Detection of non-Hodgkin's lymphoma in the peripheral blood by analysis of
antigen receptor gene rearrangements: results of a prospective study
SJ Horning, N Galili, M Cleary and J Sklar
Department of Medicine, Stanford University Medical Center, CA.
Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements,
using Southern blot hybridization, has been applied to peripheral blood
lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma.
The incidence of circulating lymphoma cells detected by gene rearrangement
analyses is related to the histologic subtype, clinical stage of disease,
and clinical status. Among 104 patients studied at diagnosis, the incidence
of positive analyses was 34% in low-grade lymphoma and only 8% in
intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected
nearly universally in the small lymphocytic histologic subtype. PBL studies
were related to the initial stage of disease: positive studies were seen in
35% of patients with stage IV disease, 29% of patients with stage III
disease, and 12% of patients with stages I-II disease. The incidence of PBL
rearrangements at the time of disease recurrence in 32 patients requiring
cytoreductive therapy was 48%, somewhat greater than at initial diagnosis.
A group of patients with low-grade lymphoma, who had treatment deferred
after diagnosis or recurrence, was also studied; the incidence of PBL
rearrangements was 38% in this population. Among 157 patients clinically
free of disease, DNA analyses of the PBL were positive in only 10%.
Subsequent relapse of disease in 26 patients was antedated by PBL
rearrangement in only one patient. Clonal rearrangements detected in 15
patients have been followed by recurrence of clinical disease in only one
patient over a median of 24 months from the time of analysis. The lack of
detectable rearrangements in the peripheral blood in the majority of
patients may be due to methodology or the biology of the disease. These
issues may be further addressed with alternative methods for assessment of
minimal disease. However, rigorous testing of any new molecular tool
requires an adequate patient population in which disease status is closely
monitored over a sufficient period of time.
Volume 75,
Issue 5,
pp. 1139-1145,
03/01/1990
Copyright © 1990 by The American Society of Hematology
