DETECTION OF MINIMAL RESIDUAL DISEASE USING FLUORESCENCE DNA IN-SITU HYBRIDIZATION - A FOLLOW-UP-STUDY IN LEUKEMIA AND LYMPHOMA PATIENTS

We used fluorescence DNA in situ hybridization (FISH) to detect chromo somal abnormalities as an indicator of minimal residual disease in fol low-up samples from the bone marrow (BM), or peripheral blood, of 25 p atients with leukemia, lymphoma and myelodysplastic syndromes. Trisomi es were detected by interphase FISH with repeat-sequence probes (RSP) or by using metaphase FISH with whole-chromosome paint probes (WCP). S pecific translocations were detected using WCP probes. Translocations were observed using metaphase FISH in two patients in uncertain or com plete remission (CR), who both later suffered relapse. Five patients w ith no abnormal cells remained in CR. Four patients with trisomies det ected during CR suffered relapse; metaphase FISH detected the trisomy in 0.17-16% of metaphase cells. Five patients for whom the trisomy occ urred in 0-0.34% of cells remained in CR. Trisomic nuclei were observe d in 0.27-2.3% of interphase cells, by means of RSPs, in four patients who later suffered relapse. Five patients with trisomic nuclei in 0-0 .61% remained in CR. When two probes were used simultaneously in a sam ple from one patient, 1% of the residual cells were abnormal. The pati ent later suffered relapse. In one patient with anaplastic large cell lymphoma, CD30-positive interphase cells were shown to have trisomic c hromsome 7 by immunophenotyping and FISH. Our results suggest that met aphase FISH using WCP probes is a sensitive and specific method for de tecting minimal residual disease especially in patients with transloca tions.