Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Orphanet journal of rare diseases - 17(2022), 1 vom: 04. Apr., Seite 151 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Dong [VerfasserIn] |
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| Links: |
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| Themen: |
BRAF-V600E mutation |
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| Anmerkungen: |
Date Completed 06.04.2022 Date Revised 18.05.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s13023-022-02276-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339091185 |
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| 100 | 1 | |a Wang, Dong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 18.05.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRAF-V600E mutation | |
| 650 | 4 | |a Dabrafenib | |
| 650 | 4 | |a Langerhans cell histiocytosis | |
| 650 | 4 | |a Macrophage activation syndrome-hemophagocytic lymphohistiocytosis | |
| 650 | 4 | |a Outcome | |
| 700 | 1 | |a Chen, Xi-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Ang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Chun-Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Hong-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Hong-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiao-Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chan-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tian-You |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhi-Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Rui |e verfasserin |4 aut | |
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