Clinical Pathology and natural history of PNH; The French Society of Hematology experience.

Abstract

Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder caused by PIG-A gene alterations. In contrast to the growing knowledge regarding the pathophysiology of the disease, data on factors influencing survival are scarce, mainly as a result of the rarity of the disease. Data on 220 patients, diagnosed with PNH over a 46-year period in reporting French centers, were collected. Kaplan-Meier survival estimates (mean +/− standard error) were 65±4% and 48±6% at 10 and 15 years after diagnosis, respectively. In this cohort of 220 patients with PNH, aplastic anemia (AA) antedated PNH in 65 patients with a median interval of 3.1 years. These 65 patients with an AA-PNH syndrome were shown to have a relative risk (RR) of death 3 times lower than the remaining 155 patients with de novo PNH. Finding a better prognosis among patients with AA before diagnosis of PNH might be surprising, we thus reassessed, the differences between the AA-PNH syndrome and de novo PNH. Age, gender and symptom distributions were similar in both groups, at diagnosis. However, when comparing these patients at presentation, anemia was less frequently, but thrombopenia and neutropenia were more frequently observed. Patients with the AA-PNH syndrome were more frequently treated initially with androgens or immimosuppressive therapy than those with de novo PNH. During follow-up, the prevalence or cumulative incidence of main complications was similar in both groups. Multivariate analysis showed that 5 factors influenced survival in both groups (thrombosis, MDS or acute leukemia, age over 54 years, thrombocytopenia at diagnosis and mitial treatment other than androgens), while 1 factor (pancytopenia durmg the evolution) increased the risk of death in patients with de novo PNH. Treatment other than androgens led to an increased risk of death (∼ 5 fold) in patients with de novo PNH while it lowered the risk of death (∼ 4 fold) in patients with the AA-PNH syndrome, compared to patients treated by androgens in either group.