FOLLOW-UP OF RESIDUAL DISEASE USING METAPHASE-FISH IN PATIENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA IN REMISSION

Metaphase-FISH (fluorescence in situ hybridization) was used to detect cells with a chromosomal trisomy and/or translocation in 25 patients with acute lymphoblastic leukemia (ALL) in remission. Twelve patients were treated with chemotherapy alone and 13 patients received bone mar row transplantation after initial chemotherapy. Patients were followed up for 8-56 months (median 18 months). In this study, a total of 82 b one marrow samples were analyzed. Metaphase-FISH identified chromosome morphology, even banding, in cells from which FISH signals were studi ed. Thus, it is as reliable as standard karyotype analysis and does no t cause false positive results. Furthermore, more than 1000 cells can he analyzed in 3-6 h which equals the time it takes to analyze 20 meta phases by standard karyotype. The time span before the first positive sample seems to be insignificant with regard to the outcome of relapse . All six patients, who had more than 1% of abnormal cells detected at any sampling or whose consecutive follow-up samples showed an increas ing frequency (up to 1%) of abnormal cells, relapsed. Absence or occur rence of low numbers of abnormal cells at a frequency of 0.05-0.8% fol lowed by their disappearance was in agreement with continuing complete clinical and hematologic remission (CR) in 16 (84%) of 19 patients. O ur results indicate that metaphase-FISH is a reliable technique far qu antifying residual leukemic eels. The technique is available in standa rd cytogenetic laboratories and can be applied to routine follow-up of ALL patients who have a suitable chromosomal aberration.