A combined risk factor analysis revealed that patients with ≥ 1 adverse factor (either co-mutations < 2 or complex karyotype) had significantly worse OS (3-y OS: 72.6% vs. 37.2%, p = 0.04) and PFS (3-y PFS: 67.7% vs. 28.9%, p = 0.02) compared to those with neither risk factor. In patients with TP53-mutated AML/MDS undergoing allo-HSCT, a low myeloid co-mutation burden (< 2) is strongly associated with poor outcomes. This evidence concerns the gene TP53 and myelodysplastic syndrome.