Pulmonary Alveolar Proteinosis in a Patient with Acute Lymphoid Leukemia Regression after G-CSF Therapy

Pamuk, Gülsüm Emel; Turgut, Burhan; Vural, Özden; Demir, Muzaffer; Hatipoğlu, Osman Nuri; Ünlü, Ercüment; Altaner, Semsi; Gerenli, Murat; Çakır, Bekir

doi:10.1080/1042819021000055093

Cited by 20 publications

(15 citation statements)

References 18 publications

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“…The diagnosis is usually made based on the presence of typical radiological manifestations and lung histopathological findings. Secondary PAP has been reported in association with various diverse clinical disorders, including hematological disorders (myelodysplastic syndrome, leukemia, lymphoma, aplastic anemia, pharmacologically induced leukopenia, others), immunological diseases (severe combined immunodeficiency, monoclonal gammopathy, selective immunoglobulin A deficiency, others), lysinuric protein intolerance, and infections (Cytomegalovirus, Mycobacterium tuberculosis , Nocardia, Pneumocystis jiroveci , others) [34; 62; 63; 64; 65; 66; 67; 68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 79; 80]. It has also been reported in association with various toxic inhalation syndromes, including inhalation of inorganic dusts (silica, cement, titanium, and aluminum), organic dusts (sawdust, fertilizer, bakery flour, others), and fumes (chlorine, varnish, others) [81; 82; 83; 84; 85; 86; 87; 88].…”

Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

“…In one report, individuals with myelodysplasia who developed PAP had functional defects in GM-CSF signaling suggesting a pathogenesis based on disruption GM-CSF stimulation of alveolar macrophage-mediated surfactant clearance [89]. In other reports, correlation of the onset and resolution of PAP with the onset and resolution of severe reductions in myeloid cell numbers [68] suggested the pathogenesis was based on reduction of the numbers of alveolar macrophages reducing their capacity for removing surfactant from the lungs. Together, these results suggest that secondary PAP may be caused by an acquired loss of GM-CSF signaling, reduced alveolar macrophage numbers, or alveolar macrophage dysfunction.…”

Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

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The molecular basis of pulmonary alveolar proteinosis

Carey¹,

Trapnell²

2010

Clinical Immunology

206

190

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Pulmonary alveolar proteinosis (PAP) comprises a heterogenous group of diseases characterized by abnormal surfactant accumulation resulting in respiratory insufficiency, and defects in alveolar macrophage-and neutrophil-mediated host defense. Basic, clinical and translational research over the past two decades have raised PAP from obscurity, identifying the molecular pathogenesis in over 90% of cases as a spectrum of diseases involving the disruption of GM-CSF signaling. Autoimmune PAP represents the vast majority of cases and is caused by neutralizing GM-CSF autoantibodies. Genetic mutations that disrupt GM-CSF receptor signaling comprise a rare form of hereditary PAP. In both autoimmune and hereditary PAP, loss of GM-CSF signaling blocks the terminal differentiation of alveolar macrophages in the lungs impairing the ability of alveolar macrophages to catabolize surfactant and to perform many host defense functions. Secondary PAP occurs in a variety of clinical diseases that presumedly cause the syndrome by reducing the numbers or functions of alveolar macrophages, thereby impairing alveolar macrophage-mediated pulmonary surfactant clearance. A similar phenotype occurs in mice deficient in the production of GM-CSF or GM-CSF receptors. PAP and related research has uncovered a critical and emerging role for GM-CSF in the regulation of pulmonary surfactant homeostasis, lung host defense, and systemic immunity.

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Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

The molecular basis of pulmonary alveolar proteinosis

Carey¹,

Trapnell²

2010

Clinical Immunology

206

190

View full text Add to dashboard Cite

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“…PAP could explain up to 10% of pulmonary manifestations during these diseases [54]. Less frequently, PAP has been associated with acute lymphoid leukaemia [55], lymphoma [56] and myeloma [57]. In haematological diseases, alveolar macrophages could be numerically or functionally unable to clear the surfactant.…”

Section: Cancermentioning

confidence: 99%

Pulmonary alveolar proteinosis

Borie¹,

Danel²,

Mp³

et al. 2011

European Respiratory Review

239

258

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Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic ''crazy paving'' pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

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“…The hematological malignancies most often related to SPAP are acute and chronic myelogenous leukemias; also linked are myelodysplastic syndrome and lymphoblastic leukemia [4-7]. CML was the most common cause of SPAP in our series (4/6 patients).…”

Section: Discussionmentioning

confidence: 87%

Secondary Pulmonary Alveolar Proteinosis

Chung

Pipavath

Myerson

et al. 2009

Journal of Thoracic Imaging

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Summary Objective We analyzed the CT and clinical findings of pulmonary alveolar proteinosis secondary to hematological malignancy. Methods Seven patients with hematological malignancy and pathologically proven secondary pulmonary alveolar proteinosis were identified from 2000−2007. Six had chest CT scans, which were analyzed retrospectively; medical records were also reviewed. Results Patient age ranged from 30−54 years. Four had chronic myelogenous leukemia, 1 had myelodysplastic syndrome, and 1 had cutaneous T cell lymphoma. As in idiopathic pulmonary alveolar proteinosis, geographic ground-glass opacities with or without septal thickening were most common (5/6). No axial or zonal predominance was present. Two patients died from respiratory failure. Conclusion It is important to consider secondary pulmonary alveolar proteinosis as a cause of geographic ground-glass opacities and septal thickening in a patient with hematological malignancy. Whereas idiopathic pulmonary alveolar proteinosis has a low mortality rate, the death of 2 of our 6 patients implies that secondary pulmonary alveolar proteinosis may have a worse prognosis. Our case of secondary pulmonary alveolar proteinosis associated with cutaneous T-cell lymphoma is the first described in the literature.

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Pulmonary Alveolar Proteinosis in a Patient with Acute Lymphoid Leukemia Regression after G-CSF Therapy

Cited by 20 publications

References 18 publications

The molecular basis of pulmonary alveolar proteinosis

The molecular basis of pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis

Secondary Pulmonary Alveolar Proteinosis

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