Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study

Elisa Cannizzo, Maddalena Raia, Maria Stefania De Propris, Anna Triolo, Barbara Scarpati, Anna Marfia, Alessandra Stacchini, Francesco Buccisano, Francesco Lanza, Antonio Regazzoli, Angela Michelutti, Simone Cesaro, Cinzia Armentano Conte, Laura Vanelli, Elisabetta Tedone, Paola Omedè, Maria Matilde Ciriello, Roberto Caporale, Virginia Catinella, Giorgia PantanoClorinda De Rosa, Catia Lo Pardo, Giovanni Poletti, Francesca Ulbar, Maria Cristina Pavanelli, Laura Del Pup, Virginia Ottaviano, Anna Maria Santonocito, Chiara Bartocci, Elisa Boscaro, Marcella Arras, Rachele Amodeo, Anna Mestice, Bianca Oliva, Luisa Ferrari, Teodora Statuto, Fiorella D'Auria, Graziano Pianezze, Donatella Tanca, Feliciano Visconte, Fabiana Rubba, Pellegrino Musto, Massimo Geuna, Arianna Gatti, Bruno Brando, Luigi Del Vecchio

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1083-1093
Number of pages11
JournalAnnals of Hematology
Volume98
Issue number5
DOIs
Publication statusPublished - May 2019

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Keywords

  • Age Factors
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Hemoglobinuria, Paroxysmal/blood
  • Humans
  • Italy
  • Male
  • Practice Guidelines as Topic

Cite this

Cannizzo, E., Raia, M., De Propris, M. S., Triolo, A., Scarpati, B., Marfia, A., Stacchini, A., Buccisano, F., Lanza, F., Regazzoli, A., Michelutti, A., Cesaro, S., Conte, C. A., Vanelli, L., Tedone, E., Omedè, P., Ciriello, M. M., Caporale, R., Catinella, V., ... Del Vecchio, L. (2019). Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study. Annals of Hematology, 98(5), 1083-1093. https://doi.org/10.1007/s00277-019-03644-8