Treatment of lymphangiomas in children: an update of Picibanil (OK-432) sclerotherapy.

Picibanil (OK-432) is a sclerosing agent derived from a low-virulence strain of Streptococcus pyogenes that induces regression of macrocystic lymphangiomas. This report describes a prospective, nonrandomized trial to evaluate the efficacy of Picibanil in the treatment of 13 affected children ranging in age from 1 to 94 months. On average, 4.1 fluoroscopically guided intracystic injections were performed per child, with an average total dose of 0.56 mg of Picibanil. As judged by physical examination and radiographic studies, 5 children (42%) showed a complete or substantial response, and 2 children (16%) showed an intermediate response. No response was seen in 5 children (42%), 2 of whom had massive craniofacial lymphangioma. Factors that contribute to failure with Picibanil sclerotherapy are the presence of a significant microcystic component to the lesion, massive craniofacial involvement, and previous surgical resection. Macrocystic lymphangiomas of the infratemporal fossa or cervical area have the best response to therapy.

An update on the treatment of hemangiomas in children with interferon alfa-2a.

OBJECTIVE: To report the benefits and complications of subcutaneous interferon alfa-2a therapy for hemangiomas in children. DESIGN: Prospective nonrandomized trial. SETTING: Tertiary care pediatric referral center. PATIENTS: Twenty-four pediatric patients diagnosed with massive or life-threatening hemangiomas. INTERVENTIONS: Each patient received daily subcutaneous injections of interferon alfa-2a to a target dose of 3 million U/m2 of body surface area for a minimum of 4 months. Nineteen patients completed therapy and have received adequate follow-up. MAIN OUTCOME MEASURES: Clinical and radiographic comparisons before, during, and after therapy. Reduction in hemangioma size was graded as complete (>90%), substantial (50%-80%), intermediate (20%-40%), or no response (<10%). RESULTS: Mean age at institution of therapy was 9.6 months, and mean duration of treatment was 10.2 months. Most patients (70%) had not received prior therapy. Responses were as follows: complete, 8 patients (42%); substantial, 3 patients (16%), intermediate, 5 patients (26%); and no response, 3 patients (16%) (n = 19). During therapy, 5 patients (26%) developed neurological abnormalities: 3 had an unsteady gait, and 2 had fine motor deficits. Only 1 of these 5 patients required premature termination from the study, and the neurological abnormalities in all 5 patients resolved after treatment was discontinued. Two of the 4 patients with neurological findings who completed therapy demonstrated complete resolution of their hemangiomas. Patients who developed neurological abnormalities began interferon alfa-2a therapy at an earlier age (4.7 months) than patients without neurological difficulties (aged 11.1 months). The mean time from initiation of therapy to the appearance of neurological complications was 4.8 months. CONCLUSIONS: In pediatric patients with massive or life-threatening hemangiomas, interferon alfa-2a therapy is an effective treatment option. However, neurological evaluation before and during therapy with interferon alfa-2a should be performed owing to a significant incidence of neurological abnormalities (28%). Although all children with neurological findings demonstrated neurological recovery after discontinuation of therapy, we have changed our protocol and now more gradually increase the dosage of interferon alfa-2a up to 3 million U/m2 per day. The effect of this modification on the development of neurological abnormalities has not yet been determined.

Treatment of massive or life-threatening hemangiomas with recombinant alpha(2a)-interferon.

OBJECTIVE: To assess the response of massive, life-threatening, or function-impairing hemangiomas in pediatric patients receiving daily alpha(2a)-interferon subcutaneously. METHODS: The effect of 3 or more months of subcutaneous alpha(2a)-interferon (3 mU/m2) was prospectively evaluated in 10 patients with hemangiomas necessitating medical intervention. Hemangioma characteristics and extent were initially assessed by radiographic imaging in all but one patient. alpha(2a)-Interferon tolerance was monitored, and reduction in hemangioma size was recorded as marked (>50%), moderate (25% to 50%), or minimal (<25%). RESULTS: Hemangiomas were apparent at birth in 8 of 10 patients, and alpha(2a)-interferon was initiated at a median age of 4.5 months. Symptoms necessitating therapeutic intervention included congestive heart failure, airway obstruction, dysphagia, infection, failure to thrive, external auditory canal occlusion, visual axis impairment, and severe facial deformity. Four patients received treatment before referral that included systemic steroids (n = 2), intralesional steroids (n = 1), or surgical/laser excision (n = 2). alpha(2a)-Interferon therapy was well tolerated. Most patients had a temporary elevation in body temperature during the first month of therapy. One patient with anorexia required nasogastric feedings and a temporary reduction in her alpha(2a)-interferon dose. An additional patient with irritability was withdrawn from the study at his parents' request even though this symptom persisted after drug cessation. Hemangioma response to alpha(2a)-interferon was marked in six patients, moderate in two, and minimal in one whose lesion had features suggestive of a vascular malformation. Early signs of involution were usually evident within 6 weeks and often heralded by cutaneous blanching. alpha(2a)-interferon therapy was concluded in four patients after a mean duration of 20 months. CONCLUSIONS: Daily subcutaneous alpha(2a)-interferon is well tolerated in pediatric patients and appears effective in hastening involution of symptomatic hemangiomas. A significant response is unlikely in lesions with features suggestive of a vascular malformation.

Pleural effusion secondary to extramedullary haemopoiesis in a patient with idiopathic myelofibrosis responding to pleurodesis and hydroxyurea.

A case of idiopathic myelofibrosis presenting with a pleural effusion secondary to extramedullary haemopoeisis is described. Approximately 2 years following the diagnosis of his myeloprolioferative disorder the patient presented with dyspnoea. Physical signs were consistent with a pleural effusion which was confirmed radiologically. Cytology of the effusion fluid demonstrated myeloid precursors, including megakaryocytes. The effusion required repeated draining and a pleurodesis was undertaken in an attempt to prevent reaccumulation of the fluid. The procedure was successful and follow up over a period of 5 months demonstrated no recurrence of the pleural effusion on that side of the chest. An effusion later occurred on the other side but was managed conservatively by drainage. Hydroxyurea was introduced at that stage, but shortly afterwards the patient died from an unrelated cause. We review the literature on this uncommon complication of myelofibrosis and discuss the options available to treat the disorder.

OK-432 therapy for lymphangiomas.

OBJECTIVE: To assess the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. DESIGN: Nonrandomized trial; follow-up, 4 to 29 months. SETTING: Academic tertiary referral medical center. PATIENTS: Six children with presumed lymphangiomas; age range at initial treatment, 1 month to 7 years 10 months. INTERVENTION: Fluoroscopically guided cyst aspiration, cystography, and injection of OK-432. OUTCOME MEASURES: Clinical and radiographic comparisons before and after therapy. RESULTS: Complete response in 2 macrocystic lymphangiomas; no response in 3 microcystic lymphangiomas; and no response in 1 venous malformation. CONCLUSION: OK-432 sclerotherapy may be effective treatment for macrocystic lymphangiomas.