Paroxysmal nocturnal hemoglobinuria clones in children with acquired aplastic anemia: a multicentre study

• Published in: PloS one Vol. 9; no. 7; p. e101948
• Main Authors: Timeus, Fabio, Crescenzio, Nicoletta, Longoni, Daniela, Doria, Alessandra, Foglia, Luiselda, Pagliano, Sara, Vallero, Stefano, Decimi, Valentina, Svahn, Johanna, Palumbo, Giuseppe, Ruggiero, Antonio, Martire, Baldassarre, Pillon, Marta, Marra, Nicoletta, Dufour, Carlo, Ramenghi, Ugo, Saracco, Paola
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.07.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Anemia; Anemia, Aplastic - complications; Anemia, Aplastic - drug therapy; Anemia, Aplastic - metabolism; Aplastic anemia; Biology and Life Sciences; Bone marrow; Child; Child, Preschool; Children; Cloning; Cyclosporine - therapeutic use; Cyclosporins; Diagnosis; Flow cytometry; Glycosylphosphatidylinositol; Glycosylphosphatidylinositols - metabolism; Granulocytes; Hematology; Hemoglobinuria, Paroxysmal - diagnosis; Hemoglobinuria, Paroxysmal - drug therapy; Hemoglobinuria, Paroxysmal - metabolism; Hemolysis; Humans; Immunosuppressive Agents - therapeutic use; Infant; Infant, Newborn; Inositol; Longitudinal Studies; Medical diagnosis; Medicine and Health Sciences; Monitoring; Mutation; Oncology; Paroxysmal nocturnal hemoglobinuria; Patients; Pediatrics; Population; Population number; Population studies; Populations; Stem cells; Tapering; Therapy; Treatment Outcome; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101948

A multicentre study evaluating the presence of glycosil phosphatidyl-inositol (GPI)-negative populations was performed in 85 children with acquired aplastic anemia (AA). A GPI-negative population was observed in 41% of patients at diagnosis, 48% during immune-suppressive therapy (IST), and 45% in patients off-therapy. No association was found between the presence of a GPI-negative population at diagnosis and the response to IST. In addition, the response rate to IST did not differ between the patients who were GPI-positive at diagnosis and later developed GPI-negative populations and the 11 patients who remained GPI-positive. Two patients with a GPI-negative population >10%, and laboratory signs of hemolysis without hemoglobinuria were considered affected by paroxysmal nocturnal hemoglobinuria (PNH) secondary to AA; no thrombotic event was reported. Excluding the 2 patients with a GPI-negative population greater than 10%, we did not observe a significant correlation between LDH levels and GPI-negative population size. In this study monitoring for laboratory signs of hemolysis was sufficient to diagnose PNH in AA patients. The presence of minor GPI-negative populations at diagnosis in our series did not influence the therapeutic response. As occasionally the appearance of a GPI-negative population was observed at cyclosporine (CSA) tapering or AA relapse, a possible role of GPI-negative population monitoring during IST modulation may need further investigation.