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21 September 1999 | Volume 131 Issue 6 | Pages 401-408
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem-cell disorder in which the affected cells are deficient in glycosylphosphatidylinositol (GPI)-anchored proteins. Paroxysmal nocturnal hemoglobinuria is frequently associated with aplastic anemia, although the basis of this relation is unknown.
Objective: To assess the PNH status of patients with diverse marrow failure syndromes.
Design: Correlation of cytofluorometric data with clinical features.
Setting: Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Patients: 115 patients with aplastic anemia, 39 patients with myelodysplasia, 28 patients who had recently undergone bone marrow transplantation, 18 patients with cancer that was treated with chemotherapy, 13 patients with large granular lymphocytosis, 20 controls who had received renal allografts, and 21 healthy participants.
Intervention: Patients with aplastic anemia, myelodysplasia, or renal allografts received antithymocyte globulin.
Measurements: Flow cytometry was used to assess expression of GPI-anchored proteins on granulocytes.
Results: Evidence of PNH was found in 25 of 115 (22%) patients with aplastic anemia. No patient with normal GPI-anchored protein expression at presentation developed PNH after therapy (n = 16). Nine of 39 (23%) patients with myelodysplasia had GPI-anchored protein-deficient cells. Abnormal cells were not detected in patients with constitutional or other forms of bone marrow failure or in renal allograft recipients who had received antithymocyte globulin. Aplastic anemia is known to respond to immunosuppressive therapy; in myelodysplasia, the presence of a PNH population was strongly correlated with hematologic improvement after administration of antithymocyte globulin (P = 0.0015).
Conclusions: Flow cytometric analysis is superior to the Ham test and permits concomitant diagnosis of PNH in about 20% of patients with myelodysplasia (a rate similar to that seen in patients with aplastic anemia). The presence of GPI-anchored protein-deficient cells in myelodysplasia predicts responsiveness to immunosuppressive therapy. Early emergence of GPI-anchored protein-deficient hematopoiesis in a patient with marrow failure may point to an underlying immune pathogenesis.
Author and Article Information
From the National Heart, Lung, and Blood Institute, Bethesda, Maryland; and MCP Hahnemann University Hospitals, Philadelphia, Pennsylvania.
Note: Drs. Dunn and Tanawattanacharoen contributed equally to this work.
Grant Support: By the National Institutes of Health, National Heart, Lung, and Blood Institute, Hematology Branch.
Requests for Reprints: Daniel E. Dunn, MD, PhD, 309 East Osceola Street, Suite 208, Stuart, FL 34994-2240.
Current Author Addresses: Dr. Dunn: 309 East Osceola Street, Suite 208, Stuart, FL 34994-2240.
Dr. Tanawattanacharoen: Department of Medicine, Division of Hematology, Siriraj Hospital, Mahidol University, 2 Prannok, Bangkok 10700, Thailand.
Dr. Boccuni: Via Aniello Falcone 153, Napoli 80127, Italy.
Dr. Nagakura: The Second Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City, Kumamoto, Japan 860-0811.
Dr. Anil Kumar: MCP Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102.
Mr. Green, Ms. Kirby, and Dr. Young: National Heart, Lung, and Blood Institute, 9000 Rockville Pike, Bethesda, MD 20892-1652. ARTICLE
Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure Syndromes
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