Date: January 29–30, 2026
Format: Hybrid Workshop
Organizer: National Heart, Lung, and Blood Institute (NHLBI)

Overview

The NHLBI convened a two-day workshop bringing together academic researchers, clinicians, patient advocates, and federal staff to advance research on cardiopulmonary complications following hematopoietic stem cell transplantation (HCT) and gene therapy for sickle cell disease (SCD) and other blood and immunological diseases.

View workshop recordings: Day 1 | Day 2

Workshop Objectives

The workshop aimed to:

• Showcase research breakthroughs on pulmonary complications of HCT in childhood (funded under NOT-HL-20-761)
• Foster collaboration to expand scientific scope to adults, devices, advanced analytics, and experimental human studies (under NOT-HL-23-116)
• Identify knowledge gaps to guide future research on pulmonary complications linked to HCT and gene therapy in SCD

Key Topics Discussed

Clinical Context and Challenges

With approximately 20,000 HCT procedures performed annually in the United States and expanding gene therapy availability for SCD, pulmonary complications represent a serious challenge across all age groups. In children, severe pulmonary complications are the leading cause of mortality after transplant, while adults face respiratory insufficiency and acute respiratory distress syndrome (ARDS) contributing to long-term morbidity.

Major Research Areas

Mechanisms and Models: Researchers presented findings from preclinical mouse models, including three transgenic SCD models (Berkeley, Townes, and Malik) that display phenotypic similarities to human cardiopulmonary complications. Animal models and clinical studies have revealed that the lung is not merely a bystander but an active target of immune cell activation and cytokine dysregulation after transplant.

The TRANSPIRE Study: This collaborative study screens 631 pediatric and young-adult patients (up to age 24) receiving allogeneic HCT across eight high-volume centers, employing advanced diagnostic tools including oscillometry, multiple breath washout, xenon magnetic resonance imaging (XeMRI), and pulmonary function tests to identify risk factors and mechanisms of lung injury.

Diagnostic Innovation: Advanced imaging modalities—including CT with parametric response mapping (PRM), XeMRI, ultra-short echo MRI, and phase-resolved functional lung (PREFUL) MRI—show promise for earlier and more sensitive detection of lung disease compared to traditional pulmonary function tests.

Therapeutic Advances: Novel FDA-approved treatments for bronchiolitis obliterans syndrome (BOS) and graft-versus-host disease (GVHD), including belumosudil, ruxolitinib, and axatilimab, demonstrate encouraging clinical response rates, particularly in patients with milder disease. The STOP-BOS trial is evaluating antifibrotic medications, while other research explores reduced-intensity preparative regimens to minimize toxicity.

Cardiovascular Considerations: The Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) is collecting comprehensive cardiovascular data to help risk-stratify patients, guide referrals, and optimize cardiovascular health before HCT.

Key Research Gaps and Opportunities

Pulmonary Disease-Specific Priorities

• Update NIH definition of bronchiolitis obliterans syndrome (BOS) and develop therapies that reverse pathological changes
• Evaluate antifibrotic medications and emphasize early screening, as response rates are higher with milder disease
• Advance understanding of idiopathic pneumonia syndrome mechanisms and develop targeted molecular therapies
• Establish evidence-based protocols for respiratory support timing and type (HFNC, NIPPV, invasive ventilation, ECMO)
• Promote clinical adoption of advanced imaging (XeMRI, parametric response mapping, UTE MRI, PREFUL MRI) through standardization and validation
• Clarify bronchoscopy's role in diagnosing post-HCT complications and standardize timing across institutions
• Investigate lung, nasal, and gut microbiomes in HCT response and explore therapies to restore the lung microbiome
• Characterize sleep-disordered breathing in hematological conditions and assess impact on neurocognitive function and HCT outcomes
• Clarify connection between post-HCT viral infections and subsequent BOS development

Sickle Cell Disease-Specific Priorities

• Develop guidelines for determining which SCD patients can safely undergo HCT or gene therapy from a cardiopulmonary standpoint
• Understand how pre-existing SCD complications (pulmonary hypertension, acute chest syndrome, asthma, sleep-disordered breathing) affect post-transplant outcomes
• Develop clinical phenotyping and risk stratification tools for pulmonary hypertension management in SCD
• Clarify asthma characteristics in SCD and address donor-transferred asthma/atopy risk in HCT recipients
• Expand use of oscillometry and novel pulmonary function tools for patients unable to perform traditional spirometry

