TY - JOUR
T1 - Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease
AU - Przepiorka, D.
AU - Kernan, N. A.
AU - Ippoliti, C.
AU - Papadopoulos, E. B.
AU - Giralt, S.
AU - Khouri, I.
AU - Lu, J. G.
AU - Gajewski, J.
AU - Durett, A.
AU - Cleary, K.
AU - Champlin, R.
AU - Andersson, B. S.
AU - Light, S.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Daclizumab, a humanized monoclonal IgG1 directed against the α chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1,8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [Cl], 13%-51%). Survival on day 120 was 29% (95% Cl, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% Cl, 24%- 71%), and survival on day 120 was 53% (95% Cl, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3+25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study.
AB - Daclizumab, a humanized monoclonal IgG1 directed against the α chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1,8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [Cl], 13%-51%). Survival on day 120 was 29% (95% Cl, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% Cl, 24%- 71%), and survival on day 120 was 53% (95% Cl, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3+25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study.
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U2 - 10.1182/blood.v95.1.83.001k18_83_89
DO - 10.1182/blood.v95.1.83.001k18_83_89
M3 - Article
C2 - 10607689
AN - SCOPUS:0033964862
SN - 0006-4971
VL - 95
SP - 83
EP - 89
JO - Blood
JF - Blood
IS - 1
ER -