Interphase in situ 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 examined by fluorescence in situ hybridization (FISH) in bone marrow cells from eight patients with high hyperdiploid (> 50 chromosomes) clones at diagnosis. Alphoid centromeric probes to chromosomes X, 10, 17, and 18, trisomic at diagnosis, were used as appropriate. Three hematologically normal marrows were used as controls. At diagnosis, trisomic interphase cells ranged from 69.3-84.4%. One month later, trisomic and tetrasomic interphase cells were significantly increased over control frequencies in 2/7 cases tested (p < 0.05 and p < 0.001) and trisomy alone 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 5/7 samples at one month and in 1/5 samples at two months. One patient examined in chromosomally normal relapse had 34.4% trisomic cells by FISH at confirmed relapse (p < 0.001). An additional hyperdiploid case, examined at central nervous system relapse, had increased numbers of trisomic cells (p < 0.01) in a morphologically 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.