Minimal residual disease in acute myelogenous leukaemia and myelodysplastic syndromes: a follow-up of patients in clinical remission.
The majority of patients with acute myelogenous leukaemia (AML) and myelodysplastic syndromes (MDS) relapse, especially those with unfavourable cytogenetics. This study was designed to investigate the presence and frequency of minimal residual disease (MRD) in patients with AML or MDS (n=35) and numerical abnormalities of chromosomes 6, 7, 8, 9, 10, 17 and 18 in clinical remission by using a combination of fluorescence activated cell sorting (FACS), fluorescence in-situ hybridization (FISH) and labelling with bromodeoxyuridine (BUdR). The technique enables the detection of as few as three leukaemic cells in 10(5) normal cells. MRD was detected in 33/35 patients in complete remission (CR). 16 patients relapsed (8/11 with monosomy 7, 4/17 with trisomy 8, and 4/7 with other cytogenetic abnormalities) after a median of 4.8 months (range 3-13). Levels of MRD (P=0.007) and proliferation index (P=0.011) were significantly higher in patients with monosomy 7 than in patients with trisomy 8 or other cytogenetic abnormalities. The percentage of cells in S-phase, the number of abnormal cells and cytogenetic class were related to time to relapse (P=0.001) with S-phase being the single most important prognostic factor (P=0.0001). We conclude that the combination of FACS/FISH/BUdR, which determines the number, phenotype and proliferation rate of very rare leukaemic cells in patients with AML or MDS in clinical remission, provides information that is useful in the identification of patients with high and low likelihood of relapse.
Engel
H
H
Department of Hematology, The University of Texas M. D. Anderson Cancer Center, Houston, U.S.A.
Goodacre
A
A
Keyhani
A
A
Jiang
S
S
Van
N T
NT
Kimmel
M
M
Sanchez-Williams
G
G
Andreeff
M
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology*; D009365:Neoplasm Regression, Spontaneous; D018365:Neoplasm, Residual; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014314:Trisomy