Post-cytotoxic myeloid neoplasms: a comprehensive analysis of clinicopathologic, genetic profile, latency determinants, and potential prognostic predictors- a single centre study

Post cytotoxic myeloid neoplasms signify a heterogenous pool of poorly understood hematologic neoplasms with unfortunate survival and ineffective therapies. There is a lack of consensus on prognostic indicators, primarily due to the heterogenous disease spectrum encompassing different pathological, cytogenomic and original disease variables. This retrospective, single-center study over 10 years duration on MN-pCT cases diagnosed at NCCCR, a member of Hamad Medical Corporation. The study aimed to analyze clinicopathologic and cytogenomic characteristics, identify key prognostic predictors, and assess their impact on mortality through univariate and multivariate analyses. We identified 42 MN-pCT patients, noting a 31.7% prevalence of autoimmune diseases as primary condition, which is higher than previously reported. TP53 was the most frequently mutated gene, found in 28.6% of tested cases. Significant determinants of a shorter latency period included prior exposure to alkylating agents and TP53 positivity (by NGS or IHC) (P < 0.05). Younger patients (≤ 50 years) exhibited longer survival (P = 0.018). Poor prognostic markers included dyserythropoiesis (P = 0.045), MPO downregulation (P = 0.026), mutated TP53 (NGS/IHC) (P = 0.004), and failure to achieve CR (P = 0.002). Multivariate Cox regression identified both a latency period of ≥ 5 years and TP53 positivity (detected by either NGS or IHC) as statistically significant independent factors associated with reduced overall survival (P < 0.05). It is important to highlight that P53 mutation by NGS was a common parameter identified by the multivariate analysis that adversely impacted both MN-Pct survival and OS. This study stands as a significant contribution to our understanding of the clinicopathologic characteristics and prognostic predictors of MN-pCT in MENA region. It also underscores the existence of adverse prognostic factors, extending beyond the genetic influences and emphasizing the necessity of recognizing it as a distinct entity in the future classification systems.