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

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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.

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