Paroxysmal nocturnal hemoglobinuria

The aim is to report on recent observations related to the natural history of paroxysmal nocturnal hemoglobinuria (PNH) and to review new therapeutic strategies for controlling the hemolysis of PNH.

This review focuses on studies designed to characterize the long-term outcome of patients with PNH treated with eculizumab and to define the relationship between PNH and bone marrow failure syndromes. New therapeutic strategies aimed at controlling extravascular as well as intravascular hemolysis are also examined.

Long-term safety and efficacy of eculizumab was observed in a large group of patients. Survival for the group was not different from that of a sex-matched and age-matched control group from the general population. Thrombotic complications were rare and deaths due to PNH or complications of therapy were not observed. These studies suggest that patients with clinical PNH who are treated with eculizumab have a benign clinical course. Patients with bone marrow failure who have PNH cells detected by high-sensitivity flow cytometry have aplastic anemia or low-risk myelodysplastic syndrome. For patients with a percentage of PNH cells that is below the threshold for producing laboratory evidence of hemolysis (subclinical PNH), expansion of the clone to a size sufficient to produce clinical PNH is not observed. Approximately 50% of patients with bone marrow failure who have clinical evidence of PNH at presentation will require PNH-specific therapy. Novel reagents that target the alternative pathway of complement C3 convertase are being developed with a goal of inhibiting both the extravascular and the intravascular hemolysis of PNH.