By: Talha Badar, Danica Wiredja, Madhu Menon, Haipeng Shao, Geoffrey D. Wool, Anamarija Perry, Qianghua Zhou, Anthony Findley, Anisha Jacob, Claudia Haferlach, Sinthujaa Velmurugan, Girish Venkataraman, Amandeep Kaur, Hong Chang, Emily Symes, Anna Stengel, Alexandra Rojek, Sharmila Ghosh, Jingjing Zhang, Peng Wang, Hamza Tariq, Daniel A. Arber, Ami B. Patel, David Sallman, Jay L. Patel, Payal Sojitra, Esha Patil, Carrie Fitzpatrick, Zenggang Pan, Madhavi Pandiri, Robert C Bell
We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed ‘CK50’)) in 495 individuals with TP53- mutated ( TP53MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%–19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.
