Clonal hematopoiesis and risk of nonmyeloid subsequent malignant neoplasms after autologous hematopoietic cell transplantation.

Abstract

The association between clonal hematopoiesis (CH) and nonmyeloid subsequent malignant neoplasms (SMNs) after autologous hematopoietic cell transplantation (HCT) has not been explored. This was a retrospective cohort study of 1931 consecutive patients who underwent HCT between 2010 and 2016 at a single center. DNA from pre-HCT mobilized blood products was sequenced to identify CH variants (variant allele frequency [VAF] ≥2%). The primary outcome was 8-year(y) cumulative incidence of nonmyeloid SMNs. Multivariable regression analysis was used to evaluate the association between CH and nonmyeloid SMNs, as well as cause-specific mortality. Median age at HCT was 58.8 y (range = 18.4-78.1 y); 389 patients (20.1% of the cohort) had at least 1 CH variant and 94 (4.9%) had ≥2 variants. The 8 y cumulative incidence of nonmyeloid SMNs was significantly higher in patients with CH compared with those without (15.1% vs 7.2%, P < .001), and increased by VAF: 7.2% (VAF <2%), 14.0% (VAF 2% to <10%), 19.4% (VAF ≥10%); P = .001. Patients with CH had a 2-fold increased risk of nonmyeloid SMNs (standardized incidence ratio = 1.9), compared with the general population. In multivariable analysis, CH was an independent and significant risk factor for nonmyeloid SMNs (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.15 to 2.59). Finally, patients with CH had significantly worse survival, primarily due to the higher risk of nonrelapse mortality (HR = 2.97, 95% CI = 1.90 to 4.64). CH was significantly associated with the risk of nonmyeloid SMNs after HCT, and the magnitude of association increased by VAF. Clonal hematopoiesis may serve as a biomarker for identifying HCT survivors at higher risk for developing nonmyeloid SMNs.