Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age

Br J Haematol. 2016 Sep;174(6):887-98. doi: 10.1111/bjh.14140. Epub 2016 Jun 7.

Abstract

The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96·6% (95% confidence interval: 95·4-97·5%) overall, improving from 92% pre-1998 to 99% post-1998 (P < 0·001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent.

Keywords: cohort study; historical comparisons; langerhans cell histiocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Child
  • Child, Preschool
  • Cohort Studies
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Histiocytosis, Langerhans-Cell / diagnosis
  • Histiocytosis, Langerhans-Cell / epidemiology*
  • Histiocytosis, Langerhans-Cell / mortality
  • Histiocytosis, Langerhans-Cell / therapy
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Population Surveillance
  • Standard of Care
  • Survival Analysis
  • Treatment Outcome