INCREASED SENSITIVITY OF MINIMAL RESIDUAL DISEASE DETECTION BY INTERPHASE FISH IN ACUTE LYMPHOBLASTIC-LEUKEMIA WITH HYPERDIPLOIDY

Interphase fluorescent in situ hybridization (FISH) for the detection of minimal residual disease detection (MRD) in patients with acute lym phoblastic leukemia (ALL) and a high hyperdiploid clone (>50 chromosom es) at diagnosis is presented. By simultaneous targetting of three chr omosomes gained, a sensitivity of 10(-4) was achieved. Control values (mean + s.d. x 2 of false positive cells in normal peripheral blood) u sing probes singly, in pairs or as a triplet were 1.4-2.0%, 0.01-0.02% and zero (in 10(4) cells), respectively. A serial dilution experiment mixing control blood lymphocytes with bone marrow from a patient with a >85% cells with >50 chromosomes and probing it with single, dual or triple probes, revealed the clone down to dilutions of 10(-1), 10(-3) and 10(-4), respectively. FISH confirmed chromosomal gains at diagnos is (13 cases) and in relapse (three cases). Positive remission samples (0.01 to 0.06% cells with chromosome gains) were more frequent during the first 7 months (7/12) from diagnosis than later (3/11). Serial st udies showed a decline in clone size with time. Conversion from a nega tive to a positive sample heralded relapse in one case. FISH confirmed an isolated central nervous system relapse and detected a hyperdiploi d clone in a chromosomally normal relapse. This technique could be app lied whenever three cytogenetic/genetic changes are found.