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Molecular quantification of residual disease in chronic myelogenous
leukemia after bone marrow transplantation
JD Thompson, I Brodsky and JJ Yunis
Department of Neoplastic Diseases, Hahnemann University, Philadelphia, PA.
Residual disease remains a major problem in the treatment of human
neoplasia. To effectively monitor minimal leukemic activity after bone
marrow transplantation (BMT), we used a competitive polymerase chain
reaction (PCR) amplification technique to quantify expression of the
characteristic bcr-abl fusion message in patients with chronic myelogenous
leukemia (CML). Quantitative results were obtained between the 0.001% and
0.1% level in control experiments. This represents a significant advantage
over cytogenetic and Southern blotting techniques routinely used to
diagnose CML, which may not be sensitive below the 1% level. To illustrate
the potential clinical usefulness of the quantitative PCR strategy, we
compared results of bcr-abl messenger RNA expression with those obtained
using cytogenetic and Southern blotting techniques, in a study of
consecutive BM and peripheral blood (PB) samples from two CML patients at
high risk for relapse after BMT. One patient received a syngeneic
transplant during the chronic phase of the disease and relapse was apparent
at the molecular level 4.5 months after BMT, while the patient was in
complete clinical remission. The second patient was treated with an
allogeneic BMT during the accelerated phase of the disease. A slow, but
progressive decrease in bcr-abl expression was observed during the first 12
months after BMT, and expression was undetectable thereafter. Our results
indicate that the competitive PCR technique can be used to monitor disease
activity in patients at high risk of relapse, while the patients are in
complete clinical remission, which should facilitate the early detection of
relapse or the identification of progressive disappearance of leukemic
activity. The approach used may serve as a model for the study of residual
disease in an increasing number of other hematologic malignancies that
express cancer-specific RNAs.
Volume 79,
Issue 6,
pp. 1629-1635,
03/15/1992
Copyright © 1992 by The American Society of Hematology

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