Relative Inactivity of Alpha-1-antitrypsin After Bone Marrow Transplantation as a Dynamic Biomarker for GVHD and Prognosis: a Prospective Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Number of patients progressing into acute or chronic GVHD
研究概览
简要总结
Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD.
PRIMARY ENDPOINT 1. Serum AAT levels and activity, before myeloablative preconditioning, as well as on days (-3),0,7,14,28 from HSCT and every 21 days thereafter.
SECONDARY ENDPOINTS 1. Correlation between AAT patterns and:
- Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.
- Patient survival
- Liver function tests
- GVHD grade: skin manifestations, weight, GI and liver histopathology
- Graft-versus-leukemia effect
详细描述
This study will focus on each individual patient from the early point of myeloablative conditioning through HSCT and GVHD. The rationale for this individualized approach is to account for the anticipated variability in patient age and primary disease, background pathology and individual therapeutic course, considering the enormous heterogeneity of this condition. To compensate for this limitation, we intend to create an individualized algorithm, based on a novel dynamic biomarker, i.e., AAT functionality, individualized per patient and placed on a timeline, with the aim of minimizing future occurrences of GVHD, and by using readily available laboratory measurements. The study is designed around patient sample collection, there is no change in standard of care, therefore there is no intervention as well.
Three types of sample tubes will be collected per indicated time point:
- Serum tube for protein levels and enzymatic activity assays.
- EDTA tube for isolation of peripheral blood mononuclear cells (PBMCs), cells will be stimulated and then analyzed by FACS and lysed for RT-PCR
- EDTA tube for whole blood stimulation assay for further FACS analysis and cytokine production measurement.
After donor and recipient informed consent forms were signed, a single blood sample should be obtained from the donor on the day of transplant extraction. Time points for recipient's samples include the day of myeloablation and again immediately prior to HSCT (set as day 0 and possibly -3 in MUDs). Serum and lysed blood samples will be collected on days 7, 14, 28, and every 21 days thereafter, through the development and progression of GVHD (where relevant). Blood samples for FACS will be collected by days 0 and 28. Sample collection is planned to end within 1 year from HSCT, or two months after appearance of symptoms of GVHD, or two months after a change is introduced in the immunosuppressive therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Candidates for allogeneic transplantation for the first time, scheduled to receive HSCT from HLA-matched sibling or an unrelated matched donor
- •Signed informed consent by the donor(Healthy volunteers) and the patient
排除标准
- •Patients undergoing immunosuppressive treatment prior to preparation for bone-marrow transplantation.
- •Pregnant and disabled patients.
结局指标
主要结局
Number of patients progressing into acute or chronic GVHD
时间窗: Up to 1 year
Evaluation of patient circulating alpha-1-antitrypsin levels and enzymatic functions as a bio-marker for GVHD progression and grading
次要结局
- Correlation between AAT pattern and survivability, response to immunosuppressive treatment. liver functions, immunocyte activities.(Up to 1 year)