Dasatinib Induced Avascular Necrosis of Femoral Head in Adult Patient with Chronic Myeloid Leukemia

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia (Ph) chromosome resulting from the reciprocal translocation t(9;22)(q34;q11). The molecular consequence of this translocation is the generation of the BCR–ABL fusion gene, which encodes a constitutively active protein tyrosine kinase. The oncogenic protein tyrosine kinase, which is located in the cytoplasm, is responsible for the leukemia phenotype through the constitutive activation of multiple signaling pathways involved in the cell cycle and in adhesion and apoptosis. Avascular necrosis of the femoral head (AVNFH) is not a specific disease. It occurs as a complication or secondary to various causes. These conditions probably lead to impaired blood supply to the femoral head. The diagnosis of AVNFH is based on clinical findings and is supported by specific radiological manifestations. We reported a case of a 34-year-old Sudanese female with CML who developed AVNFH after receiving dasatinib as a second-line therapy. Though the mechanism by which dasatinib can cause avascular necrosis (AVN) is not clear, it can be postulated because of microcirculatory obstruction of the femoral head. To the best of our knowledge and after extensive literature search, this is the first reported case of AVNFH induced by dasatinib in a patient with CML.

Nilotinib-Induced Diabetes Mellitus in a Young Female with Chronic Myeloid Leukemia

“…These agents are able to achieve long-term control of CML in the majority of patients; thus, they are the initial treatment of choice for almost all newly diagnosed patients with CML [ 8 ]. All TKIs are associated with certain common adverse effects such as cytopenias, rash [ 9 ], nausea, edema, diarrhea [ 10 ], musculoskeletal [ 11 ], and fatigue early in the course of treatment.…”

Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib

“…Some uncommon toxicities were found, such as renal function impairment, which has been described after several years of imatinib therapy in patients with chronic myeloid leukemia . Also, the patient with bilateral osteonecrosis of femoral heads did not have known risk factors and was not on corticosteroids, and thus we consider that KIT inhibition with imatinib most likely caused this toxicity, as described with other tyrosine kinase inhibitors with activity against KIT .…”

Comment on: “Team approach: Management of osteonecrosis in children with acute lymphoblastic leukemia

“…Imaging was performed if osteonecrosis was suspected based on symptoms. Patients with BCR‐ABL ALL were excluded, as dasatinib may increase the risk of osteonecrosis 3,4 …”

“…Patients with BCR-ABL ALL were excluded, as dasatinib may increase the risk of osteonecrosis. 3,4 Patients were diagnosed between January 2010 and March 2018. Study limitations include small numbers of patients from a single institution and lack of a randomized control group.…”