TY - JOUR
T1 - Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients
T2 - a multicenter Italian study
AU - Cannizzo, Elisa
AU - Raia, Maddalena
AU - De Propris, Maria Stefania
AU - Triolo, Anna
AU - Scarpati, Barbara
AU - Marfia, Anna
AU - Stacchini, Alessandra
AU - Buccisano, Francesco
AU - Lanza, Francesco
AU - Regazzoli, Antonio
AU - Michelutti, Angela
AU - Cesaro, Simone
AU - Conte, Cinzia Armentano
AU - Vanelli, Laura
AU - Tedone, Elisabetta
AU - Omedè, Paola
AU - Ciriello, Maria Matilde
AU - Caporale, Roberto
AU - Catinella, Virginia
AU - Pantano, Giorgia
AU - De Rosa, Clorinda
AU - Lo Pardo, Catia
AU - Poletti, Giovanni
AU - Ulbar, Francesca
AU - Pavanelli, Maria Cristina
AU - Del Pup, Laura
AU - Ottaviano, Virginia
AU - Santonocito, Anna Maria
AU - Bartocci, Chiara
AU - Boscaro, Elisa
AU - Arras, Marcella
AU - Amodeo, Rachele
AU - Mestice, Anna
AU - Oliva, Bianca
AU - Ferrari, Luisa
AU - Statuto, Teodora
AU - D’Auria, Fiorella
AU - Pianezze, Graziano
AU - Tanca, Donatella
AU - Visconte, Feliciano
AU - Rubba, Fabiana
AU - Musto, Pellegrino
AU - Geuna, Massimo
AU - Gatti, Arianna
AU - Brando, Bruno
AU - Del Vecchio, Luigi
PY - 2019/1/1
Y1 - 2019/1/1
N2 - In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p < 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large (> 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.
AB - In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p < 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large (> 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.
KW - Aplastic anemia
KW - Atypical thrombosis
KW - Flow cytometry
KW - Hemolytic anemia
KW - Myelodysplastic syndromes
KW - Paroxysmal nocturnal hemoglobinuria
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U2 - 10.1007/s00277-019-03644-8
DO - 10.1007/s00277-019-03644-8
M3 - Article
AN - SCOPUS:85062994845
JO - Revue d'hématologie
JF - Revue d'hématologie
SN - 0939-5555
ER -