RESUMEN
The International Prognostic Index (IPI) is the most widely used score for non-Hodgkin lymphoma but lacks the ability to identify a high-risk population in diffuse large B-cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red-cell distribution width (RDW) has been associated with inflammation and beta-2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R-CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression-free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3-4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high-risk subgroup with five-year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)-IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real-life practice without additional tests. Compared to R-IPI, it shows a more precise high-risk assessment and risk discrimination for both PFS and OS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células Sanguíneas/métodos , Linfocitos/metabolismo , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Monocitos/metabolismo , Microglobulina beta-2/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/farmacología , Prednisona/uso terapéutico , Pronóstico , Factores de Riesgo , Rituximab/farmacología , Rituximab/uso terapéutico , Vincristina/farmacología , Vincristina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.
Asunto(s)
Codón/genética , Tumores del Estroma Gastrointestinal/genética , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas c-kit/genética , Eliminación de Secuencia/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.
Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Linfoma de Células B Grandes Difuso/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Valores de Referencia , Estudios Retrospectivos , Factores Sexuales , Resultado del TratamientoRESUMEN
BACKGROUND: During the last years the appearance of the acquired V617F mutation of the Janus Kinase 2 gene (JAK2) in patients suffering different thrombotic events has been described. We decided to develop a new and rapid multiplex real-time Polymerase Chain Reaction (PCR) in order to detect the V617F mutation together with the inherited prothrombotic mutations of factors F5 and F2. DESIGN AND METHODS: The method was carried out on the LightCycler 2.0 (Roche Diagnostics, Mannheim, Germany) and consisted in a first step of simultaneous amplification by real-time PCR of the three genes to be genotyped, in a 20microl closed tube, using a primer pair together with the correspondent FRET-hybridization probes for each gene. RESULTS: We assayed 41 samples in the multiplex PCR reaction, 19 were positive (46.34%) for V617F mutation. From the V617F positive samples we found 1 sample heterozygous for F2 (5.26%) and 1 sample heterozygous for F5 (5.26%), so a 10.52% of the samples tested combine V617F mutation with inherited thrombophilic mutations. Results were clear, rapid and reliable allowing a significant time saving. CONCLUSIONS: The technique presented in this manuscript is a new achievement in the field of the molecular diagnosis that combines the genotyping of F5 and F2 with the assessment of the JAK2 (V617F) mutation load.
Asunto(s)
Factor V/genética , Janus Quinasa 2/genética , Reacción en Cadena de la Polimerasa/métodos , Protrombina/genética , Trombofilia/genética , Cartilla de ADN , Frecuencia de los Genes , Genotipo , Humanos , Métodos , Mutación Missense , Estudios RetrospectivosRESUMEN
INTRODUCTION: The Factor 5 Leiden mutation and the G20210A variant of Factor 2 are two important risk factors for hereditary thromboembolism. Several reports have demonstrated that homozygous carriers for C46T mutation of the Factor 12 gene is associated with a significant increased risk for the development of coronary disease as well as cerebral and peripheral venous thrombosis. DESIGN AND METHODS: We develop a rapid and feasible asymmetric multiplex real-time PCR-based method using fluorescence resonance emission transfer (FRET) probes followed by a melting temperature (T(m)) curve assay for the simultaneous clinical diagnosis of F2, F5 and F12 mutations in a 10 microl closed tube. This new tool uses three different fluorescence channels in a LightCycler 2.0 for the robust genotyping of each one of the mutations included in the reaction. RESULTS: Assay evaluation performed on 67 DNA samples previously genotyped with reference methods resulted in full concordance of results for the three mutations tested. Higher asymmetric ratio of primer pair concentration significantly increased the efficiency of the melting peak assay used for the mutation genotyping without modifying the Crossing Point (CP) obtained from the amplification curves. CONCLUSIONS: To our knowledge this is the first triplex real-time PCR FRET-based assay reported in bibliography that allows a rapid and simultaneous genotyping of these three thrombosis risk factors. This new and rapid tool may contribute to the better understanding of the interrelations or contributions of these gene mutations to different thrombotic or coronary disease-related events.