Diagnosing

Overview

Acute myeloid leukemia (AML) is a fast-growing cancer of the blood and bone marrow that starts in immature myeloid cells — the cells that normally become red blood cells, platelets and infection-fighting granulocytes.

AML is the most common acute leukemia in adults and becomes more frequent with age. Because it progresses quickly, rapid diagnosis and the start of treatment within days are important. Our team combines laboratory genetics, modern drug therapy and transplantation to give each patient the best chance of a lasting remission.

AML causes and risk factors

Older age (most patients are over 60)
Previous chemotherapy or radiation therapy (therapy-related AML)
Earlier blood disorders such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms
Smoking and long-term exposure to benzene
Some inherited conditions, such as Down syndrome or Fanconi anemia

AML symptoms

Fatigue, breathlessness and pallor from anemia
Fever and frequent or slow-to-heal infections
Bruising, bleeding gums, nosebleeds or heavy periods
Bone pain, swollen gums or skin lumps (in some subtypes)
Weight loss and loss of appetite

Factors that affect prognosis and treatment

The genetic and chromosome changes in the leukemia cells (for example FLT3, NPM1, IDH1/2 or core-binding-factor changes), the patient's age and fitness, whether AML developed from an earlier blood disorder, and how well it responds to the first treatment all shape the plan.

Stages of AML

AML is not staged like solid tumors. Instead it is described by its status:

Newly diagnosed (untreated) AML — the leukemia has just been found and treatment is about to start.
AML in remission — after treatment, blood counts recover and fewer than 5% blasts remain in the marrow.
Relapsed or refractory AML — the leukemia returns after remission, or does not respond to treatment.

Acute promyelocytic leukemia (APL) is a special subtype that is treated differently and has excellent cure rates when treatment starts promptly.

Several tests are combined to confirm AML, identify its subtype and genetic profile, and check overall fitness for treatment.

Blood tests

A complete blood count and blood smear show blasts and low normal blood cells. Clotting tests are important because some types of AML cause serious bleeding problems.

Bone marrow samples

Bone marrow aspiration and biopsy confirm the diagnosis when 20% or more of the marrow cells are blasts (or a defining genetic change is present).

Laboratory tests

Flow cytometry — confirms that the blasts are myeloid.
Cytogenetics and FISH — find chromosome changes that place AML in a favourable, intermediate or adverse risk group.
Molecular testing — detects mutations such as FLT3, NPM1, IDH1/IDH2, TP53 that guide targeted treatment.
HLA typing — started early for the patient and siblings in case a transplant is needed.

Spinal tap or lumbar puncture

Performed when symptoms or test results suggest leukemia in the central nervous system.

Imaging scans

Chest X-ray, echocardiogram and, when needed, CT or ultrasound check the heart, lungs and organs before intensive treatment and look for infection.

Treatment

AML treatment begins quickly and is matched to the genetic profile of the leukemia and the fitness of the patient.

Chemotherapy

Induction chemotherapy (for example the "7+3" combination) aims for complete remission. It is followed by consolidation courses to reduce the risk of relapse. Older or less fit patients may receive lower-intensity treatment such as azacitidine or decitabine combined with venetoclax.

Targeted therapy

FLT3 inhibitors (midostaurin, gilteritinib, quizartinib)
IDH1 / IDH2 inhibitors (ivosidenib, enasidenib)
Venetoclax, which blocks the survival protein BCL-2
Gemtuzumab ozogamicin, an antibody-drug conjugate for CD33-positive AML
All-trans retinoic acid (ATRA) and arsenic trioxide for acute promyelocytic leukemia

Bone marrow / stem cell transplant

For intermediate- and high-risk AML, an allogeneic transplant in first remission offers the best chance of long-term control. Matched sibling, matched unrelated and haploidentical family donors are all used.

Radiation therapy

Used rarely — for leukemia in the brain or a localized leukemia mass, or as part of conditioning before a transplant.

Supportive care

Blood and platelet transfusions, prevention and rapid treatment of infections, nutrition support and psychological care help patients through intensive treatment safely.