The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Abstract

The aim of this study was to determine whether prophylactic azithromycin treatment prevents bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HCT). A series of 1187 patients who underwent HCT between December 1993 and November 2013 at our tertiary referral center in South Korea were enrolled. The median age of these patients was 39.0 years, and 668 (56.3 %) were men. Acute leukemia was the most common indication for HCT. During a median follow-up of 30.7 months after HCT, BOS was diagnosed in 82 patients (6.9 %) at a median of 12.3 months after HCT. One hundred patients received prophylactic azithromycin, of whom 12 developed BOS. BOS was significantly more frequent in patients who were treated with than without prophylactic azithromycin (12.0 versus 6.4 %, P = 0.036). Multivariate analysis revealed that a busulfan-based conditioning regimen (HR 2.73, 95 % CI 1.66-6.45) was the only independent predictor of BOS. The prophylactic use of azithromycin was not associated with the development of BOS by multivariate analysis. Although the present study had some limitations such as its non-randomized retrospective design, differences in baseline patient characteristics between the two groups, and the preference for azithromycin use at our hospital, our findings suggest that prophylactic azithromycin seems to not prevent the development of BOS in HCT recipients.

Pulmonary hypertension associated with busulfan

“…This finding might explain the onset of late lung fibrosis, e.g., bronchiolitis obliterans, in patients treated with busulfan. 27 Bronchiolitis obliterans is a less rare complication of ASCT, [28][29][30][31][32][33][34][35][36][37][38][39] particularly after the administration of a busulfan chemotherapy as a unique risk factor, 31,32,34,37 and is associated with a circulating immunoglobulin deficiency. 40 In patients with bronchiolitis obliterans, a good correlation with the pulmonary function testing 36,38 is usually described, although contradictory findings have been reported.…”

British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease

“…The incidence of BOS in those who received azithromycin was 12% compared with 6.4% in those who did not. Subsequent multivariate analysis did not suggest that prophylactic azithromycin was associated with the development of BOS 131. In a multicentre open-labelled prospective study, Williams et al examined the effect of the FAM regimen on new-onset BOS in HSCT patients.…”

Late Noninfectious Pulmonary Complications in Hematopoietic Stem Cell Transplantation

“…Prophylactic azithromycin has been shown to prevent the onset of lung transplant-related BOS, as well as stabilize FEVI in post-lung transplant BOS [19,88]. However, prophylactic azithromycin has not shown to be effective in BOS post-HSCT in retrospective studies [44]. A prospective study on the prophylactic use of azithromycin to prevent airflow decline resulted in early termination secondary to hematological relapses [8]; an FDA warning was issued in August 2018 until further review (https://www.fda.gov/ Drugs/DrugSafety/ucm614085.htm).…”