Acute Myeloid Leukemia

Introduction

Acute myeloid leukemia forms in the bone marrow cells. The immature and abnormal white blood cells, also called blasts, occupy the bone marrow and get into the bloodstream. The bone marrow synthesizes a large amount of these immature and abnormal white blood cells derived from the myeloid stem cell. This affects the production of normal blood cells thus leading to anemia and increasing the risk of infections and problems with bleeding. There are different types of acute myeloid leukemia depending on the level of maturation and type of the cells that are cancerous. The principal subtypes include M0, M1, and other, up to M7. Sometimes these subtypes have descriptive names such as acute myelomonocytic leukemia for M4, in which there is only one blast cell that eventually develops to a monocyte. M0 is also known as acute myeloid leukemia and is characterized by minimal evidence of myeloid differentiation. It is important to note that acute myeloid leukemia is not a common cancer disease. Most often it affects people over the age of 50, and rarely occurs in people below 20. In addition, this disease affects men more often then women.

Causes of acute myeloid leukemia

Leukemia begins from the development of one abnormal, cancerous cell. Subsequently, the vital genes, responsible for controlling the processes of cell division are damaged, altered, or destroyed. This results in the production of the abnormal blast cells. The cancer cells that survive to this level begin multiplying abnormally and in large numbers, resulting in the development of leukemia. In case of acute myeloid leukemia, the transformation of an immature white blood cell to abnormal blast cells is hard to detect, which makes this disease even more hazardous. These factors include exposure to benzene, high doses of radiation, and various genetic conditions, which increase the chances of developing acute myeloid leukemia.

Symptoms of acute myeloid leukemia

As it was previously mentioned, acute myeloid leukemia involves the production of abnormal blast cells, which fill up the bone marrow. “This makes it difficult to the normal cells to survive in the bone marrow, and also reduces the number and efficiency of these normal cells” (Elworthy 67). The abnormal blast cells also enter into the blood stream, resulting into different complications. In order to detect the disease at the beginning stage of development, it is important to clarify its symptoms.

There are diverse symptoms and signs of acute myeloid leukemia, which are often nonspecific. However, these symptoms are often attributed directly to the leukemic infiltration of the bone marrow, which ultimately results in cytopenia. The time of exhibiting symptoms may vary. Young patients can have symptoms occurring from a few days to a couple of weeks, while other groups of patients exhibit a lengthy course with the mentioned symptoms, which may occur during a period of several weeks to even months. This lengthy course can imply the development of a hematologic disorder known as myelodysplastic syndrome.

Patients suffering from acute myeloid leukemia have symptoms which range from hemorrhage, fatigue, fever and infections because of the reduction in white cells, platelets and red blood cells. Other symptoms include pallor and dyspnea on exertion.

Symptoms of bone marrow failure

The symptoms of bone marrow failure are connected with neutropenia, anemia and thrombocytopenia. One of the mentioned complications, anemia, occurs because of the decrease in red blood cells. The symptoms of anemia include fatigue, breathlessness, pale skin, and other symptoms. Patients with acute myeloid leukemia retrospectively report a reduced energy level after a few weeks. Other symptoms of anemia include dizziness, dyspnea upon exertion, and angina chest pain especially in patients having coronary heart disease. In elderly patients, the initally occurring symptom of acute myeloid leukemia can be myocardial infarction.

Other symptoms of bone marrow failure include the reduced level of neutrophil in the affected patients. At the same time, the level of total white blood cell count is normal or even increased. In most cases, patients show signs of fever which can occur during presence or absence of a reported infection. The patients with the highest infection risk are those documenting the lowest absolute neutrophil counts, ie, < 500 cells/µL, especially those with less than 100 cells/µL. The other symptoms of infection reported are pain in the upper respiratory system, which does not show any signs of improvement even after empirical treatment and use of oral antibiotics.

Patients suffering from the bone marrow failure show multiple ecchymosis and also have bleeding gums. Bleeding can be a result of thrombocytopenia, or of coagulatory caused by DIC (Disseminated Intravascular Coagulation). It is crucial to consider the sites that are potentially life threatening from instant bleeding, which include gastrointestinal tract, lungs, and the central nervous system. There is also a risk of the system of blood clotting, which is also referred to as thrombosis. It occurs as a result of reduced levels of platelets, which leads to gum bleeding, easy bruising, and other bleeding related complications.

