Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 188-193 |
| Number of pages | 6 |
| Journal | Biology of Blood and Marrow Transplantation |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2005 |
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Keywords
- Denileukin diftitox
- Graft-versus-host disease
- Steroid resistance
ASJC Scopus subject areas
- Transplantation
Cite this
Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease. / Shaughnessy, Paul J.; Bachier, Carlos; Grimley, Michael; Freytes, Cesar O.; Callander, Natalie S.; Essell, James H.; Flomenberg, Neal; Selby, George; Lemaistre, C. F.
In: Biology of Blood and Marrow Transplantation, Vol. 11, No. 3, 03.2005, p. 188-193.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=14244265761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14244265761&partnerID=8YFLogxK
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 -