title: Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML.
abstract: The second generation BCR/ABL kinase inhibitor nilotinib is increasingly used for the treatment of imatinib-resistant chronic myeloid leukemia (CML). So far, nilotinib is considered a well-tolerated drug with little if any side effects, although an increase in the fasting glucose level has been reported. We examined a series of 24 consecutive CML patients treated with nilotinib in our center for the development of non-hematologic adverse events. Three of these 24 CML patients developed a rapidly progressive peripheral arterial occlusive disease (PAOD) during treatment with nilotinib. In all three cases, PAOD required repeated angioplasty and/or multiple surgeries within a few months. No PAOD was known before nilotinib-therapy in these patients, although all three had received imatinib. In two patients, pre-existing risk factors predisposing for PAOD were known, and one of them had developed diabetes mellitus during nilotinib. In the other 21 patients treated with nilotinib in our center, one less severe PAOD, one myocardial infarction, one spinal infarction, one subdural hematoma, and one sudden death of unknown etiology were recorded. In summary, treatment with nilotinib may be associated with an increased risk of vascular adverse events, including PAOD development. In a subgroup of patients, these events are severe or even life-threatening. Although the exact mechanisms remain unknown, we recommend screening for pre-existing PAOD and for vascular risk factors such as diabetes mellitus in all patients before starting nilotinib and in the follow up during nilotinib-therapy.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Aichberger
authors.forename: Susanne
authors.initials: S
authors.lastname: Herndlhofer
authors.forename: Gerit-Holger
authors.initials: GH
authors.lastname: Schernthaner
authors.forename: Martin
authors.initials: M
authors.lastname: Schillinger
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Mitterbauer-Hohendanner
authors.forename: Christian
authors.initials: C
authors.lastname: Sillaber
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000097:blood / Q000139:chemically induced / Q000601:surgery; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005215:Fasting / Q000097:blood; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000139:chemically induced* / Q000601:surgery; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D001549:Benzamides; D001786:Blood Glucose; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib