Sharma, Ashish

e19090 Background: PET/CT remains crucial for end-of-treatment (EOT) evaluation in large B-cell lymphoma (LBCL), but low specificity results in unnecessary biopsies and patient discomfort. Circulating tumor DNA (ctDNA)-based minimum residual illness (MRD) may aid in the identification of actual residual sickness. Methods: We conducted a systematic review and meta-analysis of diagnostic accuracy using MEDLINE, Embase, CENTRAL, and Scopus. Eligible studies compared EOT ctDNA-MRD to PET/CT with verified recurrence or long-term remission. The outcomes were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The study's quality was rated using the QUADAS-2 scale. A bivariate random-effects model combined sensitivity and specificity, yielding hierarchical summary receiver operating characteristic (HSROC) curves. Results: Nine studies with a total of 932 participants were included. ctDNA-MRD showed higher specificity (92%, 95% CI 88-95%) and PPV (81%, 95% CI 73-88%) than PET/CT (specificity 68%, 95% CI 60-75%; PPV 46%, 95% CI 38-55%), while maintaining similar sensitivity. The negative predictive value for ctDNA was higher (91%, 95% CI 86-95%) than for PET (79%, 95% CI 72-85%). Combined PET+ctDNA techniques had the highest diagnostic odds ratio and fewer false positives. The results were similar across Deauville criteria and testing systems. Conclusions: ctDNA-MRD has higher specificity and predictive value than PET/CT at EOT in LBCL and significantly improves risk categorization whether used alone or in conjunction with imaging. Clinical Takeaway: Incorporating ctDNA-MRD into EOT assessment can reduce unnecessary biopsies and enable more accurate, confidence-based post-treatment decision-making.

e18609 Background: Anemia is a frequent complication of myelofibrosis (MF) and is embedded in widely used prognostic systems, yet contemporary real-world estimates of its association with long-term survival and leukemic transformation remain limited. We evaluated the impact of baseline anemia (hemoglobin [Hb] <10 g/dL) on overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in adults with MF. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with myelofibrosis and stratifying them by anemia status at index (Hb <10 g/dL). Patients with the outcome of interest prior to each analytic window were excluded. To minimize confounding, cohorts were 1:1 propensity score–matched using nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the logit of the propensity score, adjusting for demographic factors, comorbidities, iron supplementation, leukocyte count, and platelet count. Balance was assessed using standardized mean differences <0.1. The primary outcome was all-cause mortality and the secondary outcome was transformation to AML, assessed at 1, 3, and 5 years. Risk estimates were calculated, and survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models, with statistical significance defined as a two-sided p<0.05. Results: After matching, 18,504 patients with MF were identified, of which 51.6% were females and 48.3% were males. The mortality rate in patients with anemia was higher than in those without at years 1, 3, and 5: 21.4%, 33.2%, and 39%, respectively, versus 5.4%, 12%, and 16.9%, respectively. The prevalence of transformation to AML was also higher in patients with anemia at 3.7%, 4.9%, and 5.3% at years 1, 3, and 5, respectively, versus 0.1%, 0.3%, and 0.4% in patients without anemia at those same time points. The HR for mortality in MF patients with anemia when compared to those without anemia at years 1, 3, 5 was statistically significant at 4.57 (95% CI 4.14-5.05, log-rank p<0.01), 3.51 (95% CI 3.28-3.76, log-rank p<0.01), and 3.04 (95% CI 2.87-3.23, log-rank p<0.01) respectively. The HR for transformation to AML in patients with MF with anemia versus those without anemia was statistically significant at years 1, 3 and 5, with HRs of 34.96 (95% CI 19.17-63.75, log-rank p<0.01) 20.75 (95% CI 13.97-30.83, log-rank p<0.01) and 17.07 (95% CI 12.11-24.07, log-rank p<0.01), respectively. Conclusions: In this large, propensity-matched real-world EHR analysis, baseline Hb <10 g/dL was associated with substantially worse OS and a markedly higher risk of AML transformation through 5 years. These findings support anemia as a pragmatic risk marker to inform risk-adapted monitoring, supportive care, and therapeutic decision-making in MF.

