Monitoring of Epstein‐Barr virus load after hematopoietic stem cell transplantation for early intervention in post‐transplant lymphoproliferative disease

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Abstract
Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease is a life‐threatening complication following hematopoietic stem cell transplantation. A quantitative polymerase chain reaction to evaluate EBV‐genome copy numbers based on a nested polymerase chain reaction and an end‐point dilution was used. Applying this assay EBV load was prospectively screened weekly in 123 patients after transplantation. The results demonstrate that EBV reactivations with more than 1,000 EBV‐genome copies measured in 105peripheral blood mononuclear cells were observed in 31 patients (25.2%). Three patients developed lymphoproliferative disease with extremely high EBV‐genome copies in peripheral blood mononuclear cells (>100,000 copies/105cells) and plasma. After combined antiviral and immune therapy two of three patients showed a dramatic decrease of EBV load and survived, while the third patient died of lymphoma. A subclinical EBV reactivation was observed in 24 cases (19.5%) with EBV‐genome copies in 105peripheral blood mononuclear cells ranging between 2,500 and mostly 10,000. After reduction of immunosuppression the EBV levels normalized. In four patients, the high copy number of ≥80,000 copies/105peripheral blood mononuclear cells and plasma positivity prompted us to start pre‐emptive therapy with rituximab and cidofovir for prevention of lymphoproliferative disease. After drug administration the high EBV load was reduced remarkably. Ninety‐two patients (74.8%) who had ≤1,000 copies/105peripheral blood mononuclear cells did not develop EBV‐associated lymphoproliferative disease. In conclusion, monitoring of EBV load is a sensitive and useful parameter in the surveillance of EBV reactivation for early intervention in EBV‐associated lymphoproliferative disease as well as for follow‐up of the efficacy of therapy. J. Med. Virol. 80:441–454, 2008.