P0465 - Focal Seizures and Arterial Ischemic Stroke as an Initial Presentation for Neonatal Leukemia

Introduction:
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood with neonatal ALL being rare at 1-5 cases per million live births. Though hyperleukocytosis (defined as leukocyte count ≥100,000 cells/microliter) occurs to some degree in the majority of neonatal ALL cases, CNS catastrophes related to hyperleukocytosis are rarely observed. We report a unique case of right parietal middle cerebral artery infarct secondary to hyperleukocytosis in a six week old infant with newly diagnosed neonatal ALL.

Case Report:
A 6-week-old female infant with past medical history of sickle cell trait was born full term, via vaginal delivery to a G2P1 mother with the only complication being inadequately treated Group B Streptococcus colonization. She presented with two days of episodic left fist clenching and left upper and lower extremity jerking. When these episodes became more frequent, she was taken to the Emergency Department of an academic university hospital where she was admitted for seizure-like activity. She was loaded with Keppra and Phenobarbital but continued to have breakthrough seizures. CT head showed a large area of hypo-density in the right frontotemporal lobe consistent with cytotoxic edema most concerning for acute ischemia. After multiple lab specimens clotted, CBC showed hyperleukocytosis to 352,000 cells/microliter with 98% lymphocytes, hemoglobin 8.0g/dL, platelets 13/microliter. She was then transferred to the Pediatric Intensive Care Unit for urgent triple volume whole blood manual exchange transfusion. Lumbar puncture showed 98% blasts, and cytogenetic chromosomal analysis was significant for KMT2A rearrangement, consistent with infant B-lineage ALL.

Discussion:
Studies estimate the annual incidence of arterial ischemic stroke (AIS) is 2.4 per 100,000 in pediatric patients with fatality rates of approximately 4%. The incidence of stroke in pediatric cancer patients is estimated at 1%, with an increased risk in children with hematologic malignancies. Hyperleukocytosis is more often associated with hemorrhagic events rather than ischemic events. The pathophysiology of the relationship of hyperleukocytosis with hemorrhagic catastrophe was first discussed in the 1950’s with post-mortem studies of patients with leukocyte counts >300,000 cells/microliter in blast crisis. These studies reported accumulation of leukemic cells in white matter capillaries, causing leukostasis and leukemic nodular formations, inadvertently leading to capillary wall disruption coalescing into large hemorrhages. This case is a unique presentation of AIS secondary to hyperleukocytosis.

Conclusion:
Although malignancy is associated with inflammation and prothrombotic states, which are both common risk factors for pediatric strokes, hyperleukocytosis specifically has not been well-correlated with AIS in children. Given that initial leukocyte count is a strong predictor of complete remission, this case highlights the need for further research regarding AIS in relation to hyperleukocytosis and most importantly, the prognostic outcomes for these patients.