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Myelodysplasias

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy

Leukemia volume 24, pages 2056–2062 (2010)Cite this article

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Abstract

Fludarabine combination chemotherapy achieves high response rates in chronic lymphocytic leukemia (CLL) and indolent lymphoma. The aim of this study was to investigate the incidence and characteristics of treatment-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) after treatment with fludarabine in combination for lymphoproliferative disorders and identify risk factors for its development. In all, 176 patients treated with fludarabine combination were followed for a median of 41 months (range 6–125 months). In all, 19 cases of t-MDS/AML have been identified for an overall rate of 10.8%. Median overall survival post-t-MDS/AML diagnosis was 11 months. Patients developing t-MDS/AML included 11/54 with follicular lymphoma (FL) (crude rate 20.4%), 5/82 with CLL (6.1%) and 3/24 with Waldenstrom macroglobulinemia or marginal zone lymphoma (12.5%). Most patients had other cytotoxic treatments (median 4, range 0–7) but three with FL had fludarabine combination as their only line of treatment. Of the eleven patients (6.3%) who received mitoxantrone with their first fludarabine combination, four (36.4%) developed t-MDS/AML (P=0.007). There was a trend toward prior cytotoxic therapy increasing the risk for t-MDS/AML (P=0.067). Fludarabine combination chemotherapy is associated with a moderate risk of t-MDS/AML particularly when combined with mitoxantrone. This complication should be considered when evaluating the potential benefit of this treatment in lymphoproliferative disorders.

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Authors and Affiliations

  1. Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia

    D A Carney, D A Westerman, H M Prince, M Kenealy, M Wolf, E H Januszewicz, D Ritchie, N Came & J F Seymour

  2. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia

    D A Carney, D A Westerman, H M Prince, M Wolf, D Ritchie, N Came & J F Seymour

  3. Department of Haematology, St Vincent's Hospital, Fitzroy, Victoria, Australia

    C S Tam

  4. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

    A Milner

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  1. D A Carney
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Correspondence to D A Carney.

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Carney, D., Westerman, D., Tam, C. et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy. Leukemia 24, 2056–2062 (2010). https://doi.org/10.1038/leu.2010.218

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