Abstract 14968: Clonal Hematopoiesis and Cardiotoxic Risk After Hematopoietic Stem Cell Transplantation

Abstract

Background: Clonal hematopoiesis (CH) occurs as part of normal hematopoietic stem cell senescence and prior chemotherapy administration. As such, CH is frequent for patients undergoing allogeneic stem cell transplants (ASCT). CH has been identified as a driver of inflammation. In animals, inflammation plays a role in atrial fibrillation (AF) development, the most common cardiotoxicity after ASCT treatment. Yet, whether the presence of post-ASCT CH associates with AF risk is unknown. Methods: We analyzed bone marrow derived mononuclear cells from 201 cancer patients treated with ASCT by deep targeted amplicon sequencing (next generation sequencing) to detect the presence of select CH (defined as DNMT3A, TET2, ASXL1, IDH1, FLT3, JAK2 at VAF of ≥ 2%), irrespective of relapse status; at median 4 months post ASCT. Observed incident AF rates were compared to Framingham heart predicted rates. Cox regression and survival analysis were used to define factors associated with incident AF and MACE, as well as the relationship between the presence of post-transplant CH mutations and MACE risk. Further, we also assessed the effect of CH on post-ASCT survival outcomes. The presence of mutations was analyzed for an association with post-ASCT incident AF and overall survival. Results: Overall, the prevalence of CH in post-ASCT patients was 42.3% (85), including 29.5% with ≥2 mutations. Over a median follow-up of 33 months, 11.5% of patients developed incident AF and 29.9% experienced MACE. In those without prior AF, the weighted average incidence was 407/10,000 person-years compared to the Framingham-predicted 63/10,000 person-years (RR 6.4, P <0.001; AER 344). In follow-up, increased CH burden associated with increased risk of incident AF (HR 3.6, P =0.04), cancer-progression (HR 2.6, P =0.006), and mortality (HR 2.09, P =0.047); Figure . There was no difference in non-AF MACE. Conclusions: The presence of CH in ASCT treated cancer patients appears to associate with increased AF risk.