NACHWEIS VON MINIMALER RESTERKRANKUNG BEI PATIENTEN MIT AKUTER MYELOISCHER LEUKAMIE UND MYELODYSPLASTISCHEM SYNDROM IN KLINISCHER REMISSION MITTELS MOLEKULARER ZYTOGENETIK

The majority of patients with acute myelocytic leukemia (AML) or myelodysplastic syndromes (MDS), especially those with unfavorable cytogenetics, relapse. The survival mechanism of residual leukemic cells in the bone marrow is unknown and sensitive detection methods are necessary to monitor their levels. The occurrence and frequency of minimal residual disease (MRD) during complete remission (CR) was investigated in 35 patients with AML or MDS exhibiting abnormalities of chromosomes 6, 7, 8, 9, 10, 17, and 18. Specimens of bone marrow were incubated with bromodeoxyuridine (BUdR) and bone marrow cells were sorted by fluorescence activated cell sorting (FACS) according to the phenotype present at the time of diagnosis. Interphases were analyzed by fluorescence in situ hybridization (FISH). As few as 3 leukemic cells in 100,000 normal cells could be detected with the method employed. MRD was found in 33 of 35 patients, 16 of them relapsed (8 of 11 with monosomy 7, 4 of 17 with trisomy 8 and 4 of 7 with other chromosomal abnormalities). MRD levels (p = 0.007) and S-phase (p = 0.011) were significantly higher in patients with monosomy 7 than in patients with trisomy 8 or other abnormalities. Cox regression analysis showed a relation of S-phase, MRD level and cytogenetical group to duration of remission (p = 0.001), the S-phase representing the best prognostic factor (p = 0.0001). It is concluded that during clinical remission the combination of FACS, FISH and BUdR allows the identification of patients with high or low risk of relapse.