Optimizing usage of measurable residual disease (MRD) for treatment decision making in acute myeloid leukemia

Acute myeloid leukemia (AML) is a malignancy affecting bone marrow, characterized by abnormal cell maturation and proliferation. Initial treatment involves intensive chemotherapy aiming for complete remission (CR), followed by consolidation therapy. Consolidation options include chemotherapy alone, autologous stem cell transplant (auto-SCT), or allogeneic stem cell transplant (allo-SCT). Selecting the appropriate consolidation therapy balances anti-leukemic efficacy with safety concerns. While allo-SCT reduces relapse risk, it also carries significant morbidity, prompting cautious use. Measurable residual disease (MRD) is increasingly influential in AML management, indicating higher relapse risk when detected pre-consolidation. Measuring MRD is subject to strict protocols and guidelines to ensure consistent and accurate identification and detection of MRD. In addition, it is important that results are harmonized between centers so that results can be compared. Within Europe, this harmonization process is led by the European LeukemiaNet (ELN). Chapter 2 discusses the technical aspects of flow MRD, which is a consensus on the entire process from administration to implementation of MRD. In addition, when MRD is used for clinical decision-making, it must comply with reliability standards and rules set by the European Union, called in vitro diagnostics rules (IVDR). In Chapter 3 we show that our MRD assay meets all requirements set by the IVDR and therefore qualifies for clinical use. While using MRD to guide treatment remains complex, following these guidelines already provides a solid basis for use in practice. In the HOVON/SAKK-132 study in Chapter 4, the choice for SCT is based on the MRD result after initial chemotherapy. With an MRD-positive result in AML patients with an intermediate-risk, there is an increased chance of the disease relapsing and an allo-SCT is advised. Whereas, when a patient is classified as MRD-negative, de-escalation is done by omitting an all