Acutenew, recent, comes with an urgent or significant sense, is sudden, sharp myeloid leukaemiacancer of blood and/or blood forming tissues (AML), also known as acute myelocytic, myelogenous, or granulocytic leukaemia, is a type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that causes an overproduction of myeloid cellsthe basic structural and functional unit of all living things in the bloodthe red bodily fluid that transports oxygen and other nutrients around the body. Myeloid cells are responsible for the production of red blood cells, plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding, and all white blood cells except for lymphocytes (one of the main immune cells in the body).
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps to remove waste from our bodies. There are three primary types of blood cells produced in the inner, spongy portion of the bone (bone marrowsoft, spongy tissue found in bones that makes blood cells) from stem cells (immature blood cells that develop into either red blood cells (RBCs), white blood cells (WBCs), or platelets). RBCs, or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. WBCs are responsible for fighting infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after injury.
AML causes excess blood cells to be produced, which reduces the capacity of the bone marrow to produce healthy RBCs, WBCs, and platelets. Unlike chronica long-lasting disease that changes slowly over time myeloid leukaemia (CML), this disease tends to develop rapidly.
AML is the less common type of acute leukaemia. It is more common in males, and is generally diagnosed in people under 24 years of age. However, anyone can develop this disease.
Types of Acute Myeloid Leukaemia
There are several types of AML, which are classified based on how the cancer cells look under the microscope. There are two classification systems used to arrange subtypes.
French-American-British (FAB) Classification System
The French-American-British (FAB) classification system was devised in the 1970’s by a group of French, American, and British leukaemia experts. This system is grouped into eight categories based entirely on how the cancer cells look under the microscope (shape, size, type of cell, and how mature the cells are).
- M0 – Undifferentiated AML.
- M1 – AML with minimal maturation.
- M2 – AML with maturation.
- M3 – Acute promyelocytic leukaemia (APL).
- M4 – Acute myelomonocytic leukaemia.
- M4 eos – Acute myelomonocytic leukaemia with eosinophilia.
- M5 – Acute monocytic leukaemia.
- M6 – Acute erythroid leukaemia.
- M7 – Acute megakaryoblast leukaemia
This classification system can be useful, but does not consider many other factors that may influence the prognosisto predict how a disease/condition may progress and what the outcome might be of AML.
World Health Organisation (WHO) Classification System
The world health organisation (WHO) classification system was revised in 2016, and includes more factors that may influence prognosis to better classify the disease.
AML with Certain Genetic Abnormalities
AML with certain genetic abnormalities are types of AML that develop due to changes in genes or chromosomes in our DNA. This can involve a genetic translocation (when part of one chromosome is moved to part of another chromosome), an inversion (when a portion of a chromosome is inverted or ‘put in reverse’), or a fusion (where two genes fuse together to make a new gene). The types of AML with certain genetic abnormalities include:
- AML with a translocation between chromosomes 8 and 21.
- AML with a translocation or inversion in chromosome 16.
- Acute promyelocytic leukaemia (FAB M3 – caused by a translocation between chromosomes 15 and 17).
- AML with a translocation between chromosomes 9 and 11.
- AML with a translocation between chromosomes 6 and 9.
- AML with a translocation or inversion in chromosome 3.
- Acute megakaryoblast leukaemia with a translocation between chromosomes 1 and 21.
- AML with the BCR-ABL1 (BCR-ABL) fusion gene.
- AML with a mutated NPM1 gene.
- AML with mutations of both CEBPA genes.
- AML with a mutated RUNX1 gene.
The aggressiveness and prognosis of these diseases vary by subtype.
AML with Myelodysplasia-related Changes
AML with myelodysplasia-related changes are common types of AML that develop in people who have previously had a myelodysplastic syndrome (MDS), or a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). This type of AML is often aggressive, and may not have as good of a prognosis as other types of AML.
For more information on MDS and MDS/MPN, please refer to the Rare Cancers Australia Myelodysplastic Syndromes page.
Therapy-related Myeloid Neoplasms
Therapy-related myeloid neoplasms are a type of AML that occur as a rare result of chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, and/or immunotherapya treatment that uses a person's immune system to fight cancer treatments. This type of AML can be aggressive, and may not have as good of a prognosis as other types of AML.
AML not Otherwise Specified
AML not otherwise specified includes all types of AML that do not meet the criteria for other groups in the classification system, and resembles the FAB classification system. Types of AML not otherwise specified include:
- Undifferentiated AML (FAB M0).
- AML with minimal maturation (FAB M1).
- AML with maturation (FAB M2).
- Acute myelomonocytic leukaemia (FAB M4).
- Acute monocytic leukaemia (FAB M5).
- Acute erythroid leukaemia (FAB M6).
- Acute megakaryoblast leukaemia (FAB M7).
- Acute basophilic leukaemia.
- Acute panmyelosis with fibrosis.
