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Detection by polymerase chain reaction of residual cells with the bcl-2
translocation is associated with increased risk of relapse after autologous
bone marrow transplantation for B-cell lymphoma
JG Gribben, D Neuberg, AS Freedman, CD Gimmi, KW Pesek, M Barber, L Saporito, SD Woo, F Coral and N Spector
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical
School, Boston, MA 02115.
Although molecular biologic techniques can now detect minimal numbers of
residual cancer cells in patients in complete clinical remission, the
clinical significance of minimal residual disease has never been
conclusively established. If the detection of minimal residual disease
predicts which patients will relapse, then therapy could be altered based
upon the detection of these cells. The t(14;18) can be detected by
polymerase chain reaction (PCR) amplification in 50% of patients with
B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in
up to 1 million normal cells. To determine the clinical significance of the
detection of minimal residual lymphoma cells in the bone marrow (BM) PCR
amplification was used to detect the presence of residual lymphoma cells
after autologous BM transplantation (ABMT) in serial BM samples from 134
patients with B-cell lymphoma in whom a bcl- 2 translocation could be
detected. PCR analysis was performed on a total of 542 BM samples obtained
while these patients were in complete remission. Disease-free survival was
markedly increased in patients with no PCR-detectable lymphoma cells in the
marrow compared with those in whom residual lymphoma cells were detected (P
< .00001), and the presence of detectable lymphoma cells was associated
with a 48-fold increase in the risk of relapse. Of the 77 patients (57%)
with no PCR- detectable lymphoma cells in their most recent BM sample, none
have relapsed. In contrast, all 33 patients (25%) who have relapsed had
PCR- detectable lymphoma cells detected in their BM before clinical relapse
occurred. In 19 patients (14%), residual lymphoma cells in the BM were
detected early following transplantation and subsequently were no longer
detectable, although these patients received no further therapy. In these
patients, residual lymphoma cells may already have been irreversibly
damaged by the high-dose therapy or an endogenous immune mechanism may be
capable of eliminating residual lymphoma cells in some patients. Therefore,
although the detection of minimal residual disease by PCR following ABMT in
patients with lymphoma identifies those patients at high risk of relapse,
the presence of residual minimal disease early after transplantation may
not be associated with poor prognosis in a small subset of patients.
Confirmatory studies will be required to determine more definitively the
role of minimal disease detection to identify which patients require
additional therapy.
Volume 81,
Issue 12,
pp. 3449-3457,
06/15/1993
Copyright © 1993 by The American Society of Hematology
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