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Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study

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Abstract

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8–15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < −1.645; n = 12), restrictive defects (TLC < 80% predicted, FEV1 and FVC z-scores < −1.645; n = 7) and non-specific pattern (FEV1 and FVC z-score< −1.645, FEV1/FVC z-score > −1.645, and TLC > 80% predicted; n = 8). HCT for malignant disease was the only factor associated with LONIPC (P = 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

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Fig. 1: Flow chart.
Fig. 2: PFT abnormalities in the whole population.
Fig. 3: PFT course of the 32 children with LONIPC, centred on the time of LONIPC diagnosis.
Fig. 4: Cumulative incidence of LONIPCs, BOS and extrapulmonary GVHD in the 32 children with LONIPCs.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the Pulmonology and Hematology’s children group: Karima Yakouben; Mohny Fahd; Laurence Le Clainche; Arthur Sterin; Caroline Thumerelle; Laurence Weiss; Tiphaine Bihouee; Hala Caron-Feghali; Sophie L’excellent; Cécile Renard; Emmanuelle Bosdure; Martin Castelle; Marine Michelet; Christophe Marguet; Nimrod Buchbinder. The authors also thank the children and parents for their contribution to the research, and Pierre Coste, Sandra Argues, Sophie Caillat Zucman and Stephane Bonacorsi for their help to this study.

Funding

The RESPPEDHEM study was supported by a research grant from the French Health Ministry (PHRC National) and sponsored by the Direction de la Recherche et de l'Innovation, APHP [AOM 12035]. The sponsor had no role in data analysis and decision to submit the manuscript.

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Véronique Houdouin and Christophe Delclaux: substantial contributions to the conception and design of the work, acquisition and analysis, and interpretation of data for the work; Drafting the work and revising it critically for important intellectual content; Final approval of the version to be published; Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Fanny Rialland, Bénedicte Bruno, Charlotte Jubert, Philippe Reix, Marlène Pasquet, Catherine Paillard, Dalila Adjaoud, Cyril Schweitzer, Muriel. Le Bourgeois: they made substantial contributions to the acquisition of data for the work; revising it critically for important intellectual content; final approval of the version to be published, and agreement to be accountable for all aspects of the work Jean Christophe Dubus, Jean Hugues Dalle, Anne Bergeron: substantial contributions to the conception and design of the work, acquisition and analysis, and interpretation of data for the work; Drafting the work and revising it critically for important intellectual content; Final approval of the version to be published; Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Sophie Guilmin-Crepon, Justine Pages, Adyla Yacoubi: substantial contributions to the conception of the work, analysis and interpretation of data for the work; Drafting the work and revising it critically for important intellectual content; Final approval of the version to be published; Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Guarantor statement: Véronique Houdouin takes responsibility for the content of the manuscript, including the data and analysis.

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Correspondence to Véronique Houdouin.

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Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study

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Houdouin, V., Dubus, J.C., Crepon, S.G. et al. Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study. Bone Marrow Transplant 59, 858–866 (2024). https://doi.org/10.1038/s41409-024-02258-7

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