Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations.
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Shah Mithun Vinod, Hung Kevin, Baranwal Anmol, Kutyna Monika M, Al-Kali Aref, Toop Carla, Greipp Patricia, Brown Anna, Shah Syed, Khanna Shreyas, Ladon Dariusz, Gannamani Vedavyas, Chen Dong, Begna Kebede, Price Zoe K, Rud Danielle, Litzow Mark R, Hogan William J, Bardy Peter, Badar Talha, Kumar Sharad, Yeung David T, Patnaik Mrinal M, Foran James M, He Rong, Gangat Naseema, Scott Hamish S, Arana Yi Cecilia Y, Alkhateeb Hassan, Mangaonkar Abhishek A, Thomas Daniel, Hahn Christopher N, Orazi Attilio, Arber Daniel A, Kok Chung Hoow, Tefferi Ayalew, Hiwase Devendra
Аннотация
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.