title: CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma.
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.
authors.affiliation: Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4095, USA.
authors.forename: Rakhshandra
authors.initials: R
authors.lastname: Talpur
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Jones
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Alencar
authors.forename: Narin
authors.initials: N
authors.lastname: Apisarnthanarax
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Herne
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077610:Bexarotene; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D017730:Ki-1 Antigen / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D017730:Ki-1 Antigen; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D013764:Tetrahydronaphthalenes; C078456:denileukin diftitox; D000077610:Bexarotene; D007770:L-Lactate Dehydrogenase