title: 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society.
abstract: BACKGROUND
  A prospective phase II Histiocyte Society study, LCH-S-98, evaluated the efficacy of 2-chlorodeoxyadenosine (2-CdA) monotherapy as salvage therapy in Langerhans cell histiocytosis (LCH).
  
  
  METHODS
  Patients with poor and intermediate risk LCH not responsive to initial therapy and patients with low-risk chronic recurrent LCH were evaluated for response and survival after treatment with 2-6 courses of 2-CdA.
  
  
  RESULTS
  Forty-six patients (55%) had involvement of risk organs; lung, liver, spleen, or hematopoetic system (RO+), 37 (45%) were RO-. Twenty-two percent of RO+ patients had a good response while 44% progressed, 62% RO- patients responded, and 11% progressed. Two-year predicted survival is 48% for RO+, 97% for RO- patients, 100% for RO+ patients reactivating in non-risk organs, 67% for RO- patients reactivating in risk organs. Two-year pSU for the entire group is 68%. Seventy-three percent of patients with a poor response to 2-CdA died. Sixty-five percent patients >2 years old and 30% <2 years old survived. There was a median of 26 months from diagnosis to 2-CdA for responders compared to a median of 5 months for non-responders. Twenty-one percent of patients treated <12 months and 57% treated >12 months from diagnosis responded.
  
  
  CONCLUSIONS
  2-CdA is active in LCH. It produces a higher response rate in patients with low-risk multisystem or multifocal bone disease than those with risk organ involvement. "Risk" patients who fail to respond to 2-CdA have a high mortality. Patient age at 2-CdA therapy and length of time from diagnosis to 2-CdA significantly affect response and survival.
authors.affiliation: Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. sheila.weitzman@sickkids.ca
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Jorge
authors.initials: J
authors.lastname: Braier
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Nicole
authors.initials: N
authors.lastname: Grois
authors.forename: Stephan
authors.initials: S
authors.lastname: Ladisch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: David
authors.initials: D
authors.lastname: Webb
authors.forename: James
authors.initials: J
authors.lastname: Whitlock
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
mesh_terms: D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000963:Antimetabolites / Q000627:therapeutic use*; D003839:Deoxyadenosines / Q000627:therapeutic use*; D005260:Female; D006644:Histiocytes / Q000187:drug effects; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D011446:Prospective Studies; D012306:Risk; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000963:Antimetabolites; D003839:Deoxyadenosines; D015762:2-Chloroadenosine; C036854:2'-chloro-2'-deoxyadenosine