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e18597 Background: TP53 mutations ( TP53 m) are uncommon in chronic-phase (CP) Philadelphia (Ph) chromosome–negative myeloproliferative neoplasms (MPN) but are increasingly reported in myelofibrosis (MF) and accelerated/blast phase (AP/BP). Their distribution, allelic configuration, and associated clinical outcomes have not been systematically synthesized. Methods: A PRISMA-guided search of EMBASE and PubMed (1974-July 1, 2025) identified cohort studies reporting adult Ph–negative MPNs with molecularly confirmed TP53 m. Case reports were excluded; Conference abstracts were included if cohort-level data were available. Extracted variables included demographics, MPN subtype, disease phase, TP53 allelic status (per International Consensus Classification), variant allele frequency (VAF), allogeneic hematopoietic cell transplantation (allo-HCT), median overall survival (mOS), and leukemic transformation. Given heterogeneity and lack of comparators, pooled proportions with (95% CI) were generated for descriptive variables; outcomes were summarized descriptively. Results: 10 retrospective studies met inclusion criteria. Pooled mean age was 61 years (95% CI 57.18–65.17) with male predominance (58%, 95 CI 53–63). TP53 m were uncommon in patients with Ph-negative MPN (3%, 95% CI 0–15%) but were higher in MF/AP/BP (10%, 95% CI 4–24%). Among patients with TP53 m, disease distribution included MF (35%, 95% CI 13–65%), AP/BP (33%, 95% CI 26–41%), essential thrombocythemia (ET) (10%, 95% CI 3–28%), and polycythemia vera (PV) (8%, 95% CI 4–14%). Multi-hit TP53 m accounted for 52% (95% CI 40–64%), while single-hit comprised 47% (95% CI 34–60%). The pooled mean TP53 VAF was 37.48% (95% CI 30.73–44.24%). Allo-HCT was used in 16% (95% CI 13–20%). One cohort reported leukemic transformation in 47% with a median follow-up of 9.6 months (m). Reported mOS in TP53 m CP-MF ranged from 11.6–18 m and was not reached in PV/ET, whereas AP/BP mOS ranged from 4.5–6 months. Conclusions: TP53 m Ph–negative MPNs are enriched in MF and AP/BP and frequently demonstrate multi-hit TP53 m with high VAF and associated with high leukemic transformation. Standardized molecular reporting and prospective studies are needed to refine prognostication and treatment strategies in TP53m MPN. Characteristics of patients with TP53 m MPN. Variable Pooled variables (95% CI) Age 61.18 years (57.18–65.17) Male/Female 58% (53–63)/42% (53–63) TP53 mutation in the cohort 3% (0–15) TP53 in MF/AP/BP 10% (CI 4–24) Primary myelofibrosis 35% (13–65) MPN in AP/BP 33% (26–41) Essential thrombocythemia 10% (CI 3–28) Polycythemia vera 8% (CI 4–14) Multi-hit/single-hit TP53 52% (CI 40–64) 47% (CI 34–60) TP53 VAF 37.48% (30.73–44.24) Abbreviations: MF: Myelofibrosis, AP: accelerated phase, BP: Blast phase, MPN: myeloproliferative neoplasm, VAF: Variant Allele Frequency.

