Comparative outcomes of leukapheresis and pharmacologic cytoreduction in hyperleukocytosis.

e18554 Background: Hyperleukocytosis, defined as a white blood cell (WBC) count ≥100 × 10⁹/L, is a hematologic emergency in acute and chronic leukemias, with morbidity and mortality driven primarily by complications such as leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC). Despite widespread use, retrospective studies and meta-analyses show no consistent survival benefit with leukapheresis over pharmacologic cytoreduction alone, yet practice patterns remain variable. We performed a large real-world analysis to compare short-term mortality and complication rates among patients treated with hydroxyurea alone, leukapheresis alone, or combination therapy. Methods: We conducted a retrospective cohort study using the TriNetX Research Network, comprising electronic health records from 111 healthcare organizations. Adult patients (≥18 years) with acute or chronic leukemia and hyperleukocytosis (WBC ≥100 × 10⁹/L) between January 2010 and December 2025 were identified. Patients were categorized into hydroxyurea alone, leukapheresis alone, or combination therapy groups, with index date defined as treatment initiation within 7 days of hyperleukocytosis diagnosis. Propensity score matching (1:1) balanced demographics, leukemia subtype, comorbidities, and baseline laboratory values, including leukocyte count. Thirty-day outcomes included mortality, TLS, neurologic complications, respiratory failure requiring mechanical ventilation, major bleeding, and DIC. Results: After matching, 976 patients were included (488 per group: hydroxyurea alone vs hydroxyurea plus leukapheresis). At 30 days, mortality was comparable (21.3% vs 20.0%; HR 1.06, 95% CI 0.80–1.40; p=0.83). Leukapheresis was associated with higher rates of neurologic events (17.8% vs 11.5%; RR 1.55; p=0.005) and respiratory failure or mechanical ventilation (35.2% vs 24.0%; RR 1.47; p<0.001), likely reflecting confounding by indication and greater baseline disease severity. TLS rates were numerically higher (28.5% vs 23.2%; p=0.057), while major bleeding/DIC rates were similar (17.8% vs 15.6%; p=0.35). Conclusions: In this large real-world analysis, leukapheresis provided no overall survival benefit over pharmacologic cytoreduction alone. Given its high cost, resource intensity, and limited accessibility, these findings support selective rather than routine use, prioritizing prompt medical cytoreduction and supportive care.