title: Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.
abstract: OBJECTIVE
  To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations.
  
  
  METHODS
  A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers.
  
  
  METHODS
  182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%).
  
  
  RESULTS
  Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001).
  
  
  CONCLUSIONS
  OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00010452.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. richard-smith@uiowa.edu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Smith
authors.forename: M Bridget
authors.initials: MB
authors.lastname: Zimmerman
authors.forename: Diane K
authors.initials: DK
authors.lastname: Burke
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Bauman
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sato
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007223:Infant; D044148:Lymphatic Abnormalities / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010844:Picibanil / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012449:Safety; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D010844:Picibanil