9021 Background: An escape room is a team-based activity in which participants collaborate to solve puzzles within a fixed time limit and escape. Prior studies demonstrate high learner satisfaction and improved teamwork and communication with medical education escape rooms. To date, no published reports describe an escape room designed specifically for hematology/oncology (hem/onc) fellows. As part of Hem/Onc Curriculum, we designed and implemented a hem/onc-focused escape room and evaluated learner satisfaction and perceived learning impact. Methods: The escape room was designed using evidence-based learning science principles (Table 1). Teams worked to solve sequential puzzles, centered on a patient case, addressing key hem/onc concepts, including transfusion medicine, peripheral blood smears, lymphoma classification, and coagulation disorders. Each solved puzzle revealed additional patient laboratory and pathology data. Successful completion required teams to diagnose the patient and select appropriate treatment. Following the activity, teams participated in a facilitator-led debrief focused on team dynamics, communication, and problem solving. Teams observed each other and shared feedback. A larger group debrief co-led by chief fellows and faculty reviewed learning objectives and key takeaways. Learner outcomes were assessed using a post-activity survey evaluating satisfaction, engagement, and impact on learning. Results: Eighteen learners participated, including 14 hem/onc fellows, 1 APP hem/onc fellow, and 3 internal medicine residents. Three of four teams escaped within 1 hour (mean completion time, 52 minutes). All participants provided positive verbal feedback. Fifteen learners completed the post-activity survey, and all respondents reported satisfaction with the activity and would recommend it for future fellows. One-word descriptors included “engaging,” “fun,” and “challenging.” Most respondents (93.3%) agreed that the activity reinforced key hem/onc concepts and improved confidence in clinical problem-solving. All learners felt the activity supported learning, and 93.3% reported that collaboration enhanced the learning experience. Participants identified team-based problem solving, clinical application, and interactive puzzles as the most effective components. Conclusions: A hem/onc escape room resulted in high learner satisfaction and reinforced hem/onc knowledge and clinical problem-solving. This feasible, fun, and innovative activity complements traditional fellowship education by leveraging adult learning principles through gamified, team-based learning and should be incorporated into training programs’ curriculum. Learning science principles applied in a hem/onc escape room. Active Learning Belonging Contrasting Cases Debriefing Deliberate Practice Elaboration Generation Listening and Sharing Reward Worked Examples

Abstract Background: KMT2A-rearranged acute myeloid leukemia (KMT2Ar AML) is characterized by chromosomal translocation involving KMT2A gene at 11q23, resulting in fusion with variety of partner genes. It is usually associated with poor outcomes, high risk of relapses and suboptimal responses to conventional therapies. While NPM1-mutated (mt) AML is considered favorable risk, they are equally dismal in relapse refractory (RR) setting. Menin inhibitors have emerged as a promising therapeutic strategy, particularly in RR AML patients (pts) with KMT2Ar and NPM1-mt genotypes. While revumenib, a menin inhibitor approved for managing RR KMT2Ar acute leukemia, no menin inhibitor is currently approved for NPM1-mt AML. In this study, we evaluated clinical outcomes of adults with KMT2Ar AML and performed a comparative analysis of pts with RR KMT2Ar and NPM1-mt AML using data from the Mayo Clinic. Methods: After screening 102 AML pts with reported KMT2A abnormalities, we identified 33 adults with confirmed KMT2Ar diagnosed between 2012 and 2024 for retrospective analysis. Clinical and molecular/cytogenetics data, induction type (intensive chemotherapy [IC] vs non-intensive chemotherapy [NIC]), response, transplant use, and survival outcomes were reviewed. A separate analysis was performed comparing 20 RR KMT2Ar AML pts with 20 propensity score matched RR NPM1-mt AML pts from a pool of 125 NPM1-mt RR pts. Results: The median age was 50 years (yrs) (range [R], 19.0-75.0), and 60.6% were < 60 yrs. Most cases were de novo AML (64%), and the most frequent translocation was t(6;11)(q27;q23)/MLLT4 (27%), followed by t(10;11)(p12;q23)/MLLT10 (21%), t(9;11)(p21.3;q23.3)/MLLT3 (15%), and t(11;19)(q23;p13.1)/ELL (12%). Other KMT2A fusion partners were rare and collectively accounted for the remaining cases. The median follow-up was 57 months (mo) (R, 7.0-109.0). The overall response rate (ORR) was 91%, and composite complete remission (CRc, , including CR, CRi, and CRh) was 73%. The CRc rates