Acute Myeloid Leukemia: 2025 Update on Diagnosis, Risk-Stratification, and Management

Abstract

Disease overview: Acute myeloid leukemia (AML) is a bone marrow stem cell cancer that is often fatal despite available treatments. Diagnosis, risk assessment, monitoring, and therapeutic management of AML have changed dramatically in the last decade due to increased pathophysiologic understanding, improved assessment technology, and the addition of at least 12 approved therapies.

Diagnosis: The diagnosis is based on the presence of immature leukemia cells in the blood, and/or bone marrow or less often in extra-medullary tissues. New biological insights have been integrated into recent classification systems.

Risk assessment: The European Leukemia Network has published risk classification algorithms for both intensively and non-intensively treated patients based on cytogenetic and on molecular findings. Prognostic factors may differ based on the therapeutic approach.

Monitoring: Our increasing ability to quantify lower levels of measurable residual disease (MRD) potentially allows better response assessment, as well as dynamic monitoring of disease status. The incorporation of MRD findings into therapeutic decision-making is rapidly evolving.

Risk adapted therapy: The availability of 12 newly approved agents has been welcomed; however, optimal strategies incorporating newer agents into therapeutic algorithms are debated. The overarching approach integrates patient and caregiver goals of care, comorbidities, and disease characteristics.

Keywords: AML diagnosis; AML therapy; AML‐molecular diagnosis and therapy; measureable residual disease in AML; neoplasia‐myeloid leukemias and dysplasias.

FIGURE 1

Comparison between WHO fifth versus ICC AML definitions. * ≥ 20% blasts are required for AML definition. Colors reflect similar subgroups between classifications. AML—acute myeloid leukemia; ICC—international consensus classification; MDS—myelodysplastic syndrome; MPN—myelodysplastic neoplasm; WHO—world health organization.

FIGURE 2

Treatment algorithm for newly diagnosed patients aged < 60 years with AML fit for intensive therapy. AlloSCT—allogeneic stem cell transplantation; AML—acute myeloid leukemia; AML‐MR—acute myeloid leukemia with myelodysplasia related changes (ELN 2017 definition); CBF—core binding factor; ELN—European Leukemia Network; FLT3i—FLT3 inhibitors; GO—gemtuzumab ozogamycin; HMA—hypomethylating agents; MRD—measurable residual disease; ND—newly diagnosed; t‐AML—therapy related AML; ven—venetoclax.

FIGURE 3

Treatment Algorithm for Newly diagnosed patients with AML aged 60–75 years eligible for intensive therapy. AlloSCT—allogeneic stem cell transplantation; AML—acute myeloid leukemia; CBF—core binding factors; ELN—European Leukemia Network; FLT3i—FLT3 inhibitors; GO—gemtuzumab ozogamycin; HMA—hypomethylating agents; ITD—internal tandem duplication; MRD—measurable residual disease; ND—newly diagnosed; Ven—venetoclax.

FIGURE 4

Treatment Algorithm for Newly diagnosed patients with AML ≥ 75 years or unfit for intensive therapy. AlloSCT—allogeneic stem cell transplantation; AML—acute myeloid leukemia; ELN—European Leukemia Network; FLT3i—FLT3 inhibitors; HMA—hypomethylating agents; IDHi—IDH inhibitor; IDH—isocitrate dehydrogenase; MRD—measurable residual disease; ND—newly diagnosed; Ven—venetoclax.

FIGURE 5

Treatment Algorithm for patients with relapsed or refractory AML. AlloSCT—allogeneic stem cell transplantation; AML—acute myeloid leukemia; DLI—donor lymphocyte infusion; FLT3i—FLT3 inhibitors; GO—gemtuzumab ozogamycin; HMA—hypomethylating agents; IDH—isocitrate dehydrogenase; KMT2Ar—Lysine methyltransferase 2A gene (KMT2A) re‐arranged; MRD—measurable residual disease; R/R—relapse or refractory; Ven—venetoclax.