Causes, Symptoms and Treatment of Acute Myeloid Leukaemia

Overview

Acute Myeloid Leukaemia (AML) is one of the types of blood-cancer and is called by several names including acute myelocytic leukaemia, acute myelogenous leukaemia, acute granulocytic leukaemia and acute non-lymphocytic leukaemia. The disease is more common in adults, than children. While chemotherapy and stem-cell transplants help treat it in the present, the condition can recur again and again, which requires the person to take life-long treatment. In this article, we will learn various aspects of the condition.

Introduction

AML is one of the most common types of blood-cancer. In the US alone, nearly 20,000 adults are diagnosed with the condition every year. Although 1 in 3 adults who are diagnosed with leukaemia have AML, the condition is still rare and accounts for just 1% of all cancer cases. Children can also develop the condition. Nearly 25% of all childhood leukaemia cases pertain to AML.

Causes

The bone-marrow is an important tissue in the body that makes immature blood-stem-cells that become mature blood-cells over time. The immature blood-stem-cell can become either a lymphoid stem-cell or a myeloid stem-cell. The lymphoid stem-cell becomes a white-blood-cell over time.

The myeloid stem-cell becomes one of the following:

• Red-blood-cells that transport oxygen and nutrients to the body’s cells
• A type of white-blood-cells called granulocytes that are involved in fighting infection or disease
• Platelets that help the blood clot and prevent uncontrolled bleeding

In people who have AML, the myeloid stem-cell become immature white-blood-cells that are called myeloid blasts or just myeloblasts. These myeloblasts are abnormal white-blood-cells that cannot become healthy white-blood-cells. In some cases, the immature blood-stem-cell can also create many abnormal red-blood-cells and abnormal platelets.

The abnormal RBCs, WBCs and platelets start accumulating in the bone marrow and crowd out the healthy RBCs, WBCs and platelets. This results in anaemia, infections and severe bleeding.

Further, the myeloblasts travel outside the blood to the brain, spinal-cord, skin, gums, testicles, spleen, liver and lymph-nodes. Here, they can form solid tumours called as myeloid sarcomas.

However, what exactly causes some people to develop AML is still not clearly known. But there are some risk factors.

Risk Factors

• Age: Being 65 years or older increases the risk for AML.
• Gender: Men are more at risk than women.
• Smoking: Both active smoking and exposure to second-hand smoke increases the risk due to benzene and other toxic chemicals present in cigarette smoke.
• Exposure to radiation: Survivors of a nuclear reactor accident are exposed to dangerous levels of ionizing radiation which increases AML risk in a big way.
• Exposure to toxins: Repeated exposure to benzene (used in oil refineries, as in the case of refinery workers), cleaning chemicals such as detergents, paint-thinners or paint-removers, and pesticides, increase AML risk.
• Blood disorders: Such as myelodysplastic syndrome, thrombocythemia, myelofibrosis and polycythemia vera
• Genetic disorders: Such as Down syndrome, Fanconi anaemia, Klinefelter syndrome, trisomy 8, Li-Fraumeni syndrome and neurofibromatosis type 1.
• Cancer treatment: Both radiation, and chemotherapy drugs such as mitoxantrone, doxorubicin, cyclophosphamide and melphalan increase the risk.
• Family history of AML: Although this risk is very low

Symptoms

Symptoms of anaemia or a low RBC count:

• Fatigue
• Pale skin
• Weakness
• Headaches
• Shortness of breath when physically active
• Dizziness, light-headedness, or fainting

Symptoms of neutropenia or a low WBC count:

• Fever
• Recurring infections

Symptoms of thrombocytopenia or a low platelet count:

• Frequent or severe nosebleeds
• Bruising easily
• Bleeding gums
• Tiny red spots on the skin, called “petechiae”
• Prolonged bleeding from minor cuts or bruises

Other general symptoms:

• Unexplained weight loss
• Loss of appetite
• Pain and discomfort in bones or joints
• Abdominal swelling due to an enlarged spleen or liver

When AML spreads to other parts of the body

• Balance problems
• Spots or a rash on the skin
• Blurred vision
• Seizures
• Numbness in the face
• Swollen lymph nodes in the neck, underarms or groin
• Swollen or bleeding gums

Complications

• Anaemia: This is the direct consequence of a low RBC count. Since the body cells are not getting enough oxygen now, the person feels tired, weak and short of breath whenever active.
• Bleeding: This is the direct consequence of a low platelet count. Now the blood does not clot easily, so injuries or nosebleeds (due to various reasons) can lead to prolonged bleeding. If the same happens inside the body, it can be very dangerous.
• Weakened immune system: This is the direct consequence of a low WBC count. Since WBCs help fight germs, infection and disease in general, a low healthy WBC count weakens the immune system. The person develops infections more easily now and falls ill often.