e18608 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) that is characterized by bone marrow fibrosis and inefficient hematopoiesis, leading to extramedullary hematopoiesis. Leukocytosis, a common disease manifestation and a minor criterion for the diagnosis of MF, has been associated with poorer clinical outcomes. This study evaluates the long term impact of leukocytosis on clinical outcomes at different time points in the real-world population of patients with MF. Methods: We conducted a retrospective cohort study using de-identified EHR data from the TriNetX Global Federated Health Research Network. Adults (≥18 years) with myelofibrosis were identified using ICD-10 and ICD-O-3 codes and stratified into leukocytosis (WBC ≥25.0 ×10³/µL; L+) and non-leukocytosis (L−) cohorts at the index diagnosis. Patients with prior or current hematopoietic stem cell transplantation were excluded. Cohorts were propensity score–matched 1:1 for demographics, comorbidities, and baseline laboratory values. Outcomes at 1, 3, and 5 years included all-cause mortality, pulmonary embolism, venous thromboembolism, and transformation to acute myeloid leukemia, with hazard ratios estimated using Cox proportional hazards models. Results: After matching, 13237 patients with MF were identified, of whom 52.12% were male, and 47.8% were female. The mean age in L+ and L- was 66.5 +/- 16.6 years and 68.1 +/- 15.5 years, respectively. The mean hemoglobin in L+ was 10.9+/- 2.8 g/dL, and in L- was 12.9+/- 2.3 g/dL. The mean platelet count in L+ was 303.4+/- 294.9 and in L- was 239.5+/- 151.4 ×10³/µL. HR for all-cause mortality in L+ when compared to L- at years 1, 3, and 5 were statistically significant at 4.079 (95% CI 3.691-4.508), 3.215 (95% CI 2.982-3.466), and 2.787 (95% CI 2.608-2.978), respectively, with log-rank p < 0.01. The HR for PE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.014 (95% CI 1.455-2.787), 1.883 (95% CI 1.451-2.787) and 1.659 (95% CI 1.318-2.088) with log-rank p<0.01. HR for VTE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.501 (95% CI 1.937-3 .229), 1.802 (95% CI 1.491-2.178), and 1.561 (95% CI 1.32-1.847) with log-rank p<0.01. Risk of transformation to AML in L+ when compared to L- at years 1, 3, and 5 was significant with HRs being 9.806 (95% CI 6.575-14.627), 8.823 (95% CI 6.334-12.29), 9.371 (95% CI 6.813-12.891) with log-rank p<0.01. Conclusions: In this large real-world, propensity-matched cohort, leukocytosis in myelofibrosis was associated with significantly higher risks of all-cause mortality, thromboembolic events, and transformation to acute myeloid leukemia across 1-, 3-, and 5-year time points. These findings underscore leukocytosis as a powerful adverse prognostic marker in MF and highlight the need for closer surveillance and risk-adapted therapeutic strategies in this high-risk population.

e18605 Background: Patients with myelofibrosis (MF), especially those with marked leukocytosis, face increased risk for thrombotic complications such as pulmonary embolism (PE) and venous thromboembolism (VTE). Hydroxyurea (HU) is often used to control blood counts. However, evidence for HU reducing thrombotic events in MF is limited, and contemporary real-world data on its impact in MF populations with significant leukocytosis remain sparse. Methods: We conducted a retrospective cohort study using the TriNetX research network. Adult patients with MF and leukocytosis (white blood cell count ≥25×10⁹/L) were identified. Patients with prior allogeneic hematopoietic stem cell transplantation were excluded. HU-exposed patients were compared with non-exposed patients using 1:1 propensity score matching. Matching criteria included age, sex, race, comorbidities, and baseline laboratory values when available. The study included 3,590 patients (1,795 per cohort). Primary outcomes were time to PE and VTE at 1, 3, and 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: In the propensity-matched cohort, HU exposure was not associated with a statistically significant reduction in thrombotic events. For PE, hazard ratios were numerically higher in the HU-exposed group at 1 year (1.5% vs 1.0%; HR 1.40, 95% CI 0.76–2.56; p=0.278) and 3 years (2.2% vs 1.8%; HR 1.29, 95% CI 0.80–2.08; p=0.289), with a modest increase observed at 5 years (2.8% vs 1.9%; HR 1.57, 95% CI 1.01–2.45; p=0.04). For VTE, no statistically significant differences were observed between HU-exposed and non-exposed patients at any time point (1 year: HR 0.95, 95% CI 0.63–1.44; p=0.821; 3 years: HR 0.97, 95% CI 0.69–1.36; p=0.85; 5 years: HR 1.14, 95% CI 0.84–1.57; p=0.40). Overall, PE and VTE event rates remained low and comparable between cohorts. Conclusions: In this large real-world cohort of patients with myelofibrosis and significant leukocytosis, hydroxyurea exposure was not associated with a statistically significant reduction in thrombotic events, including PE or VTE, over short- or long-term follow-up. Thrombotic event rates were low and generally comparable between hydroxyurea-exposed and non-exposed patients, with no consistent pattern suggesting a protective effect of cytoreductive therapy. Although a modest increase in PE risk was observed at 5 years, this finding was isolated and lacked a consistent temporal pattern, limiting its clinical interpretability. These findings suggest that the role of hydroxyurea in modifying thrombotic risk among MF patients with leukocytosis remains uncertain and highlight the need for individualized treatment decisions and further studies to better define its impact on thrombotic outcomes in this population.

