Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review

Br J Haematol. 2020 Jun;189(5):869-878. doi: 10.1111/bjh.16449. Epub 2020 Mar 19.


Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m2 . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).

Keywords: 2-chlorodeoxyadenosine; Langerhans cell histiocytosis; adult; chemotherapy; treatment.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Age of Onset
  • Aged, 80 and over
  • Antimetabolites / adverse effects
  • Antimetabolites / therapeutic use*
  • Cladribine / adverse effects
  • Cladribine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • France / epidemiology
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / mortality
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Sepsis / etiology
  • Sepsis / mortality
  • Virus Diseases / etiology


  • Antimetabolites
  • Immunosuppressive Agents
  • Cladribine