Diagnosis

• Physical examination and medical history: The doctor will investigate the medical history of the person. He/she will then examine the patient physically which involves looking for swollen lymph nodes in the neck, underarms and groin, skin conditions, bruising etc.
• Complete blood count (CBC): Blood is drawn from the patient and examined under a microscope to get a count of RBCs, WBCs, platelets and the haemoglobin concentration in the RBCs.
• Peripheral blood smear: This will look for the number of healthy WBCs, the number of myeloblasts, the shape and size of the various blood-cells, and changes in shape.
• Flow cytometry: Blood cells from a sample of the patient’s blood, or bone-marrow, or another tissue are stained with a fluorescent dye, and immersed in a fluid. They are then passed one at a time through a beam of light. This helps measure the number of cells in a sample, the number of live cells, their size, shape and the presence of tumour markers on the surface of the cells.
• Bone-marrow aspiration/biopsy: A sample of the fluid in the bone-marrow is removed using a long and thin needle (aspiration) and a sample of the solid in the bone marrow is cored out using a thicker needle. Both these samples are examined under a microscope to detect signs of cancer. Generally, the hip-bone is preferred for this procedure.
• Tumour biopsy: In case the cancer has spread to other tissues or organs (called myeloid sarcoma), a biopsy of the tumour is done to determine characteristics of the cells, pace of growth, etc.
• Cytogenetic analysis: Changes in certain chromosomes in blood-cells are a sign of blood-cancer. So, a sample of blood-cells from the blood or bone-marrow is taken and examined under a microscope. This will help detect rearranged, missing, broken or extra chromosomes. By analysing the same, the doctors can plan for the right course of treatment. Other genetic tests include fluorescence in situ hybridization (FISH), which also looks for certain changes in chromosomes of the blood-cells.
• Molecular testing: As the name implies, this laboratory test looks for certain molecules, certain proteins and certain genes in a sample of blood or bone-marrow cells. This may indicate cancer and/or the chances of developing AML. This will help the doctors plan the right treatment. It is also done when treatment has started, to check the progress.
• Immunophenotyping: This looks for antigens or certain markers on the surface of blood-cells, which can indicate the presence of blood-cancer.
• Reverse transcription–polymerase chain reaction test (RT–PCR): This is a laboratory test used to check if certain genes are activated, or if there are certain changes in a gene or chromosome, as all these will indicate the presence of cancer cells.
• Spinal tap: Also called lumbar puncture, this is a procedure in which the spinal fluid surrounding the spinal cord is extracted using a fine needle, and the same is examined under a microscope to look for cancerous blood-cells.

Treatment

There are various options and the doctors will choose the right one depending on the age of the person, his/her general health, severity of the condition, whether it’s a follow-up treatment or a fresh one, and what the patient prefers.

The treatment is done in 2 phases:

1. Remission induction therapy: The aim of this treatment is to kill all the cancer cells so that the patient is induced into Remission. Remission is when the cancer is no longer active or showing no symptoms, although the leukemia cells are still present in small numbers, so further treatment will be required to prevent the condition from flaring up again.
2. Consolidation therapy: Once the person is going through remission (post-remission or maintenance phase), the aim of treatment is to totally eliminate the residual cancer cells, so that there is no risk of relapse.

Both these phases will use one or more of the below therapies:

• This uses chemicals to destroy cancer cells in the body. If one iteration of chemotherapy does not induce remission in the patient, the same can be repeated.
• Targeted therapy. This uses certain drugs that target specific abnormalities in the cancer cells. By blocking or neutralizing these abnormalities, the cancer-cells die a natural death.
• Bone-marrow or stem-cell transplant. This is used during the consolidation phase. To begin with, high doses of chemotherapy are given to destroy cancerous tissues in the bone-marrow. Then, healthy stem-cells taken from the bone-marrow of a healthy person is transplanted into the bone-marrow of the patient. This will trigger regeneration of healthy bone-marrow tissue.
• Clinical trials. There are new drugs and therapies constantly emerging, to treat various conditions, including blood-cancer. The patient can opt for clinical trials for these drugs, therapies or combinations of the same.

Kauvery Hospital is globally known for its multidisciplinary services at all its Centers of Excellence, and for its comprehensive, Avant-Grade technology, especially in diagnostics and remedial care in heart diseases, transplantation, vascular and neurosciences medicine. Located in the heart of Trichy (Tennur, Royal Road and Alexandria Road (Cantonment), Chennai (Alwarpet & Vadapalani), Hosur, Salem, Tirunelveli and Bengaluru, the hospital also renders adult and pediatric trauma care.

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