Pharmacogenetics of Veno-Occlusive Disease (VOD) in Children With Haematological Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 436
- 试验地点
- 1
- 主要终点
- Pharmacogenetic biomarkers
研究概览
简要总结
This project aims to identify common pharmacogenetic biomarkers predisposing children with cancer to develop hepatic VOD during their cancer treatment including HSCT. The impact of VOD occurrence and significant biomarkers will also be evaluated on outcome at day 100 and one year after HSCT. It should help to highlight factors that can contribute to the initiation of hepatic VOD.
Understanding mechanisms of this toxicity and to know individual parameters of disease susceptibility becomes an important issue in the care of these children. The ultimate goal of research in this area would be to develop a personalized predictive medicine and, hopefully, prevent the occurrence of VOD from a therapeutic adaptation to each patient according to his pharmacogenetic profile (adapted prophylaxis, dose adjustment, drug combinations ...). A prospective identification of patients at risk of hepatic VOD will increase the safe use of anticancer.
详细描述
Hematopoietic stem cells transplantation (HSCT) in children with cancer is source of veno-occlusive disease (VOD). This complication is unpredictable and serious by involving the vital prognosis of the child. In addition, this complication may affect the patient's quality of life and have serious long-term sequelae. The incidence varies from 15 to 60% and the mortality is greater than 60% after severe VOD. The risk factors of occurrence of these complications are, to date, unknown except for a susceptibility to some therapeutic (busulfan, radiotherapy ...). Pharmacogenetic aspects of hepatic VOD susceptibility are supposed and targeted screening supported this hypothesis. But pharmacogenetic predisposition to VOD was never explored with as many polymorphisms and considering the whole exome.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children with cancer aged less than 18 years old treated for their first HSCT between 2000 and 2011 in France.
- •Patients are selected from the database ProMise regarding pediatric patients treated in any center of the French Society of Stem Cell transplantation (SFGM).
- •Clinical data (age, sex, initial pathology, conditioning treatment, type of graft cells, VOD occurence or not, survival status at 100 days and 1 year after transplantation) were extracted from this database.
排除标准
- 未提供
结局指标
主要结局
Pharmacogenetic biomarkers
时间窗: 12 months
The pharmacogenetic analysis will be conducted by a whole exome genotyping approach with Microarrays Illumina "Human Omni2.5-8 v1.3" (exploring more than 2,600,000 genetic variants covering the entire genome with more than 300,000 genetic biomarkers within exons).
次要结局
- Survival status at 1 year post HSCT(12 months)
- Survival status at 100 days post HSCT(100 days)