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 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. Pediatr Blood Cancer 2009; 53:1271–1276.