Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria.
Until recently, there has been no specific therapy for PNH with clinical management mainly supportive in terms of cytopenias and control of thrombotic risk. Currently, the only curative procedure for PNH is bone marrow transplantation although for the majority of patients the associated risks are too great to justify transplantation. The pioneering use of the therapeutic monoclonal antibody eculizumab, which binds to and prevents the activation of the complement protein C5, represents a significant advance in treatment for patients with PNH and is set to become the future standard therapy for hemolytic PNH. In both an initial pilot study and two phase III clinical trials, eculizumab has been shown to dramatically reduce intravascular hemolysis, hemoglobinuria, and transfusion requirements thus improving the quality of life in patients with PNH. As a clinical entity, PNH is synonymous with glycosylphosphatidylinositol (GPI) deficiency, and is an acquired clonal disorder associated with somatic mutations of the X-linked PIGA gene in hematopoietic stem cells. A recent study identified a novel autosomal recessively inherited form of GPI-deficiency involving a mutation in a promotor component of the pig-m gene and characterized by a thrombotic tendency and seizures. In both these developments, flow cytometry played a critical role. In the first instance, in monitoring direct response to a new therapeutic agent; second, in demonstrating the phenotypic/genotypic link in a new form of GPI deficiency.
Richards
Stephen J
SJ
Haematological Malignancy Diagnostic Service, Department of Haematology, Leeds Teaching Hospitals NHS Trust, The Algernon Firth Building, Leeds General Infirmary, Leeds, LS1 3EX, United Kingdom. stephen.richards2@nhs.net
Hill
Anita
A
Hillmen
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003182:Complement C5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D017261:Glycosylphosphatidylinositols / Q000172:deficiency* / Q000235:genetics; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D009154:Mutation / Q000235:genetics; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018957:CD59 Antigens; D003182:Complement C5; D017261:Glycosylphosphatidylinositols; C051590:CD59 protein, human; C481642:eculizumab