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Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is a cancer of the myeloid line of blood cells, characterised by the rapid growth of abnormal cells that accumulate in the bone marrow and blood, interfering with normal blood cell production. Symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infections. Occasionally, AML may spread to the brain, skin, or gums. Without treatment, AML progresses rapidly and can be fatal within weeks or months.

Acute myeloid leukaemia. In the cytoplasm of individual cells, you can see characteristic inclusions – Auer rods
Acute myeloid leukaemia. In the cytoplasm of individual cells, you can see characteristic inclusions – Auer rods

Signs and Symptoms

Most AML symptoms result from the crowding out of normal bone marrow cells. Lack of white blood cells makes patients more susceptible to infections. Low red blood cell counts (anaemia) cause fatigue, pallor, shortness of breath, and palpitations. A lack of platelets can result in easy bruising, nosebleeds, petechiae, and bleeding gums. Other symptoms include fever, weight loss, and loss of appetite. Gum swelling can occur due to leukaemic cell infiltration, and mild spleen enlargement is possible. Lymph node swelling is rare, except in acute myelomonocytic leukaemia (AMML).

Swollen gums due to infiltration by leukaemia cells in a person with AML
Swollen gums due to infiltration by leukaemia cells in a person with AML

Risk Factors

AML risk factors include age (most common in people aged 65-75), male gender, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome (MDS), and exposure to benzene. Genetic predispositions such as Down syndrome and conditions affecting DNA repair, like Fanconi anaemia, also increase risk.

Chemical Exposure

Chemotherapy agents, particularly alkylating agents and topoisomerase II inhibitors, are linked to AML development. Benzene exposure and the use of Agent Orange, contaminated with TCDD (a toxic dioxin), are also risk factors.

Radiation

High doses of ionising radiation, such as those used in radiotherapy for other cancers, increase AML risk. This risk diminishes to the general population level after 12 years.

Diagram showing the cells where AML develops
Diagram showing the cells where AML develops

Diagnosis

Diagnosis involves a complete blood count revealing leukocytosis or leukopenia, anaemia, and thrombocytopenia. Blood films may show leukaemic blast cells and Auer rods. Definitive diagnosis requires bone marrow aspiration and biopsy, examined under light microscopy and flow cytometry. Cytogenetic testing identifies chromosomal abnormalities, and genetic studies look for specific mutations, such as FLT3 and NPM1.

Bone marrow: myeloblasts with Auer rods seen in AML
Bone marrow: myeloblasts with Auer rods seen in AML

Treatment

First-line AML treatment primarily involves chemotherapy, divided into induction and consolidation phases. Induction aims for complete remission by reducing detectable leukaemic cells, using a regimen called "7+3" with cytarabine and an anthracycline. For acute promyelocytic leukaemia, treatment includes all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) or an anthracycline.

Consolidation

Post-remission, consolidation therapy prevents relapse by eliminating any residual disease. This typically involves further intensive chemotherapy, particularly with high-dose cytarabine in younger patients.

Stem Cell Transplantation

Allogenic stem cell transplantation is considered if the prognosis is poor, and a suitable donor is available. The graft versus leukaemia effect aids in eliminating leukaemic cells, although it carries the risk of graft versus host disease.

Supportive Treatment

Supportive treatments include blood transfusions to manage anaemia and thrombocytopenia, and antibiotics or antifungals to prevent or treat infections. Aerobic exercises may reduce fatigue and depression, but have little impact on mortality or overall quality of life.

Recent advances include targeted epigenetic therapies like ivosidenib and enasidenib for patients with specific genetic mutations. AML during pregnancy is treated urgently, considering the implications for both mother and foetus. Olutasidenib (Rezlidhia) was approved in the US in 2022 for treating AML.

Expected survival upon diagnosis of acute myeloid leukaemia in the United States
Expected survival upon diagnosis of acute myeloid leukaemia in the United States

Prognosis

Prognosis depends on specific genetic mutations and patient age, with a median survival of 8.5 months and a 5-year survival rate of 24% in the US. Younger patients fare better, with cure rates in clinical trials ranging from 20-45%, while the elderly and those unable to tolerate aggressive therapy have lower rates. Cytogenetic abnormalities and secondary AML from previous chemotherapy are associated with poorer outcomes. Prognostic factors also include lactate dehydrogenase levels, tobacco use, marital status, and treatment at high-volume centres.

Chromosomal translocation (9;11), associated with AML
Chromosomal translocation (9;11), associated with AML

Epidemiology

AML is rare, accounting for about 90% of acute leukemias in adults. Incidence increases with age, with a median diagnosis age ranging from 63 to 71 in Western countries. AML accounts for 1.2% of all cancer deaths in the US. Therapy-related AML is expected to rise due to increased chemotherapy use and an ageing population. AML is more common in men and varies by ethnicity and occupation.


Self-assessment MCQs (single best answer)

What is Acute Myeloid Leukaemia (AML)?



Which of the following is NOT a common symptom of AML?



What characterises the cells seen in the cytoplasm of individual AML cells?



Which of the following is a risk factor for developing AML?



What is the first-line treatment for AML?



Which specific therapy is used for acute promyelocytic leukaemia?



What is the median survival rate for AML patients in the US?



Which diagnostic test is NOT typically used to diagnose AML?



What is a common feature of supportive treatment for AML?



Which of the following factors is associated with a poorer prognosis in AML?



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Excellent content clearly explained.
SJ

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