Nucleoside analogues in the therapy of Langerhans cell histiocytosis: a survey of members of the histiocyte society and review of the literature.
BACKGROUND
Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH).


METHODS
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.
Weitzman
S
S
Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. sheila.weitzman@sickkids.on.ca
Wayne
A S
AS
Arceci
R
R
Lipton
J M
JM
Whitlock
J A
JA
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000008:administration & dosage* / Q000009:adverse effects; D003625:Data Collection; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D008099:Liver / Q000187:drug effects; D008297:Male; D015649:Pentostatin / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015649:Pentostatin; D017338:Cladribine