Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease

Paul J. Shaughnessy, Carlos Bachier, Michael Grimley, Cesar O. Freytes, Natalie S. Callander, James H. Essell, Neal Flomenberg, George Selby, C. F. Lemaistre

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)188-193
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume11
Issue number3
DOIs
StatePublished - Mar 2005

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Graft vs Host Disease
Steroids
Therapeutics
Interleukin-2 Receptors
Blood Vessels
denileukin diftitox
Appointments and Schedules
Lymphocytes
T-Lymphocytes
Kidney
Liver

Keywords

  • Denileukin diftitox
  • Graft-versus-host disease
  • Steroid resistance

ASJC Scopus subject areas

  • Transplantation

Cite this

Shaughnessy, P. J., Bachier, C., Grimley, M., Freytes, C. O., Callander, N. S., Essell, J. H., ... Lemaistre, C. F. (2005). Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease. Biology of Blood and Marrow Transplantation, 11(3), 188-193. https://doi.org/10.1016/j.bbmt.2004.11.022

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 journalArticle

Shaughnessy, PJ, Bachier, C, Grimley, M, Freytes, CO, Callander, NS, Essell, JH, Flomenberg, N, Selby, G & Lemaistre, CF 2005, 'Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease', Biology of Blood and Marrow Transplantation, vol. 11, no. 3, pp. 188-193. https://doi.org/10.1016/j.bbmt.2004.11.022
Shaughnessy, Paul J. ; Bachier, Carlos ; Grimley, Michael ; Freytes, Cesar O. ; Callander, Natalie S. ; Essell, James H. ; Flomenberg, Neal ; Selby, George ; Lemaistre, C. F. / Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease. In: Biology of Blood and Marrow Transplantation. 2005 ; Vol. 11, No. 3. pp. 188-193.
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