Bisphosphonate Therapy in Langerhans Cell Histiocytosis: An International Retrospective Descriptive Study
Notice bibliographique
Résumé
Abstract Introduction: Langerhans cell histiocytosis (LCH) is a monoclonal disorder characterized by proliferation and accumulation of atypical Langerhans cells and in up to 55% of all cases somatic mutations in BRAF proves to be the driver. Although uncommon, it is potentially fatal and carries significant morbidity. Bone involvement in LCH can be destructive, painful and often associated with pathologic fractures. There is no consensus in the treatment strategies for bone LCH which could vary from simple curettage with biopsy and/or intralesional steroids to more toxic systemic chemotherapy. However, the number of treatments for this disease is limited and other options need to be explored. Bisphosphonates are osteoclast inhibitors that can target certain osteoclast markers expressed by the multinucleated giant cells in the skin, bone and lymph nodes LCH lesions and can potentially be used to alleviate bone pain and possibly control the progression of disease activity. Purpose: To evaluate the efficacy and safety of bisphosphonates in treating bone LCH and extra-osseous disease. Methods: An international multicenter retrospective chart review was conducted in children and adults with LCH who received bisphosphonates between 1995 and 2014. Results: Eighteen patients were identified from 4 centers. All received bisphosphonates therapy either at diagnosis or at ≥ 1st reactivation. Median age at start of bisphosphonates was 23.7 years (range 5.7-38.3 years), and median follow-up time post-bisphosphonate therapy was 2.8 years (range 0.9-5.0 years). Patients had either single system bone disease or bone lesions as part of their multisystem disease. Patients were treated with different bisphosphonates with majority received zoledronic acid (n=10), followed by pamidronate (n=4) and alendronate (n= 3); one patient received both pamidronate and zoledronic acid. All patients reported significant reduction in pain to either no or mild pain after administration of bisphosphonates. Thirteen of 18 patients (72%) achieved complete remission (CR) in their bone lesions, including lesions in skin (n=1), lung (n=1) and pituitary (n=1); 2 had partial response and 3 had no response. Among the 13 CR patients, 12 had no active disease for a median of 4.1 years (range 2.8 - 5.1 years) and 1 developed radiographic neurodegeneration after 2 years. Bisphosphonate therapy was well tolerated by all patients with no major toxicity. Progression-free survival (PFS) was 75 ± 11% at 3 years, with a trend favoring better PFS (P=0.24) in patients with no or first reactivation compared with those having ≥ 2 reactivations. Conclusion: Bisphosphonates is a well-tolerated medication that can significantly improve bone pain in patients with bone LCH, and may even be effective in treating extra-osseous disease. A prospective randomized trial evaluating the role of bisphosphonates in multifocal bone LCH is warranted. Disclosures No relevant conflicts of interest to declare.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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