Efficacy of continuous infusion 2‐CDA (cladribine) in pediatric patients with Langerhans cell histiocytosis

Abstract

Patients with Langerhans cell histiocytosis (LCH) may behave differently depending on what sites are involved and the response or lack of response to earlier therapies. Therapy for high-risk patients or those with multiple reactivations continues to be challenging because of variable response rates and frequent toxicities. The goals of this study were to determine the long-term disease free survival in children with high-risk or multiply reactivated LCH treated with 2-CDA, and the toxicity of low dose continuous infusion (CI). Ten children with multiple reactivations or high-risk disease as defined by the Histiocyte Society were treated with CI 2-CDA and were evaluable for response and toxicity assessment. The starting dose of 2-CDA was 5 mg/M(2)/day for 3 days and escalated to 6.5 mg/M(2)/day for 3 days if tolerated. The maximum number of courses of 2-CDA per patient was limited to six. Fifty-two courses of 2-CDA were administered without difficulty. After the patient demonstrated no acute toxicity with the first administration of 2-CDA, the subsequent doses were given at home to all but one patient. All 10 patients had a clinical response, 9 documented by radiographic, or changes in physical exam or review of systems. Toxicity was limited to myelosuppression. Seven of the 10 patients required no additional therapy and remain disease free a median of 50 months from completing therapy. The three remaining patients are currently disease free after receiving other therapy. Further studies are needed to determine the role of 2-CDA in this patient population. 2-CDA can be given safely using home therapy, and may effective even in high-risk patients.

Langerhans Cell Histiocytosis in Children: A Single Center Experience from Turkey.

“…Previously used treatments that have demonstrated success include the intralesional injection of steroids 16 ; the combination of vincristine, prednisone, and cytarabine; and 2-chlorodeoxyadenosine as a single agent. 17 In our study, 3 of 9 patients with MS risk disease were treated with 2-CDA combined ARA-C as second line therapy. It has been reported that the combined therapy of 2-CDA and ARA-C may be useful for patients with refractory or recurrent disease.…”

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.…”