Acute Myeloid Leukemia Cancer
Acute Myeloid Leukemia Cancer
Leukemia is a type of cancer that originates in cells that would normally mature to form different types of blood cells.
Acute Myeloid Leukemia
Also known as acute myelocytic leukemia or acute myelogenous leukemia, AML is a cancer of blood and bone marrow. As the name suggests, it is acute which indicates that this leukemia can progress rapidly if left untreated.
AML is caused by acquired oncogenic mutations that impede the normal differentiation process of the blood cells. The accumulation of these immature blast forms suppress the formation of normal hematopoiesis which results in bone marrow failure and complications like anaemia, thrombocytopenia and neutropenia.
Bone marrow constitutes the soft inner part of some specific bones such as the bones in the skull, shoulder blades, ribs, pelvic bones, and backbones. The bone marrow is accountable for generating of new blood cells.
Inside the bone marrow, blood stem cells maturate into different types of new blood cells. During this process, the cells may become either lymphocytes (a kind of white blood cell), red blood cells, white blood cells (other than lymphocytes), or platelets.
What happens in Acute Myeloid Leukemia?
In healthy conditions, stem cells produce myeloblasts that mature into different type of blood cells but in Acute Myeloid Leukemia, the myeloid stem cells do not form mature blood cells rather they develop into a type of immature white blood cell called myeloblasts. These immature myeloblasts cannot form healthy white blood cells rather they grow abnormally and clog the bone marrow thus hindering the production of healthy blood cells. Most cases of AML develop from cells that would turn into white blood cells (other than lymphocytes), but some cases of AML develop in other types of blood-forming cells including red blood cells, or platelet-making cells (megakaryocytes).
Also, the cancer cells can travel in the bloodstream and further spread to distant organs, where they begin to form tumor in other parts of the body including the lymph nodes, liver, spleen, central nervous system, and testicles. Due to their immaturity, they are unable to function properly to prevent or fight infection. Inadequate numbers of red cells and platelets being made by the marrow results in several health hazards like anemia, and easy bleeding and/or bruising.
Types of Acute Myeloid Leukemia
AML has eight different subtypes classified on the basis of:
- Degree of differentiation.
- Lineage of the leukemic blasts
The subtypes of acute myelogenous leukemia include:
- M0, M1 and M2: These are myeloblastic leukaemia and accounts up to almost 50% of all cases.
- M3: In M3, numerous auer rods are seen in the cytoplasm. M3 leukemia is also called acute promyelocytic leukaemia and it accounts for 10% cases of AML.
- M4 and M4eos: These are myelomonocytic leukaemia and accounts for 25% of AML.
- M5: M5 or monocytic leukaemia is characterized by gum infiltration and makes up 10% of cases.
- M6:This is erythro leukaemia and its occurrence is very rare.
- M7: This is also called megakaryoblastic leukaemia and this is also very rare subtype.
Occurrence Rate of Acute Myeloid Leukemia
AML is the most chronic type of blood cancers in adults, but it can also affect children. It is more common among older people and is rarely encountered before the age of 45. The average age of a patient with AML is about 67 years. AML is slightly more common among men than among women, but the average lifetime risk in both sexes is less than 0.5%.
At the early stages, leukemia hardly shows any signs or symptoms. But as it progresses rapidly, the deficiency of healthy blood cells results in several health issues. The symptoms are generally related to the deficiency of a particular blood cell.
Symptoms related to deficiency in red blood cell
Red blood cells are responsible for transporting oxygen and removing carbon dioxide from the body. A shortage of red blood cells results in a lowered level of oxygen in the body which may cause:
- Persistent fatigue
- Dizziness or lightheaded
Symptoms due to low white blood cell
White blood cells are responsible for maintaining immunity and fighting infections, so a lowered count in WBC causes:
- Frequent Infections
- Lowered Immunity
- Persistent sickness
Symptoms from low blood platelet counts
Platelets in the blood are responsible for clumping and clotting blood vessel injuries and preventing excess bleeding. A shortage of blood platelets can lead to:
- Excess bruising and bleeding
- Frequent or severe nosebleeds
- Bleeding gums
- Heavy menstruation bleeding
- Blood in stools or urine
- red, purple, or brown bruises called “purpura”
- rashes with small red or purple dots called “petechiae”
Symptoms caused by high numbers of leukemia cells
The rapidly forming blast cells clog up the bone marrow and hinder the production of healthy functional blood cells. This condition is termed as leukostasis. Some of the symptoms related to leukostatis are:
- Severe headache
- Slurred speech
- Bone or joint pain
- Shortness of breath
- Blurry or loss of vision
Though experiencing one or more of these symptoms do not ascertain that one is suffering from acute myeloid leukemia, yet visiting a doctor and getting the tests done would elucidate the root cause of these indications.
