Hybrid ImmunoTherapy (ATG/Dexamethasone/Etoposide) for Hemophagocytic Lymphohisti

描述(由申请人提供)： 噬血细胞淋巴组织细胞增多症是一种严重损害免疫活性的异常疾病。尽管最近医学上取得了进展，但在治疗的初始阶段，仍有相当数量的HLH儿童死亡。值得注意的是，两种不同的治疗HLH的方法， 也有类似结果的报道。我们建议进行一项临床试验，名为HLH的混合免疫疗法(HIT-HLH)试验，该试验测试将两种方法(ATG和依托泊苷)相结合的治疗方案可能会为HLH患者带来更好的结果。通过进行这项多中心试点试验，HIT-HLH联盟希望在使用这种创新的疗法治疗后，能够非常精确地确定应答和存活率。我们还希望将这些患者的结果与收集到的大量研究参与者的临床数据相关联。这些目标很重要，因为推进这种破坏性疾病的治疗将需要进行大规模试验，将标准治疗与这种(或其他)新的创新疗法进行比较。如果不先测试新的“混合”方法并了解它的可行性和有效性，就不能进行这些试验。这些研究也很重要，因为目前还没有已知的临床特征可以预测HLH患者的复发或死亡，而这些知识对于根据患者的需要量身定做未来的治疗方法将是必不可少的。此外，进行HIT-HLH试验将聚集一个独特的合格的合作研究人员网络，他们有兴趣和动机为HLH患者测试新的治疗方法。这一网络的影响和努力将远远超出目前的审判。通过这项努力，我们打算提高HLH型儿童的长期存活率，并对HLH型和人类免疫功能产生重要的新见解。 公共卫生相关性： 噬血细胞淋巴组织细胞增多症是一种严重损害免疫活性的异常疾病。我们正在提议进行一项临床试验，名为HLH的混合免疫疗法(HIT-HLH)试验，该试验测试一种治疗方案，该方案结合了目前不同的治疗策略(ATG和依托泊苷)。通过这项试验和后续的研究，我们打算提高HLH型儿童的长期存活率，并对HLH型和人类免疫功能产生重要的新见解。 (摘要结束)

DESCRIPTION (provided by applicant): Hemophagocytic lymphohistiocytosis (HLH) is a disorder of abnormal and severely damaging immune activation. Despite recent medical progress, significant numbers of children with HLH still die during the initial phases of therapy. Notably, two different approaches for treating HLH, with similar outcomes, have been reported. We are proposing to conduct a clinical trial, called the 'Hybrid Immunotherapy for HLH' (HIT-HLH) trial, which tests the idea that a treatment regimen combining aspects of both approaches (ATG and etoposide) may result in better outcomes for patients with HLH. By conducting this multicenter pilot trial, the HIT-HLH consortium hopes to define response and survival rates with significant precision after treatment with this innovative regimen. We also hope to correlate outcomes of these patients with extensive clinical data collected on study participants. These goals are important because advancing therapy for this devastating disorder will require large trials comparing standard treatment with this (or other) new innovative therapies. These trials cannot be performed without first testing the new 'hybrid' approach and understanding how feasible and effective it may be. These studies are also important because there are no known clinical features which can predict relapse or death in patients with HLH, and such knowledge will be essential for tailoring future therapies to patients needs. Furthermore, conducting the HIT-HLH trial will gather together a uniquely qualified network of collaborative investigators who are interested and motivated to test novel therapies for patients with HLH. The impact and efforts of this network will extend well beyond the current trial. Through this effort we intend to improve the long term survival of children with HLH and develop significant new insights into HLH and human immune function. PUBLIC HEALTH RELEVANCE: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of abnormal and severely damaging immune activation. We are proposing to conduct a clinical trial, called the' Hybrid Immunotherapy for HLH' (HIT-HLH) trial, which tests a treatment regimen combining aspects of currently divergent therapeutic strategies (ATG and etoposide). Through this trial and subsequent studies, we intend to improve the long-term survival of children with HLH and develop significant new insights into HLH and human immune function. (End of Abstract)