Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide

Biomed Pharmacother. 2011 Aug;65(5):319-21. doi: 10.1016/j.biopha.2011.04.006. Epub 2011 Jun 1.

Abstract

We retrospectively studied four cases of t-MDS/AML among 210 (1.9%) consecutive patients with CLL treated at a single center with fludarabine and cyclophosphamide (FC) either as the first- or second-line therapy. The median follow-up of the whole cohort of patients was 46months (range: 7-60). Two of these patients (2/130, 1.7%) had been treated with FC only, and two more (2/80, 2.3%) with CHOP and CHOP+FND, respectively, prior to FC. The median age was 61.5years (range: 49-71); three were male. They developed t-MDS/AML after a median latency period of 41months (range: 7-56) from the FC completion. Chromosomal aberrations with an adverse prognostic impact were present in the karyotype of all four patients, including abnormalities of chromosome 5 in three of them, and a rare chromosomal translocation in one patient. Median survival after t-MDS/AML diagnosis was 4months (range: 2-8). Although the agents administered prior to FC make it difficult to assess the risk of t-MDS/AML attributable to FC, this report might be a valuable addition to the literature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chromosomes, Human, Pair 5 / drug effects
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Myeloid, Acute / chemically induced*
  • Leukemia, Myeloid, Acute / genetics
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / chemically induced*
  • Myelodysplastic Syndromes / genetics
  • Neoplasms, Second Primary / chemically induced*
  • Neoplasms, Second Primary / genetics
  • Prognosis
  • Retrospective Studies
  • Translocation, Genetic / drug effects
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives

Substances

  • Cyclophosphamide
  • Vidarabine
  • fludarabine