CORE--MINIMAL DISEASE DETECTION BY FISH

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We have developed a fluorescent in situ hybridization (FISH) technique for identification of the Ph chromosome in hundreds of cycling cells of the marrow in diagnosis, during, and after therapy. Since so many metaphases are exposed to such analysis the method has been named hypermetaphase FISH or HMF. The procedure enables the determination of statistically significant differences (,4%) in the frequency of Ph+ cells present in patients at presentation and also the detection of minimal levels of such cells (<1%) in patients during treatment. Data to support those contentions are presented. We will employ this procedure to: 1. Determine the frequency of Ph+ cells at presentation and the relationship between that frequency to clinical outcome. 2. Determine the frequency of Ph+ cells during treatment and/or at time points post-BMT in patients with minimal residual disease (MRD) and determine the clinical significance of statistically significant levels and differences. The Core will provide a service to the clinical projects (Projects 1, 2, and 3 involving Drs. Kantarjian, Talpaz, Champlin, and Claxton). Results will also be correlated with the quantitative RT/PCR and bcr/abl results of Dr. Arlinghaus' Core (Core D) to determine the relative benefits and shortcomings of each of the technologies in establishing the cytogenetic response to therapies involved. This information will be cycled back to the clinical projects of the Program to permit the selection of patient care algorithms of individuals for specific types of therapy. These procedures will give us new insights into determining the clinically significant levels of minimal residual disease and guide the further management of individual malignancies in CML patients.