TREATMENT STRATEGY FOR DISSEMINATED LANGERHANS CELL HISTIOCYTOSIS

Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and long-term continuatio n of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clin ical trial (DAL HX-83). One hundred six newly diagnosed patients were stratified into three risk groups (A: multifocal bone disease [n = 28] ; B: soft tissue involvement without organ dysfunction [n = 57]; C: or gan dysfunction [n = 21]). All patients received an identical initial 6-week treatment (etoposide [VP-16], prednisone, and vinblastine), and continuation treatment for 1 year, slightly adapted according to stra tification at diagnosis. It included oral 6-mercaptopurine and eight p ulses of vinblastine and prednisone for all patients, plus VP-16 in gr oup B and VP-16 and methotrexate in group C. Eighty-nine percent and 9 1% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolu tion was rapid (median 4 months) and independent of disease severity. The frequency of recurrence after initial resolution was low (12%, 23% , and 42% in groups A, B, and C); overall fully 77% of patients have r emained free of recurrence. Permanent consequences developed after dia gnosis in 20% of the patients. Diabetes insipidus after initiation of treatment occurred in only 10% of patients. Mortality (9%) was limited to patients of groups B (two patients) and C (eight patients). Finall y, among the 106 patients treated by DAL HX-83 none have developed a m alignancy (median follow-up 6 years, 9 months). The shorter duration o f active disease, low rate of recurrence and permanent consequences, a nd improved survival among patients with poor prognosis support the st rategy of rapid initiation of a predefined prolonged treatment upon th e diagnosis of disseminated LCH. (C) 1994 Wiley-Liss, Inc.