Background and objectives: TP53 mutations occur in about 10% of myeloid malignancies and are linked to poor prognosis despite intensive treatments. This study aims to improve treatment outcomes by gaining a better understanding of the clinical features, cytogenetic profiles, molecular characteristics, and outcomes of TP53-mutated myeloid neoplasms.

Methods: Next Generation Sequencing (NGS) database at King Hussein Cancer Center was used to identify adult patients (≥ 18 years) with TP53 mutated myeloid neoplasms, diagnosed and treated at KHCC between 2014 and 2023. Baseline characteristics are summarized using descriptive statistics. The Kaplan-Meier method was used to compare overall survival between different cytogenetic and treatment groups.

Results: During the study period, 55 patients with TP53-mutated myeloid neoplasms were enrolled. Median age was 57 (22-84) years, and 35 (64%) were males. Myeloid neoplasms include AML (n=26, 47.2%), MDS (n=24, 43.6%), and MPN (5, 9.1%). Prior malignancies were present in 14 (25.5%) patients, and 12 (21.8%) had therapy-related neoplasms. Cytogenetic studies showed that 26 (55.3%) patients had complex karyotypes. The most common TP53 mutation was the missense mutation, found in 43 (78.2%) patients. Intensive chemotherapy was administered to 21 (38.2%) patients, while 19 (34.5%) received low-intensity regimens. Allogeneic stem cell transplantation (AlloSCT) was performed on 21 (38.2%) patients. After a median follow-up of 11 months, the median overall survival (OS) for the entire cohort was 9 months (95% CI, 6.8-11.2). Survival was worse in patients with complex karyotypes; 5 months (95% CI 1.3-8.7), compared to 12 months (95% CI, 8.2-15.9, p=0.005) in patients with other cytogenetics. There was no significant difference in survival between intensive and low-intensity therapy groups. However, AlloSCT improved OS rates in the entire cohort (12 months, 95% CI, 9.5-4.5 vs. 4.0 months, 95% CI, 0.0-9.71, p=0.006) and among those who received intensive chemotherapy (12 months, 95% CI, 10.3- 13.7 vs. 7 months, 95% CI, 0.0-14.9,p=0.007).

Conclusions: In this limited sample of patients with myeloid neoplasms, the presence of complex karyotype, in addition to TP53 mutation, is associated with poorer prognosis. AlloSCT can improve survival, but overall outcomes remain dismal compared to other genetic groups.

Disclosures

No relevant conflicts of interest to declare.

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2024
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