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

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.

journal_name

Leukemia

journal_title

Leukemia

authors

Carney DA,Westerman DA,Tam CS,Milner A,Prince HM,Kenealy M,Wolf M,Januszewicz EH,Ritchie D,Came N,Seymour JF

doi

10.1038/leu.2010.218

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

2056-62

issue

12

eissn

0887-6924

issn

1476-5551

pii

leu2010218

journal_volume

24

pub_type

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