In a single-institution study reported in the Journal of Clinical Oncology, Ellen K. Chang, MD, of the Division of Hematology/Oncology, Children’s Hospital Los Angeles, and colleagues found that atrial fibrillation occurs in a substantial proportion of patients who have undergone allogeneic hematopoietic cell transplantation (HCT) and may be associated with poor outcomes.¹

Ellen K. Chang, MD

Study Details

The retrospective cohort study involved 509 consecutive patients undergoing allogeneic HCT at City of Hope Comprehensive Cancer Center between January 2014 and December 2016. The population included in the analysis consisted of 487 patients after exclusion of patients younger than age 18 (n = 65), those with a history of atrial fibrillation (n = 34), and those undergoing a second HCT (n = 13). Multivariate analysis was adjusted for patient demographics, comorbidities, pre-HCT echocardiogram parameters, and HCT-related exposures with P < .1 on univariate analysis.

A nested case-control study to assess associations between pre-HCT echocardiogram measures and atrial fibrillation events included atrial fibrillation cases matched with controls for age at HCT (within 5 years), sex, and length of follow-up (with control follow-up being equivalent to or longer than case follow-up).

Risk of Atrial Fibrillation

Median follow-up was 3.1 years (range = 0.0–6.0 years), with 81% of the cohort being followed through December 2019, for surviving patients, or death. Median age at HCT was 52.4 years (range = 18.1–78.6 years). More than half the patients were male (57.7%), and nearly half were White (48.7%). The most common diagnoses were acute myeloid leukemia (42.3%), acute lymphoblastic leukemia (25.7%), and myelodysplastic syndrome or myeloproliferative neoplasm (21.6%).

A total of 50 patients developed atrial fibrillation and 437 did not.  The cumulative incidence of atrial fibrillation at 1 and 5 years was 6.8% and 10.6%. The median time to atrial fibrillation was 117.5 days (range = 4.0–1,405.0 days). Among the 50 patients with atrial fibrillation, 3 (6%) had a lone incident, and 47 (94%) had paroxysmal or persistent events.

On univariate analysis among 468 patients with available pre-HCT echocardiograms, factors significantly associated with an increased risk of atrial fibrillation were age ≥ 50 years at HCT (hazard ratio [HR] = 3.52, P < .001), male sex (HR = 2.17, P = .016), diabetes at HCT (HR = 2.21, P = .033), dyslipidemia at HCT (HR = 3.19, P < .001), pre-HCT prolonged QTc interval (HR = 2.64, P = .001), HLA-unrelated donor (HR = 2.14, P = .001), and nonmyeloablative conditioning (HR = 2.39, P = .004). Factors not associated with an increased risk included race/ethnicity, other comorbidities at HCT (eg, hypertension, cardiomyopathy, coronary artery disease, ever-smoking), ventricular rate on pre-HCT echocardiogram, hematologic disease diagnosis, pre-HCT cardiotoxic treatment (anthracycline dose, chest radiation), high risk of relapse at HCT, stem cell source, donor age, and type of graft-vs-host disease prophylaxis.

On a multivariate analysis among the 468 patients, factors significantly associated with increased atrial fibrillation risk were age ≥ 50 years at HCT (HR = 2.76, 95% confidence interval [CI] = 1.37–5.58, P = .005), HLA-unrelated donor (HR = 2.20, 95% CI = 1.18–4.12, P = .014), dyslipidemia (HR = 2.40, 95% CI = 1.23–4.68, P = .011), and pre-HCT prolonged QTc interval (HR = 2.55, 95% CI = 1.38–4.72, P = .003).

A total of 39 patients with atrial fibrillation (78%) and 389 without (89%) had available pre-HCT echocardiograms. There were no significant differences in clinical or treatment characteristics between patients with vs without pre-HCT echocardiograms. In the case-control analysis among 39 patients with atrial fibrillation and 97 without, there was no difference in median left-ventricular ejection fraction between the groups (61% vs 60%, P = .582). However, atrial fibrillation cases had significantly lower median left-atrial ejection fraction (39.7% vs 53.4%, P <.001) and left-atrial reservoir function (31.1% vs 39.1%, P = .001) and a higher prevalence of abnormal tricuspid regurgitant jet velocity (30.8% vs 8.2%, P = .006).

In a multivariate analysis in the case-control population, a significantly increased risk for atrial fibrillation was associated with abnormal left-atrial ejection fraction (< 45%; odds ratio [OR] = 12.7, P < .001), low left-atrial reservoir function (< 39%; OR = 3.8, P = .010), and elevated tricuspid regurgitant jet velocity (> 2.8 m/s; OR = 4.2, P = .023). The odds ratio for the presence of at least two abnormal measures was 18.0 (P < .001).

Outcomes in Patients With Atrial Fibrillation

Among the 50 patients with atrial fibrillation, 5 (10.0%) developed stroke during 34.8 person-years of follow-up after the onset of atrial fibrillation, yielding an incidence rate of 143 per 1,000 person-years.

Overall survival in the entire cohort at 1 and 5 years was 75.4% and 55.8%, with the most common cause of death being relapse or disease progression (15.8% of cohort). Overall survival as of the cutoff in December 2019 was 20.0% among the 50 patients with atrial fibrillation vs 62.0% among 437 without. Mortality due to relapse or disease progression was 12.0% vs 16.2%. Nonrelapse mortality was higher among patients with atrial fibrillation, including death due to multiorgan failure (20.0% vs 3.7%), graft-vs-host disease (12.0% vs 5.0%), cardiovascular causes (14.0% vs 1.8%), sepsis (14.0% vs 3.2%), and pneumonia/respiratory failure (8.0% vs 3.7%).

In an adjusted analysis, atrial fibrillation was associated with significantly increased risk of all-cause mortality (HR = 12.76, 95% CI = 8.76–18.57) and nonrelapse mortality (HR = 15.78, 95% CI = 8.70–28.62), with no significant difference in risk of relapse-related mortality (HR = 1.08, 95% CI = 0.43–2.68).

The investigators concluded: “The burden of [atrial fibrillation] after allogeneic HCT population is substantial, and the development of [atrial fibrillation] is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of [atrial fibrillation], setting the stage for targeted prevention strategies during and after HCT.” 

DISCLOSURE: The study was supported by grants from the Lymphoma/Leukemia Society and National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Chang reported no conflicts of interest.

REFERENCE

1. Chang EK, Chanson D, Teh JB, et al: Atrial fibrillation in patients undergoing allogeneic hematopoietic cell transplantation. J Clin Oncol 39:902-910, 2021.