Acute Myeloid Leukemia (AML): Is it time for MRD-driven treatment?

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Background

An increasing number of genetic and epigenetic abnormalities have been shown to display prognostic value in acute myeloid leukemia (AML). Risk stratification at diagnosis, as defined by European LeukemiaNet (ELN) risk score, may accurately define prognosis for AML patients. However, minimal residual disease (MRD) assessment, during the therapeutic course, may refine risk definition, as more profound clearance of clonal cells is associated with longer disease-free survival (DFS) and increased chance of cure. Multicolor flow cytometry and real time PCR /NGS based techniques targeting recurrent specific molecular alterations are the most widely used tools per MRD assessment. The most relevant time points for MRD evaluation are after induction therapy, after consolidation and before allogeneic transplantation. Standardization is however incomplete and most information comes from trials with conventional 3+7 induction in younger patients.

Differently from acute lymphoblastic leukemia where almost all therapeutic protocols are MRD driven, in AML, despite the relevant prognostic role of MRD, most protocols do not take into account MRD information for therapeutic decisions. Furthermore for relapsing patients salvage therapy is usually given at the time of overt hematologic relapse and there are very few examples of early salvage treatment, delivered at the time of MRD reoccurrence.
An improved information on MRD during conventional and intensified treatment, both in younger and in older subgroups of patients, may help to design modern MRD protocols and to rationally exploit the recently approved innovative targeted drugs, also for preemptive therapy in patients showing MRD relapse.
In this view it would be useful to include articles reviewing available data on MRD driven protocols, the role of MRD in the context of allogeneic transplantation, the role of MRD assessment either by PCR and NGS tools in patients harboring specific genetic lesions. Original articles should cover settings where the role of MRD has not been elucidated yet, such as MRD in the context of treatment with new drugs, MRD during therapy of elderly AML patients.

• Published and ongoing experiences on MRD driven protocols (review) in order to provide an up to date background
• The role of MRD in AML patients with recurrent genetic lesions (review and original papers)
• The role of MRD in elderly AML patients (review and original papers)
• The role of MRD in specific AML settings, including secondary and therapy related AML (review and original papers)
• MRD in AML patients treated with innovative drugs (original papers)
• Salvage therapy at time of MRD reoccurrence (original papers)
• MRD in the context of allogeneic transplantation (review)
• The role of MRD in defining the overall transplant strategy including donor selection, intensity of conditioning and post-transplant immunologic intervention (review and original papers)

Keywords: Acute Myeloid Leukemia (AML), minimal residual disease, disease-free survival, lymphoblastic leukemia, allogeneic transplantation

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