MRD monitoring falls short in childhood AML assessment

Sep 19 2012

By Nikki Withers, medwireNews Reporter

Measuring treatment response by minimal residual disease (MRD) monitoring offers no more prognostic value than morphologic analysis in children with acute myeloid leukemia (AML), show study findings.

Previous studies have suggested that assessment of early treatment response by morphologic analysis of bone marrow predicts long-term outcome.

Methods to track leukemic cells based on flow cytometry or polymerase chain reaction (PCR) have the potential for superior sensitivity and accuracy, explain the researchers. They allow the recognition of leukemic cells present at levels well below those detectable by morphology.

Hiroto Inaba (St Jude Children's Research Hospital, Memphis, Tennessee, USA) and colleagues therefore investigated the prognostic value of MRD monitoring with flow cytometry in bone marrow samples from 203 children and adolescents with newly diagnosed AML. They then compared the results with those assessed by morphologic analysis and PCR.

In all, 1514 bone marrow samples were analyzed: 1514 by flow cytometry, 1382 by morphology, and 508 by PCR amplification of fusion transcripts.

Among 1215 samples with less than 5% leukemic myeloblasts when assessed by morphology, 8.2% were MRD positive (≥0.1%) by flow cytometry, whereas of the 167 samples with 5% or more myeloblasts by morphology, 57.5% were MRD negative when assessed by flow cytometry.

Of the MRD-negative samples assessed by PCR, nearly all (99%) were also MRD negative when assessed by flow cytometry. However, only 9.6% of the 197 PCR-positive samples were positive according to flow cytometry.

Multivariate analysis revealed that MRD monitoring by flow cytometry was an independent predictor for adverse outcomes. Prediction was not improved by morphologic information provided by PCR.

"Our study shows that measurements of treatment response by flow cytometry are widely applicable and provide strong prognostic information," say Inaba et al.

However, they stress that the use of MRD monitoring assessments to select treatment strategies "should be undertaken with caution."

The findings are published in the Journal of Clinical Oncology.

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