were comparable between IC and NIC (80% vs 62%, p=0.24). CRc were not significantly different by disease type (de novo [71.4%] vs secondary [sAML] [75%], p= 0.82) or KMT2A fusion partner gene (60% for t[9;11]/MLLT3 vs. 57.1% for t[10;11]/MLLT10 vs 55.6% for t[6;11]/MLLT4, p=0.069). Seventeen (52%) pts received an allogeneic stem cell transplantation (allo-HCT). The median overall survival (mOS ) for the entire cohort was 16 mo (R, 11.0-34.0). In subset analysis, IC compared to NIC was associated with significantly longer mOS (30 vs 11 mo, p=0.014). The mOS was also superior in pts <60 vs ≥60 yrs (32 vs 8 mo, p=0.005). Similarly, de novo cases had better mOS than sAML (22.0 vs 9.5 mo, p=0.052). Among KMT2Ar subtypes, t(6;11)/MLLT4 showed the longest mOS (54 mo [R, 30.0-not reached (NR)]), while t(9;11)/MLLT3 had the shortest (11.0 mo, [R 9-NR]), but differences were not statistically significant (p=0.32). The mOS was significantly longer among allo-HCT pts (30 vs 11 mo, p=0.005). Among 29 pts who experienced RR disease, the median relapse free survival (RFS) was 3 mo (R, 2.0-10.0). First salvage therapy yielded a CRc of 43.8% in 16 evaluable pts. When compared to a propensity matched cohort of 20 RR NPM1-mt AML pts, the CRc rates was 57.9% vs 50% in RR NPM1-mt and KMT2Ar AML (p= 0.68). The mRFS was not significantly different between RR KMT2Ar and NPM1-mt AML, (3 vs 4 mo, p=0.9). However, KMT2Ar pts had inferior mOS compared to NPM-mt AML (12 vs 65 mo, p=0.004). We further compared survival between NPM1-mt and KMT2Ar pts stratified by allo-HCT status. Among those who underwent allo-HCT, NPM1-mt pts had longer mOS (NR vs 22 mo, p=0.037). Among non-allo-HCT pts, mOS was numerically higher in NPM1-mt vs KMT2Ar (19 vs 8 mo, p=0.11). Conclusions: This single institusion cohort of adult AML with KMT2Ar underscores the biological and clinical heterogeneity of this high-risk group. IC was associated with a survival benefit, particularly among younger and fit patients. However, the outcomes following relapse remained poor, highlighting the urgent need for improved post-remission and salvage therapies. Comparative analysis with matched RR NPM1-mt AML pts revealed similarly dismal survival outcomes. Emerging data from single-arm studies of menin inhibitors in both frontline and RR settings among pts with NPM1-mt and KMT2Ar AML are encouraging and may represent a paradigm shift in treatment.

Abstract Introduction Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of peripheral T-cell lymphoma. It is characterized by aggressive clinical behavior and poor prognosis and treatment often includes chemotherapy, but the benefit of hematopoietic stem cell transplantation (HSCT) remains an area of ongoing investigation. Using the National Cancer Database, we analyzed the impact of HSCT on survival in a large cohort of patients with PTCL-NOS. Materials and Methods We queried the National Cancer Database (NCDB) for patients aged 18 or older diagnosed with PTCL-NOS between 2004 and 2019. Patients who lost to follow-up were excluded. We analyzed the impact of HSCT on overall survival (OS) using Kaplan-Meier estimates and multivariate Cox regression to identify factors associated with OS. Results A total of 14,301 patients with PTCL-NOS were included in this analysis. Among them, 60.1% were male, 65.7% were Caucasian, 17.1% were black and 7.4% were Hispanic. Early-stage disease (stage I or II) was present in 24.1%, while 49.3% patients had advanced-stage disease (stage III or IV). The median age at diagnosis was 65 years (range 18-90, 23.6% were above age 75), and the median overall survival (mOS) was 15.3 months (95%CI 14.6-16), with a median follow-up of 82.8 months (95%CI 80.4-85.2). Regarding first-line treatment, 11.7% received radiation therapy, 68.9% received chemotherapy, and 6.6% underwent HSCT. The percentage of patients receiving HSCT increased from 3.3% in 2004 to 9.9% in 2019, tripling over the 16-year period. Transplant utilization varied by race/ethnicity: 7.3% of white patients underwent HSCT, compared to 6.4% of Hispanic and 4.3% of Black patients (P < 0.001). Socioeconomic disparities were also observed: patients with insurance were more likely to receive HSCT (6.8%) compared to those without insurance (2.1%); HSCT rates increased with income, from 3.9% in the lowest quartile to 8.1% in the highest; and patients from areas with higher education levels had nearly double the HSCT rate (8.4%) compared to those from the lowest-education areas (4.5%) with P<0.001 for all. In patients with advanced-stage disease, the mOS was 10.5 months (95%CI 9.8-11.1). Patients who received HSCT had significantly improved survival compared to those who did not (mOS 110.9 vs. 11.1 months; P < 0.001). Among those who underwent HSCT, there was no significant difference in survival between auto (N=207) and allo (N=47) mOS 118.9 