Correction of aplastic anaemia complicating paroxysmal nocturnal haemoglobinuria: absence of eradication of the PNH clone and dependence of response on cyclosporin A administration

Paroxysmal nocturnal haemoglobinuria (PNH) is defined as a somatic mutation of a clonal population of stem cells. Consequently, when aplastic anaemia (AA) occurs in patients with a history of PNH, allogeneic bone marrow transplantation is considered as the only effective treatment. The impact of immunosuppressive therapy has not been reported in this situation. We present observations of three PNH patients who developed 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 patients after 6 and 24 months respectively. A partial response (PR) was observed in the third patient after 12 months. Transient elevated LDH and haemosiderinuria persisted in all cases. DAF and MIRL deficiency were still documented in the two patients in CR.
Two patients (one CR, one PR) ceased CSA therapy after 12 months and relapsed within 3–6 months. CSA was reinitiated and led to platelet recovery in one patient after 6 months.
The persistence of the abnormal PNH clone is coherent with the hypothesis that CSA does not act directly on the PNH clone but probably acts through regulation of the inhibitory effects of immunocompetent cells on haemopoiesis.
These observations suggest that patients suffering from severe AA complicated PNH should not be excluded from immunosuppressive therapy.