The impact of allogeneic hematopoietic stem cell transplantation on pulmonary complications in adults with inborn errors of immunity

Aurélie Le Gal; Ambroise Marçais; Céline Goyard; Anne-Laure Brun; Morgane Cheminant; Nizar Mahlaoui; Claire Givel; Colas Tcherakian; Alexandre Chabrol; Frédéric Wallyn; Leonardo Magro; Flore Sicre de Fontbrune; Regis Peffault de la Tour; Abdellatif Tazi; Amira Benattia; Remi Valter; Philippe Devillier; Louis-Jean Couderc; Felipe Suarez; Emilie Catherinot; Hélène Salvator

doi:10.1016/j.jaci.2025.04.032

The impact of allogeneic hematopoietic stem cell transplantation on pulmonary complications in adults with inborn errors of immunity

J Allergy Clin Immunol. 2025 May 14:S0091-6749(25)00516-0. doi: 10.1016/j.jaci.2025.04.032. Online ahead of print.

Authors

Aurélie Le Gal¹, Ambroise Marçais², Céline Goyard¹, Anne-Laure Brun³, Morgane Cheminant², Nizar Mahlaoui⁴, Claire Givel¹, Colas Tcherakian¹, Alexandre Chabrol¹, Frédéric Wallyn⁵, Leonardo Magro⁶, Flore Sicre de Fontbrune⁷, Regis Peffault de la Tour⁷, Abdellatif Tazi⁸, Amira Benattia⁹, Remi Valter¹⁰, Philippe Devillier¹¹, Louis-Jean Couderc¹², Felipe Suarez¹³, Emilie Catherinot¹, Hélène Salvator¹⁴

Affiliations

¹ Respiratory Diseases Department, Foch Hospital, Suresnes, France.
² Hematology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Radiology Department, Foch Hospital, Suresnes, France.
⁴ Pediatric Immuno-Hematology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Center for Primary Immunodeficiencies (CEREDIH), Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁵ Respiratory Diseases Department, Lille University Hospital, Lille, France.
⁶ Hematology Department, Lille University Hospital, Lille, France.
⁷ Hematology and Transplant Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁸ Université Paris Cité F-75006, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U976, Paris, France; Respiratory Diseases Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁹ Respiratory Diseases Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹⁰ Faculté des Sciences de la vie Simone Veil, Université Versailles Saint-Quentin, Montigny-le-Bretonneux, France.
¹¹ Faculté des Sciences de la vie Simone Veil, Université Versailles Saint-Quentin, Montigny-le-Bretonneux, France; Laboratory VIM Suresnes, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE) UMR 0892, Suresnes, France.
¹² Laboratory VIM Suresnes, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE) UMR 0892, Suresnes, France.
¹³ Hematology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Cité F-75006, Paris, France; Institut Imagine, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
¹⁴ Respiratory Diseases Department, Foch Hospital, Suresnes, France; Faculté des Sciences de la vie Simone Veil, Université Versailles Saint-Quentin, Montigny-le-Bretonneux, France; Laboratory VIM Suresnes, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE) UMR 0892, Suresnes, France. Electronic address: h.salvator@hopital-foch.com.

PMID: 40378970
DOI: 10.1016/j.jaci.2025.04.032

Abstract

Background: Pulmonary involvement (repeated lung infections, lung parenchymal inflammation, scarring, and malignancies) is frequent in patients with inborn errors of immunity (IEIs) and accounts for a significant proportion of the disease burden. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure most severe IEIs. The indications for allo-HSCT have recently been extended to adults.

Objective: We sought to assess the impact of allo-HSCT specifically on respiratory status.

Methods: We retrospectively analyzed data of 50 patients with IEIs who underwent a first allo-HSCT after the age of 16 at 3 expert centers in France.

Results: The median length of follow-up was 4.8 years (interquartile range: 1.6-9.2) before allo-HSCT and 3 years (interquartile range: 1.4-6.0) after allo-HSCT. Ten patients died as a result of allo-HSCT-related complications. Four patients developed bronchiolitis obliterans syndrome. After 1-year posttransplantation, the mean annualized rate of severe respiratory infections (0.14 [95% CI: 0.04 to 0.24]) was lower than the value recorded before transplantation (0.54 [95% CI: 0.25 to 0.82]; P = .003 for paired comparisons of equivalent durations). Lung function was declining before allo-HSCT (mean FEV₁: -2.09% predicted/year [95% CI: -7.27 to 3.09]) but increased afterward (+2.44% predicted/year [95% CI: -4.79 to 9.69], P = .0034 for paired comparisons). On computed tomography scans of the chest, bronchial disorders and lung parenchyma cavities were the most frequent abnormal findings. The bronchial thickening and bronchiolar micronodules regressed after allo-HSCT, whereas bronchiectasis and residual parenchymal cavities were stable.

Conclusions: allo-HSCT seems likely to protect the long-term pulmonary prognosis of adults with IEIs; it is associated with a significantly lower incidence of severe respiratory infections, better lung function, and radiologic stabilization of lung damage.

Keywords: Inborn errors of immunity; hematopoietic stem cell transplantation; primary immunodeficiency; respiratory infections.