Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience
1Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, India.
Insights
Cladribine (2-CDA) shows promise in treating relapsed or refractory Langerhans cell histiocytosis (LCH) in children. This pilot study found the drug to be active and well-tolerated, with promising survival rates.
Area of Science:
- Pediatric Oncology
- Hematology
- Immunology
Background:
- Langerhans cell histiocytosis (LCH) is a rare clonal bone marrow disorder.
- Current LCH treatment is often multimodal.
- 2-CDA exhibits anti-monocyte and immunomodulatory properties, making it a potential LCH therapeutic.
Purpose of the Study:
- To assess the efficacy and toxicity of 2-CDA in pediatric patients with relapsed or refractory LCH.
Main Methods:
- Pilot study of seven children with relapsed/refractory LCH.
- Patients received cladribine (2-CDA) intravenously daily for five days, repeated every four weeks.
- Median age was 2.25 years; some patients were heavily pretreated.
Main Results:
- Two patients (33%) achieved partial response (PR).
- Two patients (33%) showed stable disease (SD) with clinical improvement.
- No grade 3 or 4 hematologic toxicity was observed; five of seven patients were alive at follow-up.
Conclusions:
- Single-agent 2-CDA demonstrates activity and good tolerability in pediatric LCH.
- Further investigation into 2-CDA for relapsed/refractory LCH is warranted.
Background:
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH.
Aim:
To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH.
Setting And Design:
This is a pilot study and we present the initial data of the first seven patients treated at our institution.
Materials And Methods:
Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks.
Results:
After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died.
Conclusion:
Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.