title: Biologic correlates of response and survival in patients with cutaneous T-cell lymphoma treated with denileukin diftitox.
abstract: BACKGROUND
  Denileukin diftitox, a fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domains of diphtheria toxin and human interleukin, resulted in a response rate of 30% in the phase III registration trial in patients with recurrent or persistent cutaneous T-cell lymphoma (CTCL). Little is known with regard to the biologic correlates of response or the impact of denileukin diftitox on disease progression and survival.
  
  
  METHODS
  In our single-center series of 37 patients with early- and advanced-stage disease with CTCL treated with denileukin diftitox at a dose of 9 microg/kg or 18 microg/kg per day, we observed an overall response rate of 51%.
  
  
  RESULTS
  In 8 patients with early-stage (< IIA) CTCL, there were 5 responses (62.5%), and the median survival has not been reached, with 70% of patients still alive at 46 months. In 29 patients with advanced-stage (>/= IIB) disease, there were 14 responses (49.3%), and the median survival was 31 months. Changes in the number of CD4+ CD25+ T-cell populations were observed in 7 of 19 responders, with no overall changes in the absolute lymphocyte counts during the course of therapy. Decrease in lactate dehydrogenase was strongly correlated with clinical response (P < 0.05).
  
  
  CONCLUSIONS
  Denilekin diftitox was a well-tolerated treatment in early- and advanced-stage CTCL and was not associated with detrimental immunologic efects on lymphocyte populations.
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts New England Medical Center, Boston, MA, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Chin
authors.forename: Francine M
authors.initials: FM
authors.lastname: Foss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000209:etiology / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox