NEWS & EVENTS

Workshop on Pulmonary Complications of Pediatric Hematopoietic Stem Cell Transplantation - Executive Summary

April 26 - 27, 2018
NIH
Bethesda, MD

Description

Pediatric hematopoietic stem cell transplantation (HCT) is performed for an increasing number of life-threatening malignant and non-malignant conditions with the potential to provide definitive cure. However, its efficacy is limited by an inordinate number of complications, of which pulmonary complications constitute the leading cause of death during the initial year after transplantation. Approximately 2,500 pediatric HCTs are performed every year in the United States of which 1,600 are allogeneic. Allogeneic HCTs are associated with more severe pulmonary complications such as  pneumonitis (infectious and non-infectious) and pulmonary hemorrhage during the first year after transplant. Predictors of these life-threatening conditions are unknown. The incidence of pulmonary complications plateaus after the first two post-transplant years. Thus, the first year post-HCT offers a crucial window of opportunity for risk mitigation to improve outcome.

This Workshop, co-sponsored by NHLBI, NICHD and NCI, was a multidisciplinary effort to describe the status of pulmonary complications occurring within a year after HCT in children, to identify critical gaps in existing knowledge, and to explore avenues for research to address these knowledge gaps to advance care and optimize outcomes.

Recap

Recommendations:

Recognizing the need for coordinated basic, translational and clinical future research endeavors in this vulnerable and distinctive cohort, Workshop participants arrived at a consensus on the following important focus areas:

  1. Build, Characterize and Study Prospective, Observational Cohorts
    • Utilize, expand and link existing databases to enhance deep phenotyping of pulmonary toxicities pre- and post-transplant
    • Perform prospective observational studies of patients receiving HCT to evaluate the association of phenotype, preconditioning regimens and therapies with pulmonary complications after transplant
    • Develop a practical, robust clinical scoring system for the assessment of pulmonary risk pre- and post-transplant

  2. Improve Mechanistic Understanding of Pulmonary Disease in HCT Recipients and Translate it to Potential Therapies
    • Develop more clinically relevant experimental models including mice and larger animals (e.g. sheep, dogs and lambs)
    • Determine mechanisms contributing to acute and chronic pulmonary toxicity after allogeneic BMT including the role of micro-organisms in initiating/exacerbating inflammation, endothelial cell activation and pathways to fibrosis
    • Determine genetic/proteomic predictors that identify patients at risk of pulmonary complications after HCT
    • Translate laboratory insights into novel strategies and therapies to mitigate pulmonary toxicity in HCT recipients

  3. Improve Clinical Outcomes
    • Examine the potential of serum biomarkers, bronchoalveolar lavage findings and imaging technologies to facilitate early diagnosis, characterize disease processes and monitor progression of pulmonary disease
    • Develop and validate novel pulmonary function testing in young children
    • Develop and sustain collaborative clinical team approaches to both patient care and research initiatives with transplant physicians, oncologists, pulmonologists, intensivists, immunologists and infectious disease specialists

The Workshop succeeded in highlighting both the magnitude and complexity of the problem and the pressing need for research in this field, which has the potential to improve outcomes both in children currently receiving HCT as therapy, and in children suffering from a host of other conditions for which HCT holds the promise of lasting cure.

Workshop Co-Chairs and Organizing Committee

  • Kenneth R. Cooke, MD - Johns Hopkins University School of Medicine
  • Samuel (Sam) B. Goldfarb, MD - Children's Hospital of Philadelphia, University of Pennsylvania
  • Ashok Srinivasan, MD - St. Jude Children's Research Hospital
  • James S. Hagood, MD - University of California-San Diego
  • Dennis C. Stokes MD MPH - Children’s Hospital at Vanderbilt

Workshop Participants

  • Michael Boeckh, MD, PhD - Fred Hutchinson Cancer Research Center
  • Larisa Broglie, MD - Columbia University
  • Guang-Shing Cheng, MD - Fred Hutchinson Cancer Research Center
  • Jason Chien, MD, MS - Gilead Sciences, Inc.
  • Shane Cross, Pharm.D., BCPS - St. Jude Children's Research Hospital
  • Stella M Davies, MBBS PhD - Cincinnati Children's Hospital Medical Center
  • Christine Duncan, MD, Dana - Farber Cancer Institute
  • Brian Fisher, DO, MSCE, MPH - The Children's Hospital of Philadelphia
  • Gerhard Hildebrandt, MD, FACP - University of Kentucky
  • Joshua Hill, MD - Fred Hutchinson Cancer Research Center
  • Robert R. Jenq, MD - MD Anderson Cancer Center
  • Sonata Jodele, MD - USC Keck School of Medicine
  • Leslie Lehmann, MD - Dana Farber Cancer Institute
  • Kris M Mahadeo, MD - University of Texas MD Anderson Cancer Center
  • Jennifer McArthur, DO - St. Jude Children’s Research Hospital
  • Bethany B. Moore, PhD - University of Michigan
  • Lawrence Nogee, MD - John Hopkins University School of Medicine
  • Sophie Paczesny, MD, PhD - Indiana University School of Medicine
  • Courtney Rowan, MD - Indiana University School of Medicine
  • Kirk R. Schultz, MD, FCAHS - BC Children’s Hospital and Research Institute
  • Marie E. Steiner, MD, MS - University of Minnesota
  • Christina K. Ullrich, MD, MPH - Dana-Farber Cancer Institute
  • Alpana Waghmare, MD - Fred Hutchinson Cancer Research Center
  • Shaina M. Willen, MD - Vanderbilt University
  • Kirsten Williams, MD - Children’s National Health System
  • Jason C. Woods, PhD - Cincinnati Children’s Hospital Medical Center
  • Gregory Yanik, MD - University of Michigan Medical Center
  • Matt Zinter, MD - University of California San Francisco

NIH Program Staff

  • Neil Aggarwal, MD - NHLBI
  • Robert Tamburro, MD, MSc - NICHD
  • Aruna Natarajan, MD, PhD - NHLBI
  • Nahed El-Kassar, MD, PhD - NHLBI
  • Nancy DiFronzo, PhD - NCI
  • William Merritt, PhD - NCI
  • Nonniekaye Shelburne MS, CRNP - NCI
  • Ann O’Mara, PhD, RN - NCI