QUANTIFICATION OF THE BREAKPOINT CLUSTER REGION REARRANGEMENT FOR CLINICAL MONITORING IN PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOID-LEUKEMIA

The purpose of this report was to evaluate scintigraphy analysis of So uthern blot hybridization as a method to quantify the breakpoint clust er region (BCR) rearrangement of Philadelphia chromosome (Ph)(+) chron ic myelogenous leukemia (CML). Cytogenetic and molecular studies perfo rmed simultaneously on 474 bone marrow and/or blood samples from 300 p atients treated with alpha-interferon-based therapy were compared. Mol ecular results were expressed as the percentage of rearranged BCR band s versus the total scintigraphic signal. The percentage of Ph(+) metap hases was calculated on 25 metaphases. The results of molecular studie s obtained on both peripheral blood and bone marrow samples were ident ical. The rank correlation between the BCR quantification and the perc entage of Ph positivity in 465 samples was excellent (r = .78). Howeve r, 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 overestima ted the degree of response in 73 of 326 samples (22%). Nevertheless, s urvival analysis by BCR quantification level showed statistically bett er outcome for patients in complete or partial molecular response; (P < .01). Molecular quantification of BCR was useful in monitoring the c ourse of Ph(+) CML. This method, which can be used on peripheral brood , detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression. (C) 1995 by The American Society of Hematology.