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.