Acute Myeloid Leukemia EssayAcute Myeloid Leukemia Student number
Course Leader: Introduction
This paper discusses Acute Myeloid Leukemia (AMF) and examines its biological components, treatment options, incidence, and disease grading deploying a case study of a person with AML whose name will be changed to protect the identity of this patient out of confidentiality concerns. Becky, a 62-year-old female, was diagnosed with AML during her early 60s. Once diagnosed, she immediately sought treatment, which included multiple cycles of chemotherapy. Becky had Philadelphia chromosomal mutation problems, and his doctor advised that getting a stem cell transplant constituted his best prognosis and chance for survival. However, after Becky’s first treatment she became neutropenic and got sepsis so treatment discontinued. This case study has a variety of implications for nursing as they pertain to treatment options as they relate to overall survival, relapse, and quality of life outcomes.
Cancer develops when an abnormal proliferation of cells manifests without any intervention (Cooper, 2000). These cells can attach themselves to any tissue in the body, such as the bones, lungs, pleura, liver and the brain. Leukemia is a type of cancer that develops in the blood-forming tissue—commonly the bone marrow—and may lead to the overproduction of abnormal white cells, which constitute the component of the immune system that protects the body against attack by infection and foreign organisms (Kelaidi et al., 2011). A myeloid blood cell becomes a red blood cell, platelets, or granulocytes. Lymphoid cells develops into B and T lymphocytes and the natural killer cells. Leukemia primarily affects white blood cells and can be categorized according to how the disease progresses as well as the type of white blood cells affected (Hochhaus, 2011). The most common form of leukemia in adults, AML arises from myeloid cells that overgrow and occupy the bone marrow space and then blood plasma. (De Kouchkovsky & Abdul-Hay, 2016).
Incidence, Survival, and Mortality Rates
Adult acute myeloid leukemia refers not to a similar condition, but instead, it is an amalgamation of interrelated diseases that have an incidence of over 20,000 cases every year in just the United States(Estey,2013). Sizeable chromosomal translocations in addition to gene mutations that involves hematopoietic proliferation and differentiation cause poorly differentiated myeloid cells to accumulate (De Kouchkovsky & Abdul-Hay, 2016). Although a highly heterogeneous condition, cases of AML can be stratified into three different categories predicated on their cryogenic profile: favorable, intermediate, and adverse-risk groups. Its incidence falls within the range of three to five cases per a population of 100,000, and it increases (De Kouchkovsky & Abdul-Hay, 2016). In 2015, approximately 20,830 new cases of the patient diagnosed with this condition were made, and over ten thousand individuals with this situation died (De Kouchkovsky & Abdul-Hay, 2016). This incidence directly correlates with age' as it is most commonly diagnosed in individuals over the age of 65 years. In those under 65, the impact is an estimated 1.3 per 100,000 population, while for those older than 65, the incidence is 12.2 cases per 100,000 population (De Kouchkovsky & Abdul-Hay, 2016). Despite the fact that advances in the treatment of this condition have gained traction in treating younger patients, the prognosis for geriatric patients, which accounts for the prevalence of new cases, needs improvement. Approximately 70% of patients older than the age of 65 get rid of their condition usually within a year of diagnosis (De Kouchkovsky & Abdul-Hay, 2016).
According to the American Cancer Society, AML is a disease that mostly affects members of the geriatric population. Only under intermittent cases does it affect persons under the age of 45. In the majority of cases, AML affects men when compared to their female counterparts. However, the average lifetime risk in both males and females is less than half of 1%. The ASC (2016), in their medical reviews, also records that roughly 2 out of every 3 AML patients who receive standard induction Cytarabine to into remission. They further state in this report that older patients do not do as well as compared to patients under the age of 60 years and in most cases have trouble tolerating intensive treatment regimens and would in most cases have chromosome variations in their leukemia cells that are associated with poorer outcomes.
Cancer Cell Biology
Cancer is a type of a cell that grows and develops out of control. Different from other healthy cells cancer cells do not respond to signals to stop to specialize, divide, to shed or die. Growing uncontrollably, the cancer cells might spread to parts of the body where they are not needed. In the cancer cells, many genes mutate making the cells to be defective.
