Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease

Abstract

Background Existing therapies for recurrent or refractory histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai-Dorfman disease (RDD), have limited effectiveness. We report our experience with using clofarabine as therapy in children with recurrent or refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4 patients), and RDD (3 patients). Methods Patients treated with clofarabine for LCH, JXG, or RDD by Texas Children’s Hospital physicians or collaborators between May 2011 and January 2013 were reviewed for response and toxicity. Results Patients were treated with a median of 3 chemotherapeutic regimens prior to clofarabine. Clofarabine was typically administered at 25 mg/m2/day for five days. Cycles were administered every 28 days for a median of six cycles (range: 2–8 cycles). Seventeen of eighteen patients are alive. All surviving patients showed demonstrable improvement after 2–4 cycles of therapy, with eleven (61%) complete responses, four (22%) partial responses, and two patients still receiving therapy. Five patients experienced disease recurrence, but three of these subsequently achieved complete remission. All patients with JXG and RDD had complete or partial response at conclusion of therapy. Side effects included neutropenia in all patients. Recurring but sporadic toxicities included prolonged neutropenia, severe vomiting, and bacterial infections. Conclusion Clofarabine has activity against LCH, JXG, and RDD in heavily pretreated patients, but prospective multi-center trials are warranted to determine long-term efficacy, optimal dosing, and late toxicity of clofarabine in this population.

How I treat Langerhans cell histiocytosis

“…69 Case series have reported clofarabine monotherapy as a successful salvage therapy in LCH patients who failed to achieve a durable response to cladribine or cytarabine. 48,66,70 One-year progression-free survival was 76% for 11 LCH patients who had failed a median of 3 previous chemotherapy strategies, and most patients (64%) had complete responses after 6 months of therapy. 48 Data from phase 1 studies define the maximum tolerated dose in children as 52 mg/m 2 per day 3 5 days.…”

“…48,66,70 One-year progression-free survival was 76% for 11 LCH patients who had failed a median of 3 previous chemotherapy strategies, and most patients (64%) had complete responses after 6 months of therapy. 48 Data from phase 1 studies define the maximum tolerated dose in children as 52 mg/m 2 per day 3 5 days. 71 The majority of patients in the LCH series received 25 mg/m 2 per day (5 days per cycle) for 6 cycles as outpatients, with minimal toxicity beyond predicted cytopenias.…”

“…Mass lesions of the brain may respond to vinblastine/prednisone, cladribine, cytarabine, and clofarabine. 47,48,51,52 Although there has been no trial to suggest which of these regimens might be the best, cytarabine has been effective in a majority of patients and has possible benefit against ND LCH.…”

“…29 If patients have refractory or recurrent disease with vinblastine/prednisone, subsequent treatment with cytarabine or clofarabine may be effective. 47,48 Special situations CNS lesions. DI is the most frequent initial sign of LCH in the CNS.…”

Imaging Features of Juvenile Xanthogranuloma of the Pediatric Head and Neck

“…undefined; however, treatment regimens similar to those used for LCH have been used successfully. [27][28][29] …”