High Prevalence of Abnormal Baseline Lung Function in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report from the TRANSPIRE Study

Jane Koo^{1

2}, Richard Cooper^{2

3}, Stephanie L Edwards², Adam Lane^{1

2}, Sara Katherine Loveless², Lauren Strecker^{1

2}, Kelly E Lake^{1

2}, Kasiani C Myers^{1

2}, Christopher Towe^{1

3}, Jessica Patti³, Laura L Walkup^{1

3

4}, Kathryn A Wikenheiser-Brokamp^{1

5}, Margaret L MacMillan⁶, Philip Lacher⁷, Tamara Griffin⁷, Merve Tekman⁷, Gabriel Salinas Cisneros⁸, Kevin Wu⁸, Matthew S Zinter⁹, Fernando A Urrego¹⁰, K Scott Baker^{11

12}, Matthew F Abts^{12

13}, Sheri Ballard¹², Jason L Freedman^{14

15}, Alexander Caraballo¹⁴, Lisa R Young^{15

16}, Maureen B Josephson^{15

16}, Julian L Allen^{15

16}, Devaney M Camburn¹⁶, Erin E Doherty¹⁷, Mashid Sababi Azamian¹⁷, Martha Arredondo¹⁷, Manuel Silva-Carmona¹⁸, Leslie E Lehmann^{19

20}, Wai Wong^{19

20}, Jonathan M Gaffin^{20

21}, William McAlpine²⁰, Mona Li²⁰, Samuel B Goldfarb²², Jason C Woods⁶, Stella M Davies^{1

2}

Affiliations

¹ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
² Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³ Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁴ Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA.
⁵ Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁶ Pediatrics, Blood and Marrow Transplantation & Cellular Therapy Program, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota, USA.
⁸ Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplantation, UCSF Benioff Children's Hospital, San Francisco, California, USA.
⁹ Pediatric Critical Care Medicine, UCSF Benioff Children's Hospitals, San Francisco, California, USA.
¹⁰ Division of Pulmonary Medicine, University of California San Francisco, San Francisco, California, USA.
¹¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, Division of Hematology, Oncology, Blood and Marrow Transplantation, Seattle Children's Hospital, Seattle, USA.
¹² Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
¹³ Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
¹⁴ Cellular Therapy and Transplant Section, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁵ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Pennsylvania, Pennsylvania, USA.
¹⁶ Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁷ Baylor College of Medicine, Texas Children's Hospital, Center for Cell and Gene Therapy, Houston, Texas, USA.
¹⁸ Division of Pediatric Pulmonology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
¹⁹ Center for Stem Cell Transplantation, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
²⁰ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
²¹ Division of Pulmonary and Sleep Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
²² Division of Pediatric Pulmonary and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 40692216
DOI: 10.1002/pbc.31916

Observational Study

High Prevalence of Abnormal Baseline Lung Function in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report from the TRANSPIRE Study

Jane Koo et al. Pediatr Blood Cancer. 2025 Oct.

. 2025 Oct;72(10):e31916.

doi: 10.1002/pbc.31916. Epub 2025 Jul 21.

Authors

Affiliations

¹ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
² Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³ Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁴ Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA.
⁵ Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁶ Pediatrics, Blood and Marrow Transplantation & Cellular Therapy Program, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota, USA.
⁸ Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplantation, UCSF Benioff Children's Hospital, San Francisco, California, USA.
⁹ Pediatric Critical Care Medicine, UCSF Benioff Children's Hospitals, San Francisco, California, USA.
¹⁰ Division of Pulmonary Medicine, University of California San Francisco, San Francisco, California, USA.
¹¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, Division of Hematology, Oncology, Blood and Marrow Transplantation, Seattle Children's Hospital, Seattle, USA.
¹² Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
¹³ Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
¹⁴ Cellular Therapy and Transplant Section, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁵ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Pennsylvania, Pennsylvania, USA.
¹⁶ Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁷ Baylor College of Medicine, Texas Children's Hospital, Center for Cell and Gene Therapy, Houston, Texas, USA.
¹⁸ Division of Pediatric Pulmonology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
¹⁹ Center for Stem Cell Transplantation, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
²⁰ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
²¹ Division of Pulmonary and Sleep Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
²² Division of Pediatric Pulmonary and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 40692216
DOI: 10.1002/pbc.31916

Abstract

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), low diffusion capacity (33.8%), and imaging abnormalities (e.g., nodules 19%, interstitial changes 7.9%). These patients had significantly lower median z-scores for forced expiratory volume in 1 s (FEV1) (-2.3 vs. -0.5), forced vital capacity (FVC) (-2.0 vs. -0.3), and diffusion capacity of the lung for carbon monoxide (-2.4 vs. -0.7; all p < 0.001). Lung function impairments persisted through 2 years post-HSCT. FEV1 and FVC remained significantly lower at all time points; FEV1/FVC ratios were similar. Overall survival was lower in the abnormal group (88.4 vs. 95.9%). Seven respiratory-related deaths occurred, including acute respiratory distress syndrome (n = 3), respiratory failure (n = 2), diffuse alveolar hemorrhage (n = 1), and fibrotic lung disease (n = 1).

Conclusions: Pretransplant pulmonary dysfunction is common and predicts sustained posttransplant impairment and lower survival. Comprehensive baseline assessment may aid in risk stratification and guide early interventions to improve long-term respiratory outcomes in pediatric and young adult HSCT patients.

Gov identifier: NCT04098445.

Keywords: PFT; allogeneic stem cell transplant; pediatric; pulmonary dysfunction.

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References

1. M. Eikenberry, H. Bartakova, T. Defor, et al., “Natural History of Pulmonary Complications in Children After Bone Marrow Transplantation,” Biology of Blood and Marrow Transplantation 11, no. 1 (2005): 56–64.
1. T. T. Huang, M. M. Hudson, D. C. Stokes, M. J. Krasin, S. L. Spunt, and K. K. Ness, “Pulmonary Outcomes in Survivors of Childhood Cancer: A Systematic Review,” Chest 140, no. 4 (2011): 881–901.
1. Z. Kaya, D. J. Weiner, D. Yilmaz, J. Rowan, and R. K. Goyal, “Lung Function, Pulmonary Complications, and Mortality After Allogeneic Blood and Marrow Transplantation in Children,” Biology of Blood and Marrow Transplantation 15, no. 7 (2009): 817–826.
1. P. H. Michelson, R. Goyal, and G. Kurland, “Pulmonary Complications of Haematopoietic Cell Transplantation in Children,” Paediatric Respiratory Reviews 8, no. 1 (2007): 46–61.
1. M. G. Matt, D. Drozdov, E. Bendstrup, et al., “Allogeneic Haematopoietic Stem‐cell Transplantation for Children With Refractory Systemic Juvenile Idiopathic Arthritis and Associated Lung Disease: Outcomes From an International, Retrospective Cohort Study,” The Lancet Rheumatology 7, no. 4 (2025): e243–e251.

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High Prevalence of Abnormal Baseline Lung Function in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report from the TRANSPIRE Study

Affiliations

High Prevalence of Abnormal Baseline Lung Function in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report from the TRANSPIRE Study

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical