Rapid onset of peripheral artery disease in a chronic myeloid leukemia patient without prior arterial disorder: direct relationship with nilotinib exposure and clinical outcome

Eur J Haematol. 2015 Apr;94(4):363-7. doi: 10.1111/ejh.12367. Epub 2014 Aug 23.

Abstract

The second-generation tyrosine kinase inhibitor (TKI) of the BCR-ABL1 oncoprotein nilotinib used in patients with chronic myeloid leukemia is suspected to increase the risk of arterial occlusion, especially in patients with pre-existing cardiovascular risk factors or established cardiovascular diseases. Here, we describe a case of unexpected and rapid onset of symptomatic peripheral artery disease (PAD) associated with silent stenosis of digestive and renal arteries in a nilotinib-treated patient devoid of significant cardiovascular diseases (CVD) risk factor, prior atherosclerotic disease, or other cause of arterial damage. This is the first report to establish a direct relationship between nilotinib exposure and PAD and to reveal that arterial damage is irreversible despite rapid drug withdrawal. However, functional outcome was favorable upon rapid TKI replacement, specific cardiovascular disease management, and development of collateral arterial network.

Keywords: arterial occlusive diseases; leukemia myelogenous chronic BCR-ABL positive; nilotinib; peripheral arterial disease; pharmacovigilance.

Publication types

  • Case Reports

MeSH terms

  • Angiography
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Drug Substitution
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Middle Aged
  • Patient Outcome Assessment
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / etiology*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Fusion Proteins, bcr-abl
  • nilotinib