The International Lung GVHD Consensus Conference

GOAL: Synthesize preclinical understanding of the pathogenesis of BOS in the context of allogeneic hematopoietic cell transplant, identify trans latable targets and key priorities for preclinical investigation.

Co-Chairs: Joe Hsu and Sophie Paczesny

08:15 | Welcome participants

08:45 | Opening Remarks

• Prof Antoine Geissbuhler, Dean of the University of Geneva

09:00 | Building on the ATS research statement and our understanding of the natural history of BOS

• Guang-Shing Cheng, Fred Hutch Cancer Center

08:50 | Beyond the small airways: Mapping allo-immune and transplant-related lung injury after alloimmune HCT in Humans 

• Anne Bergeron, University of Geneva

09:05 Heterogeneity of airway pathology in clinical BOS: insights from microCT investigations in HCT, LT, and PIBO 

• Stijn Verleden, UZA, University Hospital Antwerp

09:25 | Airway epithelium as disease nexus in alloimmune lung injury

• Jamie Todd, Duke University

09:45 | Peripheral helper T cells, B cells, and tertiary lymphoid structures in CLAD: do these pathways translate to lung GVHD? 

• Stephen Juvet, University of Toronto

10:05 The role of macrophages, cellular immunity, and alloimmune pathways in chronic GVHD 

• Julie Boiko, Fred Hutchinson Cancer Center

10:25 Discussion

10:35 Break

10:30 | Role of infection, microbiome in post-HCT lung injury

• Matthew Zinter, University of California San Francisco

10:50 | Dysbiosis and metabolomics in lung GVHD

• David Michonneau, University Paris Cité

11:25 Respiratory virus as a trigger for HCT-BOS 

• Louise Bondeelle, University of Geneva

11:45 Lessons from bronchiectasies: phenotypes, endotypes, and treatable traits 

• Alan Barker, Oregon Health Sciences University

12:05 | Discussion

12:15 | LUNCH

13:15 | The Patient Perspective 

• Andreas Mall, Germany

• Den Cooke, Johns Hopkins University and Ajay Sheshadri, MD Anderson Cancer Center

13:50 | Discussion

14:00 Multiple pathways towards fibrogenesis in idiopathic pulmonary fibrosis 

• Bruno Crestani, University Paris Cité

14:20 Risk and mechanisms of CLAD 

• John Belperio, University of California Los Angeles

14:40 Targeting pulmonary fibrosis in chronic GVHD mice with lung dysfunction 

• Bruce Blazar, University of Minnesota

15:00 | Discussion

15:10 | Break

15:20 Cell-free DNA: sensitive predictive biomarker for pulmonary GVHD / CLAD risk 

• Sean Agbor-Enoh, NIH/NHLBI

15:40 Murine models of bronchiolitis obliterans and transplant pulmonary fibrosis 

• Joe Hsu, Stanford University

16:00 Modeling HCT-BOS with patient bronchoalveolar lavage fluid-derived organoids 

• Carla Kim, Harvard University

16:20 Multi-omic analyses of human lung explants in HCT-BOS and CLAD 

• Patrick Mellors, Dartmouth University

16:40 Discussion

17:20 | ADJOURN Day 1

18:30 | Networking Reception

GOAL: To derive a consensus revision of the HCT-BOS diagnostic criteria and conceptual framework for defining lung chronic GVHD.

Co-Chairs: Guang-Shing Cheng and Anne Bergeron

Rationale for a revision of the 2014 NIH Definition of BOS: Why do we need this now? 

• Anne Bergeron, University of Geneva and Daniel Wolff, University Hospital Regensburg

The historical context of the NIH cGVHD Consensus Project 

• Steve Pavletic, NIH

The diagnostic framework and introduction of the working proposal 

• Guang-Shing Cheng, Fred Hutch Cancer Center

08:50 Lung Physiology
The natural history of BOS 

• Guang-Shing Cheng, Fred Hutch Cancer Center

Pathologic correlations with lung physiology and defining pulmonary impairment 

• Gerald Weinhouse, Dana Farber Cancer Institute/Harvard University

Current interpretative strategies and PFT change metrics across the lifespan 

• Hemang Yadav, Mayo Clinic

Patterns of airflow obstruction, small airways disease, and ‘reversibility’ in BOS 

• Jane Turner, McMaster University

Current and future alternatives to conventional PFTs: oscillometry, MBW and home spirometry 

• Paul Robinson, University of Melbourne
   

09:30 Chest Imaging
Chest imaging correlates of airflow obstruction 

• Okka Hamer, University of Regensburg

The future: Quantitative CT, MRI, and novel approaches to imaging for lung GVHD 

• Gregory Yanik, University of Michigan

09:50 Discussion
Lung Physiology Group: Nicola Adderley, Paul Robinson, Matthew Rutter, Hélène Salvator, Jane Turner, Gerald Weinhouse, Hemang Yadav, Guang-Shing Cheng (Lead); Chest Imaging Group: Edward Castillo, Julien Cohen, Craig Galban, Jörg Halter, Okka Hamer, Jonathan Rayment, Gregory Yanik, Husham Sharifi (Lead)

10:30 Break

10:45 Conditions
Requirements for the presence of extrapulmonary cGVHD to diagnose lung cGVHD 

• Catherine Lee, Fred Hutchinson Cancer Center

The need for lung biopsy to diagnose BOS 

• Clare Sander, Cambridge University Hospital and Alicja Sadowska-Klasa, Medical University of Gdansk

Should absence of infection be a necessary requirement? 

