Abstract / Summary
Introduction: Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib, a third-generation TKI active against the T315I mutation, offers superior survival benefits but carries an increased risk of arterio-occlusive events (AOEs), including ischemic stroke, particularly in patients with baseline vascular risk factors. We report a suspected ponatinib-associated large vessel occlusion stroke and discuss potential mechanisms, monitoring, and management considerations. Case Report: A 60-year-old woman with Ph+ ALL on ponatinib for four years, hypertension, diabetes, hyperlipidemia, and prior deep vein thrombosis presented after waking up with dysarthria, left facial weakness, and hemisensory loss. Imaging revealed acute right parietotemporal infarction with proximal right M2 occlusion. She was initially ineligible for intravenous thrombolysis and endovascular thrombectomy (EVT) because of an absent diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch and a low National Institutes of Health Stroke Scale (NIHSS) score. Overnight, she developed dense left hemiplegia and neglect. Statim (STAT) imaging showed favorable perfusion mismatch prompting emergent EVT, which achieved successful reperfusion. Given negative comprehensive embolic stroke workup and right M2 irregularity on follow-up imaging suggestive of intracranial vasculopathy, prolonged ponatinib exposure and uncontrolled vascular risk factors were considered contributory. Ponatinib was discontinued, and she was discharged to rehabilitation with a modified Rankin Scale score of 4 at two months. Conclusion: This case highlights a suspected ponatinib-associated large vessel ischemic stroke treated with EVT in a patient with prolonged exposure and multiple vascular risk factors. It underscores the risk of cerebrovascular AOEs during ponatinib therapy and importance of vascular risk assessment, monitoring, and multidisciplinary management to reduce treatment-related morbidity while balancing leukemia control.