title: Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis.
abstract: To determine whether the EBV genome content in serum or plasma reflects clinical features and outcome in EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), we quantified the cell-free EBV genome copy number by real-time PCR in 38 patients with EBV-HLH, and compared this to the values from 15 patients with infectious mononucleosis (IM). The median (range) cell-free EBV genome copy number at diagnosis was 3.0 x 10(3) (undetectable -5.5 x 10(7)) copies/ml in EBV-HLH, which was significantly higher than the 6.6 x 10(1) (undetectable -1.0 x 10(3)) copies/ml in IM (P = 0.0008). We serially analyzed cell-free EBV genome copy number in 10 cases of EBV-HLH up to 4 months from diagnosis. In four patients who achieved remission, the EBV genome became undetectable soon after starting therapy. In the remaining six patients who responded poorly to therapy, the EBV genome copy number in the serum or plasma remained at high levels except for one case. In addition, we confirmed that the EBV genome became undetectable after hematopoietic stem cell transplantation in 4 EBV-HLH cases. These results suggest that the quantitative analysis of cell-free EBV genome copy number is useful for evaluating disease activity and for predicting the response to therapy in EBV-HLH.
authors.affiliation: Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan. ttmoko@city.kyoto.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Teramura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tabata
authors.forename: Tomohito
authors.initials: T
authors.lastname: Yagi
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Hibi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis; D005260:Female; D018628:Gene Dosage; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000175:diagnosis / Q000628:therapy / Q000821:virology*; D006801:Humans; D007223:Infant; D007244:Infectious Mononucleosis / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D019562:Viral Load
chemical_list: D015415:Biomarkers; D004279:DNA, Viral