• David Epstein, Stanford University

11:05 Pediatrics and Special Populations
The impact of growth on lung function and diagnostic considerations in children after HCT 

• Shiv Shanthikumar, University of Melbourne and Stella Davies, Cinncinnati Children’s Hospital

The minimum diagnostic criteria if no diagnostic testing can be obtained 

• Kirsten Williams, Emory University

11:20 Discussion
Conditions Group: Louise Bondeelle, David Epstein, Samuel Goldfarb, Matthew Hensley, Catherine Lee, Alicja Sadowska-Klasa, Clare Sander, Ajay Sheshadri (Lead); Pediatrics and Special Populations Group: Stella Davies, Véronique Houdouin, Anita Lawitschka, Kirk Schultz, Hemang Yadav, Kirsten Williams (Lead)

12:00 Lunch

13:00 Restrictive physiology, extrapulmonary cGVHD, and mixed phenotypes 

• Jeff Sturek, University of Virginia

Interstitial lung disease including organizing pneumonia, NSIP, PPFE 

• Yu-Kuang Lai, Stanford University, Saskia Bos, University of Leuven and Group

13:30 Discussion
Non-BOS Lung Disease Group: Mark Barash, Saskia Bos, Geoffrey Cuvelier, Katrin Hostettler, Joe Hsu, Yu-Kuang Lai, Steven Pavletic, Jeffrey Sturek and Anne Bergeron (Co-Leads)

Daniel Wolff, University of Regensburg, and Group Panelists with an introduction by Guy Livneh, Palo Alto, CA
Implementation Group: Paul Carpenter, Yves Chalandon, Anna DeSalvo, Najla El-Jurdi, Samuel Goldfarb, John Murray, Danielle Stahlbaum, Daniel Wolff (Lead)

15:00 Break
 

GOAL: Establish an ideal clinical trial design and identify clinical trial readiness gaps for Lung GVHD after HCT

Co-Chairs: Guang-Shing Cheng and Anne Bergeron

• Corey Cutler, Dana Farber Cancer Institute/Harvard University

08:10  | Guidelines versus the reality

• Helene Schoemans, University of Leuven

08:25 |  FDA-approved cGVHD agents and BOS trials: a pulmonologist’s perspective

• Anne Bergeron, University of Geneva

08:40 | Antifibrotics and the Pulmonary Drug pipeline

• Katrin Hostettler, University of Basel

09:00 | Alternative therapies and cGVHD drug pipeline.

• Daniel Wolff, University of Regensburg

09:10 | Discussion

09:30 Current NIH response criteria, endpoints and limitations 
Guang-Shing Cheng, Fred Hutch Cancer Center

09:45 When it’s OK to be out of line – modeling continuous data as a non-linear function 
Ted Gooley, Fred Hutchinson Cancer Center

10:00 How to Improve the Level of Evidence of Single-Arm Phase 2 Trials. 
Sylvie Chevret, University Paris Cité/Hôpital St. Louis

10:15 Biomarkers for Lung GVHD: how do we get there, and how do we test? 
Sophie Paczesny, Medical College of South Carolina

10:30 Innovative trial designs in interstitial lung diseases: adaptive, umbrella, basket 
Toby Maher, University of Southern California

10:45 Discussion

11:00 Insights from the Facebook BOS group: What patients are willing to do to participate in a clinical trial. 
Guy Livneh, Palo Alto, California

11:15 Lunch

Co-Chairs: Daniel Wolff and Steve Pavletic

Panelists: Val Bhatt (Incyte), Dawn Reichenbach (Sanofi), Jason Chien (Mozart Therapeutics), Gino Cortopassi (Buto Corp.), Madhuri Vusirikala (Therakos), Guy Livneh (Patient Advocate), FDA/EMA tbd

13:00 Small group breakouts

1. Overall Trial Design, 
2. Trial Inclusion and Endpoints, 
3. Agents to Test, 
4. Correlative Studies
5. Recruitment and Retention
    

Leads: Greg Yanik and Jamie Todd (1), Najla El-Jurdi and Guang-Shing Cheng (2), Catherine Lee and Bruno Crestani (3), Sean Agbor-Enoh and José Antonio Simón Pérez (4), Hélène Schoemans and Danielle Stahlbaum (5)

13:45 | Small group reports and discussion

15:30 SUMMARY and ADJOURN Day 3 and Conference