Cardiovascular Disease-Specific Priorities

• Expand CARE-BMT registry for pre-transplant cardiovascular risk assessment and health optimization
• Characterize sickle cell cardiomyopathy (myocardial fibrosis, diastolic dysfunction, HFpEF) and determine impact on HCT outcomes
• Apply cardio-oncology principles to HCT patient management throughout the treatment continuum
• Identify and validate cardiac biomarkers using proteomics to guide therapeutic interventions
• Address population health factors contributing to mortality and transplant complications in underserved populations

Cross-Cutting Priorities

• Expand longitudinal data collection through CIBMTR and SCD Natural History Data Resource
• Develop novel biomarkers from blood, bronchoalveolar lavage fluid, and microbiome analyses
• Design clinical trials with both objective measures and patient-centered outcomes
• Prioritize early detection strategies, as advanced disease responds poorly to treatment

Patient Perspective

The workshop featured testimony from a patient advocate who shared his 20-year journey through multiple cancer relapses, transplants, and complications, now working as a nurse—stressing need for adult to pediatric health care transition research. Additional research highlighted challenges faced by pediatric patients returning to school after transplant, including frequent absences, social-emotional difficulties, and academic impacts.

Looking Forward

While HCT and gene therapy offer curative or life-transforming potential for individuals with SCD and other blood diseases, continued research is essential to optimize treatments, minimize complications, and improve long-term outcomes. The integration of emerging technologies, standardized care protocols, and longitudinal outcome tracking will be critical to advancing the field.

Workshop Participants

Workshop Co-Chairs

• Stella Davies, M.B.B.S., Ph.D., MRCP - Cincinnati Children's Hospital Medical Center
• Elizabeth Klings, M.D. - Boston University Chobanian & Avedisian School of Medicine

Workshop Planning Committee

• Marrah Lachowicz-Scroggins, Ph.D. - Branch Chief, Lung Development and Pediatric Diseases Branch, NHLBI
• Aruna Natarajan, M.D. - Former NHLBI Medical Officer
• Robert Tamburro, M.D. - NICHD
• Lis Welniak, Ph.D. - NHLBI Division of Blood Diseases and Resources
• Nancy DiFronzo, Ph.D. - NHLBI Division of Blood Diseases and Resources

NHLBI Leadership

• Gustavo Matute-Bello, M.D. - Acting Director, Division of Lung Diseases, NHLBI
• Julie Panepinto, M.D., M.S.P.H. - Director, Division of Blood Diseases and Resources, NHLBI

Session Chairs and Speakers

• Julian Allen, M.D. - Children's Hospital of Philadelphia
• Bruce Blazar, M.D. - University of Minnesota
• Amanda Brandow, M.D. - Medical College of Wisconsin
• Guang-Shing Cheng, M.D. - Fred Hutchinson Cancer Center
• Kenneth Cooke, M.D., Ph.D. - Johns Hopkins University
• Zachariah DeFilipp, M.D. - Mass General Research Institute
• Ankit Desai, M.D. - Indiana University
• Samuel Goldfarb, M.D. - University of Minnesota
• Salim Hayek, M.D. - University of Texas Medical Branch
• Joe Hsu, M.D., M.P.H. - Stanford University
• Pooja Khandelwal, M.D. - Cincinnati Children's Hospital Medical Center
• Sophie Lanzkron, M.D., M.H.S. - Thomas Jefferson University
• Roberto Machado, M.D. - University of Maryland
• Punam Malik, M.D. - Cincinnati Children's Hospital Medical Center
• Bethany Moore, Ph.D. - University of Michigan
• Samal Munidasa, Ph.D. - Cincinnati Children's Hospital Medical Center
• Kasiani Myers, M.D. - Cincinnati Children's Hospital Medical Center
• Sophie Paczesny, M.D., Ph.D. - Medical University of South Carolina
• Courtney Rowan, M.D. - Indiana University School of Medicine
• Parker Ruhl, M.D., M.H.S. - National Institutes of Health
• Laura Walkup, Ph.D. - Cincinnati Children's Hospital Medical Center
• Shaina Willen, M.D. - Renown Children's Hospital
• Gregory Yanik, M.D. - University of Michigan
• Nadir Yehya, M.D., M.S.C.E. - Children's Hospital of Philadelphia
• Matt Zinter, M.D. - University of California San Francisco

Patient Advocate

• Patrick McSweeney, RN - Cincinnati Children's Hospital Medical Center

For more information, view the workshop program book.

Disclaimer: This summary represents individual opinions and ideas expressed during the workshop and does not constitute a consensus opinion or directive by NHLBI or NIH.