Journal
ORPHANET JOURNAL OF RARE DISEASES
Volume 17, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13023-022-02276-y
Keywords
Langerhans cell histiocytosis; Macrophage activation syndrome-hemophagocytic lymphohistiocytosis; BRAF-V600E mutation; Dabrafenib; Outcome
Funding
- National Natural Science Foundation of China [82070202, 82141119]
- Capital's Funds for Health Improvement and Research [2020-2-2093, 2022-2-1141]
- Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority [XTZD20180201]
- Funding for Reform and Development of Beijing Municipal Health Commission
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This study retrospectively described the clinical-biological characteristics of 28 pediatric LCH patients with MAS-HLH and analyzed the treatment outcomes of second-line chemotherapy and targeted therapy for BRAF-V600E-positive patients. The study found that the BRAF inhibitor dabrafenib provides a promising treatment option for LCH patients with MAS-HLH.
Background Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients. Results LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034). Conclusions LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.
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