INTERPHASE INSITU HYBRIDIZATION REVEALS MINIMAL RESIDUAL DISEASE IN EARLY REMISSION AND RETURN OF THE DIAGNOSTIC CLONE IN KARYOTYPICALLY NORMAL RELAPSE OF ACUTE LYMPHOBLASTIC-LEUKEMIA

Early clinical remission of acute lymphoblastic leukemia (ALL) was exa mined by fluorescence in situ hybridization (FISH) in bone marrow cell s from eight patients with high hyperdiploid (> 50 chromosomes) clones at diagnosis. Alphoid centromeric probes to chromosomes X, 10, 17, an d 18, trisomic at diagnosis, were used as appropriate. Three hematolog ically normal marrows were used as controls. At diagnosis, trisomic in terphase cells ranged from 69.3-84.4%. One month later, trisomic and t etrasomic interphase cells were significantly increased over control f requencies in 217 cases tested (p < 0.05 and p < 0.001) and trisomy al one in one case (p < 0.05). At two months post-diagnosis, trisomy and tetrasomy were in the control range. Pentasomy and hexasomy, not seen in controls, were found in 517 samples at one month and in 115 samples at two months. One patient examined in chromosomally normal relapse h ad 34.4% trisomic cells by FISH st confirmed relapse (p < 0.001). An a dditional hyperdiploid case, examined at central nervous system relaps e, had increased numbers of trisomic cells (p < 0.01) in a morphologic ally and cytogenetically normal marrow. These findings demonstrate the elimination of aberrant ploidy in most hyperdiploid cases two months from diagnosis and indicate that failure to detect the abnormal clone in relapse may result from selective mitotic activity of chromosomally normal cells, rather than relapse in a cytogenetically normal clone.