Year: 2025
Type: article
Study design: Observational Study
Abstract: ABSTRACT: This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut 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 TP53mut 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% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.
Source: Blood Advances
Authors: Mithun Vinod Shah, Kevin Hung, Anmol Baranwal, Monika M. Kutyna, Aref Al-Kali, Carla Toop, Patricia Greipp, Anna Brown, Syed Shah, Shreyas Khanna, Dariusz Ladon, Vedavyas Gannamani, Dong Chen, Kebede Begna, Zoe K. Price, Danielle Rud, Mark R. Litzow, William J. Hogan, Peter Bardy, Talha Badar, Sharad Kumar, David T. Yeung, Mrinal M. Patnaik, James M. Foran, Rong He, Naseema Gangat, Hamish S. Scott, Cecilia Y. Arana Yi, Hassan Alkhateeb, Abhishek A. Mangaonkar, Daniel Thomas, Christopher N. Hahn, Attilio Orazi, Daniel A. Arber, Chung Hoow Kok, Ayalew Tefferi, Devendra Hiwase
Institutions: Mayo Clinic, Royal Adelaide Hospital, Central Adelaide Local Health Network, South Australian Health and Medical Research Institute, The University of Adelaide, South Australia Pathology, University of South Australia, Centre for Cancer Biology, Mayo Clinic in Florida, Mayo Clinic in Arizona, Mayo Clinic Hospital, Texas Tech University Health Sciences Center, University of Chicago
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4408475480