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Prognosis in AML

Improved prognostic significance of cytokine-induced proliferation in vitro in patients with de novo acute myeloid leukemia of intermediate risk: impact of internal tandem duplications in the Flt3 gene

Leukemia volume 15, pages 1046–1053 (2001)Cite this article

Abstract

The heterogeneity of acute myeloid leukemia is reflected in many clinical, biological and genetic features that are used to predict the response to therapy. On the basis of chromosome aberrations patients can be stratified in groups reflecting either good or poor prognosis. However, the majority of patients fall in an ‘intermediate risk’ group. Internal tandem duplications in the hematopoietic growth factor receptor Flt3 have been shown to separate a subset of high risk patients from intermediate or low risk cases. In an attempt to further characterize the heterogeneity of prognosis among the cytogenetic intermediate risk group of AML, we investigated the overall survival, failure-free survival, initial therapy response and relapse rates of 103 patients with de novoAML in relation to autonomous proliferation and the proliferative response to a panel of 10 cytokines in a short-term thymidine incorporation assay. To exclude perturbation of the responses by other (known) risk factors our final intermediate risk population was comprised of patients with intermediate risk cytogenetics, having an age of 60 years of younger and not showing tandem duplications in the Flt3 gene. Among this intermediate risk group, only the responses to M-CSF and IL-1α were found to be predictive for therapy outcome. Results obtained by a 7-day culture with these cytokines revealed two subpopulations characterized by a good and a poor prognosis, respectively. The complete remission rates in these subpopulations were similar, but the relapse rates, failure-free survival and overall survival differed. If further study extends and supports our data, it should be considered to include these patients in the poor risk arms of treatment protocols and offer them intensified treatment or bone marrow transplantation.

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Acknowledgements

This project was financed by the Dutch Platform for Alternatives in Animal Research (PAD) grant no. VWS/PAD 9625. We would like to thank the staff of the bone marrow transplantation unit of the Department of Hematology for their help in obtaining the thymidine incorporation data.

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Authors and Affiliations

  1. Department of Hematology, Erasmus University, Rotterdam, The Netherlands

    WJC Rombouts, B Löwenberg & RE Ploemacher

  2. Department of Hematology, Dijkzigt University Hospital, Rotterdam, The Netherlands

    B Löwenberg

  3. Department of Statistics, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands

    WLJ van Putten

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  1. WJC Rombouts
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  3. WLJ van Putten
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Rombouts, W., Löwenberg, B., van Putten, W. et al. Improved prognostic significance of cytokine-induced proliferation in vitro in patients with de novo acute myeloid leukemia of intermediate risk: impact of internal tandem duplications in the Flt3 gene. Leukemia 15, 1046–1053 (2001). https://doi.org/10.1038/sj.leu.2402157

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