Buhtoiarov Ilia N, Minkov Milen, Vali Reza, Abla Oussama
Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Pediatric Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, R3-118, Cleveland, OH, 44195, USA.
Department of Pediatric Hematology/Oncology, University Clinic of Pediatrics, Medical University of Vienna, Vienna, Austria.
Int J Hematol. 2025 Apr 27. doi: 10.1007/s12185-025-03989-z.
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with heterogeneous presentations. The discovery of BRAFV600E and other MAPK pathway mutations drastically transformed the treatment landscape, especially for high-risk LCH and CNS-LCH. While treatment strategies for children and adults are somewhat similar, response assessment methodologies remain highly dichotomized.Currently, separate treatment response criteria exist for children and adults, especially in therapeutic trials. Considering the rapid evolution of targeted MAPK-inhibitor therapies, along with ultrasensitive detection of minimal residual disease biomarkers (e.g., circulating BRAFV600E-encoding DNA) and sophisticated imaging tools (18F-FDG-PET and whole-body MRI), harmonization of response criteria in LCH is clearly warranted. The Histiocyte Society Global LCH Treatment Response Harmonization Task Force, a collaborative network of pediatric and adult LCH experts, is set to propose updated pediatric LCH treatment response criteria, which will also serve as the foundation for a universal response assessment tool for pediatric and adult LCH. In this review, we focus on the past, present, and likely future of response assessment in LCH patients, and discuss needs that remain unmet in the targeted therapy era.
朗格汉斯细胞组织细胞增多症（LCH）是一种临床表现多样的炎症性髓系肿瘤。BRAFV600E及其他丝裂原活化蛋白激酶（MAPK）通路突变的发现极大地改变了治疗格局，尤其是对高危LCH和中枢神经系统LCH的治疗。虽然儿童和成人的治疗策略有些相似，但疗效评估方法仍存在很大差异。目前，儿童和成人有各自独立的治疗反应标准，尤其是在治疗试验中。鉴于靶向MAPK抑制剂疗法的快速发展，以及对微小残留病生物标志物（如循环中BRAFV600E编码DNA）的超灵敏检测和先进的成像工具（18F-氟代脱氧葡萄糖正电子发射断层扫描[18F-FDG-PET]和全身磁共振成像[MRI]），LCH疗效标准的统一显然是必要的。组织细胞协会全球LCH治疗反应统一工作组是一个由儿科和成人LCH专家组成的合作网络，该工作组将提出更新后的儿科LCH治疗反应标准，这也将成为儿科和成人LCH通用疗效评估工具的基础。在这篇综述中，我们重点关注LCH患者疗效评估的过去、现在和未来，并讨论在靶向治疗时代仍未满足的需求。
