Syndrome of Inappropriate Secretion of Antidiuretic Hormone Associated with Imatinib

Abstract

To describe a patient with Bcr-abl(+) acute lymphoblastic leukemia who developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) while being treated with high-dose imatinib. A 29-year-old woman was diagnosed with Bcr-abl(+) acute lymphoblastic leukemia, and treatment was initiated with chemotherapy and imatinib 800 mg daily. Following imatinib initiation, a gradual decrease in serum sodium level was noticed. Prolonged aplasia and neutropenic fever prompted discontinuation of therapy for 4 weeks. Following the patient's recovery, complete remission was achieved and monotherapy with imatinib 800 mg daily was restarted; however, hyponatremia recurred a few days later. The clinical findings and laboratory workup were compatible with the diagnosis of SIADH, which was attributed to high-dose imatinib. Fluid restriction and imatinib dosage reduction (to 600 mg/day) restored sodium levels. According to the Naranjo probability scale, this adverse reaction was probably associated with imatinib. Imatinib emerged as the first tyrosine kinase inhibitor to enter everyday clinical practice for the treatment of Ph(+) leukemias. Due to its molecular specificity, imatinib lacks the broad cytotoxicity of conventional chemotherapy. Inhibition of kinases in normal tissues accounts for many of imatinib's adverse reactions. To our knowledge, this is the first reported case of imatinib-induced SIADH. We recommend monitoring for SIADH if a patient receiving high-dose imatinib develops hyponatremia.