Therefore, the mandated stage for the conversion of a standard cell into a cancer cell, as the cancer cells must retain the capacity to reproduce under conditions that healthy cells cannot. Furthermore, it must be able to invade the surrounding tissue and diffuse throughout the human body (Couch, 1996). Both types of genetic changes, including the inactivation of the tumor suppressor gene or the activation of oncogenes as well as epigenetic alterations, figure prominently in the carcinogenesis process (Couch, 1996). Chemical agents can enhance the potentiality of malignancy via the inducement of mutations that underlie the formation of tumors because they promote the development of cancer in cells that have already been damaged or by amplifying the process in which benign tumors increasingly acquire malignant characteristics (Couch, 1996). Moreover, environmental and genetic variables can change the capacity of a cell to repair the damage done to the DNA, to metabolize carcinogens, and to react efficiently to mutagenic stimuli (Couch, 1996). All these factors are prominent features of susceptibility of cells to carcinogenesis. The various genetic changes that cause cancer frequently take several years to accumulate, as the biological behavior of the cells before malignancy change over a protracted period from the properties associated with healthy cells to those linked to cancer.
Biology of AML
A sophisticated and heterogeneous condition, AML refers to the "culmination of the interaction between epigenetic and genetic alterations in the hematopoietic progenitors, leading to dysregulation of multiple critical signal transduction pathways, resulting in hematopoietic insufficiency due to the accumulation of immature myeloid progenitors" (Arceci & Meshinchi, 2010). Clonal chromosome deletions, inversions, and translocations have persistently been examined for over thirty years in an estimated 2/3 of all AML cases. Advances in molecular biology that have manifested in the past fifty years have rendered these structural cytogenetic abnormalities have emerged as necessary signifiers to locate suspected or known genes that induce leukaemia (Caligiuri et al., 1997, p. 32). In the majority of cases, leukemogenesis in AML often spawns gene fusion when parts from two different genes amalgamate, resulting in the germination of a chimeric structure made up of the 3’ end of one and the 5’ portion of another. There are exceptions, especially for cases in which the AML does not have any discernible cytogenetic abnormalities. Researchers have increasingly shed light on the genes that contribute to malignant changes (Caligiuri et al., 1997, p. 32).
Both staging systems and cytogenetic and grading figure prominently in characterizing leukaemia, facilitating the determination of how aggressive the disease is, and informing how a patient responds to treatment and their prognosis (Byrd et al., 2002). Two staging systems are typically deployed for AML: the World Health Organization (WHO) classification, which takes into consideration evidence of dysplasia and chromosomal translocations, and the French-American-British (FAB) classification system, which is predicated on morphology to define particular immunities. The FAB staging system remains the more commonly-used system; both of the symptoms are derived from the morphological analysis of bone marrow and blood smears. Regardless of which diagnostic technique physicians choose to apply some patients need a combination of immunological, cytochemical, cytogenetic, and unique molecular genetic examinations to receive an accurate diagnosis and prognosis (Dohner et al., 2017). This type of analysis uses the WHO staging system, which is why many practitioners believe that the WHO staging system will eventually take the superior position that the FAB system currently occupies. Cytogenetic studies conducted on bone marrow with individuals who have AML play an integral role understanding various facets of the disease (Byrd et al., 2002).
Diagnosis of leukemia begins with a series of tests to establish the presence of cancerous cells in someone’s system. These methods include health history and physical exam, complete blood count, blood chemistry, cytochemistry, lumbar puncture, lymph biopsy, chest x-rays, MRI, and ultrasounds(Jabbour &Kantarjian, 2014). Lymph node biopsy is a kind of surgical biopsy where part of the lymph node is studied under the microscope to establish if there are cancerous cells in it to identify the sort of cancer and find out how quickly the cancer cells are growing ("Lymph node biopsy,” 2017).
