Increased Late Noncardiac Nonrelapse Mortality in Patients with Atrial Fibrillation Diagnosed During Their Hospital Stay for Allogeneic Stem Cell Transplantation

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in adults but its impact on allogeneic stem cell transplantation (SCT) is not well characterized. We studied AF manifestation during the hospital stay for allogeneic SCT, referred to as AF in hospital (AFiH), and analyzed the incidence of, risk factors for, and clinical impact of AFiH on intensive care unit (ICU)-/hospital-/ and overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). This retrospective matched cohort study comprised 553 consecutive SCT recipients at Hannover Medical School between January 2013 and October 2019. Patients with AFiH were compared with a non-AFiH control cohort matched for Hematopoietic Stem Cell-Specific Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) risk score, disease, conditioning regimen and availability of molecular genetic data for patients with myeloid diseases. AFiH occurred in 46 patients (8%) at a median of 2 days (interquartile range, 0 to 8 days) after SCT. Patient history of AF and elevated NT-proBNP and high-sensitivity troponin T levels, but not conventional echocardiographic parameters, were predictive for AFiH. AFiH occurred more often in patients with mutations in DNMT3A, TET2, and ASXL1 genes related to clonal hematopoiesis compared with patients with wild-type alleles, with the greatest impact from DMT3A mutations. ICU admission was significantly higher in the AFiH cohort (46% versus 7%), without significant differences in ICU or post-ICU hospital survival (62% versus 40% and 52% versus 40%, respectively). The main cause of death was sepsis. In terms of long-term outcomes, the incidences of relapse and grade II-IV acute GVHD did not differ significantly between the AFiH and the non-AFiH groups; however, OS was significantly shorter in the AFiH group (1 year OS, 39% versus 65%), owing to late noncardiac NRM (1 year NRM, 49% versus 27%). Although the underlying cellular and molecular mechanisms remain to be characterized in further detail, these data clearly demonstrate the impact of inpatient AF manifestation/AFiH on long-term outcomes of SCT recipients.

Keywords: Allogeneic stem cell transplantation; Atrial fibrillation; Noncardiac NRM; Transplantation complications.