Treatment of steroid refractory acute and chronic graft‐versus‐host disease with daclizumab

Abstract

Competitive inhibition of interleukin 2‐dependent lymphocytes by daclizumab demonstrates some beneficial effects in the treatment of graft‐versus‐host disease (GVHD). Sixteen patients with steroid refractory GVHD received daclizumab (1 mg/kg BW) on d 1, 2 (−5), 7, 14 and 21. Twelve patients suffered from grade III–IV acute GVHD and four patients from extensive chronic GVHD. Responses were observed in nine patients (six acute, three chronic GVHD). Fourteen out of 16 patients acquired infections during daclizumab treatment and three deaths were infection related. Daclizumab demonstrates limited activity and is associated with an increased incidence of infectious complications.

Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience

“…11,12 Dac was also found to be effective as second-line treatment of steroid-resistant GVHD in a limited number of reports that mostly referred to adult populations. [5][6][7][8][9][10] Response rates for aGVHD ranged between 29 and 68% in these series; however, data regarding the children who were included in these studies were not evaluable separately because they were not stratified by age. The only study on an exclusively paediatric population showed the safety and efficacy of Dac in treating both acute and chronic cutaneous GVHD.…”

“…In studies involving exclusively adults, or both adult and paediatric populations, [5][6][7][8][9][10] Dac is reportedly safe when used in children as rejection prophylaxis after organ transplantation, 11,12 and effective in the second-line treatment of refractory acute GVHD (aGVHD) and chronic GVHD (cGVHD).…”

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

“…The overall response rate was 67%, which was superior to the response rate observed by Willenbacher et al (50%). 20 Another study by Przepiorka et al evaluated daclizumab as a single agent in the treatment of steroid-refractory aGVHD. The overall response rate in their study was comparable to our overall response rate.…”

“…[14][15][16][17] The availability of humanized IL-2 receptor antibodies daclizumab and basiliximab offered the opportunity for prolonged administration of treatment with a low toxicity profile. [18][19][20] Two phase II trials have evaluated the efficiency of daclizumab in the treatment of steroidrefractory aGVHD. 19,20 In both studies, activity of daclizumab has been observed.…”

“…[18][19][20] Two phase II trials have evaluated the efficiency of daclizumab in the treatment of steroidrefractory aGVHD. 19,20 In both studies, activity of daclizumab has been observed. However, a significant failure rate on daclizumab as a single agent in treatment of steroid-refractory aGVHD was observed requiring additional immunosuppressive agents (ATG), and subsequent rates of infections and infectious mortality were significant.…”