Introduction: Acute myeloid leukemia (AML) is a highly heterogeneous disease which renders risk stratification at diagnosis of high importance to personalize therapy. Allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance for sustained remission in most AML patients, but usually comes at the risk of a significant treatment-related mortality. The red cell distribution width (RDW) is an universally accessible parameter that identifies individuals with a higher mortality in many diseases, including some hematological entities. However, the impact of diagnostic RDW levels in AML – especially in the context of a HSCT consolidation - has not been evaluated so far.
Purpose: To evaluate the prognostic impact of RDW levels at AML diagnosis.
Methods: A total of 294 newly diagnosed AML patients (median age 60.6, range 14.3-76.5 years), with available diagnostic RDW levels were retrospectively included in this analysis. All patients received a consolidation therapy with an allogeneic HSCT in curative intention between August 2007 and December 2020 at the University Medical Center Leipzig. The RDW was measured in all patients at AML diagnosis before the start of cytoreductive therapies.
Results: RDW levels at diagnosis were highly variable (median 16.6%, range 12%-30.6%) and above the upper level of normal (>15%) in 73% of the analyzed AML patients. Patients with RDW levels above 15% did not have worse outcomes compared to patients with low diagnostic RDW levels. However, when the cohort was dichotomized according to a receiver operating characteristic (ROC)-based optimal cut-point (20.7%), patients with high RDW levels had a significantly higher non-relapse mortality (NRM), shorter overall survival and a trend for shorter event-free survival, while the risk of relapse or disease progression was similar in both groups. In multivariate analyses, the RDW remained an independent prognostic factor for higher NRM after adjustment for the body mass index at diagnosis. Patients with a higher RDW were more likely to harbor a secondary AML, as well as to harbor secondary AML-associated gene mutations (i.e. JAK2, ASXL1, or spliceosome mutations, especially SRSF2).
Conclusion: High RDW levels at diagnosis represent an independent risk marker for a higher mortality following allogeneic HSCT. When confirmed in prospective clinical trials, the RDW might help to personalize AML consolidation therapy including conditioning regimens before allogeneic HSCT.:1. Bibliographische Beschreibung
2. Abkürzungsverzeichnis
3. Einführung / Introduction
3.1. Acute Myeloid Leukemia
3.1.1. Definition
3.1.2. Epidemiology and etiology
3.1.3. Clinical presentation
3.1.4. Diagnosis of AML
3.1.4.1. Morphology
3.1.4.2. Immunophenotyping
3.1.4.3. Cytogenetic and molecular analyses
3.1.5. AML classification according to WHO classification
3.1.6. Prognostic factors in AML
3.1.6.1. Patient-related risk factors
3.1.6.2. Genetic risk factors
3.1.6.3. Measurable residual disease
3.1.7. Treatment of AML
3.1.7.1. Induction therapy in curative intention
3.1.7.2. Consolidation therapies
3.1.7.3. Palliative treatment approaches
3.1.7.4. New substances
3.2. Allogeneic HSCT
3.2.1. Principles of allogeneic HSCT
3.2.2. Conditioning regimens
3.3. Red cell distribution width
4. Aufgabenstellung / Objectives
5. Materialien und Methoden / Materials and Methods
5.1. Patients and treatments
5.1.1. Treatment protocols
5.1.2. Allogeneic HSCT and immunosuppression
5.1.3. Assessment of GvHD
5.2. Disease characterization
5.2.1. Evaluation at AML diagnosis
5.2.1.1. Morphology
5.2.1.2. Flow cytometry
5.2.1.3. Genetic analyses
5.2.1.4. Evaluation of RDW levels
5.2.2. Evaluation at HSCT
5.2.2.1. Definition of remission status at HSCT
5.2.2.2. Evaluation of measurable residual disease at HSCT
5.3. Statistical Analyses
5.3.1. Associations
5.3.2. Clinical endpoints
5.3.3. Definition of an optimal cut-point for RDW levels
5.3.4. Multivariate analyses
6. Ergebnisse / Results
6.1. Overall outcomes of the patient cohort
6.2. RDW levels at AML diagnosis regarded as continous parameter
6.3. The role of RDW levels at diagnosis as a predictor for outcomes after
allogeneic HSCT
6.4. Associations of RDW levels at diagnosis
7. Diskussion / Discussion
8. Zusammenfassung / Summary
9. Literaturverzeichnis / References
10. Erklärung über die eigenständige Abfassung der Arbeit
11. Curriculum Vitae
12. Komplette Publikationsliste (Peer-reviewed)
13. Danksagung
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:77043 |
| Date | 21 December 2021 |
| Creators | Vucinic, Vladan |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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