Deepak Chellapandian, Polyzois Makras, Gregory Kaltsas, Cor van den Bos, Lamia Naccache, Raajit Rampal, Anne-Sophie Carret, Sheila Weitzman, R. Maarten Egeler, Oussama Abla
  • Deepak Chellapandian
    Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada, Canada |
  • Polyzois Makras
    Department of Endocrinology & Diabetes, 251 Hellenic Airforce & VA General Hospital, Athens, Greece, Greece
  • Gregory Kaltsas
    Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece, Greece
  • Cor van den Bos
    Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands, Netherlands
  • Lamia Naccache
    Hémato-oncologue pédiatrique, Centre hospitalier universitaire de Québec, Quebec City, Canada, Canada
  • Raajit Rampal
    Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, USA, United States
  • Anne-Sophie Carret
    Division of Hematology-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, Canada
  • Sheila Weitzman
    Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada, Canada
  • R. Maarten Egeler
    Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada, Canada
  • Oussama Abla
    Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada, Canada


Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.


Langerhans cell histiocytosis; bisphosphonate; chemotherapy; bone pain of LCH; disease reactivation

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Published: 2016-07-01 00:00:00
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