TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
Mithun Vinod Shah, Elizabeth Ngoc Hoa Tran, Syed Shah, Rakchha Chhetri, Anmol Baranwal, Dariusz Ladon, Carl Shultz, Aref Al‐Kali, Anna Brown, Dong Chen, Hamish S. Scott, Patricia T. Greipp, Danièl Thomas, Hassan B. Alkhateeb, Deepak Singhal, Naseema Gangat, Sharad Kumar, Mrinal M. Patnaik, Christopher N Hahn, Chung Hoow Kok, Ayalew Tefferi, Devendra Hiwase
Abstract
Abstract Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53 -mutated ( TP53 mut ) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53 mut . We analyzed 488 t-MN patients for TP53 mut . At least one TP53 mut with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53 mut t-MN had a VAF ≥10%. TP53 mut t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53 mut VAF < 10% and wild-type TP53 ( TP53 wt ) cases. Notably, TP53 mut VAF ≥ 10% had a significantly shorter survival compared to TP53 wt (8.3 vs. 21.6 months; P < 0.001), while the survival of TP53 mut VAF < 10% was comparable to TP53 wt . Within TP53 mut VAF ≥ 10% cohort, the inferior outcomes persisted irrespective of the single- or multi-hit status, co-mutation pattern, or treatments received. Finally, survival of TP53 mut patients was poor across all the blast categories and MDS patients with >10% blasts had inferior survival compared to <5%. In summary, TP53 mut VAF ≥10% signified a clinically and molecularly homogenous cohort regardless of the allelic status.