TY - JOUR
T1 - Nucleoside analogues in the therapy of langerhans cell histiocytosis
T2 - A survey of members of the histiocyte society and review of the literature
AU - Weitzman, Sheila
AU - Wayne, Alan S.
AU - Arceci, Robert
AU - Lipton, Jeffrey M.
AU - Whitlock, James A.
AU - De Rossi, Giulio
PY - 1999/11
Y1 - 1999/11
N2 - 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/m2/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/m2/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.
AB - 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/m2/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/m2/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.
KW - 2-CdA
KW - Langerhans cell histiocytosis
KW - Salvage therapy
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U2 - 10.1002/(SICI)1096-911X(199911)33:5<476::AID-MPO7>3.0.CO;2-Q
DO - 10.1002/(SICI)1096-911X(199911)33:5<476::AID-MPO7>3.0.CO;2-Q
M3 - Article
C2 - 10531572
AN - SCOPUS:0032758108
SN - 0098-1532
VL - 33
SP - 476
EP - 481
JO - Medical and Pediatric Oncology
JF - Medical and Pediatric Oncology
IS - 5
ER -