Correlation of minimal residual disease cell frequency with molecular genotype in patients with acute myeloid leukemia

Corine J. Hess, Nicole Feller, Fedor Denkers, Angèle Kelder, Pauline A. Merle, Michael C. Heinrich, Amy Harlow, Johannes Berkhof, Gert J. Ossenkoppele, Quinten Waisfisz, Gerrit J. Schuurhuis

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    8 Scopus citations

    Abstract

    Background: About 70-80 percent of patients with acute myeloid leukemia enter complete remission, but at least half of these patients who achieve remission go on to relapse. Improved treatment is likely to come from increasing the time to relapse, especially for younger patients. With the vastly increasing number of targeted therapies there is a strong need for shortterm end-points to efficiently test such therapies for further pursuance. Minimal residual disease assessment may offer such an end-point since it is a strong independent prognostic factor. As proof of principle we examined this concept for FLT3-ITD status at diagnosis. Design and Methods: We determined FLT3-ITD status in bone marrow samples from 196 patients with newly diagnosed acute myeloid leukemia. The frequencies of residual leukemic cells of these 196 patients were assessed in 267 follow-up bone marrow samples using immunophenotypic assessment of minimal residual disease. Results: The median frequency of residual leukemic cells after the first cycle of chemotherapy was 8.5-fold higher in patients with FLT3-ITD than in those with wild type FLT3. Such a difference translates into differences in survival, even if other potentially outcome-modulating mutations, such as NPM1, KIT, NRAS, KRAS, FLT3-exon 20 and PTPN11 are included in the analysis. Conclusions: This study shows that it could be possible to study the efficacy of FLT3 inhibitors using the level of minimal residual disease as a short-term end-point.

    Original languageEnglish (US)
    Pages (from-to)46-53
    Number of pages8
    JournalHaematologica
    Volume94
    Issue number1
    DOIs
    StatePublished - Jan 1 2009

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    Keywords

    • Acute myeloid leukemia
    • FLT3
    • Minimal residual disease

    ASJC Scopus subject areas

    • Hematology

    Cite this

    Hess, C. J., Feller, N., Denkers, F., Kelder, A., Merle, P. A., Heinrich, M. C., Harlow, A., Berkhof, J., Ossenkoppele, G. J., Waisfisz, Q., & Schuurhuis, G. J. (2009). Correlation of minimal residual disease cell frequency with molecular genotype in patients with acute myeloid leukemia. Haematologica, 94(1), 46-53. https://doi.org/10.3324/haematol.13110