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Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan

Haruyuki Ishii1, John F Seymour2, Ryushi Tazawa3, Yoshikazu Inoue4, Naoyuki Uchida5, Aya Nishida5, Yoshihito Kogure6, Takeshi Saraya1, Keisuke Tomii7, Toshinori Takada8, Yuko Itoh3, Masayuki Hojo9, Toshio Ichiwata10, Hajime Goto1 and Koh Nakata3*

Author Affiliations

1 Department of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 shinkawa, Mitaka-shi, Tokyo 1818611, Japan

2 Department of Haematology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 8006, Australia

3 Bioscience Medical Research Center, Niigata University Medical & Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata 9518520, Japan

4 Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka 5918555, Japan

5 Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 1058470, Japan

6 Department of Respiratory Medicine, NHO Nagoya Medical Center, 4-1-1 Sannomal, Naka-ku, Nagoya, 4600001Japan

7 Department of Pulmonary Medicine, Kobe City General Hospital, 4-6 Minatojimanakamachi, Chuo-ku, Kobe-city, Hyogo 6500046, Japan

8 Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-754 Asahimachi-dori, Chuo-ku, Niigata 9518520, Japan

9 Division of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 1628655, Japan

10 Department of Respiratory Medicine, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji-shi, Tokyo 1930998, Japan

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BMC Pulmonary Medicine 2014, 14:37  doi:10.1186/1471-2466-14-37

Published: 5 March 2014



Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS.


Thirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups.


In contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis.


Development of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

Proteinosis; Myelodysplastic syndrome; GM-CSF; WPSS; Secondary pulmonary alveolar proteinosis; MDS; PAP; Refractory anemia