FLUDARABINE-INDUCED BRADYCARDIA IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract

Objective

Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in allo-HSCT recipients and to increase awareness of this issue.

Methodology

This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia (FİB).

Results

Fludarabine doses were higher in the bradycardia group, but not statistically significant. Age was the only independent predictor of FİB (OR 0.93, 95% CI: 0.89-0.98, p =0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p=0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients.

Conclusion

Bradycardia was observed in 17.8% of our patients who used fludarabine in the conditioning regimen. Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients. Although our results are promising, further studies evaluating the fludarabine intermediate fluoroadenosine are needed to support our results.