title: Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventy-four patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0·60% in granulocytes and 0·15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH- patients, both after first- and second-line IST: 68% vs. 45%, P = 0·0164 and 53% vs. 13%, P = 0·0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH- patients (P = 0·0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2·56, P = 0·0180) and baseline absolute reticulocyte count (ARC) ≥30 × 10(9) /l (odds ratio 5·19, P = 0·0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 × 10(9) /l showed significant distinctions for cumulative incidence of response, overall and failure-free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.
authors.affiliation: First Pavlov State Medical University of St. Petersburg, St. Petersburg, Novosibirsk, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kulagin
authors.forename: Igor
authors.initials: I
authors.lastname: Lisukov
authors.forename: Maria
authors.initials: M
authors.lastname: Ivanova
authors.forename: Irina
authors.initials: I
authors.lastname: Golubovskaya
authors.forename: Irina
authors.initials: I
authors.lastname: Kruchkova
authors.forename: Sergey
authors.initials: S
authors.lastname: Bondarenko
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vavilov
authors.forename: Natalia
authors.initials: N
authors.lastname: Stancheva
authors.forename: Elena
authors.initials: E
authors.lastname: Babenko
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sipol
authors.forename: Natalia
authors.initials: N
authors.lastname: Pronkina
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kozlov
authors.forename: Boris
authors.initials: B
authors.lastname: Afanasyev
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Aplastic anaemia; Paroxysmal nocturnal haemoglobinuria; bone marrow failure; flow cytometry; immunosuppressive therapy