Investigating age of onset and prognosis of p53 mutant myeloid malignancies in African Americans.

6547 Background: TP53 mutations drive poor outcomes in Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), aggressive hematologic malignancies characterized by clonal abnormalities in myeloid hematopoiesis. Prognostic scoring systems incorporate cytogenetic and molecular abnormalities based on data from majority White populations and have limited applicability to minorities. Racial disparities in survival are well-known, with Black patients experiencing worse outcomes. While TP53 mutations are associated with poor outcomes, there is limited data about their implications in minority populations. Objective: To study TP53 mutation status, variant allele frequency (VAF), and co-mutations on outcomes in MDS and AML between White and minority populations in the Bronx, a racially diverse region. Methods: This retrospective cohort study analyzed 84 patients diagnosed with TP53 mutated AML and MDS between 2014 and 2024 at Montefiore Medical Center. Data included race/ethnicity (Black, White, Hispanic), age, age at diagnosis, gender, diagnosis, first-line chemotherapy, and bone marrow blast percentage. Molecular data included TP53 mutation status (bi- vs. mono-allelic), variant allele frequency (VAF), and co-mutations. Co-mutation patterns will be presented at the meeting. Comparisons were made using descriptive statistics, and survival outcomes were analyzed using Cox proportional hazards models adjusted for age and gender. Results: Black patients were diagnosed at a younger age than White or Hispanic patients (mean: 63.7 vs. 72.6 vs. 65.9 years, p = 0.029) and had shorter median overall survival (3.9 vs. 16.4 vs. 10 months, p = 0.014). Black patients had higher mean VAF (48.1 vs. 31.9 vs. 38.2, p = 0.047) and were more likely to have co-mutations than isolated TP53 mutations, though this was not significant (OR 4.21, p = 0.06). Patients with VAF above the median had a threefold increased risk of death (aOR 3.14, p = 0.019), independent of age or gender. Conclusions: Black patients with TP53 mutant MDS and AML present younger and have worse outcomes than White patients, associated with a higher TP53 VAF and more frequent co-mutations. This is to our knowledge the largest dataset of TP53 in minorities with MDS and AML; highlighting the need for personalized prognostic models that incorporate minorities to overcome racial disparities in myeloid malignancies.