CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma

J Invest Dermatol. 2006 Mar;126(3):575-83. doi: 10.1038/sj.jid.5700122.

Abstract

Denileukin diftitox (Ontak), a recombinant fusion protein of diphtheria toxin and ligand, IL-2, binds to the IL-2 receptor, is internalized, and causes cell death. Denileukin diftitox was approved for the treatment of cutaneous T-cell lymphomas (CTCLs) with CD25+ expression. We prospectively stained lesional skin biopsy specimens from 113 mycosis fungoides and Sézary Syndrome patients for activation markers CD25 and CD30 to correlate expression with clinical tumor-node metastasis (TNM) stage, histologic grade, and response to denileukin diftitox. High expression was defined as positivity of > or =20% of lesional T-cells using immunohistochemistry (IHC). CD25 and CD30 expression was more common in lesions from advanced patients (P = 0.04 and 0.002, respectively). Advanced TNM (T3 or T4) was significantly associated with intermediate-grade (P = 0.002) and large-cell transformation histology (P = 0.04). Of interest, clinical responses were observed in 78.5% of patients with high CD25 expression versus 20% with low to undetectable CD25 expression (P = 0.01) among 24 patients receiving standard 5-day infusions of denileukin diftitox at 18 microg/kg/day. These data suggest that high CD25 expression by IHC is associated with advanced CTCL and with clinical response to denileukin diftitox therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Bexarotene
  • Diphtheria Toxin / therapeutic use*
  • Female
  • Humans
  • Interleukin-2 / therapeutic use*
  • Ki-1 Antigen / analysis
  • L-Lactate Dehydrogenase / blood
  • Lymphoma, T-Cell, Cutaneous / drug therapy*
  • Lymphoma, T-Cell, Cutaneous / immunology
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Male
  • Middle Aged
  • Receptors, Interleukin-2 / analysis*
  • Recombinant Fusion Proteins / therapeutic use
  • Skin / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Tetrahydronaphthalenes / therapeutic use

Substances

  • Antineoplastic Agents
  • Diphtheria Toxin
  • Interleukin-2
  • Ki-1 Antigen
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Tetrahydronaphthalenes
  • denileukin diftitox
  • Bexarotene
  • L-Lactate Dehydrogenase