A successful treatment option of severe bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious bronchopulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with an unfavorable prognosis. This article presents a case of effective BOS treatment after allo-HSCT with therapeutic response achievement in a short time.

1. Pulmonology. National guidelines. Short edition / edited by A. G. Chuchalin. Moscow, GEOTAR-Media, 2020. 768 p. ISBN 978-5-9704-5323-0.(In Russ.).

2. Bronchiolitis. The monograph. Edited by A. S. Belevsky. Series of the Russian Respiratory Society. Moscow, Publishing Company Atmosphere, 2023. 176 p. ISBN: 978-5-902123-90-3. (In Russ.).

3. Barker A. F., Bergeron A., Rom W. N., Hertz M. I. Obliterative bronchiolitis // N Engl J Med. 2014. Vol. 370, № 19. P. 1820–8. https://doi.org/10.1056/NEJMra1204664. PMID: 24806161.

4. Кулагин Е. А., Волкова А. Г., Николаев И. Ю. и др. Частота, факторы риска и клиническая характеристика облитерирующего бронхиолита после аллогенной трансплантации гемопоэтических стволовых клеток // Пульмонология. 2022. Т. 32, № 1. С. 77–88. https://doi.org/10.18093/0869-0189-2022-32-1-77-88.

5. Cooke K. R., Luznik L., Sarantopoulos S. et al. The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease // Biol Blood Marrow Transplant. 2017. Vol. 23, № 2. P. 211–234. https://doi.org/10.1016/j.bbmt.2016.09.023.

6. Zeiser R., Blazar B. R. Pathophysiology of Chronic Graft-versus-Host Disease and Therapeutic Targets // N Engl J Med. 2017. Vol. 377, № 26. P. 2565–2579. https://doi.org/10.1056/NEJMra1703472. PMID: 29281578.

7. Filipovich A. H., Weisdorf D., Pavletic S. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft- versus-host disease: I. Diagnosis and staging working group report // Biol Blood Marrow Transplant. 2005. Vol. 11, № 12. P. 945–56.

8. Jagasia M. H., Greinix H. T., Arora M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report // Biol Blood Marrow Transplant. 2015. Vol. 21, № 3. P. 389–401.

9. Carpenter P. A., Kitko C. L., Elad S. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report // Biol Blood Marrow Transplant. 2015. Vol. 21, № 7. P. 1167–87. https://doi.org/10.1016/j.bbmt.2015.03.024.

10. Bos S., Murray J., Marchetti M. et al. ERS/EBMT clinical practice guidelines on treatment of pulmonary chronic graft-versus-host disease in adults // Eur Respir J. 2024. Vol. 63, № 3. P. 2301727. https://doi.org/10.1183/13993003.01727-2023.

11. Kim K. H., Lee J., Kim H. J. et al. Efficacy and safety of high-dose budesonide/ formoterol in patients with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplant // J Thorac Dis. 2020. Vol. 12, № 8. P. 4183–4195. https://doi.org/10.21037/JTD-19-3475.

12. Lim J. U., Park S., Yoon J. H. et al. Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation // Respir Med. 2023. Vol. 218. P. 107410. https://doi.org/10.1016/j.rmed.2023.107410.

13. Zeiser R., Lee S. J. Three US Food and Drug Administration-approved therapies for chronic GVHD // Blood. 2022. Vol. 139, № 11. P. 1642–1645. https://doi. org/10.1182/blood.2021014448.

14. Kulagin E. A. The effect of bronchiolitis obliterans syndrome on survival of allogeneichematopoietic stem cell transplantation recipients. New St. Petersburg Medical Records. 2025;(1):89–91. (In Russ.) https://doi.org/10.24884/1609-2201-2025-104-1-68-76.

15. Fujii N., Nakase K., Asakura S. et al. Bronchiolitis obliterans with allogeneic hematopoietic cell transplantation: a 10-year experience of the Okayama BMT Group // Int J Hematol. 2014. Vol. 99, № 5. P. 644–51. https://doi.org/10.1007/s12185-014-1556-4.

16. Bergeron A., Chevret S., Peffault de Latour R. et al. Noninfectious lung complications after allogeneic haematopoietic stem cell transplantation // Eur Respir J. 2018. Vol. 51, № 5. P. 1702617. https://doi.org/10.1183/13993003.02617-2017.

17. Dini N., Khoshbin A. P., Aliannejad R et al. A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS) // Trials. 2024. Vol. 25, № 1. P. 243. https://doi.org/10.1186/s13063-024-08051-7.

18. Zeiser R., Polverelli N., Ram R. et al. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease // N Engl J Med. 2021. Vol. 385, № 3. P. 228–238. https://doi.org/10.1056/NEJMoa2033122.

19. Modi B., Hernandez-Henderson M., Yang D. et al. Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease // Biol Blood Marrow Transplant. 2019. Vol. 25, № 2. P. 265–269. https://doi.org/10.1016/j.bbmt.2018.09.003.

20. Zhao Y., OuYang G., Shi J. et al. Salvage Therapy With Low-Dose Ruxolitinib Leads to a Significant Improvement in Bronchiolitis Obliterans Syndrome in Patients With cGVHD After Allogeneic Hematopoietic Stem Cell Transplantation // Front Pharmacol. 2021. Vol. 12. P. 668825. https://doi.org/10.3389/fphar.2021.668825.

21. Khoury H. J., Langston A. A., Kota V. K. et al. Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease // Bone Marrow Transplant. 2018. Vol. 53, № 7. P. 826–831. https://doi.org/10.1038/s41409-017-0081-5.

22. Moiseev I. S., Morozova E. V., Bykova T. A. et al. Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults // Bone Marrow Transplant. 2020. Vol. 55, № 7. P. 1379–1387. https://doi.org/10.1038/s41409-020-0834-4.

23. Kulagin E. A., Volkova A. G., Dotsenko A. A. et al. Ruxolitinib for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation // Blood. 2021. Vol. 138, Supplement 1. P. 3899. https://doi. org/10.1182/blood-2021-153548.

24. DeFilipp Z., Kim H. T., Cheng G. S. et al. A phase 2 multicenter trial of ruxolitinib to treat bronchiolitis obliterans syndrome after allogeneic HCT // Blood Adv. 2025. Vol. 9, № 2. P. 244–253. https://doi.org/10.1182/bloodadvances.2024014000.

25. Moiseev I. S., Balashov D. N., Bronin G. O. et al. Russian National Society for Hematopoietic Stem Cell Transplantation, Gene and Cell Therapy. Recommendations of Russian Society for Hematopoietic Stem Cell Transplantation, Gene and Cell therapy for diagnosis and treatment of graft- versus-host disease // Cell Ther Transplant. 2025. Vol. 14, № 2. P. 55–86. https://doi.org/10.18620/ctt-1866-8836-2025-14-2-55-86.