Treatment of Paroxysmal Nocturnal

By Wendell F. Rosse P A ROXYS MA L nocturnal hemoglobin uria (PNH) is a complex stem cell disorder that is manifested by hemolytic anemia with hemoglobinemia and hemoglobinuria, unusual venous thromboses, and episodes of severe pain in the abdomen and back.”2 In some patients, the bone marrow is relatively or absolutely hypoplastic with the resultant reticulocytopenia, leukopenia, and thrombocytopenia.3 In rare instances, the syndrome eventuates in acute myeloblastic leukemia. The major clinical manifestations of PNH appear to be ultimately due to a dysplastic process of the marrow that results in a population of abnormal cells of all three cell lines of the peripheral blood.4 This population is, in each case, characterized by an unusually great fixation of the terminal components of complement and by an abnormal susceptibility of the membrane to rupture by these components. Thus, in the red cell, activation of serum complement results in hemolysis; in the platelet, such activation may result in the initiation of the platelet release phenomenon,8 leading to thrombosis. The ideal treatment of PNH would be the replacement of the abnormal stem cells with stem cells capable of proliferating normally and producing normal cellular descendants. This has been accomplished by transplantation in several cases, particularly when marrow hypoplasia is an important clinical manifestation of the disorder.9 The patients have been prepared for transplantation by the usual therapy for the ablation of the recipient’s marrow, including the abnormal population. When the donor marrow was infused, the PNI-I population did not recur. In two patients, pretreatment with cytotoxic drugs or irradiation was omitted; nevertheless, upon infusion of syngeneic bone marrow from an identical twin, the abnormal population of PNH cells disappeared.’#{176}” Because PNI-I may be very chronic and long-lasting and because of the difficulties of marrow transplantation, even in allogeneic transplantation between HLA-