Follow-up of Minimal Residual Disease in Pediatric Acute Myeloblastic Leukemia Using Metaphase-FISH

Abstract

In acute myeloblastic leukemia (AML) the follow-up of minimal residual disease (MRD) has focused on specific chromosomal aberrations (e.g. t(15;17), t(8;21), inv16/t(16;16)) mostly employing reverse transcriptase-PCR. High or increasing levels of MRD are associated with an increased risk of relapse but low levels may persist in patients with prolonged or even durable remission. In adult patients with AML the increased risk of relapse has also been demonstrated using flow cytometry and fluorescence in situ hybridization (FISH). We evaluated the presence of MRD among pediatric patients with AML during and after the cessation of therapy. We were able to establish a clonal marker for the follow-up in 80% of our cases; 11 of the 15 with a clonal marker had detectable MRD at some point during follow-up while 4/15 relapsed 12-14 months after diagnosis. In two there was hematological relapse preceded by an increase in their FISH-detectable number of clonal cells. In 7 of the 11 remaining in CR1 there were small (< 1%) numbers of clonal cells detectable at one or more time-points. Out of the group of 15 pediatric patients with AML, 12 are currently alive in CCR with a median follow-up of 44 months (range 7–63 months). Our data establish the role of metaphase-FISH in the follow-up of AML in children and emphasize the importance of an increasing level of MRD in predicting a relapse. Yet, low and stable levels of marrow MRD a ppear compatible with CCR.