Treatment strategy for disseminated langerhans cell histiocytosis

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Abstract
Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and longterm continuation of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clinical 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: organ 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 stratification at diagnosis. It included oral 6‐mercaptopurine and eight pulses of vinblastine and prednisone for all patients, plus VP‐16 in group B and VP‐16 and methotrexate in group C. Eighty‐nine percent and 91% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolution 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 remained free of recurrence. Permanent consequences developed after diagnosis 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). Finally, among the 106 patients treated by DAL HX‐83 none have developed a malignancy (median follow‐up 6 years, 9 months). The shorter duration of active disease, low rate of recurrence and permanent consequences, and improved survival among patients with poor prognosis support the strategy of rapid initiation of a predefined prolonged treatment upon the diagnosis of disseminated LCH.