PERSISTENCE OF THE SAME VIRAL STRAIN IN EARLY AND LATE RELAPSES OF EPSTEIN-BARR VIRUS-ASSOCIATED HODGKINS-DISEASE

Twelve cases of relapsing Hodgkin's disease were investigated for the presence of Epstein-Barr virus (EBV). Of these, 7 cases contained EBV gene products (LMP1, EBER RNA) in the diagnostic Reed-Sternberg cells and variants at first presentation and at relapse(s), whereas 5 cases were negative at both first diagnosis and relapse. Among the 7 EBV-pos itive cases, material for DNA extraction was available in 2 cases at b oth diagnosis and relapse(s). Ig and T-cell receptor gene rearrangemen ts displayed a germline configuration in the 2 cases. However, Souther n blot analysis of the terminal repeats (TR) of EBV genome showed that , in 1 of the 2 cases, the fragment was of the same size at diagnosis and in the subsequent two relapses (1 early and 1 late). The second ca se contained monoclonal EBV genome at diagnosis, but the Southern anal ysis of the TR was negative at relapse. The latent membrane protein (L MP1) sequence analysis confirmed the persistence of a distinctive Vira l strain in each of the 2 cases with individual abnormalities within t he carboxy terminal region (5 point mutations and a 30-bp deletion for the first case! and 6 point mutations for the second case). The persi stence of a given strain in early and late relapses is evidence toward s the view that in Hodgkin's disease such relapses are related to a si ngle residual tumor cell clone. (C) 1994 by The American Society of He matology.