Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions
- Allan R. Glanville1⇑,
- Christian Benden2,
- Anne Bergeron3,
- Guang-Shing Cheng4,
- Jens Gottlieb5,
- Erika D. Lease6,
- Michel Perch7,
- Jamie L. Todd8,
- Kirsten M. Williams9 and
- Geert M. Verleden10
- 1St Vincent's Hospital Sydney, Sydney, NSW, Australia
- 2University of Zurich Medical Faculty, Zurich, Switzerland
- 3Université de Paris, APHP, Hôpital St Louis, Paris, France
- 4Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, United States of America
- 5Department of Respiratory Medicine OE6870, Hannover Medical School, Hannover, Germany
- 6Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, United States of America
- 7Department of Cardiology, Section for Lung Transplantation, Rigshospitalet, University of Copenhagen,Copenhagen, Denmark
- 8Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Durham, NC, United States of America
- 9Children's Healthcare of Atlanta, Emory University of School of Medicine, Atlanta, GA, United States of America
- 10University Hospital Gasthuisberg Herestraat 49, Leuven
- Corresponding author: Allan Glanville (allan.glanville{at}svha.org.au)
Abstract
Bronchiolitis obliterans syndrome (BOS) may develop after either lung or haematopoietic stem cell transplantation (HSCT), with similarities in histopathological features and clinical manifestations. However, there are differences in the contributory factors and clinical trajectories between the two conditions. BOS after HSCT occurs due to systemic graft-versus-host-disease (GVHD), whereas BOS after lung transplantation is limited to the lung allograft. BOS diagnosis after HSCT is more challenging, as the lung function decline may occur due to extrapulmonary GVHD, causing sclerosis or inflammation in the fascia or muscles of the respiratory girdle. Treatment is generally empirical with no established effective therapies. This review provides rare insights and commonalities of both conditions, that are not well elaborated elsewhere in contemporary literature, and highlights the importance of cross disciplinary learning from experts in other transplant modalities. Treatment algorithms for each condition are presented, based on the published literature and consensus clinical opinion. Immunosuppression should be optimised, and other conditions or contributory factors treated where possible. When initial treatment fails, the ultimate therapeutic option is lung transplantation (or re-transplantation in the case of BOS after lung transplantation) in carefully selected candidates. Novel therapies under investigation include aerosolised liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and (in patients with BOS after lung transplantation) B-cell–directed therapies. Effective novel treatments that have a tangible impact on survival and thereby avoid the need for lung transplantation or re-transplantation are urgently required.
Footnotes
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Conflict of interest: A.R. Glanville has received honorarium for an advisory role from Zambon, and is chair of the Zambon DSMB for the Boston trials.
Conflict of interest: G.M. Verleden has received honorarium for an advisory role from Zambon.
Conflict of interest: M. Perch has received honorarium for an advisory role from Zambon, a research grant (institutional) from Roche, speaker fees from Novartis, GSK and Therakos, and other financial support from Boehringer.
Conflict of interest: E.D. Lease has received honorarium for an advisory role from Zambon.
Conflict of interest: G-S. Cheng has received honorarium for an advisory role from Zambon.
Conflict of interest: A. Bergeron has received honorarium for an advisory role from Zambon.
Conflict of interest: C. Benden has received honorarium for an advisory role from Zambon and speaker fees from Therakos.
Conflict of interest: J. Gottlieb has received honorarium for advisory roles from Zambon, research grants from Zambon and Deutsche Forschungsgemeinschaft and advisory funding from Theravance, Merck and Altara.
Conflict of interest: J.L. Todd has received honorarium for an advisory role from Zambon, Altavant and Natera and research grants (institutional) from Boehringer Ingelheim, Astra Zeneca and CareDx.
Conflict of interest: K.M. Williams has received honorarium for an advisory role from Zambon.
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- Received April 13, 2022.
- Accepted May 18, 2022.
- Copyright ©The authors 2022
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