e14102 Background: High-quality glioma surgery requires multidisciplinary expertise, yet access to high-volume centers varies. National estimates of inpatient morbidity and resource utilization can identify actionable quality gaps and disparities. Methods: We analyzed the HCUP National Inpatient Sample (NIS) for adult admissions undergoing intracranial glioma resection from 2016–2022. Primary outcomes were in-hospital mortality and major complications (neurologic, infectious, thromboembolic, hemorrhagic). Secondary outcomes included length of stay (LOS), total charges, non-home discharge, and weekend admissions. Survey-weighted methods generated national estimates, and multivariable regression evaluated associations with hospital volume, teaching status, region, and patient-level socioeconomic variables, adjusting for age, comorbidities, and admission urgency. Results: Among 23,874 weighted admissions, in-hospital mortality was 2.1%, and major complications occurred in 14.7%. High-volume centers had lower odds of mortality (adjusted OR 0.62, 95% CI 0.51–0.75) and complications (OR 0.71, 95% CI 0.63–0.80) compared with low-volume hospitals. LOS was shorter at high-volume centers (median 5 vs 7 days, p < 0.001), with lower total charges. Patients from lower-income quartiles and rural areas had higher odds of complications and non-home discharge (OR 1.33, 95% CI 1.11–1.59). Weekend admissions were associated with modestly higher complication rates (OR 1.12, 95% CI 1.01–1.24). Conclusions: National inpatient outcomes for glioma resection vary by hospital volume and patient socioeconomic factors, highlighting disparities in access to high-quality surgical care. Clinical takeaway: Referral to high-volume centers and targeted support for vulnerable populations may reduce complications, optimize resource utilization, and improve equity in glioma surgical care.

e14101 Background: Pediatric and adolescent/young adult (AYA) malignant brain tumors remain a leading cause of cancer-related death. Population-level geographic and rural–urban disparities may reflect differences in access to specialized care and supportive services. Methods: Using CDC WONDER mortality data (1999–2023), we identified deaths from malignant brain tumors using ICD-10 codes. Pediatric (0–14 years) and AYA (15–39 years) populations were analyzed separately. Age-adjusted mortality rates (AAMR) per 100,000 were calculated by state, region, and urban–rural classification. Joinpoint regression assessed temporal trends, and interactions evaluated differential trends by rurality and geography. Results: A total of 14,532 deaths were analyzed. National AAMR declined modestly in pediatric patients (AAPC −1.1%, p < 0.01) but remained relatively stable in AYA patients (AAPC −0.3%, p = 0.12). Rural areas consistently showed higher mortality than urban areas in both age groups (p < 0.01). Regional disparities were evident, with highest pediatric and AYA mortality in the Southeast and Midwest. Inflection points indicated modest improvements following 2007 and 2015, likely reflecting advances in treatment and supportive care, but rural–urban gaps persisted. Rolling averages confirmed stability of these trends despite small-area data suppression. Conclusions: Geographic and rural–urban disparities in pediatric and AYA malignant brain tumor mortality persist despite modest national improvements, highlighting populations at greatest risk. Clinical takeaway: Targeted resource allocation and improved access to specialized neuro-oncology care in high-burden and rural regions are needed to reduce mortality and close disparities.

e14098 Background: For IDH-mutant WHO grade 2 gliomas, extent of resection (EOR) is thought to improve long-term outcomes, but optimal thresholds and survival benefit remain uncertain. Quantifying the impact of EOR can guide surgical planning and patient counseling. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, CENTRAL, and Web of Science. Eligible studies reported EOR (continuous or categorical) and outcomes including overall survival (OS), progression-free survival (PFS), malignant transformation, seizure control, and treatment-related morbidity. Random-effects models pooled hazard ratios (HRs) for survival outcomes, and meta-regression assessed relationships between EOR, histologic subtype (astrocytoma vs oligodendroglioma), measurement method (MRI volumetrics vs surgeon estimate), and adjuvant therapy. Results: Twelve studies including 1,052 patients were analyzed. Higher EOR was associated with improved survival: pooled HR for OS per 10% incremental resection was 0.88 (95% CI 0.83–0.93), and for PFS 0.85 (95% CI 0.79–0.91). Patients achieving ≥90% resection had the greatest benefit, with 10-year OS of 88% versus 62% for <90% resection (p < 0.001). Higher EOR also reduced risk of malignant transformation (HR 0.67, 95% CI 0.53–0.85) and improved seizure control in 68% of evaluable patients. Results were consistent across histologic subtypes and measurement methods, with minimal heterogeneity (I² < 35%). Conclusions: Greater EOR in IDH-mutant grade 2 gliomas is strongly associated with improved survival, lower malignant transformation risk, and better seizure control, supporting maximal safe resection as the standard of care. Clinical takeaway: Surgical planning aiming for ≥90% resection can optimize long-term outcomes and quality of life in patients with IDH-mutant grade 2 gliomas.