferasa pi/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Mutación Missense , Polimorfismo Genético , Sustitución de Aminoácidos , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Prednisona/administración & dosificación , Estudios Prospectivos , Rituximab , Tasa de Supervivencia , Investigación Biomédica Traslacional , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Tumor-infiltrating immune cells influence diffuse large B-cell lymphoma (DLBCL) outcomes. Relatively little, however, is known about the significance of peripheral blood immune cell numbers on DLBCL behavior. PATIENTS AND METHODS: In the present study, 43 patients with newly diagnosed DLBCL had pretreatment multiparameter peripheral blood flow cytometry performed to assess the immune cell numbers. These cell numbers were correlated with the outcomes of progression-free survival (PFS) and overall survival. RESULTS: After follow-up period of 0.8 to 152 months (median, 73), 25 patients (56%) were still alive. As continuous variables on univariate analysis, the predictors of PFS were patient age and absolute CD4 cell count (ACD4C), with the International Prognostic Index (IPI) marginally significant. Age was also a significant predictor of overall survival, and the IPI and ACD4C were marginally significant (P = .08). The 17 patients with a greater ACD4C (≥ 450/mm3) had better 5-year PFS than the 26 with a low ACD4C (88% vs. 50%; P = .02). Multivariable analysis, including age as a continuous variable, IPI group, and ACD4C of 450/mm3 showed that age and ACD4C were significant for PFS (P = .01 and P = .02, respectively). CONCLUSION: Our data, although from a small series, suggest that the blood ACD4C might be a predictor of PFS for patients with DLBCL, independent of age and the IPI.
Asunto(s)
Linfocitos T CD4-Positivos/patología , Linfoma de Células B Grandes Difuso/patología , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Linfocito CD4/métodos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenAsunto(s)
Alelos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/genética , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Prednisona/efectos adversos , Prednisona/uso terapéutico , Pronóstico , Rituximab , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.
Asunto(s)
Biomarcadores de Tumor/genética , Fijadores/química , Formaldehído/química , Perfilación de la Expresión Génica/métodos , Linfoma de Células B Grandes Difuso/genética , Adhesión en Parafina , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fijación del Tejido/métodos , Transcriptoma , Anciano , Asia , Biopsia , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Perfilación de la Expresión Génica/normas , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , América del Sur , Factores de TiempoRESUMEN
PURPOSE: The choice between chemotherapy alone and chemotherapy plus consolidative radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) remains controversial. We aimed to define factors affecting treatment selection and the resulting survival outcomes. PATIENTS AND METHODS: Using the National Cancer Data Base, we identified 59,255 patients with stages I and II DLBCL treated with multiagent chemotherapy alone or chemotherapy plus consolidative RT between 1998 and 2012. Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of overall survival (OS) and treatment use. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Of the 59,255 patients with DLBCL enrolled onto the study, 46% had stage II disease, 42% had extranodal disease, and 58% were more than 60 years of age. Only 39% received combined-modality therapy, and this proportion significantly declined from 47% in 2000 to 32% in 2012 (P < .001). Treatment selection was significantly influenced by race, comorbidity, insurance type, education quartile, facility type, age, stage, B symptoms, distance from treatment facility, and year of diagnosis. The median follow-up time was 60 months (interquartile range, 33 to 93). Estimated 5-year and 10-year OS rates were, respectively, 79% and 59% for all patients, 75% and 55% for patients receiving chemotherapy alone, and 82% and 64% for patients receiving combined-modality therapy (P < .001). Even after adjusting for immortal times and indication bias, combined-modality therapy was associated with better OS (HR, 0.66; 95% CI, 0.61 to 0.71; P < .001) than was chemotherapy alone. CONCLUSION: Use of consolidative RT after multiagent chemotherapy in DLBCL is decreasing in the modern era. Selection of treatment strategy is affected by both classical prognostic features and socioeconomic factors. Abandonment of combined-modality therapy in favor of chemotherapy alone negatively affects patient survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/radioterapia , Radioterapia Adyuvante , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Valor Predictivo de las Pruebas , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
The authors started a clinical trial to assess the efficacy and toxicity of rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma, with poor prognostic factors, who were in complete response (CR) after dose-dense chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced stages (III and IV), older (median age >60 years old), and high clinical risk, were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1; vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day 1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8, 15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five patients achieved CR (70%) and were allocated to receive R (151 patients) or not (174 patients). Actuarial curves at 5 years showed that progression-free survival (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95% CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95% CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities were more frequent in the R group. The authors showed that the use of R as a consolidation treatment was not useful to improve PFS and OS and toxicity secondary to R was frequent. They did not recommend the use of R as consolidation in this patient setting.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Adolescente , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Rituximab/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificación , Adulto JovenRESUMEN
Currently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus+ diffuse large B-cell lymphoma of the elderly (EBV+DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV+DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV+ and four EBV- samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV+DLBCLe and 65 EBV-DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV+DLBCLe by in situ hybridization. In multicenter study, EBV+DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV+DLBCLe was significantly inferior to that of EBV-DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV+DLBCLe cases compared to EBV-DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV+DLBCLe. The present study proposed a miRNA signature for EBV+DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets.
