Fatal Epstein-Barr Virus Reactivation in an Acquired Aplastic Anemia Patient Treated with Rabbit Antithymocyte Globulin and Cyclosporine A

Abstract

Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a nontransplant setting and has not been well described. This report describes a severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was diagnosed as having severe AA. He was started on CsA followed by administration of ATG for five consecutive days. One month after the start of ATG, persistent fever which was not responsive to antibiotics or antifungal agents developed and atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were negative. An extremely high level of EBV virus in his peripheral blood plasma was detected by means of a quantitative real-time PCR assay. Even after the cessation of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated rapidly. The patient suffered from respiratory failure, liver dysfunction, and metabolic acidosis. Rituximab was administered without success and he died.

Reactivation and dynamics of cytomegalovirus and Epstein‐Barr virus after rabbit antithymocyte globulin and cyclosporine for aplastic anemia

“…Our study showed rare, but evident, cases of CMV‐ or EBV‐related disease, even though Sheinberg et al concluded that there is no need to routinely monitor EBV or CMV reactivation based on the absence of cases of CMV‐ or EBV‐related disease, except for subclinical viral reactivation in their cohort. A series of case reports of CMV‐ or EBV‐related disease following rATG‐CsA supports our observation . The cohort in the study by Scheinberg et al included a relatively small number of patients (n = 14) treated with rATG‐CsA and mainly included patients receiving IST with horse ATG (n = 59).…”

“…All seven reported cases with EBV‐LD occurred after rabbit ATG, not horse ATG, although the ATG source and peak EBV load were not described for one case. Furthermore, among five case reports measuring EBV load using the same method as in the current study, the median EBV peak load was 6.6 log (range, 2.08‐6.9 log), which was higher than that of the respective cohort in the study by Sheinberg et al and the subsets without EBV‐LD in our study. Based on the current data, the findings of Sheinberg et al, and corroborating case reports from previous literature, higher CMV and EBV loads could be an important cue to raise clinicians' awareness of the potential risk for CMV‐ and EBV‐related diseases during periodic follow‐up in AA patients receiving rATG‐CsA.…”

“…A series of case reports of CMV-or EBV-related disease following rATG-CsA supports our observation. [33][34][35][36] The cohort in the study by Scheinberg et al 18,29 included In our study, a maximum CMV load of 5 log and maximum EBV load of 7 log showed 100% sensitivity as cutoff values to predict the occurrence of virus-associated disease in the CMV and EBV cohorts, respectively. However, an obvious limitation was that the specificity of cutoff values could not be statistically proven due to the extremely rare incidence of CMV/EBV-related disease.…”

“…Furthermore, among five case reports measuring EBV load using the same method as in the current study, 34,36,[41][42][43] the median EBV peak load was 6.6 log (range, 2.08-6.9 log), which was higher than Despite these limitations, our data reveal frequent reactivation of CMV and EBV and indicate that periodic monitoring of CMV and EBV loads is essential to detect the possible occurrence of CMV-or EBV-related disease in AA patients treated with rATG-CsA. In particular, the monitoring of CMV and EBV is emphasized in patients who receive rATG-CsA 1 year after the diagnosis of AA and whose ALC does not reach 0.4 × 10 9 /L after 1 month of rATG-CsA, respectively.…”

“…A series of case reports of CMV-or EBV-related disease following rATG-CsA supports our observation. [33][34][35][36] The cohort in the study by Scheinberg et al 18,29 included EBV-LD occurred after rabbit ATG, not horse ATG, although the ATG source and peak EBV load were not described for one case.…”