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Pulmonary alveolar proteinosis following allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 46, pages 1480–1483 (2011)Cite this article

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Pulmonary alveolar proteinosis (PAP) is a rare diffuse pulmonary disease characterized by the accumulation of periodic acid-Schiff (PAS)-positive lipoproteinaceous material, primarily phospholipid surfactant and surfactant apoproteins in the distal air spaces.1 The underlying etiopathogenesis is incompletely elucidated, but evidence suggests a central role for GM-CSF and macrophage function.2, 3, 4, 5, 6, 7 Congenital, autoimmune and secondary forms have been described. Congenital PAP has been described to result from inherited mutations in genes for surfactant, or the GM-CSF receptor. An autoimmune form has been attributed to anti-GM-CSF Abs that undermine macrophage function.8 Finally, secondary PAP has been reported following diverse conditions, including toxic inhalation and associated pneumoconioses, infections such as Pneumocystis jirovecii, viral infections, or Nocardia, and both hematologic malignancies and post-hematopoietic cell transplantation (HCT) for hematologic malignancies.9, 10, 11, 12, 13, 14, 15 Dyspnea and cough predominate in the clinical presentation, whereas some cases may be discovered radiographically in the absence of symptoms. Radiographic imaging commonly demonstrates diffuse bilateral alveolar opacities, with a predilection for the central middle and lower lung, and high-resolution computed tomography scan (CT) demonstrates diffuse ground-glass opacity; typical radiographic findings seen in autoimmune PAP may not be seen in secondary PAP.16 Samples from bronchoalveolar lavage (BAL) demonstrate opaque or milky appearance, and cytologic findings include alveolar macrophages containing PAS-positive material. Definitive diagnosis is made by pathologic examination of lung biopsy, confirming the presence of PAS-positive material in the terminal bronchioles and alveoli. Serum or BAL anti-GM-CSF titer has been reported to have high diagnostic accuracy for autoimmune PAP. There have been few reports of secondary PAP being associated with hematologic malignancies and even less specifically after HCT. We report, herein, a case of secondary PAP following allogeneic HCT for CML.

A 40-year-old woman was originally diagnosed with CML in chronic phase in July 2007. Her initial presentation was notable for constitutional symptoms, splenomegaly and the following hematologic parameters: total WBC count of 250 000, hemoglobin 11.7 g/dL and platelet count of 225 000. BM biopsy demonstrated a hypercellular marrow, 10% myeloid blasts, 5% basophils and the cytogenetic finding of t(9:22). Initial leukoreduction was achieved with hydroxyurea, and she was treated thereafter with imatinib 600 mg daily. With disease progression to accelerated phase, therapy was changed to dasatinib 70 mg twice daily. Anagrelide was also utilized to control progressive thrombocytosis. Clonal evolution was demonstrated with the development of trisomy8 on BM cytogenetics. Given disease progression, she was referred for allogeneic HCT. Other past medical history was notable for an ∼12 pack × year smoking history. Pre-HCT pulmonary function tests demonstrated the following: forced vital capacity 105%, forced expiratory volume in 1 second 112% and diffusion capacity carbon monoxide 64% of predicted values, respectively. High-resolution chest CT did not demonstrate any pulmonary parenchymal abnormalities.

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA

    J Pidala & H Fernandez

  2. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

    F Khalil

  3. Department of Oncological Sciences, University of South Florida, Tampa, FL, USA

    J Pidala, F Khalil & H Fernandez

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Correspondence to J Pidala.

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Pidala, J., Khalil, F. & Fernandez, H. Pulmonary alveolar proteinosis following allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 46, 1480–1483 (2011). https://doi.org/10.1038/bmt.2010.321

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