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836 Aims: PTLD associated with EBV infection has been shown to be associated with very high circulating EBV viral load at presentation. The natural history of circulating viral load during treatment of PTLD and non-PTLD 10 EBV infection is not well documented. Methods: EBV viral load in peripheral blood mononuclear cells (PBMC) was determined by a quantitative competitive PCR in 19 pediatric thoracic recipients with EBV driven PTLD or other 10 EBV infection. All patients had reduction of immunosuppression and 17 received anti-viral therapy. Viral load was expressed as number of copies of genome/105 PBMC; virological clearance was defined as viral load of <200. "Rebound" was defined as viral load ≥ 200 after prior clearance. Results: A total of 192 EBV PCR assays were performed in 19 pts (average 10.1/pt) (PTLD n=13; non-PTLD n=6). Viral loads at presentation were comparable between the two groups (range 200 to >5,000/105 PBMC). Of the 6 without PTLD, 2 were asymptomatic and 4 had EBV-associated viral syndromes. Three of these 6 have persistent high viral loads during follow-up of 6-40 months; 1 pt remaining asymptomatic, 1 with recurrent tonsillitis, and 1 with chronic neutropenia & pancreatitis. The other 3 cleared their viral load 12 days to 8 weeks after presentation; 1 rebounded to 400/105 PBMC without recurrent symptoms. Thirteen developed PTLD 6 months to 6 years (median 4 months) after heart (8) or lung/heart-lung (5) transplantation. Serial viral load levels differed between heart and heart-lung/lung recipients. Five of 8 heart recipients cleared their viral load between 7 days and 9 months (median 2 months) concomitant with resolution of PTLD; 1 showed transient rebound without clinical symptoms. Of the remaining 3 patients, 1 died of progressive PTLD without clearance and 2 had PTLD resolution despite chronic high viral loads. By contrast, none of the 5 lung/heart-lung recipients with PTLD had viral load clearance; 2 had progressive, fatal PTLD; 3 survivors have persistently high viral loads despite PTLD resolution during follow-up of 40-53 months. During weaning of immunosuppression, rebound acute rejection occurred in 6/19 patients (31%) at 9-63 days (median 25 days). PCR at that time revealed low viral loads (8-200), Treatment for rebound rejection did not cause clinical relapse. Conclusions: Initial viral load did not distinguish pts with 10 EBV viral syndromes from those with PTLD. Heart recipients cleared their viral load more effectively than lung recipients, likely, in part, due to the greater ability to reduce immunosuppression. Rebound rejection was usually associated with low viral loads and was not seen when loads exceeded 200/105 PBMC. Very high viral loads persisted long-term in a significant proportion of patients with either resolved PTLD or other 10 EBV infections. We speculate that these patients may be at high risk for recurrent symptomatic disease if augmentation of immunosuppression is performed.
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Webber et al. (1999) studied this question.