vs. 95.7 months; P = 0.128. A similar trend of improved survival with HSCT and no significant difference between autologous and allogeneic HSCT was observed across all racial/ethnic groups: in Hispanic patients mOS in HSCT (N=31) vs. no HSCT (N=456) 106.2 vs. 8.8 months; P < 0.001. comparison between auto and allo was not performed due to the low number of allogeneic transplants (N=2). In Black patients mOS inHSCT (N=47) vs. no HSCT (N=1,215) 69.7 vs. 8.8 months; P < 0.001 and mOS in auto vs. allo NR in both groups; P = 0.764. InCaucasian patients mOS in HSCT (N=419) vs. no HSCT (N=4,111) 111.8 vs. 8.8 months; P < 0.001 and mOS in Auto vs. allo 118.9 vs. 99.4 months; P = 0.263. On multivariate analysis, older age, male gender, black race, presence of B-symptoms at diagnosis, HIV positive status, higher comorbidity score and receiving allogeneic (vs. autologous) HSCT were associated with worse survival. In contrast, having medical insurance, receiving radiation therapy, chemotherapy, and undergoing HSCT (vs. no HSCT) were associated with improved survival. Conclusion HSCT was associated with significantly improved overall survival in patients with PTCL-NOS, especially in those with advanced-stage disease. This survival benefit was consistently observed across racial and ethnic groups. These findings might be related to transplant eligibility. However, allogeneic HSCT was linked to worse outcomes compared to autologous HSCT, likely due to higher transplant-related mortality or selection bias of more aggressive diseases to undergo allogeneic transplant. Even though the trend reflects a growing adoption of HSCT as part of treatment strategies in advanced-stage PTCL-NOS over time, transplant utilization varied significantly by sociodemographic factors (insurance, education and income level), highlighting potential disparities in access to this potentially life-prolonging therapy. Further prospective studies are needed to refine transplant strategies and improve patient selection.

Abstract Zieve's syndrome is a rare and often overlooked complication of alcohol misuse, likely under-recognized due to limited physician awareness. We present a unique case with an atypical and misleading clinical presentation that initially raised concern for a hepatic mass. Despite the diagnostic uncertainty, the astute clinical vigilance and thoughtful evaluation by the treating team led to the correct diagnosis of Zieve's syndrome. This case highlights the importance of maintaining a broad differential and considering alcohol-related syndromes even when initial findings suggest alternative etiologies. We present the case of a 29-year-old man with a history of essential tremor managed on propranolol, who was transferred for further evaluation of worsening jaundice following a brief, self-resolving viral-like illness. He denied abdominal pain, ongoing gastrointestinal symptoms, intravenous drug use, or alcohol intake. Initial CT abdomen/pelvis showed hepatic steatosis and a 4.5 × 2.5 × 7.0 cm lobulated hypodense lesion in the right hepatic lobe, raising concern for pyogenic abscess versus neoplasm. Gallbladder wall was mildly thickened (5 mm) without pericholecystic fluid or biliary dilation. He was transferred for further evaluation. Laboratory evaluation revealed macrocytic anemia (Hb 9.9 g/dL, MCV 102 fL), thrombocytopenia (PLT 148), markedly elevated bilirubin (total 12.9 mg/dL, direct 6.8 mg/dL), transaminitis (ALT 93 U/L, AST 217 U/L), and evidence of hemolysis with low haptoglobin (30 mg/dL), elevated LDH (339 U/L), and a low reticulocyte count (0.39%). Sodium was 127 mmol/L, and INR was normal. Hepatitis viral panel, urine drug screen, and urinalysis were negative. Lipid panel revealed extreme hyperlipidemia with triglycerides 1500 mg/dL, LDL 687 mg/dL, and total cholesterol 1300 mg/dL. Peripheral smear showed macrocytic anemia with mild anisocytosis, slight polychromasia, and mild red blood cell agglutination. RUQ ultrasound showed hepatic steatosis with no focal lesion. MRI liver protocol revealed hepatomegaly and diffuse hepatic steatosis with sparing in the falciform ligament, gallbladder fossa, and portions of the right hepatic lobe explaining the CT “lesion” as focal fat sparing rather than a true mass. Although the patient denied alcohol misuse, phosphatidylethanol (PEth) testing was positive, confirming recent heavy alcohol consumption. The clinical picture was consistent with alcohol-associated liver injury, hemolysis, and secondary hyperlipidemia. In conclusion, Zieve's syndrome is characterized by a triad of hemolytic anemia, cholestatic jaundice, and transient hyperlipidemia. Prompt recognition of this underdiagnosed condition is crucial, as it can prevent unnecessary invasive interventions and shift the clinical focus toward supportive care and alcohol cessation, which remains the cornerstone of treatment.

