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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3948-3952
NEOPLASIA
Level of minimal residual disease after consolidation therapy
predicts outcome in acute myeloid leukemia
Adriano Venditti,
Francesco Buccisano,
Giovanni Del Poeta,
Luca Maurillo,
Anna Tamburini,
Christina Cox,
Alessandra Battaglia,
Gianfranco Catalano,
Beatrice Del
Moro,
Laura Cudillo,
Massimiliano Postorino,
Mario Masi, and
Sergio Amadori
From the Cattedra di Ematologia, Università di
Roma Tor Vergata, Divisione di Ematologia, Rome, Italy.
We used flow cytometry to quantify minimal residual disease (MRD)
in 56 patients with acute myeloid leukemia (AML) expressing a
leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years
were entered into the AML-10 protocol (induction, consolidation, and
autologous stem-cell transplantation [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 × 10 4 residual leukemic cells. However, the
outcome in patients with at least 4.5 × 104 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 × 104
cells: 22 patients had an MRD level of 3.5 × 104 cells
or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P < .001). An MRD level of 3.5 × 104 cells or higher after
consolidation was significantly correlated with poor or
intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1)
phenotype, short duration of overall 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) and a short duration of overall
(P = .025) and relapse-free survival
(P = .007). ASCT did not alter the prognostic effect of
high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of
3.5 × 104 cells or higher at the end of consolidation
strongly predicts relapse and is significantly associated with an MDR1
phenotype and intermediate or unfavorable cytogenetic findings.
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