High Prevalence of Peripheral Artery Occlusive Disease (PAOD) Among Patients with Chronic Myeloid Leukemia (CML) Receiving Tyrosine Kinase Inhibitors (TKIs): A Cross-Sectional Study

Background: Although TKIs become the standard of care in CML, the long-term complication has not been well recognized. There were reports of nilotinib associated metabolic derangements including diabetes and PAOD while these complications in other TKIs have not been well recognized.

Objectives: To compare the prevalence of PAOD among CML patients and matched-control population.

Methods: A cross-sectional case control study was conducted among CML patients receiving TKIs at Chiang Mai University Hospital between February to December 2014. The control group was matched by age, sex and diabetes. Screening PAOD using Fukuda VS-1500 to measure ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) for arterial stiffness were performed in both groups. The cutoff value of pathologic ABI and CAVI were less than 0.9 and higher than 8, respectively.

Results: Seventy-eight CML patients and 156 matched-control population(1:2 ratio) were included. For CML patients, the median age was 55 years (21-86). Atherosclerotic risks including hypertension(20.5%), diabetes(12.8%), dyslipidemia(26.9%), metabolic syndrome(19.2%) and smoking(2.6%). Sixty-one patients(78.2%) were on imatinib, all as first-line, 13 patients(16.7%) on nilotinib (7.7%first-line, 92.3%second-line) while 4 patients(5.2%) were on dasatinib(all third-line). Median duration of imatinib, nilotinib and dasatinib treatment were 89.6, 46.7 and 22.1 months, respectively. The prevalence of pathologic ABI and CAVI were 9.0% and 26.7%, respectively. Patients receiving nilotinib had highest prevalence of abnormal ABI of 30.7% while patients receiving imatinib and dasatinib had abnormal ABI of 5% and 0%, respectively (p=0.004). Abnormal arterial stiffness by CAVI in nilotinib users were 15.4% compared to 27.8% and 50% in imatinib and dasatinib (p=0.815). Patients with CML had higher prevalence of pathologic ABI than in control group with an odds ratio(OR) of 2.09(95%CI 0.71-6.21, p=0.181). The only factor independently associated with pathologic ABI was level of HbA1C over 7 g/dl [OR2.41(95%CI 1.11-5.25; p=0.026)]. Age over 60 years [OR 3.95(95%CI 1.22-12.73, p=0.022)] and fasting plasma glucose over 126 mg/dl [OR 7.96(95%CI 1.21-52.26, p=0.031)] were independently associated with pathologic CAVI.

Conclusions: The prevalence of PAOD by using ABI was higher among CML patients than in control population. CML patients receiving TKIs who have diabetes and older than 60 years old have a higher chance of developing PAOD and should be carefully monitored.