Introduction: Secondary pulmonary alveolar proteinosis(SPAP) is so rare that clinical information is scarce and the pathogenesis and prognosis are unknown. Although we have previously reported clinical studies of SPAP in ERS 2018, the adequate prognostic analysis has remained unclear. Aims: We have accumulated 91 cases of SPAP through a large-scale clinical study in Japan. The majority of SPAP had underlying hematologic diseases, with myelodysplastic syndrome(MDS) accounting for 70% of all. Therefore, the aim of this study was to focus on MDS complicated with SPAP(MDS-SPAP) and to analyze its prognosis and etiologic factors. Methods: We analyzed clinical information at diagnosis and prognosis after diagnosis of MDS-SPAP. Exome analysis and target sequence were performed using peripheral blood mononuclear cells from cases of MDS-SPAP. Results: Sixty-three cases of MDS-SPAP were enrolled. MST after the diagnosis of MDS-SPAP in all cases was 17 months. MST of transplanted cases(n=13) was 24 months, but it wasn?t significantly longer than that of non-transplanted cases(n=50). There was also no significant difference in MST between mild and severe MDS severity. Chromosome 1 and 8 aberrations were highly prevalent, with trisomy 8 occurring in 29 cases (46%). U2AF1 gene mutation, one of RNA splicing factors, was the most frequently detected in MDS-SPAP. Conclusion: MDS-SPAP is a rare disease, and this clinical multidisciplinary study of 63 cases is the largest analysis to date. The prognosis of MDS-SPAP was remarkably poor. The suggestion that trisomy8 and U2AF1 mutations may be associated with the development of MDS-SPAP may provide useful information for understanding the pathogenesis of the disease.