Daclizumab Ciclosporin

A 47-year-old multiparous Hispanic woman received a living-unrelated kidney transplant for end-stage renal disease secondary to polycystic kidney disease. On the day of transplantation she received intravenous daclizumab 1 mg/kg plus methylprednisolone 300 mg and mycophenolate mofetil 3 g/day, and on day 3 ciclosporin emulsion 4 mg/kg/day. On day 8 she developed thrombotic microangiopathy without evidence of rejection. Ciclosporin was withdrawn. Plasmapheresis with fresh frozen plasma was started. Daclizumab on day 14 was postponed for 24 hours and plasmapheresis was stopped to avoid clearance of daclizumab. Thereafter she was given tacrolimus, without recurrence of hemolysis. 

Daclizumab, a humanized antibody directed against the alfa chain of the interleukin-2 receptor, has been used for initial immunosuppression in transplant patients. In a phase III trial in 275 patients who received ciclosporin, glucocorticoids, and daclizumab or placebo, there were no specific adverse effects associated with daclizumab (1). In particular, the cjhokine-release sjmdrome did not occur, and there was no difference in the incidence of fungal or cjhomega-lovirus infections between the two groups. 

However, in one clinical study in heart transplant patients taking ciclosporin, mycophenolate, and corticosteroids, use of daclizumab with another antilymphocyte (such as mnromonab-CD3 or antithymocyte immunoglobniin) appeared to be associated with a higher incidence of fatal infection 8 of 40 patients died, compared with 2 of 37 who received an antilymphocyte and placebo. The manufacturer suggests that concurrent use of daclizumab with another antilymphocyte antibody in patients receiving intensive immunosuppression may be a factor leading to fatal infection. Caution may be warranted, and more study is needed. 

In a randomized, open, single-center study of two monoclonal antibodies to IL-2 receptors combined with triple immunosuppression (ciclosporin microemulsion, mycophenolate mofetil, and methylpredniso-lone), 212 adult recipients of at least 1HLA-mismatched dead donor renal graft were randomized to induction with basiliximab or daclizumab, given in standard doses. Hospital treatment was required in 50 and 59 patients with infections who received basiliximab and daclizumab respectively. There were one case of renal cell carcinoma and one of basal cell carcinoma in the basiliximab group, and one melanoma in the daclizumab group. There was one hypersensitivity reaction with daclizumab [119 ]. 

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