Hematologic Malignancy
Conditions
Keywords
allo-HSCT
Brief summary
This study investigates how metabolism in cancer and immune cells shapes the bone marrow environment, influences therapy resistance, and affects outcomes in hematological malignancies.
Detailed description
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.
Interventions
None listed
Sponsors
University Hospital, Basel, Switzerland
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* age \> 18 years, * signed written informed consent * For participants with hematological cancers: diagnosis of MDS, AML, ALL, PMF or post-ET/PV MF
Exclusion criteria
* 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,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic function | 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. |
| Concentration of metabolites | 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 | 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 | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Switzerland
Contacts
Primary ContactPetya Apostolova, Prof. Dr.
Backup ContactJohannes Tossounidis, MD
Outcome results
None listed