RESUMO
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.
Assuntos
DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Humanos , DNA Tumoral Circulante/genética , Carga Tumoral , Inteligência Artificial , Prognóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/diagnóstico , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos RetrospectivosAssuntos
Canalopatias/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Trombose/genética , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita/patologia , Canalopatias/complicações , Canalopatias/patologia , Eritrócitos/patologia , Mutação com Ganho de Função , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Trombose/complicações , Trombose/patologiaAssuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Anemia Hemolítica Congênita/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Transtornos do Neurodesenvolvimento/genética , ATPases Vacuolares Próton-Translocadoras/genética , Anemia Hemolítica Congênita/patologia , Medula Óssea/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pré-Escolar , Heterozigoto , Humanos , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Transtornos do Neurodesenvolvimento/patologia , Neuroimagem , Contagem de Reticulócitos , Sequenciamento Completo do GenomaRESUMO
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.
