Treatment Optimization for Children with De Novo and Relapsed Langerhans cell Histiocytosis (LCH) as Part of the International Collaborative Study LCH IV

朗格汉斯细胞组织细胞增多症（LCH）是一种恶性疾病，影响3-5/ 100万儿童。先前的试验通过强化诱导化疗降低了死亡率，但高达40%的LCH患者仍然会重新激活，并且高达50%的患者会出现永久性后遗症。拟议的III期开放标签多中心随机试验将评估所有新生LCH（第一级）患者的维持治疗策略[延长（12个月vs 24个月）±6-巯基嘌呤强化]，并将评估一种新的化合物（吲哚美辛）用于复发LCH（第二级）患者以降低复发率和永久性发病率。主要终点是无再激活生存期，次要终点包括毒性和永久性后果的风险。虽然许多患者有显著的发病率，但LCH是一种罕见的疾病。仅德国没有足够的患者进行足够有力的研究，因此必须在国际环境中进行。一项合作试验（LCH-IV）已经在几个国家开始，德国参与拟议的研究框架是必要的，因为德国预计将招募100 - 20%的患者。该试验可能最终降低复发和永久性后遗症的风险，从而改善LCH患者的生活质量，减轻社会经济负担。

Langerhans cell Histiocytosis (LCH) is a malignant disorder affecting 3-5/1 million children. Previous trials decreased mortality by intensifying induction chemotherapy, but up to 40% of patients with LCH still reactivate, and permanent sequelae occur in up to 50% of patients. The proposed phase III open-label multicenter randomized trial will evaluate strategies of maintenance therapy [prolongation (12 vs 24 months)±intensification with 6-mercaptopurine] in all patients with de novo LCH (Stratum I) and will evaluate a new compound (indomethacin) in patients with relapsed LCH (Stratum II) to decrease relapse rate and permanent morbidity. Primary endpoint is reactivation-free survival, secondary endpoints include toxicity and risk of permanent consequences. Although many patients suffer from significant morbidity, LCH is a rare disease. Germany alone does not have enough patients for a sufficiently powered study, which has therefore to be done in an international setting. A collaborative trial (LCH-IV) has already started in several countries, and the participation of Germany in the frame of the proposed study is necessary, as Germany is expected to enroll >20% of all patients. This trial may ultimately decrease the risk of relapse and permanent sequelae, thus improving quality of life and reducing socio-economic burden in patients with LCH.