Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Infecciones por Virus de Epstein-Barr/genética , Leucemia Mielomonocítica Crónica/genética , Linfoma de Células B Grandes Difuso/genética , Neoplasias Primarias Múltiples/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biopsia , Médula Ósea/patología , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN/efectos de los fármacos , ADN Metiltransferasa 3A , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Dioxigenasas , Epigénesis Genética/efectos de los fármacos , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/virología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/virología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/virología , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/virología , Tomografía de Emisión de Positrones , Proteínas Proto-Oncogénicas/genética , Resultado del TratamientoRESUMEN
Epstein-Barr virus lymphoproliferative disease (EBV-LPD) following allogeneic stem cell transplantation (allo-SCT) has a poor prognosis. We used a sensitive real-time polymerase chain reaction (PCR) assay for quantitative detection of EBV-DNA in plasma and serially measured EBV-DNA levels to assess the response to treatment in allo-SCT recipients with EBV-LPD. Fourteen allo-SCT recipients with EBV-LPD who received a T cell-depleted (TCD) sibling (n = 5) or matched unrelated donor (n = 9) graft were monitored from the time of EBV-LPD diagnosis, during therapy and assessment of clinical response. Seven patients had complete responses of EBV-LPD to therapy, of whom 21% (3 out of 14) survived beyond 6 months from EBV-LPD diagnosis. Clinically responding patients showed a rapid decline of EBV-DNA plasma levels within 72 h from the start of therapy. In contrast, all clinical non-responders showed an increase of EBV-DNA levels. Absolute EBV-DNA levels at the time of EBV-LPD diagnosis did not predict for response, but the pattern of EBV-DNA levels within 72 h from the start of therapy (> 50% decrease versus increase) strongly predicted for clinical response (P = 0.001). Quantitative monitoring of EBV-DNA levels from the start of and during therapy for EBV-LPD rapidly and accurately predicts for response to therapy as early as within 72 h. It may thus provide a powerful tool to adjust and select treatment in individuals with EBV-LPD following allo-SCT.