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98

Background: Zanubrutinib and acalabrutinib are next-generation Bruton's tyrosine kinase (BTK) inhibitors used in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). They have demonstrated lower cardiotoxicity compared to first-generation BTK inhibitor ibrutinib. However, there is limited data comparing cardiovascular outcomes between zanubrutinib and acalabrutinib. This study aims to investigate the cardiovascular risks associated with these two agents in a real-world setting. Method: A retrospective, propensity score-matched study was conducted using the TriNetX database, which includes de-identified electronic health records from over 101 million individuals across 70 healthcare organizations. Patients with CLL and SLL treated with either zanubrutinib or acalabrutinib were included, excluding those who received ibrutinib. The primary outcome of interest was major cardiovascular adverse events, composed of heart failure, myocardial infarction, and cardiac arrest. Other outcomes of interest were new-onset hypertension, new-onset atrial fibrillation/flutter, ventricular arrhythmia, myocardial infarction, new-onset heart failure, conduction block, and stroke within 18 months of therapy initiation. Propensity score matching accounted for demographics, comorbidities, disease status, other CLL/SLL-directed therapies, and concomitant cardiovascular agents. Relative risk and 95% confidence intervals were calculated to assess the outcomes. Results: A total of 907 patients treated with zanubrutinib were matched to 907 patients treated with acalabrutinib. At 18 months, the zanubrutinib group experienced 106 major cardiovascular adverse events, compared to 144 in the acalabrutinib group (RR (relative risk), 0.73 [95% CI: 0.58-0.93]; p=0.009). New-onset hypertension occurred in 35 zanubrutinib and 31 acalabrutinib patients (RR, 1.14 [95% CI: 0.72-1.82]; p=0.579). New-onset atrial fibrillation/flutter occurred in 15 zanubrutinib and 30 acalabrutinib patients (RR, 0.49 [95% CI: 0.27-0.91]; p=0.020). Ventricular arrhythmia occurred in 13 zanubrutinib and 9 acalabrutinib patients (RR, 1.44 [95% CI: 0.62-3.36]; p=0.402). Myocardial infarction occurred in 18 zanubrutinib and 25 acalabrutinib patients (RR, 0.72 [95% CI: 0.40-1.31]; p=0.286). New-onset heart failure occurred in 34 zanubrutinib and 40 acalabrutinib patients (RR, 0.82 [95% CI: 0.52-1.28]; p=0.385). Conduction block occurred in 43 zanubrutinib and 48 acalabrutinib patients (RR, 0.90 [95% CI: 0.60-1.34]; p=0.593). Stroke occurred in 20 zanubrutinib and 19 acalabrutinib patients (RR, 1.05 [95% CI: 0.57-1.96]; p=0.873). Conclusion: Zanubrutinib was associated with a 27% lower risk of major cardiovascular adverse events and a 51% lower risk of new-onset atrial fibrillation/flutter compared to acalabrutinib, suggesting its preference for patients with high cardiovascular risks. The risks of new-onset hypertension, ventricular arrhythmia, myocardial infarction, new-onset heart failure, conduction block, and stroke were similar between the two groups. Further studies with long-term follow-up data will be valuable for evaluating the safety of next-generation BTK inhibitors.