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 Scopus citations

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 1 2005

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Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Shaughnessy, P. J., Bachier, C., Grimley, M., Freytes, C. O., Callander, N. S., Essell, J. H., Flomenberg, N., Selby, G., & 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