A. Venditti et al., Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia, BLOOD, 96(12), 2000, pp. 3948-3952
We used flow cytometry to quantify minimal residual disease (MRD) in 56 pat
ients with acute myeloid leukemia (AML) expressing a leukemia-associated ph
enotype, Thirty-four patients aged 18 to 60 years were entered into the AML
-10 protocol (induction, consolidation, and autologous stem-cell transplant
ation [ASCT]), whereas 22 patients older than 60 years received the AML-13
protocol (induction, consolidation, and consolidation II). After induction,
the level of MRD that was best associated with treatment outcome was 4.5 x
10(-4) residual leukemic cells. However, the outcome in patients with at l
east 4.5 x 10-4 cells (n = 26) was not significantly different from that in
patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses
in the first group and 12 (40%) relapses in the second. After consolidation
, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients
had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these pati
ents had relapse, compared with 5 of 29 patients (17%) with lower MRD level
s (P < .001), An MRD level of 3.5 x 10-4 cells or higher after consolidatio
n was significantly correlated with poor or intermediate-risk cytogenetic f
indings, a multidrug resistance 1 (MDR1) phenotype, short duration of overa
ll survival, and short duration of relapse-free survival (P = .014, .031, .
00022, and .00014, respectively). In multivariate analysis, this MRD status
was significantly associated with a high frequency of relapse (P < .001) a
nd a short duration of overall (P = .025) and relapse-free survival (P = .0
07). ASCT did not alter the prognostic effect of high MRD levels after cons
olidation: the relapse rate after transplantation was 70%, Thus, we found t
hat an MRD level of 3.5 x 10-4 cells or higher at the end of consolidation
strongly predicts relapse and is significantly associated with an MDR1 phen
otype and intermediate or unfavorable cytogenetic findings, (C) 2000 by The
American Society of Hematology.