Abstract

Flow-cytometric detection of minimal residual disease (MRD) has proven in several single-institute studies to have an independent prognostic impact. We studied whether this relatively complex approach could be performed in a multicenter clinical setting. Five centers developed common protocols to accurately define leukemia-associated (immuno)phenotypes (LAPs) at diagnosis required to establish MRD during/after treatment. List mode data files were exchanged, and LAPs were designed by each center. One center, with extensive MRD experience, served as the reference center and coordinator. In quarterly meetings, consensus LAPs were defined, with the performance of centers compared with these. In a learning (29 patients) and a test phase (35 patients), a mean of 2.2 aberrancies/patient was detected, and only 1/63 patients (1.6%) had no consensus LAP(s). For the four centers without (extensive) MRD experience, clear improvement could be shown: in the learning phase, 39–63% of all consensus LAPs were missed, resulting in a median 30% of patients (range 21–33%) for whom no consensus LAP was reported; in the test phase, 27–40% missed consensus LAPs, resulting in a median 16% (range 7–18%) of ‘missed' patients. The quality of LAPs was extensively described. Immunophenotypic MRD assessment in its current setting needs extensive experience and should be limited to experienced centers.

Highlights

  • IntroductionThe interest in minimal residual disease (MRD) assessment as a prognostic tool in acute myeloid leukemia (AML) is growing

  • The interest in minimal residual disease (MRD) assessment as a prognostic tool in acute myeloid leukemia (AML) is growing.Molecular markers, allowing a greater sensitivity, enable MRD monitoring only in a minority of cases.[1]

  • Immunophenotypic detection of MRD using flow cytometry can be performed by defining aberrant expression of markers or marker combinations on the leukemic cells at diagnosis

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Summary

Introduction

The interest in minimal residual disease (MRD) assessment as a prognostic tool in acute myeloid leukemia (AML) is growing. Allowing a greater sensitivity, enable MRD monitoring only in a minority of cases.[1] Immunophenotypic. MRD detection using flow cytometry turned out to offer an attractive alternative. Several early studies have shown the prospective value of the frequency of MRD cells for survival of AML patients both in adults[2,3,4,5,6] and in children.[7,8,9] many other studies have confirmed these data.[1,10] Immunophenotypic detection of MRD using flow cytometry can be performed by defining aberrant expression of markers or marker combinations on the leukemic cells at diagnosis

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