Acute myeloid leukemia (AML) is a malignant disease of hematopoietic stem cells, characterized by uncontrolled proliferation and impaired differentiation, leading to failure of normal hematopoiesis. According to the World Health Organization classification, AML with a mutation in the NPM1 gene is defined as a distinct genetic subtype of the disease. The NPM1 gene encodes a protein involved in numerous cellular processes, including ribosome biogenesis, DNA repair, and regulation of tumor suppressor pathways. Mutations in the NPM1 gene (NPM1c), most commonly insertions in exon 12, result in loss of tumor suppressor function, leading to leukemic transformation. Due to the specificity and stability of this mutation, NPM1 represents an ideal molecular target for monitoring measurable residual disease (MRD), a sensitive laboratory marker used to detect residual leukemic cells remaining in the patient’s body after treatment. MRD monitoring enables clinicians to assess treatment response, predict the risk of relapse, and adjust therapy in a timely manner. According to the European LeukemiaNet guidelines (2021), which are intended for monitoring patients receiving intensive chemotherapy, MRD assessment in NPM1-mutated AML is recommended after two cycles of induction chemotherapy using peripheral blood, after completion of consolidation therapy using bone marrow, and during remission, typically every 3 months from bone marrow and every 4–6 weeks from peripheral blood during the first two years of follow-up. Molecular methods are suitable for MRD monitoring, most commonly quantitative reverse transcription PCR (RT-qPCR).
The aim of this master’s thesis was to evaluate how consistently the European guidelines for MRD monitoring are applied in clinical practice for patients with AML and NPM1 mutation, and to determine whether such monitoring influences clinical decision-making and improves patient management. In addition, we aimed to compare MRD monitoring before and after the introduction of the guidelines in 2021. We collected data from 97 patients who were treated at the Department of Haematology between 2016 and 2024. We found that MRD was assessed after the second cycle of chemotherapy in 46,9 % of patients; however, only 26,7 % had the recommended sample (peripheral blood) collected, whereas at the end of treatment, 80 % of patients had MRD assessed from the recommended sample (bone marrow). During follow-up, we observed that patients diagnosed before the introduction of the guidelines were monitored inconsistently, with long intervals between assessments, often exceeding one year, which in some cases contributed to delayed detection of disease relapse. After the implementation of the guidelines, monitoring improved markedly, as assessments became more frequent, more consistent, and largely aligned with recommendations. Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) continued to be monitored over a longer period, whereas patients receiving less intensive therapy or palliative care were generally not monitored.
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