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Influence of molecular characteristics on clinical outcome in human
immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of
a subgroup with favorable clinical outcome
LD Kaplan, B Shiramizu, B Herndier, J Hahn, TC Meeker, V Ng, PA Volberding and MS McGrath
Department of Medicine, San Francisco General Hospital, CA 94110, USA.
The relationship between clinical and molecular characteristics of 45
treated individuals with histologically-documented human immunodeficiency
virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to
determine whether differences in molecular features of lymphoma were
associated with differences in clinical outcome. Tissue specimens from
these tumors were evaluated for evidence of Ig heavy- chain gene
rearrangements using both Southern blot analysis and reverse transcriptase
polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the
presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene
rearrangements. Twenty-five lymphomas were characterized as polyclonal and
20 as monoclonal. PCR amplification of expressed Ig variable (V)-region
genes confirmed polyclonality in three extensively studied polyclonal
lymphomas. The median CD4 count was significantly higher in the group with
polyclonal disease (277/microL) than in the group with monoclonal disease
(123/microL), P = .04. The complete response rate to therapy was
significantly higher in patients with polyclonal disease (78%) and CD4
greater than 200/microL (81%) than in those with monoclonal disease (31%)
and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of
EBV DNA sequences were the most important predictors of survival. Both
Kaplan-Meier and Cox proportional hazards analyses showed a markedly
prolonged survival in those patients with both CD4 > or = 200/microL and
polyclonal disease. Histologically the polyclonal lymphomas were high grade
in appearance and contained prominent macrophages. All seven surviving
patients were in this group. Median survival for those individuals whose
tumors contained EBV sequences 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 characteristics define a distinct subset of patients with polyclonal
EBV- tumors and CD4 counts greater than 200/microL that appear to have a
less aggressive clinical course.
Volume 85,
Issue 7,
pp. 1727-1735,
04/01/1995
Copyright © 1995 by The American Society of Hematology
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