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Eradication of polymerase chain reaction detectable immunoglobulin gene
rearrangement in non-Hodgkin's lymphoma is associated with decreased
relapse after autologous bone marrow transplantation
CS Zwicky, AB Maddocks, N Andersen and JG Gribben
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical
School, Boston, MA 02115, USA.
In B-cell non-Hodgkin's lymphoma (NHL), as in other B-cell malignancies,
clonal rearrangement of the third complementarity determining region (CDR
III) of the immunoglobulin heavy chain gene (IgH) provides a useful marker
for the detection of minimal residual disease (MRD) after treatment. To
determine the clinical utility of IgH polymerase chain reaction (PCR), we
analyzed peripheral blood (PB) and bone marrow (BM) samples from 25
patients with NHL with no PCR detectable chromosomal rearrangement who have
undergone autologous bone marrow transplantation (ABMT). Patients with
histologic bone marrow infiltration at the time of bone marrow harvest were
selected for study since this provided us with diagnostic tissue samples.
As an initial strategy DNA was amplified using consensus variable (VH) and
joining (JH) region primers. In those cases failing to amplify using
consensus region primers, PCR was performed using a panel of VH
family-specific framework region 1 (FR1) primers. The clonal products were
directly sequenced. From the V-N-D region nucleotide sequences, clone
specific probes were constructed and used for subsequent detection of MRD.
A clonal PCR product could be PCR amplified and directly sequenced in 18
(72%, 90% confidence intervals 54%-86%) of these 25 patients, 8 with
diffuse and 10 with follicular NHL. Eight of these 18 patients have
relapsed after ABMT. All had detectable lymphoma cells before relapse and
the sequence of the CDR III region at the time of relapse was identical to
that obtained at the time of ABMT. All 10 patients who remain in complete
remission from 18 to 36 months after ABMT had eradication of PCR detectable
lymphoma cells after ABMT, although in three patients PCR detectable MRD
was detected early after ABMT. We conclude that sequencing and the use of
patient specific IgH CDR III oligonucleotides probes provides a simple and
highly reliable method to determine the specificity of the IgH PCR
technique. The clinical utility of this technique is demonstrated by the
finding that eradication of PCR detectable lymphoma cells in these patients
is associated with decreased relapse after ABMT (P = .0002).
Volume 88,
Issue 9,
pp. 3314-3322,
11/01/1996
Copyright © 1996 by The American Society of Hematology

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