Acute myeloid leukemia (AML) is the malignant clonal proliferation of myeloid precursor cells — the marrow cells that normally mature into granulocytes, monocytes, red cells and platelets — and it is the second most common childhood leukemia, a distant second. AML accounts for 15–20% of pediatric acute leukemias, with the remaining 80% or so made up by acute lymphoblastic leukemia (ALL). One subtype, acute promyelocytic leukemia (APL), behaves differently from every other acute leukemia: its promyelocytes are held short of maturation by a single fusion protein, and the treatment makes them mature rather than killing them.
How AML presents
As in acute lymphoblastic leukemia, the presenting signs come from a marrow whose normal production has been displaced by immature cells, the blasts: anemia, neutropenia, thrombocytopenia and hepatosplenomegaly can be the opening picture in either disease.
A few clinical patterns point toward a myeloid leukemia. Monocytic differentiation (the M4 and M5 subtypes of the morphological classification described below) is associated with gum hypertrophy, skin infiltration, and a higher rate of central nervous system involvement. Myeloid sarcoma, also called chloroma, is an extramedullary mass of myeloid blasts — a tumor outside the marrow — that can appear before the marrow is visibly involved.
White cell counts run higher in AML than in ALL, which brings a separate emergency: leukostasis, the sludging of blasts in small vessels of the brain, lungs and other organs, producing headache, confusion, dyspnea, visual disturbance or priapism. It needs urgent cytoreduction — lowering the blast count with leukemia-directed treatment — rather than a wait for the definitive diagnosis.
These clues suggest AML, but none of them settles it; the lineage is decided in the laboratory rather than at the bedside.
Telling AML from ALL
Telling the two lineages apart matters because their treatment backbones differ. Three laboratory tools answer the question, and they are used together: cytochemistry, which stains the blasts for enzymes; morphology, the appearance of the blasts under the microscope; and flow cytometry, which reads the surface markers carried by individual cells. Each has a finding that indicates AML.
| Tool | Finding that indicates AML |
|---|---|
| Cytochemistry | Myeloperoxidase (MPO) positivity — the single most useful stain, because it is present in myeloid blasts and essentially absent in lymphoid ones. |
| Morphology | Auer rods, needle-shaped cytoplasmic inclusions of fused azurophilic granules, are pathognomonic of myeloid lineage (seen in no other lineage) and are often abundant in APL. |
| Flow cytometry | Myeloid surface markers — CD13, CD33, CD117 — in place of the B- or T-lineage markers of ALL. |
Classification has moved from appearance to genetics
Once the lineage is known to be myeloid, the next question is which kind of AML it is, and two classifications answer it.
The older French-American-British (FAB) scheme divided AML by morphology into M0 to M7: M0 minimally differentiated, M1 myeloblastic without maturation, M2 myeloblastic with maturation, M3 promyelocytic (which is the subtype APL falls into), M4 myelomonocytic, M5 monocytic, M6 erythroleukemia, and M7 megakaryoblastic. It remains useful vocabulary.
Current WHO (World Health Organization) classification is instead built on defining genetic abnormalities — the fusion genes PML::RARA, RUNX1::RUNX1T1 and CBFB::MYH11, KMT2A rearrangement, NPM1 mutation, and the myelodysplasia-related category. FLT3 mutation is not defining, but it carries prognostic weight and now directs therapy. Therapy-related myeloid neoplasms form a separate WHO category.
The treatment backbone
Pediatric AML treatment is more intensive and shorter than ALL treatment, with less emphasis on prolonged maintenance. The chemotherapy runs in sequence:
- Induction: the long-standing backbone is daunorubicin with cytarabine, the “7 + 3” schedule of 7 days of cytarabine and 3 days of anthracycline, adapted in pediatric regimens.
- Consolidation: high-dose cytarabine blocks, usually two or more, which do most of the work of preventing relapse.
Central nervous system prophylaxis with intrathecal therapy is also given, though AML invades the meninges less often than ALL.
Other elements depend on the child’s risk and on the biology of the disease:
- Allogeneic hematopoietic stem cell transplantation (from a donor) for high-risk disease in first remission and for many children with relapsed disease.
- Gemtuzumab ozogamicin, an anti-CD33 antibody-drug conjugate (an antibody that carries a cytotoxic drug to cells bearing its target), in CD33-positive disease.
- FLT3 inhibitors where the disease is FLT3-mutated.
Reported 5-year overall survival for childhood AML is now in the region of 65–70%, with wide variation by subtype; relapse remains the main cause of treatment failure.
Down syndrome and myeloid leukemia
Children with Down syndrome have a substantially increased risk of acute leukemia, and specifically of acute megakaryoblastic leukemia (AML M7) — the category now called myeloid leukemia of Down syndrome, defined by blasts with GATA1 variants in a child with trisomy 21. Its features are distinctive: the outcome with chemotherapy is generally excellent, but these children experience significantly greater treatment toxicity, so reduced-intensity regimens are used to obtain the same result with less harm.
The lesson is not confined to Down syndrome. The biology of a myeloid leukemia decides how much treatment a child can safely be given — and in acute promyelocytic leukemia it decides which drugs are used at all.