Cyclosporine therapy for refractory Langerhans cell histiocytosis

Optimal treatment for Langerhans Cell Histiocytosis (LCH) has not yet been established. Preliminary reports suggest some effect of cyclosporine (CSA), both alone or in combination with steroids and/or vinblastine, in untreated cases. Twelve children (6 females and 6 males, age at diagnosis 3 months to 4 years) with biopsy proven, systemic LCH received oral CSA (12 mg/kg/day in two divided doses given daily) as a second-line therapy following chemotherapy including vinblastine and/or etoposide (10 cases) or steroid alone (one case); one child was not pretreated. A total of 16 CSA courses were administered to the 12 patients: 8 were completed, 4 were interrupted as unsuccessful, and 4 are still ongoing. CSA related toxicity consisted of hypertrichosis and transient hypertension and was never limiting. Treatment was associated with a clinical response in 8/12 patients: 3 had a complete response and are off therapy, and 5 had a partial response; disease reactivation following first favorable response required additional CSA courses in 3 patients. Four patients failed to respond to CSA: two died of progressive disease, while two had a favorable response to CSA + VP16. Favorable response to CSA was not related to CSA trough and peak levels and was usually observed during the first 2 weeks of CSA therapy. CSA is effective for treatment of LCH also in pretreated children with progressive disease including life-threatening organ dysfunction. Long-lasting complete remission may be achieved after 6 to 12 months of CSA therapy. When disease reactivation occurs after treatment withdrawal, a second course may be followed by favorable response. As minimal or no adverse effects are observed during or after prolonged CSA therapy, this may also be safely used in young patients.