Acute myeloid leukaemia is a malignant neoplastic disease that affects white blood cells. It is also known as acute myelogenous or myelocytic leukaemia. AML is largely responsible for 25% of childhood leukaemias, and the incidence increases with age. AML is the most common acute leukaemia in adults, with the median age of onset being 68 years.
AML is caused by the uncontrolled growth of the myeloid cell line in the bone marrow. The growth of these cells results in non-functional immature white blood cells, which interfere with the normal formation of blood cell components, leading to pancytopenia (a reduction in WBCs, RBCs, and platelets). Pancytopenia can result in anaemia, bleeding and bruising, and increased susceptibility to infection. Furthermore, blast cells may spread to other organs such as the brain, liver, and skin.
The main risk factor for AML is myelodysplastic syndrome and other pre-existing haematological disorders. However, in the majority of cases, AML appears suddenly in individuals who were previously healthy.
The following risk factors are associated with acute myeloid leukaemia (AML):
Some patients with AML may be asymptomatic and present with only laboratory abnormalities. Symptoms of AML can be present for only days to weeks before diagnosis. The most common symptoms are due to disrupted hematopoiesis. These symptoms include:
Other important questions to ask include:
The clinical presentation of AML can vary greatly. Typical clinical findings in AML may include weight loss, physical signs of anaemia (pallor and a cardiac flow murmur), fever, signs of infection (lung findings consistent with pneumonia), thrombocytopaenia (petechia, dermal bleeding and ecchymoses), and leukaemic infiltration of the organs (hepatosplenomegaly, lymphadenopathy, and swollen gums). Less common findings, which usually appear in later stages, include leukaemia cutis (infiltration of the skin with leukaemia cells) and respiratory distress and altered mental status (indicative of leukostasis, a medical emergency characterised by an extremely elevated blast cell count).
Pancytopenia can be caused by a variety of diseases with a wide range of severities. A patient with AML needs to be distinguished from a patient with another haematological disorder. Table 1 outlines the differential diagnoses of leukaemia.
HaematologicalInfectionsAutoimmune diseasesOther
Aplastic anaemia
Myelodysplastic syndrome
Myelofibrosis
Lymphoma
Lymphoproliferative disorders
Paroxysmal nocturnal haemoglobinuria
Epstein-Barr virus
Cytomegalovirus
HIV
Parvovirus B19
Systemic lupus erythematous
Cytotoxic therapies
Radiation
Drug-induced (e.g. phenothiazines)
The diagnosis of acute myeloid leukaemia (AML) is made by integrating the patient's history, clinical presentation, and laboratory results. A diagnosis is confirmed by either identifying at least 20% myeloid blasts in either the bone marrow or peripheral blood or by detecting specific cytogenetic abnormalities.
Relevant laboratory investigations include:
A bone marrow biopsy is needed to stage the disease. The percentage of blasts determines the classification of a chronic, accelerated, or blast crisis.
Typically, both a bone marrow aspiration and a bone marrow trephine biopsy are performed. An aspirate is a syringe of liquid bone marrow while a trephine is a 1-2cm piece of core bone marrow removed in one piece. Characteristically, the bone marrow is hypercellular due to the replacement of normal cellular components by immature or undifferentiated cells.
Analysis typically performed on the bone marrow includes immunophenotyping by flow cytometry, cytogenetics, fluorescence in situ hybridisation, and molecular analyses.
Flow cytometry may be done with a peripheral blood or marrow aspirate and is used to identify circulating myeloblasts by characteristic patterns of surface antigen expression. Most AML subtypes express CD34, HLA-DR, CD117, CD13, and CD33.
AML is classified using either the World Health Organization (WHO) classification or the French-American-British (FAB) classification.
The World Health Organization (WHO) classification system for Acute Myeloid Leukaemia (AML) is formulated based on a combination of morphological, immunophenotypical, genetic, and clinical factors. These include:
The French-American-British (FAB) classification is based on the type of cell from which the leukaemia developed, as well as its degree of maturity. This includes:
The WHO classification is more clinically suitable and generates more accurate prognostic information than the FAB criteria.
Chemotherapy is the primary treatment for AML and consists of an induction phase, consolidation phase, and maintenance therapy.
Induction chemotherapy is a shorter and more intense period of treatment, lasting 2-6 weeks. Its aim is to clear the blood of leukaemic cells (blasts) and to reduce the number of blasts in the bone marrow to a normal level. This requires high-dose chemotherapy, which can be accompanied by severe side-effects.
