Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study

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 060% in granulocytes and 015% in red blood cells. The response rate at 6months was higher in PNH+ patients than that in PNH- patients, both after first- and second-line IST: 68% vs. 45%, P=00164 and 53% vs. 13%, P=00502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH- patients (P=00029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 256, P=00180) and baseline absolute reticulocyte count (ARC) 30x10(9)/l (odds ratio 519, P=00011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC 30x10(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.