Oncology
Chronic Graft-versus-Host Disease
Bronchiolitis Obliterans Syndrome in Chronic Graft-versus-Host Disease
If we detect asymptomatic BOS, we have the opportunity to potentially intervene before the patient becomes symptomatic. Moreover, if we can arrest the deterioration of lung function, we may have the opportunity to reduce morbidity and mortality. There are a small number of patients in whom BOS is the presenting or defining feature of their cGVHD. These individuals do not have skin, mouth, or eye involvement. Therefore, screening for BOS is very important because, by the time patients are symptomatic, they may have already lost a substantial amount of lung function.
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BOS is not hard to detect early if you are doing the appropriate screening. The current guidelines recommend that pulmonary function tests (PFTs) be performed every 3 months during the first year after transplantation and with less frequency during the following 4 years in adults. In addition, PFTs should be performed whenever someone is diagnosed with cGVHD and at regular intervals afterward. However, PFTs require pulmonary function laboratories, which are not available to everyone, and patients who live in rural areas may have to drive many hours to get to one. In addition, standard PFTs cannot be performed in young children, so work on other ways to screen for BOS, including computed tomography scanning methodologies and magnetic resonance imaging–based techniques, is ongoing. There are also efforts underway to evaluate home-based screening using spirometers to help guide physicians in selecting patients for a full evaluation with PFTs.
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Early therapy with active agents is important, and the best evidence for this comes from a phase 2a dose-finding study and a randomized phase 2 study evaluating belumosudil in patients with BOS. In a combined analysis of these trials, belumosudil was associated with not only a halting of the deterioration of lung function but also improvements in lung function in a number of patients, and those who had early BOS seemed to benefit the most.
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Although steroids and inhaled fluticasone, azithromycin, and montelukast (the FAM regimen) are useful, they do not reverse changes in lung function. People have evaluated antifibrotics for BOS, including pirfenidone, but a problem with this approach is that many available antifibrotics are not well tolerated. There are several potential molecular pathways and targets for fibrosis, and a dual-pronged approach targeting both fibrosis and the inflammatory pathways of bronchiolitis is required.
Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;138(22):2278-2289. Published correction appears in Blood. 2022;139(11):1772.
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DeFilipp Z, Alousi AM, Pidala JA, et al. Nonrelapse mortality among patients diagnosed with chronic GVHD: an updated analysis from the Chronic GVHD Consortium. Blood Adv. 2021;5(20):4278-4284. doi:10.1182/bloodadvances.2021004941
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DeFilipp Z, Kim HT, Yang Z, et al. Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. Blood Adv. 2022;6(24):6263-6270. Published correction appears in Blood Adv. 2023;7(22):7006.
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Jagasia M, Lazaryan A, Bachier CR, et al. ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease. J Clin Oncol. 2021;39(17):1888-1898. doi:10.1200/JCO.20.02754
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Renne J, Lauermann P, Hinrichs JB, et al. Chronic lung allograft dysfunction: oxygen-enhanced T1-mapping MR imaging of the lung. Radiology. 2015;276(1):266-273. doi:10.1148/radiol.15141486
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Rotz SJ, Bhatt NS, Hamilton BK, et al. International recommendations for screening and preventative practices for long-term survivors of transplantation and cellular therapy: a 2023 update. Transplant Cell Ther. 2024;30(4):349-385. doi:10.1016/j.jtct.2023.12.001
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Shanthikumar S, Gower WA, Srinivasan S, et al. Detection of bronchiolitis obliterans syndrome after pediatric hematopoietic stem cell transplantation: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2024;210(3):262-280. doi:10.1164/rccm.202406-1117ST
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Sharifi H, Bertini CD, Alkhunaizi M, et al. CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant. Blood Adv. 2024;8(19):5156-5165. doi:10.1182/bloodadvances.2024013748
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Sharifi H, Moss CT, Musa Z, et al. Pirfenidone for the treatment of bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant: results from a single-arm extension trial. Am J Respir Crit Care Med. 2025;211:A1133. doi:10.1164/ajrccm.2025.211.Abstracts.A1133
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Turner J, He Q, Baker K, et al. Home spirometry telemonitoring for early detection of bronchiolitis obliterans syndrome in patients with chronic graft-versus-host disease. Transplant Cell Ther. 2021;27(7):616.e1-616.e6. doi:10.1016/j.jtct.2021.03.024
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Williams KM, Cheng GS, Pusic I, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(4):710-716. doi:10.1016/j.bbmt.2015.10.009
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