Another symptom of the bone marrow failure is a serious infection. The abnormal blast cells do not act like the normal white blood cells in protecting or fighting against infections. Acute myeloid leukemia causes a reduction in the number of these normal white cells that are responsible for fighting infections. There the production of abnormal blasts as a result of this form of cancer leads to the development of serious infections. These infections vary depending on the type and location of the infection.

Symptoms of organ infiltration with leukemic cells

Acute myeloid leukemia may also result in infiltration of the vital organs with leukemic cells. The abnormal blasts developing from the acute myeloid leukemia accumulate in various parts of the body. This may cause swelling of glands, enlargement of liver or spleen, and other rare symptoms. Organ infiltration with leukemic cells can also be detected through pains in joints or bones, weight loss and persistent fever. Letal outcome of this disease can occur only after several months if the disease is left untreated.

The organs that most often are affected with leukemic infiltration include liver (hepatomegaly), spleen (splenomegaly), skin (leukemia cutis), gums, gingiva, lymph nodes (lymphadenopathy), bone (bone pain), and central nervous system. Leukemic infiltration mostly occurs in patients with the monocytic subtypes of acute myeloid leukemia. Patients exhibiting splenomegaly show symptoms of fullness especially in the upper left quadrant, and they also report to have an early satiety. Patients with symptoms of gum infiltration most often identify the problem after visiting dentists. Thus, it is established that swollen gums result from gingivitis caused by neutropenia, while bleeding gums can be caused by thrombocytopenia. A separated mass of leukemic blasts or cells are often known as granulocytic sarcoma (Silverstein, Virginia and Laura 89). A count of over 100,000 white cells per cubic millimeter) can cause hyperleukocytosis, and other symptoms of leukostasis, such as cerebrovascular and ocular bleeding or dysfunction. There can also be symptoms of metabolic abnormalities although they can rarely be interpreted as symptoms of a dangerous illness. Examples of these abnormalities include hypocalcemia and hyperuricemia.

Diagnosing of acute myeloid leukemia

Diagnosing and assessment of acute myeloid leukemia can be done with the help of different tests and procedures. One of them is the blood test, which reveals a reduced level of normal white blood cells, red blood cells and platelets. The blood test also shows the invasion of the blast cells from the bone marrow into the blood stream. In cases when high numbers of blast cells can be found in the bloodstream, a patient may need further tests to confirm the diagnosis.

The bone marrow test is another effective test that involves obtaining a small fraction of the bone marrow by inserting a needle into the bone of the pelvis of sternum. The site for injection has to be initially numb. Another way to do this test is to do the trephine biopsy, which involves removal of a small core of the marrow. Examination of the samples has which helps to identify the abnormal blast cells has to be conducted using a microscope.

One more procedure that is used for diagnosing the acute myeloid leukemia is the cell and chromosome analysis, which involves detailed examination of the abnormal cell taken from the blood test or bone marrow sample. Transformations or changes in the cells and chromosomes are checked in this form of analysis. Diagnosing the different subtypes of acute myeloid leukemia is possible only by means of detecting changes and transformations in different parts of chromosomes of the leukemia cells, compared to the normal immune cells.

Another kind of tests is lumbar puncture, which can reveal symptoms of the abnormal blast cells spreading in the spinal cord or brain. This test involves collecting small quantities of fluid, also known as cerebrospinal fluid, from the spinal cord. This can be done by inserting a needle in the vertebrae region of the back. Later, this fluid has to be examined for the presence of leukemia cells. In order to achieve greater accuracy, other supplementary tests can be done including blood tests, chest X-ray and other test requested by the physician.

Treatment of acute myeloid leukemia

The main aim of fighting the acute myeloid leukemia is to kill all the abnormal, cancerous cells. This can enable the bone marrow to restore the production of normal blood cells. The main means of treatment of acute myeloid leukemia is chemotherapy, which in some cases is followed by stem cell transplantation. The treatment regime for this disease includes taking drugs long enough and in required doses, and also consideration of the various factors involved. These factors “rely on the research trial with the goal of determining the best treatment for the different subtypes of acute myeloid leukemia” (Goldsmith 234). These factors include age, general health status, sex of the patient, the exact subtype of leukemia, and the amount of blasts identified on the stage of testing and diagnosing. Another important factor is the change of condition during the first phase of treatment. It is important to indicate whether the condition has spread to the spinal cord and brain, or whether it is a secondary or subsequent complication from an initial infection of the bone marrow.

