Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study.

BACKGROUND: Single-system (SS) disease is the most common presentation in Langerhans cell histiocytosis (LCH) with a heterogenous clinical picture and course. Mostly bone and rarely skin or lymph nodes are involved. PROCEDURE: One hundred and seventy patients with SS-LCH were registered in the DAL-HX 83/90 studies. They were diagnosed according to uniform diagnostic criteria and followed by a standardised schedule. RESULTS: Single bone lesions were most common (68%), followed by multiple bone lesions (19%), isolated skin disease (11%), and isolated lymph node involvement (4 patients). In the detection of bone lesions radiographic skeletal survey proved to be superior to bone scan (97% vs. 82%). Treatment comprised surgery, irradiation and local instillation of steroids, and standardised chemotherapy for multifocal bone disease. After initial therapy 81% of the patients remained disease free. Reactivations restricted to the skeleton occurred in 18% of both unifocal and multifocal bone disease. Two skin patients had a chronic course. Fatality occurred only in one infant with skin disease who progressed to multi-system disease. Twenty-five percent of all patients developed permanent consequences, which were already present at diagnosis in about half of these patients and comprised mainly orthopedic problems related to lesional sites. Diabetes insipidus occurred in 3% and anterior pituitary dysfunction in 2% of the patients. CONCLUSIONS: The course in SS%LCH was benign. In bone disease reactivations remained restricted to the skeleton and did not influence survival. However, reactivations had an impact on morbidity, as permanent consequences were mostly related to the site of disease activity. Med Pediatr Oncol 2001;37:108-114.

Response of untreated stage IV Wilms' tumor to single dose carboplatin assessed by "up front" window therapy.

A total of nine children with previously untreated stage IV Wilms' tumor of favorable histology were treated according to the Austrian/Hungarian Wilms' Tumor Protocol 89 and received a preoperative single dose of carboplatin as an "up front" window therapy. The treatment consisted of carboplatin as a single-dose of 600 mg/m2 over 30 minutes on day 1. Response evaluation by chest X-ray, serial CT scans, and sonography was performed on day 22. Investigation of the abdominal tumors revealed seven partial responses (78%), one nonresponse, and one progressive disease with a median tumor volume reduction of 62%. Response of metastases evaluated by CT scans was as follows: four complete remission, four partial response, and one nonresponse. Thrombocytopenia (WHO grade III 1, grade II 2, grade I 2) and leukocytopenia (WHO grade II 1, grade I 5) were the main side effects. No renal or liver toxicity were observed. The overall response rate after a preoperative single-dose of 600 mg/m2 carboplatin in untreated patients with stage IV Wilms' tumor is encouraging and the toxicity acceptable. This data indicate that carboplatin seems to be an additional effective drug in patients with previously untreated Wilms' tumor of favorable histology.

Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study.

Diabetes insipidus (DI) in Langerhans cell histiocytosis (LCH) is a common complication of unclear etiology. The incidence varies among different publications from 15% to 50%. In the prospective DAL-HX 83 study, 19 out of 199 patients (9.5%) registered with newly diagnosed LCH were diagnosed to have DI. All patients were stratified according to uniform criteria. One hundred and six patients with disseminated disease were treated with standardized polychemotherapy promptly after diagnosis. At the time of diagnosis of LCH, DI was already established in 8 out of 199 patients (4%). After diagnosis, DI occurred in only one out of the remaining 91 patients with localized disease (1%) and in 10 out of 100 remaining patients with disseminated disease (10%). In 8 patients, the onset of DI was associated with other signs of active LCH. The cumulative risk to develop DI after a median observation time of 5 years 3 months was 11%. Retrospective analysis of clinical features revealed multisystem involvement, skull and orbital lesions, and in particular intracranial extension from osseous lesions to constitute risk factors for DI. Magnetic resonance imaging studies (MRI) were available in 12 patients and showed abnormalities of the pituitary region in 10 children. In none of the patients with established DI was it reversed or ameliorated by any treatment. However, the rapid institution of systemic chemotherapy for disseminated disease seems to prevent the occurrence of DI and may be responsible for the low frequency of DI in the DAL-HX83 study.