People who have different subtypes of AML often possess different outlooks or respond differently to treatment (De Kouchkovsky & Abdul-Hay, 2016). Treatment for AML must begin as soon as it is diagnosed because of how quickly it progresses. Health status, age, and other factors need to be put into consideration when evaluating treatment options (Ribera et al, 2014). The primary and standard treatment for Acute Myeloid Leukemia is chemotherapy (De Kouchkovsky & Abdul-Hay, 2016). However, these can be done in combination with other methods of treatment, including targeted therapy. Treatment of AML comprises a variety of chemotherapy designs. As such, it is recommended that all patients should be assessed for entry into well- designed clinical trials. According to the FAB and WHO classification, AML can be categorized into subtypes ranging from MO (Undifferentiated acute Myeloblastic Leukemia) to M7 (Acute Megakaryocytic Leukemia). The World Health Organization (WHO) classification reviews chromosome and transformations and evidence of dysplasia (Seiter, 2015). The treatment for adults with AML consists of two phases, the remission induction therapy phase, and post-remission therapy. During the remission induction therapy, the objective is to kill the leukemia cells in the bone marrow and blood, therefore propelling leukemia into remission (De Kouchkovsky & Abdul-Hay, 2016).
Chemotherapy refers to a treatment for cancer that utilizes drugs to halt the multiplication of cancerous cells, either by killing or hindering them from dividing. Chemotherapy is administered either by oral means, or it is injected into the muscles and veins, thereby enabling the drug to enter the bloodstream. The treatment, known as systemic chemotherapy, can subsequently reach the cancer cells within the body. If chemotherapy is administered directly into the cerebrospinal fluid, which is known as intrathecal chemotherapy, body parts like an organ, or the abdomen the administered drugs primarily impact the cancer cells in those locales. This type of chemotherapy can be utilized to treat AML in adults and who have had cancer spread to the spinal cord and brain (Hayakawa et al., 1970). The anticancer drugs get injected into the intrathecal space, which refers to the space that retains the cerebrospinal fluid. This can be carried out through two ways: by inserting the drugs into an area called the Ommaa reservoir, or by injecting the drugs directly into the lower part of an individual’s spinal column once that area of the back is numbed (Hayakawa et al., 1970).
It is during chemotherapy that patients receive cytotoxic drugs to treat their debilitating conditions. AML patients are treated using cytotoxic drugs, which tend to interfere with how the cells multiply. Preclinical studies, as well as retrospective assessments of clinical trials conducted on a vast array of cytotoxic drugs, have proffered a rationale for treating AML with a high dose of chemotherapy in adults with it (Stasi et al., 1996). To maximize remission and cure rates at an acceptable cost of toxicity, researchers have tested various combinations and schedules of dose-intensive chemotherapy on patients suffering from a de novo disease (Chari, 2007). The most extensively assessed drug was cytosine arabinoside, and the results showed that the drug, when used in high doses, did not substantially benefit above regular doses of the drug (Cross et al, (2012). Conversely, consolidation with Ara-C has proven to profoundly help those with AML condition, especially for those who have AML and are under the age of 60 (Stasi et al., 1996). Unfortunately, the role of HIDAC retains no pertinence for younger patients. Because there are new cytotoxic agents that have yet to be amply tested, well-run, randomized trials involving the high dose of the chemotherapy drugs must "be performed to optimize schedules and combinations of drugs in patients with AML" (Stasi et al., 1996). The type of cytotoxic drug used hinges on the stage of cancer and the kind of the disease patient has, as there are several subtypes of AML that must be treated in an idiosyncratic fashion.
The preponderance of cancer patients develops neutropenia as a result of their chemotherapy treatment. Solid tumor malignancies can additionally cause it, mainly if they get into the bone marrow, or by specific lymph proliferative malignancies, including “natural killer cell lymphomas,” (Schouten, 2006). Neutropenia refers to a drop in neutrophils or a type of white blood cells. For patients suffering from neutropenia, even a slight infection can quickly result in a serious complication. Contextually, neutropenia developed during chemotherapy is drug-induced when drug ingestion causes failures of the bone marrow to produce sufficient numbers of white blood cells. Cancer-fighting medicines work by denaturing fast-growing cells within the body, both good and bad. It occurs 7 to 12 days after receiving chemotherapy, although through this period may be different contingent on the type of chemo that the patient gets (“Neutropenia and risk for infection,” 2017). Once the neutrophil count drops, a patient is more likely to develop an infection. The neutrophil level rises when the bone marrow resumes normal reproduction. At that point, the body is prepared for the next round of chemo (“Neutropenia,” 2017). However, several rounds of chemo may affect how quickly the marrow regenerates the neutrophils.
