TP53 Mutant Variant Allele Frequency and Cytogenetics Determine Prognostic Groups in MDS/AML for Transplantation

• TP53-mutated AML/MDS patients represent a unique and heterogenous high-risk group that should not be treated as one single entity.

• Transplant candidates can be identified based on TP53 allelic state, variant allele frequency and cytogenetic abnormalities.

Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT. We aimed to identify the patients that benefit most from HSCT. The primary outcome was progression-free survival (PFS). Fifty-two percent of the cohort had AML and the median age of the cohort was 62. AML and MDS outcomes were similar. We identified several favorable prognostic factors for PFS including the absence of complex cytogenetics/5q deletion/7q deletion, a lower variant allele frequency (VAF), a mono-hit status and the use of a matched-related donor. Using classification and regression tree analysis, we identified VAF and cytogenetics as the two most important prognostic factors. Patients with TP53mut VAF ≥ 50% had a 2-year PFS of 3%, patients with TP53mut VAF < 50% and complex/5q/7q cytogenetics abnormalities had 2-year PFS of 22%. Patients with TP53mut VAF < 50% and without complex/5q/7q cytogenetics had 2-year PFS of 60%. This data informs clinical practice and helps patients decide whether to pursue HSCT.