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Detection of minimal residual disease in T-cell acute lymphoblastic
leukemia using polymerase chain reaction predicts impending relapse
GA Neale, J Menarguez, GR Kitchingman, TJ Fitzgerald, M Koehler, J Mirro and RM Goorha
Department of Virology, St Jude Children's Research Hospital, Memphis, TN
38101.
After achieving remission, approximately one-third of patients with T- cell
acute lymphoblastic leukemia (T-ALL) relapse due to the resurgence of
residual leukemic cells that cannot be detected in remission by morphologic
methods. Thus, the early detection of residual disease is highly desirable
to monitor the efficacy of therapy, or to institute an alternative mode of
therapy. Toward this aim, we have examined the applicability of polymerase
chain reaction (PCR) amplification in the detection of minimal residual
disease (MRD) in bone marrow samples from patients with T-ALL in
morphologic remission. Two different approaches were taken to identify
leukemic clone-specific sequences that could be used as targets for PCR
amplification. The first technique used T-cell receptor-delta (TCR-delta)
gene rearrangements that were sequenced directly after PCR amplification of
leukemic DNA. This method was successful in generating clone-specific
probes for 76% of T-ALL patients screened. An alternative method was used
to clone and sequence a TCR-beta chain gene from leukemic cells to generate
a specific probe. The PCR assays that we used were specific for each
patient's leukemic clone, and were capable of routinely detecting one
leukemic cell in 10(4) normal cells. Using these sensitive PCR-based
assays, we found no evidence for persistence of the leukemic clone in any
of the bone marrow samples from four T-ALL patients who are in long-term
(3.9 + to 8.1 + years) remission. In contrast, we detected residual disease
in clinical remission samples from two patients who subsequently relapsed.
In one patient, where we had appropriate samples, we observed a dramatic
expansion of the leukemic clone 3 months before clinical relapse. These
results suggest that PCR-based assays for detection of MRD in T-ALL
patients have great potential in predicting impending relapse, and in
determining the efficacy of the anti-leukemic therapy. These methods may
also allow the identification of long-term survivors.
Volume 78,
Issue 3,
pp. 739-747,
08/01/1991
Copyright © 1991 by The American Society of Hematology
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