Clinical Characteristics of Intracranial Hemorrhage in Pediatric Acute Leukemia

BACKGROUND: Intracranial hemorrhage (ICH) is a life-threatening complication of pediatric acute leukemia. However, whether early-onset ICH and late-onset ICH are distinct clinical entities remains unclear. This study investigated the characteristics, neuroimaging findings, and outcomes of ICH. METHODS: Children with newly diagnosed acute leukemia were retrospectively reviewed. Clinical characteristics and OS were compared between patients with and without ICH, while neuroimaging findings and neurological outcomes were evaluated in patients with ICH. Early-onset ICH was defined as hemorrhage within 7 days after leukemia diagnosis, and late-onset ICH was defined as hemorrhage occurring thereafter. RESULTS: Among 340 children with acute leukemia, 11 (3.2%) developed ICH. Patients with ICH were significantly younger and more frequently had KMT2A rearrangements, hyperleukocytosis, thrombocytopenia, and coagulation abnormalities than those without ICH. Patients with ICH had a significantly lower 5-year OS rate than those without ICH (55.4% vs. 90.4%, p < 0.001). Early-onset ICH predominantly occurred in patients with acute myeloid leukemia, and it was characterized by multifocal hemorrhages at presentation. Late-onset ICH occurred exclusively in patients with acute lymphoblastic leukemia (ALL). Three infants with KMT2A-rearranged B-cell ALL developed marked cerebral atrophy, followed by subdural hematoma. Five patients required neurosurgical intervention, and all survivors had persistent neurological sequelae. CONCLUSIONS: In pediatric acute leukemia, ICH comprises two clinically distinct patterns. Early-onset ICH is primarily associated with leukemia-related coagulopathy. Late-onset ICH is characterized by cerebral atrophy, followed by subdural hematoma, in infants with KMT2A-rearranged B-cell ALL. Recognizing these distinct patterns may lead to earlier diagnosis, neuroimaging evaluation, and timely neurosurgical intervention.