RESUMEN
Approximately 20%-50% of patients with large B-cell lymphoma (LBCL) experience poor outcomes. We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single-centre study included 112 newly diagnosed LBCL patients, receiving R-CHOP/R-CHOP-like chemotherapies. CtDNA load was calculated following next-generation sequencing of cell-free DNA (cfDNA) using a targeted 40-gene lymphopanel. TMTV was measured using a fully automated artificial intelligence-based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3.15 log haploid genome equivalents per mL. TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3.57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1-year PFS (44% vs. 83%, p < 0.001 and 64% vs. 97%, p = 0.002, respectively). When combined, three prognostic groups were identified. The shortest PFS was observed when both TMTV and ctDNA load were high (p < 0.001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high-risk patients could benefit from CAR T-cell therapy or bispecific antibodies as first-line treatments.
Asunto(s)
ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Humanos , ADN Tumoral Circulante/genética , Carga Tumoral , Inteligencia Artificial , Pronóstico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/diagnóstico , Fluorodesoxiglucosa F18/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios RetrospectivosAsunto(s)
Canalopatías/genética , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/genética , Trombosis/genética , Anemia Hemolítica Congénita/complicaciones , Anemia Hemolítica Congénita/genética , Anemia Hemolítica Congénita/patología , Canalopatías/complicaciones , Canalopatías/patología , Eritrocitos/patología , Mutación con Ganancia de Función , Hemólisis , Humanos , Masculino , Persona de Mediana Edad , Mutación Puntual , Trombosis/complicaciones , Trombosis/patologíaAsunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/genética , Anemia Hemolítica Congénita/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Trastornos del Neurodesarrollo/genética , ATPasas de Translocación de Protón Vacuolares/genética , Anemia Hemolítica Congénita/patología , Médula Ósea/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Preescolar , Heterocigoto , Humanos , Amaurosis Congénita de Leber/genética , Amaurosis Congénita de Leber/patología , Imagen por Resonancia Magnética , Masculino , Mutación Missense , Trastornos del Neurodesarrollo/patología , Neuroimagen , Recuento de Reticulocitos , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Congenital hemolytic anemia constitutes a heterogeneous group of rare genetic disorders of red blood cells. Diagnosis is based on clinical data, family history and phenotypic testing, genetic analyses being usually performed as a late step. In this study, we explored 40 patients with congenital hemolytic anemia by whole exome sequencing: 20 patients with hereditary spherocytosis and 20 patients with unexplained hemolysis. RESULTS: A probable genetic cause of disease was identified in 82.5% of the patients (33/40): 100% of those with suspected hereditary spherocytosis (20/20) and 65% of those with unexplained hemolysis (13/20). We found that several patients carried genetic variations in more than one gene (3/20 in the hereditary spherocytosis group, 6/13 fully elucidated patients in the unexplained hemolysis group), giving a more accurate picture of the genetic complexity of congenital hemolytic anemia. In addition, whole exome sequencing allowed us to identify genetic variants in non-congenital hemolytic anemia genes that explained part of the phenotype in 3 patients. CONCLUSION: The rapid development of next generation sequencing has rendered the genetic study of these diseases much easier and cheaper. Whole exome sequencing in congenital hemolytic anemia could provide a more precise and quicker diagnosis, improve patients' healthcare and probably has to be democratized notably for complex cases.