Quantification of the breakpoint cluster region rearrangement for clinical
monitoring in Philadelphia chromosome-positive chronic myeloid leukemia
CF Verschraegen, M Talpaz, CF Hirsch-Ginsberg, R Pherwani, MB Rios, SA Stass and HM Kantarjian
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA.
The purpose of this report was to evaluate scintigraphy analysis of
Southern blot hybridization as a method to quantify the breakpoint cluster
region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic
myelogenous leukemia (CML). Cytogenetic and molecular studies performed
simultaneously on 474 bone marrow and/or blood samples from 300 patients
treated with alpha-interferon-based therapy were compared. Molecular
results were expressed as the percentage of rearranged BCR bands versus the
total scintigraphic signal. The percentage of Ph+ metaphases was calculated
on 25 metaphases. The results of molecular studies obtained on both
peripheral blood and bone marrow samples were identical. The rank
correlation between the BCR quantification and the percentage of Ph
positivity in 465 samples was excellent (r = .78). However, of 99 samples
with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no
BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial
cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR
rearrangement. In samples with a minor or no cytogenetic response (Ph+
metaphases, > 34%), BCR analysis overestimated the degree of response in
73 of 326 samples (22%). Nevertheless, survival analysis by BCR
quantification level showed statistically better outcome for patients in
complete or partial molecular response (P < .01). Molecular
quantification of BCR was useful in monitoring the course of Ph+ CML. This
method, which can be used on peripheral blood, detected residual disease
not shown by cytogenetic analysis and was prognostically relevant as a
measure of disease suppression.
Volume 85,
Issue 10,
pp. 2705-2710,
05/15/1995
Copyright © 1995 by The American Society of Hematology
