BACKGROUND AND OBJECTIVES: Granulocyte macrophage-colony-stimulating factor (GM-CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis (aPAP). Upon response to short-term treatment, patients are divided into responders and non-responders. The aim of this study was to test the hypothesis that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that attainment of remission permits gradual de-escalation of the dose to the lowest effective safe dose. METHODS: Patients were treated with iGM-CSF 250 μg once a day given 4 days on and 4 days off for as long as necessary (the "as far as it takes" protocol). Upon remission, defined as absence of symptoms, oxygen desaturation <4 % at the walking test, and significant radiographic reduction of the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated. In the case of relapse, the patient was repositioned at the previous effective dose. Patients were investigated at 6-month intervals. To detect hematopoietic effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony-forming-units, and burst-forming-unit erythroid were measured. RESULTS: Six (five female) patients 43.8 ± 15.7 years of age were treated for 14-65 months and all responded to treatment. Remission was achieved after 25.6 ± 10 months. Three patients maintained remission at their lowest effective dose. Two patients relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM-CSF had no impact on any of the hematological parameters tested. CONCLUSIONS: In aPAP, long-term adherence to the dose schedule permitted remission in all patients. Long-term treatment with iGM-CSF also permitted the definition of lower effective doses, minimizing disease burden and treatment costs safely, since no stimulating activity on hematopoiesis was observed, a fact that is of paramount importance for those aPAP patients needing lifelong treatment.
BACKGROUND AND OBJECTIVES:Granulocyte macrophage-colony-stimulating factor (GM-CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis (aPAP). Upon response to short-term treatment, patients are divided into responders and non-responders. The aim of this study was to test the hypothesis that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that attainment of remission permits gradual de-escalation of the dose to the lowest effective safe dose. METHODS:Patients were treated with iGM-CSF 250 μg once a day given 4 days on and 4 days off for as long as necessary (the "as far as it takes" protocol). Upon remission, defined as absence of symptoms, oxygen desaturation <4 % at the walking test, and significant radiographic reduction of the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated. In the case of relapse, the patient was repositioned at the previous effective dose. Patients were investigated at 6-month intervals. To detect hematopoietic effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony-forming-units, and burst-forming-unit erythroid were measured. RESULTS: Six (five female) patients 43.8 ± 15.7 years of age were treated for 14-65 months and all responded to treatment. Remission was achieved after 25.6 ± 10 months. Three patients maintained remission at their lowest effective dose. Two patients relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM-CSF had no impact on any of the hematological parameters tested. CONCLUSIONS: In aPAP, long-term adherence to the dose schedule permitted remission in all patients. Long-term treatment with iGM-CSF also permitted the definition of lower effective doses, minimizing disease burden and treatment costs safely, since no stimulating activity on hematopoiesis was observed, a fact that is of paramount importance for those aPAP patients needing lifelong treatment.
Authors: U Dirksen; R Nishinakamura; P Groneck; U Hattenhorst; L Nogee; R Murray; S Burdach Journal: J Clin Invest Date: 1997-11-01 Impact factor: 14.808
Authors: J F Seymour; J J Presneill; O D Schoch; G H Downie; P E Moore; I R Doyle; J M Vincent; K Nakata; T Kitamura; D Langton; M C Pain; A R Dunn Journal: Am J Respir Crit Care Med Date: 2001-02 Impact factor: 21.405
Authors: E Stanley; G J Lieschke; D Grail; D Metcalf; G Hodgson; J A Gall; D W Maher; J Cebon; V Sinickas; A R Dunn Journal: Proc Natl Acad Sci U S A Date: 1994-06-07 Impact factor: 11.205
Authors: Takuro Sakagami; Kanji Uchida; Takuji Suzuki; Brenna C Carey; Robert E Wood; Susan E Wert; Jeffrey A Whitsett; Bruce C Trapnell; Maurizio Luisetti Journal: N Engl J Med Date: 2009-12-31 Impact factor: 91.245
Authors: Ali Ataya; Vijaya Knight; Brenna C Carey; Elinor Lee; Elizabeth J Tarling; Tisha Wang Journal: Front Immunol Date: 2021-11-22 Impact factor: 7.561
Authors: Matthias Griese; Panagiota Panagiotou; Effrosyni D Manali; Mirjam Stahl; Nicolaus Schwerk; Vanessa Costa; Konstantinos Douros; Maria Kallieri; Ruth Maria Urbantat; Horst von Bernuth; Lykourgos Kolilekas; Lurdes Morais; Ana Ramos; Kerstin Landwehr; Katrin Knoflach; Florian Gothe; Karl Reiter; Vassiliki Papaevangelou; Athanasios G Kaditis; Christina Kanaka-Gantenbein; Spyros A Papiris Journal: ERJ Open Res Date: 2022-03-21