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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1308-1314.
Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-06-2485.
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CLINICAL TRIALS AND OBSERVATIONS
Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia
Chiharu Sugimori,
Tatsuya Chuhjo,
Xingmin Feng,
Hirohito Yamazaki,
Akiyoshi Takami,
Masanao Teramura,
Hideaki Mizoguchi,
Mitsuhiro Omine, and
Shinji Nakao
From the Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa; the Preventive Environment Unit, Kanazawa University Hospital, Ishikawa; the Division of Hematology, Tokyo Women's Medical University, Tokyo; and the Division of Hematology, Fujigaoka Hospital, Showa University School of Medicine, Yokohama, Japan.
We investigated the clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells in patients with acquired aplastic anemia (AA). We quantified CD55-CD59- granulocytes and red blood cells (RBCs) in peripheral blood from 122 patients with recently diagnosed AA and correlated numbers of PNH-type cells and responses to immunosuppressive therapy (IST). Flow cytometry detected 0.005% to 23.1% of GPI-AP- cells in 68% of patients with AA. Sixty-eight of 83 (91%) patients with an increased proportion of PNH-type cells (PNH+) responded to antithymocyte globulin (ATG) + cyclosporin (CsA) therapy, whereas 18 of 39 (48%) without such an increase (PNH-) responded. Failure-free survival rates were significantly higher (64%) among patients with PNH+ than patients with PNH- (12%) at 5 years, although overall survival rates were comparable between the groups. Numbers of PNH-type and normal-type cells increased in parallel among most patients with PNH+ who responded to IST, suggesting that these cells are equally sensitive to immune attack. These results indicate that a minor population of PNH-type cells represents a reliable marker of a positive IST response and a favorable prognosis among patients with AA. Furthermore, immune attack against hematopoietic stem cells that allows PNH clonal expansion might occur only at the onset of AA.
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