Clonal Hematopoiesis and Risk of Heart Failure After Autologous Hematopoietic Cell Transplantation for Lymphoma

Abstract

Background

Patients with lymphoma are at high risk for developing heart failure (HF) after autologous hematopoietic cell transplantation (HCT). More accurate risk determination pre-HCT may facilitate screening and prevention of HF.

Objectives

The aim of this study was to examine the association between clonal hematopoiesis of indeterminate potential (CHIP) and the risk for HF after HCT for lymphoma.

Methods

This was a retrospective cohort study of 861 patients who underwent autologous HCT for lymphoma between 2010 and 2016 at City of Hope Comprehensive Cancer Center. Targeted DNA sequencing was performed to determine the presence of CHIP (variant allele frequency ≥ 2%). The primary outcome of interest was the 5-year cumulative incidence of de novo HF. Other outcomes of interest included overall and cause-specific mortality.

Results

Overall, 186 patients (21.7% of the cohort) had at least 1 CHIP variant, and 59 (6.9%) had ≥2 variants. DNMT3A, PPM1D, and TET2 were the most frequently mutated genes. The 5-year incidence of HF was significantly higher in patients with CHIP compared with those without CHIP (13.8% vs 4.7%; P < 0.001; sub-distribution hazard ratio [sHR]: 2.48; 95% CI: 1.32-4.68); the HF incidence increased by variant allele frequency: 0-2% (4.7%), 2-10% (11.7%), and >10% (18.5%), P < 0.001. Patients with CHIP had significantly worse overall survival after HCT, compared with those without (63.4% vs 80.3%; P < 0.001), due primarily to the higher risk for nonrelapse mortality (subdistribution HR: 5.37; 95% CI: 2.34-12.35).

Conclusions

CHIP was highly prevalent and associated with risk for HF and nonrelapse mortality after HCT. These findings highlight the role of CHIP as a novel biomarker and potential target for intervention to improve outcomes after autologous HCT.