title: Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group.
abstract: Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and long-term 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.
authors.affiliation: St. Anna Children's Hospital, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: A
authors.initials: A
authors.lastname: Heitger
authors.forename: N
authors.initials: N
authors.lastname: Grois
authors.forename: I
authors.initials: I
authors.lastname: Gatterer-Menz
authors.forename: S
authors.initials: S
authors.lastname: Ladisch
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003919:Diabetes Insipidus / Q000209:etiology; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D005047:Etoposide; D015122:Mercaptopurine; D011241:Prednisone; D008727:Methotrexate