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The objective of this study was to analyze the T cell metabolism and immune phenotype in AML patients during the course of the disease before and after allo-HCT.
Patients who experience relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. Infusion of donor T cells can induce graft-versus-leukemia (GVL) effects, indicating the importance of intact T cell function for leukemia control. Recent studies have shown the importance of metabolic fitness for an effective T cell response.
In this study we have analyzed the T cell metabolism and immune phenotype in AML patients at different time points before and after allo-HCT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Primary Diagnosis | Analysis of patient blood at primary diagnosis of AML | ||
| Relapse | Analysis of patient blood at time point of relapse after allo-HCT | ||
| Remission | Analysis of patient blood during remission after allo-HCT |
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| Measure | Description | Time Frame |
|---|---|---|
| T cell metabolism | Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer | 4 years |
| T cell phenotype | T cell cytokine and effector molecule production | 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolite abundance in serum | Serum metabolites as measured by mass spectrometry | 4 years |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients with acute myeloid leukemia at primary diagnosis, at relapse after allo-HCT or in remission after allo-HCT.
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| Name | Affiliation | Role |
|---|---|---|
| Robert Zeiser, Prof. Dr. | Medical Center University of Freiburg | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27293185 | Background | Buck MD, O'Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, Qiu J, Kretz O, Braas D, van der Windt GJ, Chen Q, Huang SC, O'Neill CM, Edelson BT, Pearce EJ, Sesaki H, Huber TB, Rambold AS, Pearce EL. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. Cell. 2016 Jun 30;166(1):63-76. doi: 10.1016/j.cell.2016.05.035. Epub 2016 Jun 9. | |
| 26321679 |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| Chang CH, Qiu J, O'Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, Tonc E, Schreiber RD, Pearce EJ, Pearce EL. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell. 2015 Sep 10;162(6):1229-41. doi: 10.1016/j.cell.2015.08.016. Epub 2015 Aug 27. |
| 17909197 | Background | Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A, Volin L, Gurman G, Maertens J, Bordigoni P, Holler E, Ehninger G, Polge E, Gorin NC, Kolb HJ, Rocha V; EBMT Acute Leukemia Working Party. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007 Nov 1;25(31):4938-45. doi: 10.1200/JCO.2007.11.6053. Epub 2007 Oct 1. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |