Cancer and Immune Cell Metabolism in Patients With Hematological Malignancies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Concentration of metabolites
研究概览
简要总结
This study investigates how metabolism in cancer and immune cells shapes the bone marrow environment, influences therapy resistance, and affects outcomes in hematological malignancies.
详细描述
Hematological malignancies, such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myelofibrosis, are aggressive cancers of the blood and immune system. While chemotherapy is commonly used, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for many patients. Allo-HSCT relies on donor immune cells, particularly T cells, to eliminate residual malignant cells, but relapse occurs in a significant proportion of patients, underscoring the need for improved therapeutic strategies.
Recent research has highlighted the critical role of cellular metabolism in both cancer cell survival and immune cell function. AML cells, for example, rely on mitochondrial respiration, while immune cells are sensitive to metabolic changes in the bone marrow microenvironment. These metabolic interactions may influence disease progression, therapy resistance, and immune-mediated anti-tumor responses, yet they remain poorly understood.
The primary goal of this study is to investigate how cancer and immune cell metabolism shapes the bone marrow environment and influences treatment outcomes in patients with hematological malignancies. By performing detailed metabolic profiling of malignant cells, immune cells, and extracellular metabolites across disease stages and treatment time points, the study aims to identify key metabolic pathways and interactions that could serve as targets for novel therapies and guide personalized treatment approaches.
This research is expected to deepen the understanding of metabolic mechanisms underlying hematological cancers and allo-HSCT outcomes, potentially leading to improved strategies to enhance anti-tumor immunity, prevent relapse, and optimize patient-specific therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 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
- •age > 18 years,
- •signed written informed consent
- •For participants with hematological cancers: diagnosis of MDS, AML, ALL, PMF or post-ET/PV MF
排除标准
- •pregnant or lactating women,
- •inability to give consent,
- •active malignant disease (other than MDS, AML, ALL, PMF or post-ET/PV MF in the last 3 - years prior to study inclusion).
- •For healthy donors: previous or current hematological disease, previous or current other malignant disease,
结局指标
主要结局
Concentration of metabolites
时间窗: at primary diagnosis (month 0); after initial chemotherapy (month +0.5-2); before allo-HSCT (month +3-12); 1, 3, 6, 12 month after allo-HSCT (month 4-13, 6-15, 9-18, 15-24), and at relapse (if applicable, up to 5 years)
the concentration of metabolites in malignant cells, immune cells, and extracellular fluid in each sample at the time point at which the sample is obtained. Metabolite and lipid concentrations will be measured by mass spectrometry.
Concentration of lipids
时间窗: at primary diagnosis (month 0); after initial chemotherapy (month +0.5-2); before allo-HSCT (month +3-12); 1, 3, 6, 12 month after allo-HSCT (month 4-13, 6-15, 9-18, 15-24), and at relapse (if applicable, up to 5 years)
the concentration of lipids in malignant cells, immune cells, and extracellular fluid in each sample at the time point at which the sample is obtained. Metabolite and lipid concentrations will be measured by mass spectrometry.
Expression profiling
时间窗: at primary diagnosis (month 0); after initial chemotherapy (month +0.5-2); before allo-HSCT (month +3-12); 1, 3, 6, 12 month after allo-HSCT (month 4-13, 6-15, 9-18, 15-24), and at relapse (if applicable, up to 5 years)
the expression of metabolite-related genes and proteins that will be measured by (single-cell) RNA-sequencing, quantitative polymerase chain reaction (PCR), proteomics, flow cytometry, western blotting, or another appropriate technique.
Metabolic function
时间窗: at primary diagnosis (month 0); after initial chemotherapy (month +0.5-2); before allo-HSCT (month +3-12); 1, 3, 6, 12 month after allo-HSCT (month 4-13, 6-15, 9-18, 15-24), and at relapse (if applicable, up to 5 years)
Metabolic function will be assessed by extracellular flux assays, flow cytometry, or another appropriate technique.
次要结局
- Response to treatment(s)(during whole study, up to 5 years after allo-HSCT)
- Duration of the response(during whole study, up to 5 years after allo-HSCT)
- Progression-free survival(during whole study, up to 5 years after allo-HSCT)
- Overall survival(during whole study, up to 5 years after allo-HSCT)