Impact of early intracranial hemorrhage on survival and critical care utilization in acute promyelocytic leukemia: A population-based propensity-matched study.

Abstract

e18539 Background: Intracranial hemorrhage (ICH) remains a leading cause of early death in acute promyelocytic leukemia (APL), but the extent to which excess risk persists among survivors, and the longer-term critical care burden in this population, are not well known. Methods: Using the TriNetX multi institutional network (2014-2025),we compared APL with ICH within 14 days of initial diagnosis of APL versus APL without ICH. Cohorts were 1:1 propensity-score matched (PSM) for key clinical and laboratory variables. Co-primary outcomes were all-cause mortality and ICU admission-rate (ICUAR; critical care procedure-based definition) at 30 days, 90 days, 1 year, and 5 years, analyzed with risk estimates and Kaplan–Meier/Cox proportional hazard models. Landmark analyses were performed among patients alive at 30 days (n=425/group), 6 months (n=350/group), and 1 year (n=332/group) to delineate the long-term impact on survivors. Results: We identified 16,301 patients with APL, including 789 patients with early ICH (4.8%) and 15,512 without ICH. Before matching, median age was 55.1 (range 37.0-73.2) versus 54.9 years (range 34.9-74.9), and female sex comprised 49% versus 48% of cohorts, respectively. After 1:1 PSM, 776 patients were included per group. Estimated mortality was higher in the early-ICH cohort versus no-ICH at 30 days (32% vs 6%; HR 6.1), 90 days (41% vs 11%; HR 5.0), 1 year (54% vs 25%; HR 3.1), and 5 years (64% vs 39%; HR 2.5). ICUAR was likewise higher at 30 days (42% vs 7%; HR 5.10), 90 days (45% vs 10%; HR 5.9), 1 year (48% vs 16%; HR 4.5), and 5 years (51% vs 21%; HR 3.9) (all p<0.001). Among 30-day survivors, estimated 1-year mortality remained higher (21% vs 11%) and ICUAR remained higher (39% vs 12%). Among 6-month survivors, 5-year mortality was similar (16 vs 15%), but ICUAR remained higher (40% vs 14%). Among 1-year survivors, 5-year mortality was lower in the prior-ICH cohort (10% vs 17%) consistent with probable survivorship bias, but ICUAR remained higher (38.0% vs 16.0%). Conclusions: Early ICH in APL is associated with significant early mortality and persistent increase in ICU utilization beyond the first year. As survivorship landmarks advance, the effect of ICH on mortality attenuates, but the critical care burden persists indicating ongoing morbidity among ICH survivors. Our study highlights the need to optimize early diagnosis and tailored management as well as downstream supportive care. Analysis/Window Matched n per group KM Estimated mortality (%) (ICH vs no ICH) ICU admission (%) (ICH vs no ICH) Diagnosis to 30 days 776 32 vs 6 42 vs 7 Diagnosis to 90 days 776 41 vs 11 45 vs 10 Diagnosis to 1 year 776 54 vs 25 48 vs 16 Diagnosis to 5 years 776 64 vs 39 51 vs 21 Landmark analyses Alive at 30 days: 1-year rate 425 21 vs 11 39 vs 12 Alive at 30 days: 5-year rate 425 35 vs 27 43 vs 16 Alive at 6 months: 5-year rate 350 16 vs 15 40 vs 14 Alive at 1 year: 5-year rate 332 10 vs 17 38 vs 16