Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

D. Przepiorka, N. A. Kernan, C. Ippoliti, E. B. Papadopoulos, S. Giralt, I. Khouri, J. G. Lu, J. Gajewski, A. Durett, K. Cleary, R. Champlin, B. S. Andersson, S. Light

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalBlood
Volume95
Issue number1
StatePublished - Jan 1 2000
Externally publishedYes

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Interleukin-2 Receptor alpha Subunit
Graft vs Host Disease
Grafts
Lymphocytes
Antibodies
Interleukin-2 Receptors
Therapeutics
Survival
Refractory materials
daclizumab
Blood
Immunoglobulin G
Steroids
Confidence Intervals
Serum

ASJC Scopus subject areas

  • Hematology

Cite this

Przepiorka, D., Kernan, N. A., Ippoliti, C., Papadopoulos, E. B., Giralt, S., Khouri, I., ... Light, S. (2000). Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood, 95(1), 83-89.

Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. / Przepiorka, D.; Kernan, N. A.; Ippoliti, C.; Papadopoulos, E. B.; Giralt, S.; Khouri, I.; Lu, J. G.; Gajewski, J.; Durett, A.; Cleary, K.; Champlin, R.; Andersson, B. S.; Light, S.

In: Blood, Vol. 95, No. 1, 01.01.2000, p. 83-89.

Research output: Contribution to journalArticle

Przepiorka, D, Kernan, NA, Ippoliti, C, Papadopoulos, EB, Giralt, S, Khouri, I, Lu, JG, Gajewski, J, Durett, A, Cleary, K, Champlin, R, Andersson, BS & Light, S 2000, 'Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease', Blood, vol. 95, no. 1, pp. 83-89.
Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000 Jan 1;95(1):83-89.
Przepiorka, D. ; Kernan, N. A. ; Ippoliti, C. ; Papadopoulos, E. B. ; Giralt, S. ; Khouri, I. ; Lu, J. G. ; Gajewski, J. ; Durett, A. ; Cleary, K. ; Champlin, R. ; Andersson, B. S. ; Light, S. / Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. In: Blood. 2000 ; Vol. 95, No. 1. pp. 83-89.
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abstract = "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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