Quantitation of minimal residual disease in acute myelogenous leukemia andmyelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells
H. Engel et al., Quantitation of minimal residual disease in acute myelogenous leukemia andmyelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells, LEUKEMIA, 13(4), 1999, pp. 568-577
Detection of karyotypic clonal abnormalities are prognostically useful in p
atients with acute myelogenous leukemia (AML) and myelodysplastic syndromes
(MDS), but cytogenetic methods are not sensitive enough to detect low numb
ers of residual leukemic cells in patients who have achieved complete remis
sion (CR). Fluorescence in situ hybridization (FISH) and fluorescence activ
ated cell sorting (FACS) were used to investigate the frequency and presenc
e of minimal residual disease (MRD) in AML and MDS patients (n=28) with mon
osomy of chromosomes 7, 17 and 18 and trisomy of chromosomes 6, 8, 9 and 10
in CR. MRD was detected in all patients with monosomy 7 (n=10) and followe
d by relapse in eight patients after 4.8 +/- 3.1 months. In contrast, persi
stent leukemic cells occurred in 11/12 patients with trisomy 8, but only th
ree of them relapsed after 7.7+/-4.0 months. Cox regression analysis showed
that cytogenetic class and levels of clonal cells at CR were related to ti
me to relapse (P=0.001). The level of MRD identified patients at high and l
ow risk of relapse. High absolute levels of proliferating residual leukemic
cells correlated with monosomy 7 and high risk of relapse.