AUTHOR=Beeckmans Hanne , Ambrocio Gene P. L. , Bos Saskia , Vermaut Astrid , Geudens Vincent , Vanstapel Arno , Vanaudenaerde Bart M. , De Baets Frans , Malfait Thomas L. A. , Emonds Marie-Paule , Van Raemdonck Dirk E. , Schoemans Hélène M. , Vos Robin , for the Leuven Lung Transplant Group , Ceulemans Laurens J. , Verleden Geert M. , Dupont Lieven J. , Godinas Laurent , Schaevers Veronique , Claes Dirk , Denaux Karen , Desschans Bruno , Daniëls Liesbeth , Verbeken Eric K. , Weynand Birgit , Verschakelen Johny , Dubbeldam Adriana , Haghedooren Renata TITLE=Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.931153 DOI=10.3389/fimmu.2022.931153 ISSN=1664-3224 ABSTRACT=

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP.