INFLUENCE OF MOLECULAR CHARACTERISTICS ON CLINICAL OUTCOME IN HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED NON-HODGKINS-LYMPHOMA - IDENTIFICATION OF A SUBGROUP WITH FAVORABLE CLINICAL OUTCOME

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficie ncy virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma wer e associated with differences in clinical outcome. Tissue specimens fr om these tumors were evaluated for evidence of Ig heavy-chain gene rea rrangements using both Southern blot analysis and reverse transcriptas e polymerase chain reaction (RT-PCR). Lymphomas were also evaluated fo r the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gen e rearrangements. Twenty-five lymphomas were characterized as polyclon al and 20 as monoclonal. PCR amplification of expressed Ig variable (V )-region genes confirmed polyclonality in three extensively studied po lyclonal lymphomas. The median CD4 count was significantly higher in t he group with polyclonal disease (277/mu L) than in the group with mon oclonal disease (123/mu L), P = .04. The complete response rate to the rapy was significantly higher in patients with polyclonal disease (78% ) and CD4 greater than 200/mu L (81%) than in those with monoclonal di sease (31%) and CD4 less than 200/mu l (33%). CD4 count, clonality, an d presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses show ed a markedly prolonged survival in those patients with both CD4 great er than or equal to 200/mu L and polyclonal disease. Histologically th e polyclonal lymphomas were high grade in appearance and contained pro minent macrophages. All seven surviving patients were in this group. M edian survival for those individuals whose tumors contained EBV sequen ces was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV(- ) tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These chara cteristics define a distinct subset of patients with polyclonal EBV(-) tumors and CD4 counts greater than 200/mu L that appear to have a les s aggressive clinical course. (C) 1995 by The American Society of Hema tology.