title: Molecular quantification of viral load in plasma allows for fast and accurate prediction of response to therapy of Epstein-Barr virus-associated lymphoproliferative disease after allogeneic stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Haematology, University Hospital Rotterdam/Daniel den Hoed Cancer Centre, The Netherlands. esser@hemh.azr.nl
authors.forename: J W
authors.initials: JW
authors.lastname: van Esser
authors.forename: H G
authors.initials: HG
authors.lastname: Niesters
authors.forename: S F
authors.initials: SF
authors.lastname: Thijsen
authors.forename: E
authors.initials: E
authors.lastname: Meijer
authors.forename: A D
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: K C
authors.initials: KC
authors.lastname: Wolthers
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: L M
authors.initials: LM
authors.lastname: Budel
authors.forename: B
authors.initials: B
authors.lastname: van der Holt
authors.forename: A M
authors.initials: AM
authors.lastname: van Loon
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: L F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000741:Anemia, Aplastic / Q000401:mortality / Q000601:surgery / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000601:surgery / Q000821:virology; D007951:Leukemia, Myeloid / Q000401:mortality / Q000601:surgery / Q000821:virology; D015477:Leukemia, Myelomonocytic, Chronic / Q000401:mortality / Q000601:surgery / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000401:mortality / Q000601:surgery* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000601:surgery / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000601:surgery / Q000821:virology; D011379:Prognosis; D015996:Survival Rate; D014184:Transplantation, Homologous; D019562:Viral Load
chemical_list: D004279:DNA, Viral