The effect of cyclosporine on haematological parameters in patients with paroxysmal nocturnal haemoglobinuria

Abstract

Four patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with cyclosporine. The treatment with cyclosporine was based on the hypothesis that immune-mediated bone-marrow damage is the common pathogenetic mechanism of aplasia and PNH, with lack of GPI-linked ligands for an immune attack (i.e. LFA-3, CD58) rendering PNH cells a growth advantage over other bone marrow cells. In the first patient, presenting with a mixed AA/PNH syndrome, a gradual recovery from aplasia was seen after prolonged treatment with cyclosporine. In a second patient, with a mixed AA/PNH syndrome, no haematological improvement was noted during cyclosporine administration, but this patient became transfusion-independent with increasing neutrophil and platelet counts after a course of ATG in combination with androgen therapy. Both these patients showed an increment in the proportion of neutrophils with normal expression of GPI-linked proteins concurrently with the improvement of haematological characteristics. In the two other patients, presenting with typical PNH, cyclosporine treatment did not result in any change in haematological characteristics, nor in PNH parameters. No significant change in haemolytic parameters was seen in any of the patients. It is concluded that immunosuppressive therapy may be of benefit in patients with a mixed AA/PNH syndrome. This effect became apparent after prolonged treatment with cyclosporine in one patient, and after a subsequent course of ATG with concomitant androgen therapy in another.

Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria

“…A second patient who presented with an AA/PNH syndrome responded to treatment with ATG. The two patients with typical haemolytic PNH failed to improve with cyclosporin (van Kamp et al, 1995). Recently, three patients with severe AA and PNH were reported to respond to cyclosporin therapy (Stoppa et al, 1996).…”

“…Detailed clinical information was not reported for those individuals. Recently, two of four patients with PNH were reported to respond to immunosuppression, both of whom had an AA/PNH syndrome (van Kamp et al, 1995). One patient who had a history of ATGresponsive AA and later evolved PNH with peripheral blood cytopenias responded to cyclosporin therapy.…”

Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP

“…1, 12 Indeed, immunosuppressive therapy ameliorates their marrow failure. 1,12,14,15 Of interest, combination therapy with antithymocyte globulin and cyclosporine A, these immunosuppressants having individual target spectra, 16,17 gives better results than therapy with each 1 of the 2 immunosuppressants. 12,18 In general, both cytotoxic T lymphocytes (CTLs) of adaptive immunity and natural killer (NK) cells of innate immunity operate in combination rather than independently.…”

Portal Vein Thrombosis in Paroxysmal Nocturnal Haemoglobinuria

“…Immunosuppressive therapy appears to selectively benefit patients with PNH; some PNH patients with peripheral blood cytopenia responded to antilymphocyte globulin, antithymocyte globulin or cyclosporine therapy [15, 16, 17]. Androgens (including danazol) appear useful in the management of anaemia and thrombocytopenia [18].…”