A rare, widespread lung condition known as Pulmonary Alveolar Proteinosis (PAP) is characterised by surfactant buildup in the small airways as a result of suboptimal alveolar macrophage clearance, impairing gas exchange. The current gold standard of care for PAP is whole lung lavage. When whole lung lavage or other experimental therapy approaches are inadequate or in cases of severe pulmonary fibrosis brought on by PAP, lung transplantation is a recognised alternative for treatment. Recurrence of PAP in the transplanted lungs, especially in hereditary PAP, is a drawback of lung transplantation. The Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) receptor genes are the source of the genetic abnormalities that lead to the hereditary form of PAP, an extremely rare illness that directly affects bone marrow-derived monocytes that later develop into macrophages in the lung. As a result, these macrophages frequently exhibit faulty GM-CSF receptor signalling, which impairs surfactant clearance. In cases of hereditary PAP, a bone marrow or hematopoietic stem cell transplant may be able to cure the pulmonary condition. Theoretically, hematopoietic stem cell transplantation after lung transplantation could prevent post-lung transplant PAP recurrence in patients with hereditary PAP, which would enhance long-term outcomes because it causes a graft-versus-disease (PAP) effect. We discuss a rare case of end-stage respiratory failure brought on by hereditary PAP-induced pulmonary fibrosis that was effectively treated with bilateral lung transplantation and a subsequent allogeneic hematopoietic stem cell transplant. In selected patients with end-stage hereditary PAP, our findings recommend treatment with serial lung and hematopoietic stem cell transplantation to enhance quality of life and lengthen survival without PAP recurrence.
