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

Stephen J. Simko, Huy D. Tran, Jeremy Jones, Mrinalini Bilgi, Lynda Kwon Beaupin, Don Coulter, Timothy Garrington, Timothy L. Mccavit, Colin Moore, Francisco Rivera-Ortegón, Linda Shaffer, Linda Stork, Lucie Turcotte, Esperanza C. Welsh, M. John Hicks, Kenneth L. Mcclain, Carl E. Allen

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63 Scopus citations

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 three chemotherapeutic regimens prior to clofarabine. Clofarabine was typically administered at 25mg/m2/day for 5 days. Cycles were administered every 28 days for a median of six cycles (range: 2-8 cycles). Seventeen of 18 patients are alive. All surviving patients showed demonstrable improvement after two to four cycles of therapy, with 11 (61%) complete responses, 4 (22%) partial responses, and 2 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.

Original languageEnglish (US)
Pages (from-to)479-487
Number of pages9
JournalPediatric Blood and Cancer
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2014

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Keywords

  • Clofarabine
  • Histiocytosis
  • Juvenile xanthogranuloma
  • Langerhans cell histiocytosis
  • Rosai-Dorfman disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Simko, S. J., Tran, H. D., Jones, J., Bilgi, M., Beaupin, L. K., Coulter, D., Garrington, T., Mccavit, T. L., Moore, C., Rivera-Ortegón, F., Shaffer, L., Stork, L., Turcotte, L., Welsh, E. C., Hicks, M. J., Mcclain, K. L., & Allen, C. E. (2014). Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatric Blood and Cancer, 61(3), 479-487. https://doi.org/10.1002/pbc.24772