The patients suffering from acute myeloid leukemia fall in various categories depending on the mentioned factors. These classes are standard, low or high risk. The form and intensity of treatment also depends on the risk groups, for instance, patients in the high risk group will receive intensive treatment.

Chemotherapy

As it was mentioned earlier in this paper, chemotherapy is one of the main procedures in treating acute myeloid leukemia. It is based on using anti cancer drugs in order to eliminate the cancerous cells and stop the process of multiplication of these abnormal blast cells. That is why, “the process of chemotherapy involves administrating numerous doses of anti cancer drugs through the vein over a stipulated time frame” (Apel 145). It is mostly performed by use of a plastic tube inserted in the large blood vessel. As a rule, this procedure is done in the central area of a vein located in the chest or a central line in the arm. This tube remains in the vein until the treatment is finished, in order to avoid the pain of repeated injections. Chemotherapy is often given in cycles, with each cycle involving a set of treatment followed by a resting period. This resting period allows the body to recover from possible side effects, and also gives an “opportunity for the damaged cells to renew prior to the subsequent cycle of treatment” (Parker and Inc International 12).

Chemotherapy treatment for acute myeloid leukemia has two phases. The first phase, known as the induction phase, involves the initial treatment cycles, which aim at destroying majority of the cancerous cells. The end of this phase exhibits no traces of abnormal blast cells situated in the bone marrow or blood sample. This is known as the state of remission, which does not necessarily means total cure, but rather the entire elimination of abnormal blast cells. The second phase, also known as consolidation or intensification phase, comprises the remaining treatment cycles with the use of different drugs from the induction phase. This phase involves elimination of the remaining cancerous cells present in the organism and not detectable by any of the existing tests.

Along with the mentioned benefits for the patient, chemotherapy also has a number of side effects. They can occur either during treatment or after completion of the chemotherapy session. The unwanted and noticeable side effects occur due to the powerful drugs used in chemotherapy. “These side effects vary depending on the drugs being used for chemotherapy” (Hook 176). The most common side effects include loss of hair, nausea, a high level of infection risk because of the negative effect of the treatment on the normal blood cells. In some cases, side effects can occur after several months or years following a period of intensive chemotherapy. Such side effects can range from cases of infertility to dysfunction of some glands responsible for secreting certain hormones.

During the chemotherapy, some helping preparations can be used in order to enhance the influence of the procedures.  To specify, all-trans retinoic acid that targets acute promyelocytic leukemia can be used. This drug comprises a form of vitamin A, also called tretinoin. This drug is useful alongside chemotherapy and can only be administered for three months. The mode of action of all-trans retinoic acid is differentiation or maturation of leukemia cells, which quickly improves the symptoms of leukemia. Another form of treatment is by stem cell transplant, also called bone marrow transplant and “used on a single form of acute myeloid leukemia” (Siegel and Newton 78). It is usually applied in cases of recurring or relapses in leukemia after chemotherapy. Other supportive treatments entail use of antifungal drugs in cases of infection, platelets or blood transfusion in order to enhance the levels of platelets and red blood cells, and other supportive measures to reduce the side effects of chemotherapy.

Prognosis of acute myeloid leukemia

For quite a long time, acute myeloid leukemia has reported poor prognosis, but this condition has improved over the years because of the continuous improvement in the treatment regimes. The exact figures are not traceable, but there exists a satisfactory response to the various modes of treatment. This response depends on various factors, such as age and the exact form of acute myeloid leukemia. For instance, patients under the age of 60 have an excellent chance of response to treatments when their classification of acute myeloid leukemia is in the low risk group.

Conclusion

There is a wide variation of the symptoms of acute myeloid leukemia as they depend on factors such as age and subtype of the AML. In most cases, acute myeloid leukemia develops rapidly or acutely and worsens after a short period of time, usually after a few weeks, unless the affected individual seeks treatment. Therefore, it is extremely important to know the risk factors of the acute myeloid leukemia development. Patients exhibiting high counts of white blood cells (>100, 000 cells/µL) can show symptoms that vary from mental status to respiratory distress, a condition also known as leukostasis. This is a condition that demands medical emergency and immediate intervention. Additionally, patients with a great burden of leukemic cells may show symptoms of bone pains as a result of high levels of pressure in the bone marrow. The prognosis is, in most cases, not beneficial for patients over 60 years, because such patients may lack the ability to tolerate intensive chemotherapy. They also do not respond effectively to treatment because most of them have suffered from bone marrow complications previously. Therefore, it is evident that acute myeloid leukemia is a serious disease that should be well understood and handled.