Paroxysmal Nocturnal Hemoglobinuria (PNH): Long-Term Epidemiological Study.

PNH is a rare acquired disorder. We aimed to analyze a large cohort of patients on the long term to better determine prognostic factors. We already reported the analysis on 220 patients in 1996 (Socié et al, Lancet). Data were updated and we collected additional data on 247 patients (total of 467 patients, 252 female), diagnosed from 1950 to 2005 from 58 centers. The date of diagnosis was based on flow cytometry analysis if there was no prior positive Ham’s test. The age at diagnosis was 34 years (±17.3). The median follow-up time was 6.8 years (±0.5). Kaplan-Meier 10-year survival estimate was 76.3% (± 2.6). Sixty seven (14.6%) patients developed pancytopenia during follow-up [10-year cumulative incidence (CIn) rate of 18.3% (14% – 22%)]. Deep-vein thrombosis occurred in 108 patients (23.5%) [10-year CIn 28% (23% – 33.1%)]. Nineteen patients developed myelodysplastic syndrome (MDS) [10-year CIn 4.6% (2.4% to 6.8%)]. Eight patients developed acute leukemia [10-year CIn 2.3% (0.4% to 3.9%)]. The following factors were related to poor survival: Older age at diagnosis; age between 40 and 55 years [relative risk RR=2.4 (95% CI 1.4–4.1); p value<10⁻³], age over 55 years [RR 3.6 (95% CI 2.1–6); p<10⁻³], no thrombocytopenia [RR 3.2 (95% CI 1.4–7); p<10⁻³ ], pancytopenia at diagnosis [RR 3.4 (95% CI 1.5–7.9); p<10⁻²], progression to aplastic anemia (AA) [RR 2.3 (95% CI 1.3–3.9); p<10⁻²], thrombosis as a complication [RR 8.9 (95% CI 5.7–14.4); p<10⁻³]; secondary MDS or acute leukemia [RR 13.7 (95% CI 6.1–30.5); p <10⁻³]. However, we also found a strong effect of time period. Diagnosis before 1986 among 114 patients with classical PNH (hemolytic anemia and/or thrombosis at diagnosis) was associated with worse outcome [RR 2.8 (95% CI 1.1–7.2); p: 0.025]. Similar results were found for 227 patients with marrow failure (AA-PNH syndrome) diagnosed before 1996 [RR 2.9 (95% CI 1–8.7); p: 0.04]. For the remaining 96 patients (here called Unclassified PNH), the cutoff time period was to be diagnosed before 1986 [RR 3.6 (95% CI 1–12.4); p: 0.046]. Fifteen years Kaplan-Meier survival estimates were 76% (± 6.6) for patients with unclassified PNH, 70% (± 4.6) for AA-PNH patients and 63.4% (± 1.4) for patients with classical PNH. Older age and evolution to thrombosis were found to be associated with bad prognosis in each of the 3 groups. Evolutions to AA or malignant disease (MD) were related to poor prognosis in 2 of the 3 groups (Classical PNH and AA-PNH for AA; AA-PNH and Unclassified PNH for MD). We also found a protective role of the treatment in the AA-PNH group [RR without treatment 3.1 (95% CI 1.5–6.5); p<10⁻²] while all 20 patients with unclassified PNH treated with immunosuppressive therapy were alive.