Parikh, Neel Ketankumar

e18624 Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Although meta-analyses identify systemic corticosteroid exposure as a strong relative risk factor for IFI, the absolute burden attributable to corticosteroids across heterogeneous baseline risk settings remains poorly defined. We applied meta-analysis-based projection modeling to translate relative risk estimates into absolute, population-level IFI outcomes. Methods: Using pooled odds ratios for IFI associated with systemic corticosteroid exposure from a published meta-analysis (OR 2.84; 95% CI 1.42–5.70), we projected IFI incidence under a proportional odds framework. The primary analysis assumed a baseline IFI incidence of 15% in patients not receiving corticosteroids, with sensitivity analyses conducted across baseline incidences ranging from 10% to 25%. IFI-related mortality was estimated using a case-fatality rate of 45%. Outcomes were expressed as projected IFI incidence, excess IFIs and IFI-attributable deaths per 1,000 patients, population attributable fractions, and one-way sensitivity analyses. Results: At a baseline IFI incidence of 15%, systemic corticosteroid exposure increased projected IFI incidence to approximately 34%, corresponding to an excess of ~190 IFIs per 1,000 patients. This translated into approximately 80 excess IFI-attributable deaths per 1,000 patients, with a plausible range of 25–160 based on uncertainty in the pooled effect estimate. Sensitivity analyses demonstrated a monotonic increase in projected IFI incidence with rising baseline risk, with corticosteroid-associated IFI incidence approaching 50% at higher baseline levels. Population-attributable fraction modeling indicated that when corticosteroid use prevalence exceeded 40%, nearly half of IFIs in the population were attributable to corticosteroid exposure. One-way sensitivity analyses identified the corticosteroid effect size as the dominant driver of excess IFI mortality, exceeding the influence of baseline incidence or IFI case-fatality assumptions. Conclusions: Projection modeling based on meta-analytic risk estimates demonstrates that systemic corticosteroid exposure is associated with a substantial and clinically meaningful absolute increase in IFIs and IFI-related mortality. Translating relative risk estimates into absolute population-level outcomes highlights the potential magnitude of preventable infectious harm associated with corticosteroid use and provides actionable insight to inform risk-mitigation strategies in high-risk hematologic populations.

e18536 Background: Nucleophosmin 1 (NPM1) mutation is traditionally associated with a favorable prognosis in acute myeloid leukemia (AML), leading to classification of these patients within the European LeukemiaNet (ELN) favorable risk group. However, emerging evidence indicates that co-occurring secondary-type mutations (STMs), including ASXL1 , RUNX1 , EZH2 , and SRSF2 , may substantially modify this prognosis. While meta-analyses have quantified the relative risk associated with STMs using hazard ratios, the corresponding absolute survival impact remains unclear, limiting clinical interpretability and decision-making. Methods: We performed meta-analysis–based projection modeling using pooled overall survival hazard ratios reported in a recent systematic review and meta-analysis of 4,022 NPM1-mutated AML patients. For the ELN-favorable subgroup, the pooled hazard ratio for overall survival associated with STMs (HR 1.95; 95% CI 1.39–2.73) was combined with externally derived baseline 5-year survival estimates under a proportional hazards framework. Absolute survival probabilities were calculated using established survival–hazard transformations, and results were translated into projected outcomes for a hypothetical cohort of 1,000 future ELN-favorable NPM1-mutated AML patients. Uncertainty was quantified using the meta-analytic confidence interval. Results: Assuming a baseline 5-year overall survival of 70% for ELN-favorable NPM1-mutated AML patients without STMs, the presence of STMs was projected to reduce 5-year survival to approximately 50%. Based on the confidence interval of the pooled hazard ratio, projected survival with STMs ranged from 38% to 61%. In a simulated cohort of 1,000 patients, this corresponds to approximately 300 deaths at 5 years in the absence of STMs versus 501 deaths in the presence of STMs, yielding an estimated 200 excess deaths per 1,000 patients (plausible range: 90–320 excess deaths). These findings were robust across visualizations including absolute survival projections, stacked outcome distributions, and excess mortality estimates. Conclusions: Meta-analysis–based projection modeling demonstrates that secondary-type mutations may negate much of the favorable prognosis traditionally attributed to ELN-favorable NPM1-mutated AML, translating into a large absolute survival decrement in future patient cohorts. Converting relative risk estimates into absolute survival and event projections provides clinically actionable insight and supports the incorporation of secondary-type mutation status into risk stratification, trial design, and therapeutic decision-making.