CORRECTION OF APLASTIC-ANEMIA COMPLICATING PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA - ABSENCE OF ERADICATION OF THE PNH CLONE AND DEPENDENCE OF RESPONSE ON CYCLOSPORINE-A ADMINISTRATION

Paroxysmal nocturnal haemoglobinuria (PNH) is defined as a somatic mut ation of a clonal population of stem cells. Consequently, when aplasti c anaemia (AA) occurs in patients with a history of PNH, allogeneic bo ne marrow transplantation is considered as the only effective treatmen t. The impact of immunosuppressive therapy has not been reported in th is situation. We present observations of three PNH patients who develo ped AA and were effectively treated with cyclosporin A (CSA). Because of lack of improvement with other treatments, CSA alone was given at a dose of 5-10 mg/kg/d. Complete response (CR) was obtained in two pati ents after 6 and 24 months respectively, A partial response (PR) was o bserved in the third patient after 12 months, Transient elevated LDH a nd haemosiderinuria persisted in all cases, DAF and MIRL deficiency we re still documented in the two patients in CR. Two patients (one CR, o ne PR) ceased CSA therapy after 12 months and relapsed within 3-6 mont hs, CSA was reinitiated and led to platelet recovery in one patient af ter 6 months. The persistence of the abnormal PNH clone is coherent wi th the hypothesis that CSA does not act directly on the PNH clone but probably acts through regulation of the inhibitory effects of immunoco mpetent cells on haemopoiesis. These observations suggest that patient s suffering from severe AA complicated PNH should not be excluded from immunosuppressive therapy.