Nucleoside analogues in the therapy of Langerhans cell histiocytosis: a survey of members of the histiocyte society and review of the literature

Med Pediatr Oncol. 1999 Nov;33(5):476-81. doi: 10.1002/(sici)1096-911x(199911)33:5<476::aid-mpo7>3.0.co;2-q.

Abstract

Background: Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH).

Procedure: To assess the efficacy of 2-CdA and 2'-DCF as salvage therapy for LCH, a survey of members of the Histiocyte Society and a literature review were undertaken. Twenty-three patients treated with 2-CdA and 4 treated with 2'-DCF were found, age range 2 months to 49 years.

Results: All 15 survey patients had multiorgan involvement, and 14 were heavily pretreated. Doses of 2-CdA ranged from 0.1 mg/kg/day continuous infusion for 5-7 days (majority of patients) to 13 mg/m(2)/day for 5 days, for 1-6 courses. One of the 15 patients had an early death, 5 had no response (NR), 3 had partial response (PR), and 6 achieved complete response (CR). Among 8 published patients, 7 achieved stable CR and 1 NR. Among 4 patients treated with 2'-DCF (4 mg/m(2)/week for 8 weeks then q 2 weekly), 2 achieved CR for 16+ and 18+ months and 2 PR for 2 and 5 months. Toxicity consisted mainly of combined myelo- and immunosuppression but no significant infections occurred and there were no toxic deaths. A cumulative thrombocytopenia was noted, which in 1 case took up to 6 months to resolve. Transient gastrointestinal toxicity and elevation of liver enzymes was seen, and 2 patients developed renal tubular acidosis. The peripheral neuropathy reported in adult patients receiving high doses was not seen.

Conclusions: 2-CdA and 2'-DCF appear to have a useful role in LCH and are worthy of prospective trial in patients unresponsive to routine therapy.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Child
  • Child, Preschool
  • Cladribine / administration & dosage*
  • Cladribine / adverse effects
  • Data Collection
  • Female
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / pathology
  • Humans
  • Infant
  • Liver / drug effects
  • Male
  • Pentostatin / administration & dosage*
  • Pentostatin / adverse effects
  • Thrombocytopenia / chemically induced
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Pentostatin
  • Cladribine