Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction.

The aim of this study was to assess the efficacy and adverse effects of 2-chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (Ara-C) in children with refractory Langerhans cell histiocytosis (LCH) and haematopoietic dysfunction. Ten patients, with a median age at diagnosis of 0.5 years, were enrolled in this study. Treatment comprised at least two courses of Ara-C (1000 mg/m(2)/d) and 2-CdA (9 mg/m(2)/d) administered for 5d every 4 weeks; subsequent median follow-up was 2.8 years (range 0.03-6.4 years). Among the 7 patients who received at least two courses of therapy, disease activity decreased in 6 patients, and control of disease was achieved in all patients after a median delay of 5.5 months. All patients suffered World Health Organisation (WHO) grade 4 haematological toxicity. Two septic deaths occurred shortly after administration of the first course of 2-CdA/Ara-C; a third patient was withdrawn from the trial after the first course and subsequently died following haematopoietic stem cell transplantation. This series is small, but we conclude that 2-CdA and Ara-C combined chemotherapy probably has major activity in childhood refractory Langerhans cell histiocytosis.

A new clinical score for disease activity in Langerhans cell histiocytosis.

OBJECTIVE: To develop an objective tool for assessing disease activity in patients with Langerhans cell histiocytosis (LCH). METHOD: Scoring system was developed and applied to a database containing information on 612 patients. RESULTS: At diagnosis, the score distribution was highly asymmetrical: the score was between 0 and 2 in 74% of cases, 3-6 in 16%, 7-10 in 3%, and more than 10 in 6%. The 5-year mortality rates were 1, 4.4, and 43.4%, respectively, among patients with initial scores of 0-2, 3-6, and >6. Stability or an increase of the score at 6 weeks was highly predictive of death among patients with initial scores above 6, while score stability had no significant impact on vital outcome among patients with low or moderate scores at diagnosis. CONCLUSIONS: This LCH disease activity score provides an objective tool for assessing disease severity, both at diagnosis and during follow-up and treatment.