Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous...

Knowledge of the toxicity profile of long-term treatment with imatinib is limited. In the present study, we sought to evaluate renal function and hemoglobin levels during long-term imatinib treatment. Eighty-two patients with chronic myelogenous leukemia in chronic phase who had been on imatinib for over 5 years were retrospectively analyzed. The mean estimated glomerular filtration rate (eGFR) was significantly decreased over 5 years (77 ± 17 to 62 ± 14 ml/min/1.73m², P < 0.001). Higher age and lower eGFR value at initiation of imatinib were significantly associated with development of renal dysfunction by multivariate analyses. Mean hemoglobin levels also significantly decreased over the 5-year period (12.9 ± 1.7 to 12.4 ± 1.3 g/dl, P < 0.01). The rate of decrease in eGFR correlated significantly with hemoglobin levels (correlation coefficient = - 0.249, P < 0.05). Serum erythropoietin (EPO) levels did not increase in 16 patients with both renal dysfunction and anemia (median, 31.9 mIU/ml). In patients who participated in a clinical trial of imatinib discontinuation, mean eGFR (50.0 ± 6.5 to 56.0 ± 10.2 ml/min/1.73m², P < 0.05) and hemoglobin levels (12.0 ± 1.7 to 14.0 ± 1.6 g/dl, P < 0.01) improved significantly at 1 year after discontinuation. These findings suggest that long-term imatinib results in a partially reversible continuous decline in renal function and decreased hemoglobin levels.