Acute Myelogenous Leukemia (AML)

Acute Myelogenous Leukemia (AML) is a fast-growing blood cancer which involves the production of large number of immature myeloblasts, a type of white blood cells (WBC) in the bone marrow. AML, also known as acute myeloblastic leukemia, acute myeloid leukemia, or acute non-lymphocytic leukemia (ANLL), is commonly found in adults, particularly in men.

Based on the traditional FAB classification, AML is classified into type M0 to M7 with excellent prognosis of AML-M3.

M0 – Undifferentiated leukemia

M1 – Myeloblastic without differentiation

M2 – Myeloblastic with differentiation

M3 – Promyelocytic

M4 – Myelomonocytic; M4eo – Myelomonocytic with eosinophilia

M5 – Monoblastic leukemia; M5a – Monoblastic without differentiation; M5b – Monocytic with differentiation

M6 – Erythroleukemia

M7 – Megakaryoblastic leukemia

Causes of AML

  1. Antecedent hematologic disorders, such as MDS, aplastic anemia and myelofibrosis. MDS or Myelodysplastic Syndrome is a bone marrow disease of unknown etiology that occurs most often in older patients and manifests as progressive cytopenias that occur over months to years.
  2. Congenital syndromes, such as Bloom syndrome, Down syndrome, congenital neutropenia, Fanconi anemia, and neurofibromatosis, usually developed during childhood.
  3. Environmental exposures, such as receiving early radiations like therapeutic irradiation for ankylosing spondylitis; survivors of the atomic bomb explosions in Japan; smokers have a small but statistically significant; exposure to benzene is associated with aplastic anemia and pancytopenia; exposure to soot, creosote, inks, dyes, tanning solutions and coal dust.
  4. Drug exposures such as chemotherapeutic agents.
  5. Familial syndromes, such as Germline mutations in the gene

However, most patients who are recently diagnosed (de novo) AML have no identifiable risk factor.

Occurrence of Acute Myelogenous Leukemia (AML)

  • AML is more commonly diagnosed in developed countries
  • AML is more common in whites than in other populations.
  • The prevalence of AML increases with age. The median age of onset is approximately 70 years. However, AML affects all age groups.
  • AML is more common in men than in women.
  • The difference is even more apparent in older patients

Symptoms of AML

Patients with AML have symptoms either resulting from bone marrow failure or those due to organ infiltration with leukemic cells, or from both. The time course is variable.

Bone marrow failure symptoms

Bone marrow failure symptoms related to anemia, neutropenia, and thrombocytopenia include fatigue, decreased energy level over past weeks, dyspnea upon exertion, dizziness in patients.

In fact, myocardial infarction (a heart attack) may be the first visible symptom of acute leukemia in an older patient, fever, history of upper respiratory infection, bleeding gums and multiple ecchymoses, and bleeding of life-threatening sites like lungs, gastrointestinal (GI) tract, and the central nervous system.

Symptoms due to organ infiltration with leukemic cells in spleen, liver, gums, and skin

Patients with spleen enlargement face fatigue and fullness in the left upper abdomen that may spread to the left shoulder. Gum infiltration involves swelling and bleeding.

Patients with markedly elevated WBC counts (>100,000 cells/µL) can present with symptoms of leukostasis (i:e, respiratory distress and altered mental status). Leukostasis is a medical emergency that calls for immediate intervention. Patients with a high leukemic cell burden may have bone pain caused by increased pressure in the bone marrow.

Investigations required for AML

  • Blood tests
  • Bone marrow aspiration and biopsy (the definitive diagnostic tests)
  • Analysis of genetic abnormalities
  • Diagnostic imaging
  • Immunophenotyping to distinguish AML from acute lymphocytic leukemia (ALL) and further classify the subtype
  • Cytogenetic study performed to get important prognostic information
  • Human Leukocyte Antigen (HLA) or DNA typing for patients who are potential candidates for allogeneic bone marrow transplantation
  • Computed tomography (CT) or magnetic resonance imaging (MRI) in patients with signs suggesting central nervous system (CNS) involvement
  • Lumbar puncture performed in patients, if no CNS mass or lesion detected in CT scan or MRI.
  • Chest radiographs to assess pneumonia and cardiac disease signs
  • ECG & Echocardiography for patients who have a history or symptoms of heart disease or risk

Treatment for Acute Myelogenous Leukemia (AML)

Acute Myelogenous Leukemia (AML) is treated with chemotherapy. Appropriate blood transfusion support is also provided to patients with AML.

The five-year survival rate of AML is 40%, except for APL (Acute Promyelocytic Leukemia) which has a survival rate greater than 90%.

Treatment options for Acute Myelogenous Leukemia (AML)

1)       Variety of chemotherapy regimens

a)       Induction therapy – different protocols are followed according to age and general condition of the patient. Approximately 50% of patients achieve remission with one course. Another 10-15% of patients enter remission after a second course of therapy.

b)       Consolidation therapy in younger patients – This includes high dose chemotherapeutic drugs along with bone marrow transplant.

2)       Stem cell transplantation – Autologus or allogenic BMT