TY - JOUR
T1 - Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease
AU - Shaughnessy, Paul J.
AU - Bachier, Carlos
AU - Grimley, Michael
AU - Freytes, Cesar O.
AU - Callander, Natalie S.
AU - Essell, James H.
AU - Flomenberg, Neal
AU - Selby, George
AU - Lemaistre, C. F.
N1 - Funding Information:
This study was funded in part by and had study drug supplied by Ligand Pharmaceuticals Inc. (San Diego, CA). The authors thank Brad Pollock, MPH, PhD, for his statistical help and research nurses Sherri Shade, RN, and Maureen Hougham, RN, for their hard work and dedication.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/3
Y1 - 2005/3
N2 - Acute graft-versus-host disease (aGVHD) is partly mediated through activated T cells, and these cells are known to express the high-affinity receptor for interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high-affinity IL-2R. We describe the results of a phase II study of denileukin diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were treated at dose level 1 (4.5 μg/kg daily on days 1-5 and then weekly on study days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0 μg/kg delivered on the same schedule). Dose level 2 was associated with grade 3/4 renal and hepatic toxicity and vascular leak syndrome, and no further patients were treated at this level. Dose level 1 was generally well tolerated. The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%) responded, all with a complete response at study day 36, and 6 patients (27%) responded at study day 100 (4 complete responses and 2 partial responses). Denileukin diftitox has promising activity in steroid-resistant aGVHD, and further study is warranted.
AB - Acute graft-versus-host disease (aGVHD) is partly mediated through activated T cells, and these cells are known to express the high-affinity receptor for interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high-affinity IL-2R. We describe the results of a phase II study of denileukin diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were treated at dose level 1 (4.5 μg/kg daily on days 1-5 and then weekly on study days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0 μg/kg delivered on the same schedule). Dose level 2 was associated with grade 3/4 renal and hepatic toxicity and vascular leak syndrome, and no further patients were treated at this level. Dose level 1 was generally well tolerated. The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%) responded, all with a complete response at study day 36, and 6 patients (27%) responded at study day 100 (4 complete responses and 2 partial responses). Denileukin diftitox has promising activity in steroid-resistant aGVHD, and further study is warranted.
KW - Denileukin diftitox
KW - Graft-versus-host disease
KW - Steroid resistance
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U2 - 10.1016/j.bbmt.2004.11.022
DO - 10.1016/j.bbmt.2004.11.022
M3 - Article
C2 - 15744237
AN - SCOPUS:14244265761
VL - 11
SP - 188
EP - 193
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 3
ER -