Shah, M.V.Hung, K.Baranwal, A.Kutyna, M.M.Al-Kali, A.Toop, C.Greipp, P.T.Brown, A.L.Shah, S.N.Khanna, S.Ladon, D.Gannamani, V.Chen, D.Begna, K.Price, Z.Rud, D.Litzow, M.R.Hogan, W.J.Bardy, P.G.Badar, T.et al.2025-10-132025-10-132025Blood advances, 2025; 9(13):3370-33802473-95292473-9537https://hdl.handle.net/2440/147730This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53(mut)) myeloid neoplasms (MNs). Of 580 MNs harboring TP53(mut) with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53(mut) AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53(mut) MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.en© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.Myeloid NeoplasiaHumansMyelodysplastic SyndromesPrognosisRisk AssessmentRetrospective StudiesGene FrequencyMutationAdultAgedAged, 80 and overMiddle AgedFemaleMaleTumor Suppressor Protein p53Leukemia, Myeloid, AcuteJournal article10.1182/bloodadvances.2024015238732305Kutyna, M.M. [0000-0003-2315-091X]Brown, A.L. [0000-0002-9023-0138]Price, Z. [0000-0001-5306-3468]Kumar, S. [0000-0001-7126-9814]Yeung, D.T. [0000-0002-7558-9927]Scott, H.S. [0000-0002-5813-631X]Hahn, C.N. [0000-0001-5105-2554]Kok, C.H. [0000-0002-3181-7852]Hiwase, D.K. [0000-0002-6666-3056]