For most cases of AML, the exact causes could not be traced. However, AML is thought to be linked with a gene mutation in the blood developing cells in the bone marrow. This mutation of genes interferes with the healthy production of blood cells and results in abnormal growth of immature blood cells that develop into leukemic white blood cells called myeloblasts. These leukemic cells are incapable of functioning as the healthy blood cells. This rapid production of immature blood cells crowd out the healthy cells resulting in leukemia.
It is yet under scrutinization as to what causes this DNA mutation. Throughout these years of study and research, it has been concluded that certain factors like radiations, tobacco, exposure to certain chemicals increase the risk of developing AML.
Since the exact causatives of AML are not yet clear, so stating the precautions becomes a bit tricky. However, controlling the known risk factors is believed to provide some shielding to AML.
- Quitting smoking helps in preventing AML as it is the most significant controllable risk factor of AML.
- Avoiding known cancer-causing chemicals, such as benzene, can lower the risk of getting AML.
- Taking precautions against exposure to workplace and environmental chemicals.
- In case, if one is at a risk due to familial or health conditions, it is advised to go for regular screenings to facilitate early detection and cure against AML.
The general approach to stage cancer is by using a standardized numbered staging system. The stage of cancer describes the size of the tumor, the spread of the disease and its relative possibility of getting cured. Staging is essential for determining the most viable treatment option and the prognosis of the same.
However, in case of Acute Myeloid Leukemia, this conventional method of staging does not work, as the disease originates within the bone marrow and spreads rapidly to other organs usually without the trace of any tumor. There is no standard staging system for AML. It is rather categorized as untreated, in remission, or recurrent.
This stage is assigned for newly diagnosed AML. The leukemic cells are not yet treated except to relieve signs and symptoms such as fever, bleeding, or pain. At this stage the following conditions are checked:
- The complete blood count is abnormal
- At least 20% blast cells are found in the bone marrow
- No prominent sign or symptom of leukemia is reported.
At this stage, treatment for leukemia has already began but it is not completely cured yet. Following conditions are checked:
- The complete blood count has been restored to normal.
- The percent of blast cells in the bone marrow has reduced to less than 5%.
- There are no signs or symptoms of leukemia in the brain and spinal cord or elsewhere in the body.
Recurrent AML indicates that the leukemic cells have reappeared in the bone marrow after it has been treated completely once.
As already mentioned, age is a risk factor for AML, so the mortality rates are also higher in the elderly than in children. For most cases of early detection, treatment works well to cure AML. However, there are several factors that play a major role in determining the prognosis and outlook for a particular patient.
Without treatment, most patients with acute leukemia would live only a few months. Some types of AML may respond well to treatment and can be cured. The survival rate gives a general idea of the number of patients who were treated successfully in the past; but they cannot predict the outcome of any particular patient. Here is the 5 year survival rate statistics based on the age groups of the patients:
|Age Group||5 year Survival Rate|
|less than 14 years||65%|
|Over 65 years||5%|
The outlook for AML patients depends largely on several factors like type of AML, spread of the disease, other health conditions and response to treatment. What may work for one may not necessarily bring the same results for another. As each body is unique so is its response to treatment. Here are some of the key factors that impact the outlook for AML:
- Age: AML is more severe in case of older patients and younger people have a better prognosis.
- Gene alteration: Some specific genetic abnormalities in the leukaemia cells may make the treatment harder and the prognosis poor.
- Stage of Leukemia: As with any other cancer, even in AML the earlier it is detected the better is the chances of recovery. As AML is a rapid cancer which means it spreads fast to the bloodstream and eventually to other organs, earlier detection and treatment aids in curing and inhibiting its spread to distant organs.
- Response to treatment: As it is already mentioned the general health conditions of a patient determines his or her response to a specific treatment and the time taken for remission of leukemic cells. Remission means there are no more active leukemic cells in the bone marrow
AML do not show any prominent sign or symptom at the earlier stages or until it has spread enough to cause health hazard, it is often possible that AML goes unnoticed.
However, going for regular health check-ups and screenings and reporting any symptom to the health care aids in early detection of AML. In case, AML is suspected following tests and procedures might be recommended:
Physical Examination and Medical History: This is the first step of diagnosing leukemia. The patient may visit for a regular health check-up or to consult regarding the symptoms of the disease. During the physical examination, the overall health record of the patient is taken into account. If the person complains about any of the mentioned symptoms then the doctor suspects leukemia
Blood Tests: Since leukaemia is the cancer of the blood, a blood test can be helpful in getting a lot of information. Blood test is done to check the following parameters:
- A complete blood count showing the number of red cells, white cells and platelets is done.
- A peripheral blood smear examines the cells within the blood and checks the number of immature white cells. The blood smear sample can also be used for
- Cytogenetic analysis, which identifies certain changes in the number and size of chromosomes within cells.
- Immunophenotyping: This is done to identify cells based on the types of antigensor markers on the surface of the cell.. E.g."Flow cytometry".
