Continuous‑infusion cytarabine for leukoreduction in hyperleukocytic AML: A single‑center retrospective study

Abstract

Abstract Background: Hyperleukocytosis (WBC > 50 × 10⁹/L) in acute myeloid leukemia (AML) is a medical emergency associated with a ≥20% early mortality rate, due to leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC). Hydroxyurea, bolus cytarabine, and leukapheresis are standard cytoreductive tools but carry toxicity or logistic limitations. We examined the safety and outcomes of continuous-infusion low-dose cytarabine (CI-Ara-C) for initial leukoreduction at our institution. Methods: In this single-center retrospective study, we screened all adults (≥18 y) with newly diagnosed AML admitted between June 2020 and June 2025 at Baylor St. Luke's Medical center. Inclusion required presentation WBC > 50 × 10⁹/L and receipt of CI-Ara-C before definitive induction (intensive chemotherapy or lower intensive chemotherapy). The primary endpoint was 4-week all-cause mortality; secondary endpoints included TLS incidence, dialysis requirement, and overall survival (OS). Survival was estimated by Kaplan–Meier (KM); median follow-up used reverse KM. Results: Eighteen patients met criteria (median age 65 y, range 27–82; 56% female; 33% Black, 11% Hispanic). Median presenting WBC was 116 × 10⁹/L (range 50–277); 61% had WBC ≥ 100 × 10⁹/L. FLT3 mutations were enriched in the highest WBC stratum (>150 × 10⁹/L; 5/6 patients). Leukostasis occurred in 11/18 (61%) and DIC in 8/18 (44%). CI-Ara-C was delivered at 100 mg/m²/day in 16/18 (89%) patients (range 20–200 mg/m²) for a median of 5 days (3–7). The dose was doubled in three cases after day 3 without non-hematological toxicity. Fifteen patients (83%) received hydroxyurea before CI-Ara-C and none of our patients underwent or required leukapheresis. TLS occurred in 3/18 (17%), which was managed conservatively and none required dialysis. Four-week mortality was 17% (3/18). Seventeen patients proceeded to induction therapy; complete remission or CRi was achieved in 10/17 (59%), with measurable residual disease detected in 8/10 at end of induction. After a median follow-up of 17.6 months (95% CI 6.8–not reached), median OS was 17.2 months (95% CI 4.2–NR). Conclusions: Continuous infusion cytarabine at 100 mg/m²/day provide rapid leukoreduction with low TLS related morbidity and obviated leukapheresis in our cohort with hyperleukocytic AML. A 17% four-week mortality compares favorably to historical reports although the small, single-center cohort limits statistical power. Prospective, multi-center evaluation and head-to-head comparison with hydroxyurea, bolus cytarabine, and leukapheresis are warranted to define the optimal leukoreductive strategy.