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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1746-1751
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Early immunophenotypical evaluation of minimal
residual disease in acute myeloid leukemia identifies different patient
risk groups and may contribute to postinduction treatment
stratification
Jesús F. San Miguel,
María B. Vidriales,
Consuelo López-Berges,
Joaquín Díaz-Mediavilla,
Norma Gutiérrez,
Consuelo Cañizo,
Fernando Ramos,
María J. Calmuntia,
José J. Pérez,
Marcos González, and
Alberto Orfao
From the Department of Hematology, University Hospital;
Department of Cytometry, University of Salamanca; Centro de
Investigación del Cancer, Salamanca; Department of Hematology,
San Carlos University Hospital, Madrid; Department of Hematology,
Complejo Hospitalario, León; and Department of Hematology,
General Hospital, Segovia, Spain.
Early response to therapy is one of the most important prognostic
factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk
for relapse from those who may remain in complete remission (CR). Using
multiparametric flow cytometry, the level of minimal residual disease
(MRD) was evaluated in the first bone marrow (BM) in morphologic CR
obtained after induction treatment from 126 patients with acute myeloid
leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on
MRD level, 4 different risk categories were identified: 8 patients were
at very low risk (fewer than 10 4 cells), and none have
relapsed thus far; 37 were at low risk (104 to
103 cells); and 64 were at intermediate risk (fewer than
103 to 102 cells), with 3-year cumulative
relapse rates of 14% and 50%, respectively. The remaining 17 patients
were in the high-risk group (more than 102 residual
aberrant cells) and had a 3-year relapse rate of 84% (P = .0001). MRD level not only influences relapse-free
survival but also overall survival (P = .003). The
adverse prognostic impact was also observed when M3 and non-M3 patients
with AML were separately analyzed, and was associated with adverse
cytogenetic subtypes, 2 or more cycles to achieve CR, and high white
blood cell counts. Multivariate analysis showed that MRD level was the
most powerful independent prognostic factor, followed by cytogenetics
and number of cycles to achieve CR. In conclusion, immunophenotypical
investigation of MRD in the first BM in mCR obtained after AML
induction therapy provides important information for risk assessment in
patients with AML.
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