Paediatrics: Acute myeloid leukaemia

Acute myeloid leukaemia

Acute myeloid leukaemia (AML) accounts for 75% of all childhood malig-nancies and <20% of all acute leukaemias. It is also known as acute non-lymphoblastic leukaemia (ANLL). AML results from malignant prolifera-tion of myeloid cell precursors. AML can be subdivided morphologically using the French–American–British (FAB) classification system:

·  M1: AML without maturation.

·  M2: AML with maturation.

·  M3: acute promyelocytic leukaemia (PML).

·  M4: acute myelomonocytic leukaemia with eosinophilia (M4Eo).

·  M5: acute monocytic/monoblastic leukaemia.

·  M6: acute erythroleukaemia.

·  M7: acute megakaryocytic leukaemia.

Presentation

·  Symptoms and signs of bone marrow replacement.

·  Lymphadenopathy less prominent than in ALL.

·  Intrathoracic extramedullary disease less common than in ALL.

·  M3 may present with coagulopathy from proteolytic enzyme activity.

·  Solid deposits (chloroma) occasionally seen in M2, M4, or M5.

Cytogenetics

Cytogenetic analysis shows characteristic abnormalities:

·  M1 and M2 AML: t(8;21) translocation observed in 15% of all cases.

·  M3 AML: t(15;17) translocation observed in 100% of cases;

·  M4Eo: inv(16) frequently observed.

These translocations are regarded as good prognostic indicators. Other complex karyotypes are associated with poor risk.

Treatment

In AML prolonged continuation therapy is not used:

·  4 courses intensive myeloablative chemotherapy. The role of the gemtuzumab or Myelotarg (a monoclonal antibody directed against CD33) given alongside chemotherapy is being explored in the context of clinical trials.

·  PML: all-trans retinoic acid given in induction, before chemotherapy, improves survival.

·  High risk cases, including those who fail to achieve complete remission

after 2 courses, are usually offered BMT in first remission.

Prognosis 

Overall survival is >60%.

Relapsed AML

All cases require BMT after intensive re-induction, usually in conjunction with ‘FLAG’ or ‘FLAG-Ida’ regimen (i.e. fludarabine, ara-C, and G-CSF sup-port +- idarubicin).

Leukaemia and Down syndrome

The risk of developing acute leukaemia is increased 20–30 times, com-monly either a pre-B (common) ALL or AML (especially M7). Response to chemotherapy is good and better relapse-free survival is found in those with AML. Children with Down syndrome-associated leukemia experi-ence more complications of treatment.

Other genetic conditions predisposing to AML

·Fanconi syndrome.

·Bloom syndrome.

·Ataxia telangiectasia.

·Kostmann’s syndrome.

·Diamond–Blackfan syndrome.

·Klinefelter’s.

·Turner’s syndrome.

·Neurofibromatosis.

·Incontinentia pigmenti.