Consolidation chemotherapy is administered after the patient has recovered from the induction phase. Its goal is to kill any remaining blast cells. It is recommended even if there is no evidence of tumour cells remaining after induction. Consolidation is usually given in cycles and while the dosage of chemotherapy is lower, it can still cause severe side-effects.
Maintenance chemotherapy involves repeatedly administering a low dose of chemotherapy to maintain remission. This period can last from months up to 2 years.
The most common chemotherapeutic agents used in AML are cytarabine (cytosine arabinoside – ara-C) (an anti-metabolite), daunorubicin (daunomycin) or idarubicin (an anthracycline), and All-trans retinoic acid (ATRA) and arsenic (typically used in the treatment of acute promyelocytic leukaemia (APML)).
A bone marrow transplant (also called a stem cell transplant or hematopoietic stem cell transplant) is an allogenic transplant, where stem cells come from another person (a donor). The donor's stem cells are given to the patient after the patient has undergone chemotherapy and/or radiation therapy.
Bone marrow transplant is usually indicated in patients with high cytogenetic risks, lack of complete remission after first induction treatment, or high initial leukocyte count.
Supportive therapies for AML include blood cell transfusions (platelet transfusions are performed when platelets fall below < 10 × 109/L, and red cell transfusions are performed when haemoglobin is < 7 or 8 g/dL), adequate analgesia, and good oral hygiene (Mycostatin and chlorhexidine mouthwash and parenteral feeding may be considered in patients undergoing hematopoietic cell transplantation).
Acute myeloid leukaemia (AML) is a cancer of white blood cells arising from the uncontrolled growth of the myeloid cell line in the bone marrow. It is responsible for about 25% of childhood leukaemias but is the most common acute leukaemia in adults.
The most common risk factor is myelodysplastic syndrome and other pre-existing haematological disorders. Symptoms of AML may be asymptomatic or include anaemia, thrombocytopaenia, neutropenia and leukaemic infiltration.
Diagnosis of AML requires identifying ≥20% myeloid blasts in the bone marrow (or peripheral blood). Investigations include full blood count, LDH, uric acid and peripheral blood smear which may be followed by a bone marrow aspirate and biopsy.
The main treatment for AML is chemotherapy usually consisting of an induction period, consolidation period and maintenance therapy.
Due to an increased risk of bacterial, fungal and viral infections, antimicrobial prophylaxis is used. This includes PCP prophylaxis with co-trimoxazole, an anti-viral such as valacyclovir to prevent re-activation of HSV or antifungals. Allopurinol is used to prevent the build-up of uric acid and anti-emetics are used in the prophylaxis and treatment of nausea and vomiting.
Complications of AML include leukostasis, tumour lysis syndrome and disseminated intravascular coagulation. Life-threatening complications have been associated with certain subclassifications of AML.
Age is the most significant patient-specific risk factor with a 5-year survival rate of 25% for people 20 and older and 67% for people younger than 20. For those >60 years old, the prognosis is improving but remains poor.
Acute myeloid leukaemia (AML) is a type of blood cancer that affects the myeloid cells, which form red and white blood cells and platelets. Several resources have been consulted to understand the diagnosis and classification of this condition. Vakiti et al reviewed the pathophysiology, diagnosis and treatment of AML and Angelescu et al outlined the value of a multifaced approach to the diagnosis and classification of acute leukemias. Jonathon and Kolitz overviewed the condition in 2020 and Younes S. described it in PathologyOutlines.com. Percival et al. investigated the role of bone marrow in diagnosis and monitoring of AML, while the Armed Forces Institute of Pathology (AFIP) provided an image of two myeloblasts with a single, prominent Auer rod.
Arber et al. published a revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemias in 2016, which was followed by Sabattini et al. in 2008. The American Cancer Society (ACS) provided information about treating AML and Magina et al. conducted a systematic review and meta-analysis on cytarabine dose in the consolidation treatment of AML. Murphy and Yee focused on cytarabine and daunorubicin for this condition and Müller et al. discussed the indications for allogeneic stem cell transplantation in myeloid malignancies. Ashkan and Law provided information about AML in the MDS Manual Professional Version, while Hong et al. conducted a systematic review into basic oral care for the management of oral mucositis in cancer patients. Rajesh et al. detailed the management of oral mucositis in cancer patients, Krakoff examined the use of allopurinol for the prevention of hyperuricemia, Rose-Inman and Kuehl looked into the broader aspects of acute leukaemia, and Döhner et al. and Liersch et al. discussed prognostic factors.
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