Developmental stage modulates the prognostic impact of RAS pathway mutations in AML patients undergoing Allo-HSCT

The RAS pathway and developmental stage are known to influence leukemic cell proliferation and drug resistance. However, their impact on the prognosis of acute myeloid leukemia (AML) patients, particularly post-allo-HSCT, remains unclear. This study aimed to explore the effects of RAS-pathway mutations and developmental stage on the outcomes of AML patients who received allo-HSCT. A total of 364 consecutive adult AML patients who underwent their first allo-HSCT with myeloablative conditioning were enrolled in this study. The primary endpoint of this study was the cumulative incidence of relapse (CIR) and secondary endpoints were OS and leukemia-free survival (LFS). RAS-pathway mutations were detected in 57 patients (15.7%). Subgroup analysis revealed opposite outcomes: RAS-pathway mutations were associated with a higher cumulative incidence of relapse (CIR) (38.6% vs. 14.8%, P = 0.016) in the primitive AML subgroup and a lower CIR (3.4% vs. 26.8%, P = 0.013) and better leukemia-free survival (LFS) (93.1% vs. 66.9%, P = 0.013) in the monocytic subgroup, compared with AML patients without RAS-pathway mutations. Subgroup multivariable analyses in the primitive subgroup revealed that patients with RAS-pathway mutations had a higher CIR (hazard ratio [HR] = 2.55, 95% confidence interval [CI]: 1.21-5.40). Meanwhile, subgroup multivariable analyses in the monocytic subgroup showed that patients with RAS-pathway mutations exhibited a significantly improved LFS (HR = 0.23, 95% CI: 0.06-0.96). In summary, the prognosis of AML patients with RAS-pathway mutations who received allo-HSCT can be significantly influenced by the developmental stage at which the mutation occurs.