Figure 3.
CHIP and risk of developing myeloid neoplasms. (A) Definition of a score based on specific mutational patterns (CHIP) and RBC indices to predict the risk of developing myeloid neoplasms. To define a risk score for developing myeloid neoplasms, we used HR from a multivariable Cox analysis on the Health_&_Anemia cohort (learning cohort) adjusted for age and sex, including mutational status (splicing mutations; comutation patterns involving TET2, DNMT3A and ASXL1; and VAF >0.096) and nonmutational parameters (RBC indices) as covariates. A diagnosis of myeloid neoplasm (including myelodysplastic syndrome and acute myeloid leukemia) was considered as event; subjects were censored at the end of follow-up or at time of death. (B) Cumulative incidence (C.I.) of myeloid neoplasms for individuals aged ≥80 years stratified into 3 risk categories (learning cohort). Cumulative incidence was calculated by Kaplan-Meier method (death for any cause was considered as competing-event in the estimation of cumulative incidence function). Left truncation was applied to calculate the cumulative incidence of myeloid neoplasms with age as the time scale. MDS/AML, myelodysplastic syndrome/acute myeloid leukemia. (C) Validation of the score on an independent cohort of 727 subjects aged ≥75 to <80 years from the Health_&_Anemia study.