Pathological findings suggesting vascular endothelial damage in multiple organs in chronic myelogenous leukemia patients on long-term tyrosine kinase inhibitor therapy


A 66-year-old man with hypertension was diagnosed with chronic myelogenous leukemia in 1996. Treatment was started with hydroxycarbamide and imatinib 400 mg in 1996 + 6, which was increased to 600 mg. Although he achieved a complete cytogenic response in 1996 + 9, he could not continue imatinib because of edema; the regimen was changed to nilotinib 800 mg in 1996 + 13. After he achieved a molecular response better than 4.5 in 1996 + 19, he was referred to our hospital. His urinalysis had shown urine protein since 1996 + 13, and his creatinine level increased in 1996 + 16. Renal biopsy, performed in 1996 + 20, revealed abdominal distention and massive ascites. After the nilotinib dosage was reduced to 400 mg, liver biopsy, also performed in 1996 + 20, revealed hypertrophy of renal small blood vessels and endothelial cells of the hepatic artery and loss of endothelial cells of the renal glomeruli, portal vein, and hepatic sinusoids. Both renal and liver biopsies revealed marked pathological vascular damage. The patient took oral imatinib for approximately 3.5 years and nilotinib for 11 years. Pathological findings indicated a tendency for thrombosis, which could induce vascular occlusive disease. Accumulation of cases, such as the present case, is needed to further analyze the pathophysiological processes.

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Correspondence to Yoshinobu Seki.

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Seki, Y., Nagano, O., Koda, R. et al. Pathological findings suggesting vascular endothelial damage in multiple organs in chronic myelogenous leukemia patients on long-term tyrosine kinase inhibitor therapy. Int J Hematol (2020).

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  • Chronic myelogeous leukemia
  • Tyrosin kinase inhibitor
  • Vascular endothelial damage
  • Off target effect