Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

OBJECTIVES: 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. STUDY DESIGN: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00010452.

Spastic diplegia and other motor disturbances in infants receiving interferon-alpha.

OBJECTIVE: To determine how frequently the use of -interferon (-IFN) is associated with the development of spastic diplegia. STUDY DESIGN AND METHODS: Meta-analysis of 600 English manuscripts published January 1991 to June 2002 reporting -IFN use in infants/children. We identified 3,113 children 18 years of age or younger and an estimated 3,055 children 12 years of age or younger who received -IFN therapy. Sixty-nine percent were treated for chronic hepatitis and 14% for vascular neoplasms. OUTCOME MEASURE: Neurologic examination to confirm spastic diplegia or a motor developmental disturbance other than spastic diplegia such as hyperactive deep tendon reflexes, gait disturbances, or impaired fine motor control. RESULTS: Including our index case, 11 of 441 children with vascular lesions developed spastic diplegia and an additional 16 of 441 developed a motor developmental disturbance. All of these children were less than 1 year of age at initiation of therapy. Mean age of initiation and duration of -IFN therapy were not significantly different between groups (P >.05); however, motor developmental disturbances improved with cessation of therapy, whereas spastic diplegia did not. No child receiving treatment for chronic hepatitis developed neurologic complications; however, only 49 children were less than 1 year of age at initiation of therapy. CONCLUSION: -IFN should not be used in infants under 1 year of age unless life-threatening conditions do not respond to any other form of treatment. If -IFN must be used, children should have monthly neurologic examinations. If a motor developmental disturbance is detected and -IFN therapy can be discontinued, it should be.

Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial.

OBJECTIVE: To describe and to determine the robustness of our study evaluating the efficacy of OK-432 (Picibanil) as a therapeutic modality for lymphangiomas. DESIGN AND SETTING: Prospective, randomized trial and parallel-case series at 13 US tertiary care referral centers. SUBJECTS: Thirty patients diagnosed as having lymphangioma. Ages in 25 ranged from 6 months to 18 years. Twenty-nine had lesions located in the head-and-neck area. INTERVENTION: Every patient received a 4-dose injection series of OK-432 scheduled 6 to 8 weeks apart unless a contraindication existed or a complete response was observed before completion of all injections. A control group was observed for 6 months. OUTCOME MEASURES: Successful outcome of therapy was defined as a complete or a substantial (>60%) reduction in lymphangioma size as determined by calculated lesion volumes on computed tomographic or magnetic resonance imaging scans. RESULTS: Overall, 19 (86%) of the 22 patients with predominantly macrocystic lymphangiomas had a successful outcome. CONCLUSIONS: OK-432 should be efficacious in the treatment of lymphangiomas. Our study design is well structured to clearly define the role of this treatment agent.