The aggressiveness and prognosis of these diseases vary by subtype.
Myeloid Sarcoma
Myeloid sarcomacancer arising from bones and/or soft tissue, also known as a chloroma or a granulocytic sarcoma, is a rare type of AML that presents as a sarcoma (cancer arising from bone and/or soft tissuetissue/the material that joins, holds up or surrounds inside body parts such as fat, muscle, ligaments and lining around joints) outside of the bone marrow and blood. This type of AML is often aggressive, and may not have as good of a prognosis as other types of AML.
Myeloid Proliferations Related to Down Syndrome
Myeloid proliferations related to down syndrome is a rare type of AML associated with down syndrome, a genetic condition caused by a trisomy (a condition where a person has three copies of a chromosome instead of two) of chromosome 21. While this type of AML can be aggressive, it can have a good prognosis when caught early.
Treatment
Staging and Grading of AML
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, because of how rare AMLs are, there is currently no standard staging and grading system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- The type of AML you have.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumoura tissue mass that forms from groups of unhealthy cells DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Phases of Treatment
Treatment for AML is generally done in phases:
Phase 1: Remission Induction Therapy
Remissiona reduction or absence of symptoms in disease, can be partial or complete induction therapy is an intensive course of treatment aimed at inducing disease remission. For this phase, the patient is admitted to hospital. In some cases, the disease won’t respond to treatment as expected, and it may be said that the patient has a resistant or refractory disease. In these cases, the doctor may recommend a more intensive form of therapy to treat the disease more effectively.
Phase 2: Post-remission (Consolidation) Therapy
After remission is achieved, post-remission or consolidation therapy is used to help destroy any remaining cancer cells left in the body. This phase is crucial for ensuring the cancer does not return (or relapsethe return of disease), and that it does not spread into the central nervous system (CNS) (the system responsible for all sensory and motor functions in the body that is composed of the brain and the spinal cord). The intensity of this phase depends on how well the patient responds to phase one of treatment.
Phase 3: Maintenance Therapy
Maintenance therapy is the final phase of treatment, and is designed to keep the patient’s disease in remission, and to prevent it from relapsing. This phase generally lasts for several months, and the patient is generally treated as an outpatient; however, in some cases they may need to be admitted into hospital.
Treatment Options
Treatment is dependent on several factors, including age, stage of disease and overall health.
Treatment options for AMLs may include:
- Chemotherapy.
- Radiation therapy.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
While the cause of AML remains unknown, the following factors may increase the likelihood of developing the disease:
- Exposure to high levels of radiation (either as a treatment or accidentally).
- Exposure to industrial chemicals, such as benzene.
- Prior treatment with certain types of chemotherapy.
- Having certain genetic conditions, such as:
- Down syndrome (trisomy 21).
- Neurofibromatosis type 1 (NF1).
- Bloom syndrome.
- Fanconi anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.
- Ataxia-telangiectasia.
- Li-Fraumeni syndrome.
- Diamond-Blackfan anaemia.
- Shwachman-Diamond syndrome.
- Kostmann syndrome (also known as severe congenital neutropeniaa condition where there are low levels of neutrophils (a type of white blood cell) in the body).
- Trisomy 8.
- Having a family history of AML.
- Having certain blood disorders, such as:
- Myelodysplastic syndromes (MDS).
- Myelofibrosis.
- Anaplastica term used to describe abnormal cancer cells that grow uncontrollably in the body and have little or no resemblence to regular cells anaemia.
- Paroxysmal nocturnal haemoglobinuria.
- Having a history of smoking.
Not everyone with these riskthe possibility that something bad will happen factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Symptoms
In the early stages of disease, some patients may appear symptomatic. As the cancer progresses, some of the following symptoms may appear:
- Anaemia, which carries its own set of symptoms:
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Dizziness.
- Paleness.
- Dyspneadifficulty breathing, shortness of breath.
- Frequent or persistent infections.
- Easy bruising and/or bleeding.
- Bone and/or joint pain.
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy in the neck, underarms, stomach, and/or groinarea between the abdomen and thighs.
- Abdominal discomfort, potentially caused by a swollen liver, thymus, and/or spleen.
- Purpuraa rash of small, red dots due to small superficial capillary bleeds; generally larger than petichiae or petechiaea rash of small, red dots due to small superficial capillary bleeds; generally smaller than purpura.
- Unexplainable weight loss and/or loss of appetite.
- Fever and/or drenching night sweats.
- Unusually heavy menstrual periods.
- Leukostasis, which carries its own set of symptoms:
- Headache.
- Weakness on one side of the body.
- Slurred speech.
- Confusion.
- Fatigue.
- Problems with blood clotting.
Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have an AML, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests (if the cancer is thought to have spread beyond blood and bone marrow), potentially including:
- X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Lumbar puncturea procedure that involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Biopsyremoval of a section of tissue to analyse for cancer cells.