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Biomarcadores de Tumor/genética , Linfoma de Células B Grandes Difuso/genética , MicroARNs/genética , Transcriptoma , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Infecciones por Virus de Epstein-Barr , Femenino , Humanos , Hibridación in Situ , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Análisis de Matrices TisularesRESUMEN
UNLABELLED: Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. METHODS: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. RESULTS: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%-86%) for event-free survival (EFS) and 88% (83%-91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%-89%) for EFS and 88% (77%-94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%-95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%-64%) for EFS and 55% (32%-73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48-4.79) for EFS and 3.94 (1.93-8.06) for OS. CONCLUSION: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow (18)F-FDG uptake identified on the staging PET scan. Abnormal (18)F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.
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Células de la Médula Ósea/citología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Biopsia , Médula Ósea/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The overall survival and relapse-free survival have increased with current chemotherapy in patients with non-lymphoma Hodgkin. A useful tool to evaluate projections is the International Prognostic Index. Our aim was to evaluate the relation between the prognosis established with the International Prognostic Index and the survival obtained in two years by patients with diffuse large B-cell lymphoma. METHODS: An observational, longitudinal, prospective study was carried out. Patients included were those with diagnosis and treated along a year, who, at some point in their evolution, required hospitalization. All the patients received ciclofosfamide, doxorrubicine, vincristine and prednisone; additionally, some of them received rituximab. The follow-up average was 26 months. Survival was estimated with Kaplan-Meier curves. RESULTS: Forty-nine patients were included and classified according to the International Prognostic Index risk. The survival was 90 % for patients with International Prognostic Index low risk, 66.7 % for the patients with intermediate-low risk, 80 % for patients with intermediate-high risk, and 81 % for patients with high risk. The survival for all risk groups was 77.6 %. When we compared the survival of patients with the expected prognosis through the International Prognostic Index, we obtained p = 0.0000. CONCLUSIONS: Two years after diagnosis, the survival of patients with diffuse large B-cell lymphoma in the study was better than the prognosis estimated through the International Prognostic Index, and similar to that reported in American studies.
INTRODUCCIÓN: la quimioterapia actual ha incrementado la supervivencia total y la libre de recaída en los pacientes con linfoma no Hodgkin. Un recurso que permite hacer proyecciones al respecto es el Índice Pronóstico Internacional (IPI). El objetivo del presente análisis fue determinar la correspondencia entre el pronóstico determinado mediante ese índice y la supervivencia obtenida a dos años. MÉTODOS: estudio longitudinal, observacional y prospectivo. Se incluyeron pacientes diagnosticados y tratados durante un año que hubieran requerido hospitalización. Todos recibieron ciclofosfamida-doxorrubicina-vincristina- prednisona, y en algunos casos también rituximab; el seguimiento en promedio fue de 26 meses. La supervivencia se estimó mediante curvas de Kaplan-Meier. RESULTADOS: se incluyeron 49 pacientes, clasificados de acuerdo con el grupo de riesgo determinado mediante el IPI. La supervivencia total fue de 90 % en los pacientes de riesgo bajo, de 66.7 % en los de riesgo intermedio bajo, de 80 % para los de riesgo intermedio alto y de 81 % para los de riesgo alto. La supervivencia global fue de 77.6 %. Se obtuvo p = 0.0000 al realizar la comparación con el pronóstico esperado según el IPI a dos años. CONCLUSIONES: a dos años del diagnóstico, en el hospital analizado la supervivencia de los pacientes con linfoma no Hodgkin difuso de células B grandes fue mejor a la pronosticada para ese mismo periodo mediante el IPI y semejante a la referida en investigaciones norteamericanas.
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Linfoma de Células B Grandes Difuso/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). AIM: To analyze the benefit of Rituxi-mab in overall survival (OS) of patients with NHL. MATERIAL AND METHODS: Review of medical record of 230 adult patients with a first episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. RESULTS: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). CONCLUSIONS: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma Folicular/mortalidad , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Pronóstico , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A) overall survival (OS) at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables), and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor); (B) prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox), and multivariate analysis with Cox's regression model (all the variables together). The data were considered significant at p ≤ 0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3%) occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p = 0.042), clinical stage (p = 0.007) and performance status (p = 0.031). These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status.