Researchers have ascertained very few ways from preventing the development of neutropenia, but the risk of developing an infection while there is a low count of white blood cell can be reduced. Neutropenia itself often is asymptomatic, and so patients learn they have neutropenia when they have a blood test for an unrelated reason (Neutropenia, 2017). However, people may show symptoms of infections or other problems that cause the neutropenia, which affects the mucous membranes like the ones inside of the skin and mouth. These can look like ulcers, rashes, abscesses and when wounds take a longer time to heal. When deciding on the treatment of neutropenia, health care specialists consider the source and seriousness of the neutropenia (“Neutropenia,” 2017). Among the recommended approaches for preventing and managing neutropenic sepsis include:
• Antibiotics for bacterial infections, if underlying causes is an infection
• Granulocyte colony-stimulator factor (G-CSF). This causes cells from the bone marrow to become mature and activated. Thus, after a high dose chemotherapy and stem cell transplantation, to help catalyze white blood cells production and give room for faster recovery, G-CSF is administered. By and large, preventive treatment with colony stimulating factors are used on patients who are considered at higher risk of fever and severe infection (Feldman et al, 2011).
• Stem cell transplant may also be necessary for nursing some people with severe neutropenia, including those resulting from marrow problems.
Cytotoxic drugs: Narrow therapeutic index
Th monitoring of therapeutic drugs is not regularly used for making cytotoxic agents.There are many reasons, but the main limitation is lack of appropriate established concentration ranges. The chemotherapy combinations makes the designing of therapeutic ranges for personal medicine complicated, the effect of concentration relationship for the single application of a drug might not have similar impact as compared when the drug is used in combination of other medications.Therefore, use of cytotoxic medicines in cancer therapy has a very narrow therapeutic index, implying that specific dosages have to be cautiously administered while avoiding any tendency to exceed the appropriate prescription (Junutula, 2008). Different drugs have varying types of toxicity and strength depending on the concentration. Patients who take more units of a dosage of cytotoxic drugs by mistake thereby exceeding the prescribed quantity are much likely to develop complications (Chari, 2007). This does not necessarily imply fatalities but a range of conditions as tested. Cytotoxic drugs are to be used by tested and prescribed standards. Extra amounts of the drugs have always proven to be a concern due to the high toxicity to patients undergoing treatment. When using cytotoxic drugs, implementation of therapeutic drug monitoring procedures is therefore emphasized in the treatment and therapy of leukemia. This includes determination of the size of blood vessels of the patient through the taking of measurements. The endpoint of toxicity is used to establish the recommended dose that is to be administered. However, for cytotoxic drugs, the more delayed a toxicity is, the higher the probability is that the treatment of the disease is less efficient. Hematological toxicity has been identified to be life-threatening.
Becky underwent chemotherapy process through the injection of the therapeutic drugs into muscle, under the skin, vein, and by mouth, toxic effects are likely to be evident some months or years after the administration of a cytotoxic drug. At the same time in this case of leukemia treatment, some cytotoxic medicines may result in toxicities immediately or shortly after a patient uses them(Grimwande et al,2010). Some may occur in the course of the intercycle period. Examples of such drugs include dexamethasone, prednisone, cyclophosphamide, methotrexate, 6-mercaptopurine (Purinethol or 6-MP), Teniposide (Vumon), etoposide (VP-16), cytarabine and daunorubicine among others (Cross, 2012). The administration of these drugs at times includes the combination of two or more of the medicines to attain the required results. They may present specific side effects which should be known during prescription and stated. For instance, in Becky's case, the side effects attached to toxicity may include fatigue resulting from the low count in the red blood cells, vomiting as well as appetite loss, diarrhea, sores on the mouth, high risk of contracting infections and diseases because of a reduced number of white blood cells in the body, fever, fatigue and hair loss among other slight anomalies that were also experienced by Becky. Possible effects of Becky's Chemotherapy treatment
The chemotherapy drugs administered to Becky attacks cells that generally quickly dividing as they work against cancerous cells. However, the boy cells such as the red blood cells (found in the bone marrow), and the one in the intestines linings, and hair follicles multiply quickly. These cells are more likely to be killed by cytoxic drugs, which leads to severe side effects such as mouth sores, diarrhea, loss of appetite, hair loss, and nausea and vomiting (Junutula el al, 2008).
