Acute Myeloid Leukemia – Causes, Syptoms And Diagnosis
Acute myeloid leukemia (AML) is a clonal malignancy of hemopoietic tissue characterised by anarhic proliferation of abnormal blast cells in the marrow and impaired production of normal blood cells resulting in anemia and thrombocytopenia. Acute myeloid leukemia occurs in seven morphologic types, each with characteristic
clinical and laboratory features. Acute myeloid leukemia accounts for 80% of acute leukemias in adults and 15% -20% in children.
Acute Myeloid Lukemia Causes
Three environmental factors are certain causative agents:
- Ionizing radiation.
- Chronic benzene and organic chemicals exposure.
- Treatment with alkylating agents or other cytotoxic drugs.
Other possible involved factors are:
- Genetic factors (Down syndrome, Bloom syndrome, Fanconi anemia).
- Viral agents (HIV).
- Genetic alterations reflected in multiple chromosome abnormalities are frequent in acute myeloid leukemia patients, famillial aggregation beeing reported but its significance is unknown.
- Chronic myeloproliferative disorders and preleukemic syndromes ream progress to acute myeloid leukemia.
Acute Myeloid Leukemia Symptoms
Acute myeloid leukemia onset frequent with symptoms and signs of:
- Anemia: pallor, fatigue, weakness, palpitations, dyspnea on exertion.
- Thrombocytopenia (low platelet count): bruising, petechiae, epistaxis, gingival bleeding, conjunctival hemorrhages, prolonged bleeding after minor cuts.
- Neutropenia (low neutrophil counts): infections (eg. cutaneous) with pyogenic Gram-negative microorganisms or systemic candidosis.
- Fever, anorexia and weight loss may be present. Hepatomegaly and splenomegaly occur in about 1/3 of acute myeloid leukemia patients.
- Lymph node enlargement is uncommon except with the monocytic type.
- Leukemic cells may infiltrate any organ or tissue in the body, but organ dysfunction is unusual. Occasionally large aggregates of myeloblasts or monoblasts (granulocytic sarcomas) may develop.
Acute Myeloid Leukemia Diagnosis
- Anemia and thrombocytopenia are constant present.
- Leukopenia below 4.000/ul occurs in about 50% of patients, and neutropenia below 1.000/ul is encountered in over one half of patients at diagnosis. Mature neutrophils may be hyper- or hyposegmented and hypogranular.
- Myeloblasts comprise from 3 to 95% of the leukocytes and in one third of the patients up to 10% of the myeloblasts contain Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts. They are composed of fused lysosomes and contain peroxidase, lysosomal enzymes and large crystalline inclusions).
- In 5% of patients occurs extreme elevation of the leukocyte count which became symptomatic (leukostasis) at counts greater than 100.000/ul. Leukostasis occurs most likely in the circulation of the central nervous system, leading to intracerebral hemorrhage, in the lungs, resulting in pulmonary insufficiency or in the penis, causing priapism (prolonged and painful erection).
- Hyperuricemia and elevated serum lactic dehydrogenase levels.
- Patients with high leukocyte counts may have false hypoglycemia and hypoxia.
- Electrolyte abnormalities are infrequent but there may occur:
- Hypercalcemia and hypophosphatemia.
- Severe hypokalemia or false hyperkalemia in patients with very high leucocyte counts.
Is most often hyprecellular with monomorphic blastic metaplasia. Blast cells are identified by the presence of Auer rods, reactivity with cytochemical stains (myeloperoxidase present in myeloblasts, chloracetate esterase present in monoblasts) or rectivity with monoclonal antibodies to epitopes specific for myeloblasts. Cytogenetic abnormalities are present in about 50% of patients.
Unusual Presentations Of Acute Myeloid Leukemia
- Hypoplastic leukemia: pancytopenia (a reduction in the number of red and white blood cells, as well as platelets) and hypoplastic marrow.
- Oligoblasticc leukemia: anemia and thrombocytopenia, a few blast cells in the blood and marrow (this type is often considered a myelodisplastic syndrome).
- Congenital or neonatal leukemia is 10 times more common in newborns with Down syndrome than in apparently normal babies.
- Hybrid (biphenotypic) leukemias are characterised by cells which have both myeloid and lymphoid markers (chimeric) or cells that have either myeloid or lymphoid markers but arise from the same clone (mosaic).
- Mixed leukemias have myeloid and lymphoid cells present simultaneously, each derived from a distinct clone.
- Coexistence of Acute myelogenous leukemia and mediastinal germ cell tumors has been reported, and there is evidence for a aclonal relationship between the neoplastic cells of the two diseases.