Content area
Full Text
Abstract
Rationale: Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects.
Objectives: To evaluate the effectiveness and tolerance of budesonide/ formoterol as an alternative treatment for BOS after HSCT.
Methods: In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV^sub 1^ after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV^sub 1^. Those who had initially received placebo were switched to budesonide/ formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account.
Measurements and Main Results: At M1, the median FEV^sub 1^ increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV^sub 1^ at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV^sub 1^ between the baseline and after 1 month of treatment for these patients was 1240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV^sub 1^ was maintained in the 13 patients who completed 6 months of treatment.
Conclusions: Budesonide/formoterol administration led to a significant improvement in the FEV^sub 1^ in patients with mild/severe BOS after allogeneic HSCT.
Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
Keywords: obstructive lung disease; inhaled long-acting bronchodilator and steroids; lung chronic graft-versus-host disease
Obstructive lung disease may occur after allogeneic hematopoietic stem cell transplantation (HSCT), and its incidence has been reported to be up to 30% among transplant recipients (1, 2). This condition is known as bronchiolitis obliterans syndrome (BOS), and it is associated with significant mortality, especially when it is diagnosed within the first years after transplantation (3, 4). The resulting alteration in lung function contributes to an impaired quality of life. Because BOS is attributed to pulmonary chronic graft-versus-host disease (GVHD), the first-line treatment is systemic steroids (5, 6), despite the fact that these...