Abstract 3367: Determinants of survival in acute megakaryocytic leukemia: A real-world database analysis

Background: Acute megakaryocytic leukemia (AMKL) is a rare and aggressive subtype of acute myeloid leukemia (AML), characterized by the malignant proliferation of megakaryoblasts. It accounts for less than 1% of AML cases in adults but is more prevalent in pediatric patients, particularly those with Down syndrome. AMKL poses unique diagnostic and therapeutic challenges due to its distinct clinical and biological features, and overall prognosis remains poor. The prognostic factors influencing survival in AMKL are not well-defined, prompting this pooled real-world database analysis to identify clinicopathological characteristics and treatment strategies associated with survival outcomes. Methods: A pooled database of confirmed AMKL cases was analyzed to assess demographic characteristics, molecular and immunohistochemical profiles, therapeutic interventions, and survival outcomes. Kaplan-Meier survival curves were used to estimate overall survival (OS), while Cox proportional hazards models and Log-rank tests assessed the impact of clinicopathologic factors on OS. Results: A total of 220 patients with confirmed AMKL were included, with a median age of 3 years. The M:F was 1.3 overall, differing between pediatric (M:F of 1) and adult (M:F of 2) subgroups. The median duration of symptoms before diagnosis was 1 month. Constitutional symptoms, lymphadenopathy, splenomegaly, hepatomegaly, and bone involvement were present in 40%, 19%, 34%, 26%, and 13% of cases, respectively. The cohort median OS was 13 months, with pediatric patients showing significantly better OS compared to adults (44 vs. 5.9 months, p<0.0001). Patients with constitutional symptoms (p=0.05), lymphadenopathy (p=0.06), or elevated LDH (>500 U/L, p=0.07) had worse OS, with borderline statistical significance. However, patients with Down syndrome had significantly improved OS (NR vs. 12 months, p=0.01). Positive staining for CD4 (<0.0001), CD7 (p=0.04), or CD13 (p=0.03) was associated with better OS. Sex, WBC count, hemoglobin levels, platelet count, t(1;22), inv(16), and splenomegaly did not significantly impact OS. AMKL arising in the context of malignancy or myeloproliferative disorders was associated with worse OS (p<0.0001). Chemotherapy and stem cell transplantation provided superior OS compared to no treatment (10 vs. 23 vs. 1.5 months, p<0.0001). Low-intensity regimens offered no significant benefit over no treatment. Patients who achieved complete remission (CR) had significantly improved OS compared to those who did not (44 vs. 4 months, p<0.0001). Conclusion: The analysis of this large pooled cohort of AMKL patients identified key factors influencing survival, including age, Down syndrome status, association with malignancy or myeloid disorders, treatment intensity, and quality of response. These findings provide valuable insights for improving prognostication and guiding treatment strategies in AMKL. Citation Format: Philip A. Haddad, Sireesha Vutukuri, Ankita Gupta. Determinants of survival in acute megakaryocytic leukemia: A real-world database analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3367.