Treatment of children with Langerhans cell histiocytosis with 2‐chlorodeoxyadenosine

Abstract

Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a signi®cant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5±7 mg/m 2 /day for 5 days, repeated every 21±28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3±25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study. Am.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: A single institutional experience

“…These results further confirm and extend the observations made in other studies of 2-CDA in children with LCH. [9][10][11] 2-CDA is a purine analog resistant to the catalyzation by enzyme ADA. The metabolite inhibits the DNA synthesis.…”

“…This strong rationale led to the usage of 2-CDA in histiocytic disorders. Many small studies [9][10][11][12]16,17] have been conducted which are summarized in Table 3.…”

“…The response rate in these studies has ranged from 33% to 100%. [9][10][11][12]16,17] The response rate (33%) in our study has been modest which could potentially be due to a small patient number and short follow up as it has been observed that response with 2-CDA may continue to occur even months after the treatment cessation. The dose and schedule is unlikely to have had any impact on the response since studies in adults have shown that moderate doses in 2-h schedule may be as effective as a 24-h continuous schedule.…”

“…[8] Many small recent studies have shown this drug to have a promising activity in LCH. [9][10][11][12] We, therefore, have evaluated the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH in a pilot study and hereby present the initial data of the first seven patients treated at our institution.…”

Histiocytic Sarcoma in a 3-Year-Old Male: A Case Report

“…Several studies have shown the efficacy of 2CdA when used against LCH. [14][15][16] Because histiocytes are derived from monocytes, we are hopeful that histiocytic sarcoma may show a favorable response to 2CdA. Although there are no published studies suggesting the efficacy of 2CdA in histiocytic sarcoma, we are aware of an adult patient with this entity who remained free of the disease for 6 months after 5 cycles of 2CdA.…”