Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children

• Published in: Journal of cancer research and clinical oncology Vol. 148; no. 9; pp. 2517 - 2527
• Main Authors: Yang, Ying, Wang, Chanjuan, Wang, Dong, Cui, Lei, Li, Na, Lian, Hongyun, Ma, Honghao, Zhao, Yunze, Zhang, Liping, Liu, Wei, Wang, Yizhuo, Wu, Wanshui, Zhang, Rui, Li, Zhigang, Wang, Tianyou
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022; Springer Nature B.V
• Subjects: Autoimmune diseases; Cancer Research; Children; Hematology; Histiocytosis; Internal Medicine; Langerhans cell histiocytosis; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Original Article – Clinical Oncology; Patients; Prognosis; Langerhans cell histiocytosis; Mutation; Children
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03810-4

Purpose To analyze the genetic and clinical features of children with MAP2K1 -mutated Langerhans cell histiocytosis (LCH). Methods We compared the clinical features of 37 children with MAP2K1 -mutated LCH with those of the BRAF V600E mutation group ( n  = 133) and no known mutation group ( n  = 59) in the same period. Results We found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53–62 and p.98–103. The most common mutation site was c.172_186del (12/37). Compared with the BRAF V600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single-system multiple bone involvement ( P  = 0.022), with later disease onset ( P  = 0.029) as well as less involvement of risk organs, especially liver ( P  = 0.024). There was no significant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of first-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1 -mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769–22.526), P  = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P  = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P  = 0.688) and limb bone involvement (5/12 vs. 5/25, P  = 0.240), were not correlated to disease progression or relapse. Conclusion The children with MAP2K1- mutated LCH have specific clinical features requiring clinical stratification and precise treatment. MAP2K1 -mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.