Treatment Options for Bronchiolitis Obliterans After Hematopoietic Stem Cell Transplant: A Systematic Review of Clinical Trials in the Last 10 years

Author Type(s)

Faculty, Resident/Fellow

Document Type

Abstract

Publication Date

9-2023

DOI

10.1016/S2152-2650(23)01428-3

Journal Title

Clinical Lymphoma Myeloma and Leukemia

Department

Medicine

Abstract

Background

One of the severe manifestations of chronic graft-versus-host-disease (cGVHD) is bronchiolitis obliterans syndrome (BOS), which occurs as progressive airway fibrosis after hematopoietic stem cell transplantation (HSCT). Due to the higher morbidity and mortality, multiple treatment studies are still done without clear standard therapy of care. This systematic review aims to assess the efficacy of different treatment options for BOS.

Methods

A literature search was conducted on PubMed and Embase with keywords “Bronchiolitis Obliterans” and “Stem Cell Transplant” from 1/1/2012 to 2/10/2023. 635 articles were screened, and we included 2 randomized clinical trials (RCTs, N=54) and 6 non-randomized clinical trials (nRCTs, N=187).

Results

In an RCT by Lam et al. (N=22), the mean FEV1% change was -1.21±13.09 with azithromycin compared to the placebo change of +0.74±10.79. In an nRCT by Brownback et al. (N=13), corticosteroids+azithromycin+montelukast showed an FEV1 decline slope of -5.12 cc/month without and +2.27 cc/month with rituximab. In an RCT (N=32) by Bergeron et al., budesonide/formoterol showed an absolute FEV1 change of 267.5±69.28 vs 17.5±135.6 (P=0.012) with placebo. In an nRCT by Kim et al. (N=61), budesonide+formoterol+montelukast+N-acetylcysteine showed an FEV1 change of 6.36%±12.72 (P=<0.001) after 3 months of treatment. In an RCT by Zhao et al. (N=30), ruxolitinib showed a predicted change of 11%(P=0.029) in mean FEV1. In an RCT by Matthieu et al. (N=22), pirfenidone showed mean rate of change in FEV1 %slope +0.59%/month(P=0.046). In an nRCT by Williams et al. (N=25), montelukast alone showed a median FEV1 % predicted change of -2 (-5 to-3%) with median FEV1 slope after 2 years Rx +1.32 (P<0.0001). In a study by Williams et al. (N=36), fluticasone+azithromycin+montelukast showed absolute improvement in %predicted FEV1 5-10% in 24% and >10% in 10% of the patients.

Conclusion

Budesonide+formoterol significantly improved lung function compared to placebo, but azithromycin did not. In single-arm trials, lung function tests significantly improved in patients with BOS after treatment with rituximab, ruxolitinib, pirfenidone, and montelukast. Randomized phase 3 trials are needed to confirm these results.

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