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).

PROCEDURES:

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.

CONCLUSION:

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: Sheila Weitzman, Jorge Braier, Jean Donadieu, R Maarten Egeler, Nicole Grois, Stephan Ladisch, Ulrike Pötschger, David Webb, James Whitlock, Robert J Arceci
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 53 Issue 7 Pg. 1271-6 (Dec 15 2009) ISSN: 1545-5017 [Electronic] United States
• PMID: 19731321 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Antimetabolites
• Deoxyadenosines
• 2-Chloroadenosine
• 2'-chloro-2'-deoxyadenosine

Topics

• 2-Chloroadenosine (analogs & derivatives, therapeutic use)
• Antimetabolites (therapeutic use)
• Deoxyadenosines (therapeutic use)
• Female
• Histiocytes (drug effects)
• Histiocytosis, Langerhans-Cell (drug therapy)
• Humans
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Male
• Prospective Studies
• Risk
• Salvage Therapy
• Treatment Outcome