Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

Br J Haematol. 2020 Dec;191(5):825-834. doi: 10.1111/bjh.16944. Epub 2020 Jul 22.

Abstract

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO-) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO- LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3-19·7 years) and the median follow-up after was 5·4 years (range, 0·6-15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO- LCH. Appropriate management of induced immune deficiency is mandatory.

Keywords: 2-chlorodeoxyadenosine; Langerhans cell histiocytosis; children; cladribine; long-term follow-up.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cladribine / administration & dosage*
  • Cladribine / adverse effects
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • France
  • Histiocytosis, Langerhans-Cell / blood
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / mortality*
  • Humans
  • Infant
  • Lymphocyte Count
  • Male
  • Registries*
  • Survival Rate

Substances

  • Cladribine