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Acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a malignant disease of the myeloid cell line in the bone marrow. There is uncontrolled clonal cell proliferation which infiltrates the normal bone marrow and displaces the normal haematopoiesis. It is characterised by acute neoplastic proliferation of myeloid blast cells in the bone marrow. There is at least 20% blast rate in bone marrow and/or peripheral blood, and the cells are proven to be of myeloid origin.

Peak incidence is 65 years, and 80% of acute leukaemia during adulthood are myelogenous.

Etiology

De novo AML:

Secondary AML results from chemo- or radiotherapy and occur in most cases 5-10 years after treatment.

Pathomechanism

Acquired somatic mutations in early hematopoietic precursors lead to rapid proliferation of abnormal and dysfunctional blasts. This disrupts the normal haematopoiesis leading to leukopenia, thrombocytopenia, and anaemia.

Clinical features

General features of acute leukaemia (both AML and ALL) are characterized by subacute onset and rapid progression. They include:

  • Symptoms of anaemia
    • Fatigue
    • Pallor
  • Symptoms of thrombocytopenia
    • Epistaxis
    • Bleeding gums
    • Petechiae, purpuras
  • Frequent infections and fever due to immature leukocytes
  • Hepatosplenomegaly
    • Not as common as in ALL but might occur

Some present with oncological emergencies like tumour lysis syndrome or DIC.

Diagnosis and evaluation

Some cell lines may be normal at the time of diagnosis.

Diagnosis is confirmed on detection of >20% blasts in the bone marrow or finding specific genetic mutations on cytogenic examination (PCR). This requires a bone marrow aspiration and biopsy. If it’s not possible, a peripheral blood smear might be used.

Immunophenotyping is achieved with flow cytometry to determine the origin of the leukemic cell line. For example, precursor cells are CD34+, while monocytic markers are CD14 and CD36. Certain subtypes of AML can only be diagnosed by this method.

Immunophenotyping, molecular diagnostics, and cytogenic examination are important to determine the exact subtype, which is important for prognosis and to guide treatment.

Treatment

At first, induction therapy is initiated. High doses of chemotherapy are given to achieve massive reduction of tumor cell count. This step also carries the highest risk of infection and death caused by the toxic damage to bone marrow and GIT. A 7+3-day scheme is usually used. Cytarabine and idarubicin are the preferred agents.

After induction, consolidation therapy is the next step. 2-4 cycles high dose cytarabine therapy for 5 days. This destroys any remaining tumor cells after induction.

Maintenance chemotherapy is not a part of AML treatment due to lacking evidence of benefits.

For those who don’t achieve remission with chemotherapy or have unfavourable cytogenetic factors, allogenic stem cell transplantation might be an option.

Complications such as neutropenia and tumour lysis syndrome are common during and sometime after the treatment. Some prophylactic measures:

  • Acyclovir for reactivation of HSV and HZV.
  • TMP-SMX for PCP
  • Allopurinol and IV fluids for tumour lysis syndrome
  • Granulocyte colony-stimulating factor (Filgrastim) to decrease the duration of aplasia and neutropenia.
  • Isolation to prevent infections while being neutropenic.
  • Broad-spectrum antibiotics if neutropenic fever. NB: find the source of infection if possible!
  • Transfusion of erythrocytes or platelets if needed.

Prognosis

Age is an independent and a bad prognostic factor. It is also important to consider the overall health status of the patient and comorbidities. The ECOG scale is a good indicator of this. AML associated with genetic abnormalities increases with age and might make the disease resistant to therapy.

Despite the advancement in therapy for AML, the long-term survival rate remains 20-40 %, and with cell stem transplantation up to 40-50%.