Effectiveness: Status of AML after Treatment
The side effects usually are short-term, and once treatment is finished, they go away. There are several ways to lessen and reduce the occurrence of the side effects. For instance, antidiarrheal medication can be given to assist reduce or prevent diarrhea (Döhner, 2010). The treatment suppresses the immune system, thereby exposing the body to infections that could be fatal (Feldman, 2011). There may be dysfunction of organs as well as hyperfusion and septic shock which has led to deaths in many related cases (Stycznski et al, 2009). Successful resuscitation, in this cheap essay writing help case, may only rely on limited options, such as hypovolemia correction and reestablishment of the delivery and supply of oxygen by using a sodium lactate solution compound (Kelaidi& Fenaux, 2011).
The instances whereby single or multiple body organs may fail to function are in acute injury of the kidney, disseminated intravascular coagulation, extreme distress syndrome of the respiratory system and congestive cardiac failure, like in the case of Becky. Such extreme conditions are best-taken care of in an intensive care environment (Hochhaus, 2011). Among other treatment options for acute myeloid leukemia is consolidation which implies trying to destroy any existing leukemia cells to reduce chances of relapse and recurrence of cancer (Ribera, 2010). Here, only cytarabine is administered, which differentiates it from induction therapy. It is applied over five days at high doses and repeated after four weeks, conducted in three or four cycles. Alternatively, it may be done by following the chemotherapy dosages with allogeneic or autologous stem cell transplant. Patients of advanced age like Becky may be unable to withstand the intense consolidation therapy since it increases the number of possible resultant side effects. Consequently, consolidation for the specific patient such as Becky may include only one or two cycles of a low dosage of the cytarabine plus idarubicin, mitoxantrone, as well as daunorubicin. A mini-transplant or transfusion may also be applicable (Styczynski, 2009). This kind of treatment is, however, not as useful as the active use of cytotoxic drugs in the treatment and control of leukemia. Apart from Becky’s age, other factors that may be considered in the treatment include her wishes, the number of chemotherapy cycles, prognostic factors, availability of a donor as well as the ability to collect a bone marrow which is free from leukemia. Implications
After and during the chemotherapy process, it is essential to create awareness to the patient about the possible risks that may be attached to the process (De Naurois, 2010). The strategy will help in making the patient psychologically ready for any implication or complication which may result from the effect of the cytotoxic drugs administered in the therapy process. It should include making the patient aware of her role in the recovery process. The patient should be encouraged to be ready to offer personal input and to cooperate with the treatment schedule and dosages. The patient should carry herself in a manner suggesting independent control over the situation. The significance of each process of treatment should be made clear so that the patient becomes more willing and open to follow the procedure. Principles of healthy living are to be made part of the patient education. The techniques should encompass strategies to employ in preventing infection and the appropriate management of the environment and the surroundings. She should be allowed to choose a caregiver to ensure she is comfortable in the process. General information about the services provided and the daily routine should be relayed to the patient. They should be educated about the treatment options available for leukemia and the advantages of choosing the best over the others (Estey, 2013). However, they should be made aware of their responsibility and to select the treatment option they are willing to embrace. Prompt management of leukemia should be considered including early diagnosis of leukemia and consultation to increase the chances of survival of patients (Jabbour, 2014). When diagnosed with the condition, prompt treatment is to follow this minimizes morbidity and mortality.
The prognosis of the elderly AML patients such as the case of Becky remains very poor despite the recent development and therapeutic advances. The efficient treatment for the patients can be chosen by considering a risk-benefit assessment. Therefore, clinical trials assessing new treatments of AML are urgently needed References
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