Bone marrow test: A blood test can suggest leukemia, but a bone marrow test is conducted to confirm the diagnosis. During a bone marrow biopsy, a sample of bone marrow usually from the hipbone is removed using a needle and is tested for leukemic cells. Bone marrow testing involves two steps:
- A bone marrow aspiration to remove a liquid marrow sample
- A bone marrow biopsy to remove a small amount of bone filled with marrow
Genomic testing: These tests are conducted to identify specific genes, chromosome changes, and other issues unique to leukemia and to find any genetic changes or mutations. This test helps in determining the prognosis.
Once AML has been diagnosed, several tests are done to determine the stage and spread the disease. The following tests are generally conducted to determine the spread of leukemia:
- Lumbar puncture : In this procedure, a sample of cerebrospinal fluid (CSF) is collected from the spinal column which is then checked under a powerful microscope for determining if leukemic cells have spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
- Imaging Tests: As leukemia does not form tumors, imaging tests aren’t as useful as they are for other types of cancer. However, imaging tests like CT scan, X- ray, MRI may be performed to detect infections or other problems, rather than for the leukemia itself. These imaging tests may use radioactive particles to highlight the spread of cancer cells. Imaging tests also give a fair idea of the extent of the disease.
The treatment of AML mainly focuses on:
- Killing leukemia cells
- Returning blood counts to normal
- Ridding the body of any signs of the disease
Treatment needs to begin soon after AML is diagnosed, as it progresses very quickly. The type of treatment used will depend on a number of factors including the sub-type of AML, the genetic make-up of the leukaemic cells, general health and age.
- Remission induction therapy. The first phase of treatment i.e. remission induction is focused to kill the leukemia cells. However, it is not the full proof option to wipe out all of the leukemia cells. So further treatment is required to prevent the disease from returning.
- Consolidation therapy. This is the post-remission therapy that is aimed at destroying the left over leukemia cells. It begins once the induction therapy is complete. The goal of post-remission therapy is to kill any remaining leukemia cells that may not be active but may re-grow and cause a relapse.
- Targeted therapy: Targeted therapy refers to the use of drugs that target specific parts of cancer cells and tend to have less severe side effects. Monoclonal antibody therapy stops the action of an enzyme within the leukemia cells and causes the cells to die. Some of the widely used drugs for targeted therapies include :
- Midostaurin: It blocks FLT3 and other proteins on cancer cells to starve off the cancerous cells.
- Enasidenib: It is targeted to block IDH2 protein on leukemia cells and help the leukemia cells mature into more normal cells. It is also known as a differentiation agent.
- Gemtuzumab ozogamicin: The antibody attaches to protein called CD33 and directs the chemo drugs towards the leukemia cells. The chemo drug then penetrates into the cancerous cells and kills them.
- Bone marrow transplant. Also called stem cell transplant it aids in re-establishing healthy stem cells. Stem cells are removed from the blood or bone marrow of the patient or a donor and is infused once remission is completed. These re-infused stem cells are healthy and functional cells that grows into the body's blood cells.
- Radiation therapy: Radiation therapy is the use of high-energy x-ray beams to kill cancer cells or inhibit its growth. Though Radiation therapy is not a part of the main treatment it might come to aid in a few situations like:
- It may be used to treat metastatic leukemia that has spread to the brain and spinal fluid or to the testicles.
- Radiation may be given before a stem cell transplant.
- Radiation may be used to combat pain in the bone that is invaded by leukemia, in case chemotherapy has failed to solve the purpose.
Treatment of Acute Promyelocytic Leukemia – A subtype of AML
In Acute promyelocytic leukemia, immature granulocytes called promyelocytes gets accumulated. In most cases of APL, the treatment differs from usual AML treatment. Initial treatment may include the non-chemotherapy drug all-trans-retinoic acid (ATRA), often combined with a complementing chemotherapy drug.
Early diagnosis and treatment of APL is important because patients with APL can develop serious blood-clotting or bleeding problems at later stages. However, with the latest advent in cancer drugs today there are multiple procedures to treat APL. Some preferred treatment options are:
- Use of differentiating drugs like all-trans-retinoic acid (ATRA)
- Transfusions of platelets or other blood products.
Side effects are more of an individual thing rather than a general thing. The type and severity of side effects varies from individuals to individuals, depending on the type of treatment used and how each individual responds to it. In general, more intensive treatment is associated with more severe side-effects.
Other possible side-effects of chemotherapy include:
- Chemotherapy reduces the ability of bone marrow to produce adequate number of blood cells. Blood transfusions and platelet transfusions are done to reduce the risk of anaemia and bleeding.
- Sickness - nausea and/or vomiting
- hair loss and thinning
- mucositis or ulcers
- diarrhoea or constipation
- skin problems including dryness, rash or sensitivity to sunlight
Acute leukemia can often be cured with proper treatment. Bone marrow transplantation can successfully enhance lifespan of a patient. Chronic leukemia is known to give much longer life if treated properly e.g. CLL or CML. Treatments are often able to control the cancer and manage symptoms in case of chronic leukemia.
Going for regular checkups and being attentive to even the slightest of health hazards may prove to be a life saving habit.