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

被引:91
|
作者
Carney, D. A. [1 ,2 ]
Westerman, D. A. [1 ,2 ]
Tam, C. S. [3 ]
Milner, A. [4 ]
Prince, H. M. [1 ,2 ]
Kenealy, M. [1 ]
Wolf, M. [1 ,2 ]
Januszewicz, E. H. [1 ]
Ritchie, D. [1 ,2 ]
Came, N. [1 ,2 ]
Seymour, J. F. [1 ,2 ]
机构
[1] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia
[2] Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia
[3] St Vincents Hosp, Dept Haematol, Fitzroy, Vic 3065, Australia
[4] Peter MacCallum Canc Ctr, Ctr Biostat & Clin Trials, Melbourne, Vic, Australia
关键词
fludarabine; myelodysplasia; toxicity; CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL MOBILIZATION; NON-HODGKINS-LYMPHOMA; INITIAL THERAPY; CYCLOPHOSPHAMIDE; RITUXIMAB; MITOXANTRONE; REGIMEN; CHLORAMBUCIL; DURATION;
D O I
10.1038/leu.2010.218
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Leukemia (2010) 24, 2056-2062; doi:10.1038/leu.2010.218; published online 21 October 2010
引用
收藏
页码:2056 / 2062
页数:7
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