Acute Myeloid Leukemia: Pathophysiology, Pharmacology, and Nursing

This report provides a comprehensive overview of Acute Myeloid Leukemia (AML), a type of cancer originating in the bone marrow. It begins with an introduction to the disease, including the normal physiology of blood cell production and the mechanisms that lead to AML, such as genetic alterations and chromosomal abnormalities. The report then delves into the core pharmacology related to AML treatment, focusing on chemotherapy, specifically Cytarabine, including its mechanism of action, pharmacokinetics, route of administration, indications, contraindications, precautions, and side effects. The report also emphasizes the relevance of understanding AML to nursing practice, highlighting the role of nurses in pre-operative planning, treatment planning, and patient care. The report concludes with a summary of the key points and references used in the research.

Running head: ACUTE MYELOID LEUKEMIA 1
Acute Myeloid Leukemia
Name
Institutional Affiliation

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1. Introduction
There are various types of cancers. Leukemia is a type of cancer that originates in cells that
would have otherwise developed into normal blood cells. Researchers and scientists have it that
Acute Myeloid Leukemia (AML) originates from the soft vascular blood-forming tissue found
within bone cavities, commonly known as bone marrow, responsible for the production of new
blood cells (Nagarajan, 2010). In many scenarios, the development of AML in the blood is
usually quick. Most often, the development of AML arises from pre-mature cells that would have
turned into white blood cells upon maturity.
Normal bone marrow, blood, and lymph tissue
In certain bones, the soft inner part is known as the bone marrow. The bone marrow consists of
supporting tissues, blood-forming cells as well as fat cells. Inside the bone marrow, new blood
cells develop from blood stem cells. During the development phase, the blood stem cells may
develop into either myeloid cells or lymphocytes (Lanza, et al., 2009). It is from the myeloid
cells that the development of platelets, white blood cells, and red blood cells occur. For patients
of AML, it is the myeloid cells that are abnormal.
There are three types of blood cells. The Red blood cells are responsible for transport of oxygen
to various body tissues from the lungs and carbon II oxide to the lungs for excretion. Platelets are
made by megakaryocytes, which are a type of bone marrow cells. White blood cells (WBCs) on
the other side aid the body in fighting infections (Lanza, et al., 2009). There are three types of
WBCs. Mature WBCs that develop into myeloblasts are known as granulocytes. On the other
side, white blood cells that emanate from the formation of blood-forming monoblasts found in
the bone marrow are known as monocytes. Lastly, lymphocytes, the main contents of the lymph
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tissues, develop from lymphoblasts. Lymph tissue is located in the lymph nodes, the spleen, the
thymus, adenoids, and the tonsils, as well as throughout the bone marrow, respiratory and
digestive systems (Ciesla, 2011).
2. Pathophysiology and the mechanisms leading to AML
Although various people with Acute Myeloid Leukemia usually have at least one or more than
one known risk factors, many do not have the risk factors. Even where the risk factors exist, it is
extremely hard to make a conclusion of it as the main cause of cancer (Karp, 2009). However,
normal bone marrow cells may undergo DNA alterations and thus making them leukemia cells.
Genes, which are made up of DNA, are the controllers of cells’ functioning. Additionally, there
are genes whose main role is to facilitate growth, survival or division of cells. They are known as
Oncogenes. Tumor suppressor genes on the other hand aids in control of cell division as well as
ensuring that the death of cells occurs at the right time.
Located in each cell are chromosomes where DNA is found. As such, new copies of
chromosomes must be made each time a cell divides into two new cells. However, the
occurrence of errors during this process can occur affecting the genes in the chromosomes.
Precisely, mutations causing turning off of tumor suppressor cells or turning on of oncogenes
lead to the development of AML. FLT3, RAS, and c-KIT are examples of genes commonly
found in the AML that undergo mutations for Acute Myeloid Leukemia to occur (Woolley,
2010). Mutations in these genes may cause bone marrow cells to grow out of control or lead to a
deviation of the cells from the normal maturity.
There are a number of types of chromosomal alterations in the bone marrow cells that result in
the development of AML. First, are translocations where part of a chromosome breaks of and
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attaches itself to another chromosome. Subsequently, genes nearby are adversely affected by, for
example, turning off of RARa and RUNX1 genes or turning on of oncogenes (Coleman &
Tsongalis, 2016). As a result, normal maturation of blood cells does not occur resulting in AML.
Deletion is another change that results from the total loss of a chromosome part. Subsequently,
tumor suppressor genes responsible for controlling growth are lost leading to AML. Inversions,
on the other hand, are changes that occur when part of a chromosome positions itself in reverse
order. As a result, genes responsible for various cells activities are lost since the cell can no
longer read the instructions in the inverted chromosome. The last chromosomal change that may
lead to AML is duplication or Addition of extra chromosome(s) or part of a chromosome (Liotta,
2012). Consequently, a certain gene(s) may have too many copies within the cells leading to
deformations which lead to AML.
3. Core pharmacology related to the treatment of AML
For many AML patients, typical treatment is divided into two phases of chemotherapy. The first
phase is known as Remission induction while the second phase is called Consolidation (Karp,
2009). However, there are people whose blood contain too many leukemia cells at first
diagnosis. This is known as leukostasis and may hinder the normal circulation of the blood
(Faderl & Kantarjian, 2011). As such, it becomes necessary for doctors to perform Leukapheresis
to lower the blood count of leukemia cells before the commencement of Chemotherapy.
The first phase of chemo is induction which is basically aimed at eradicating the highest number
of leukemia cells possible. The patients’ health and age are the determinants of the intensity of
treatment (Muggia, 2012). For younger patients below 60 years, there are two types of chemo
drugs mainly used. They are Cytarabine (ara-C) and an Anthracyline drug, for example,
idarubicin or daunorubicin. A combination of the two drugs is commonly known as 7+3 regimen
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since it involves a seven-day use of cytarabine along with an infusion of anthracyline for the first
three days (Orkin, et al., 2009). To increase the chances of remission, Midostaurin which is a
targeted therapy drug is prescribed twice daily for patients with an FLT3 gene mutation. If
remission is achieved, induction is then considered to be successful.
After induction, consolidation commences in an attempt to completely destroy the remaining
leukemia cells. Consolidation also helps prevent relapse. For patients below 60 years old,
consolidation may be achieved through several chemo cycles with cytarabine, also known as
HiDAC, at high doses (Acton, 2013). Another option is the transplant of the allogeneic stem cell
while the last option is the transplant of the autologous stem cell. For older patients above 60
years, intensive consolidation treatment may be unbearable. However, they may be treated with
higher doses of cytarabine. A combination of standard dose cytarabine is also effective if
combined with mitoxantrone, daunorubicin or idarubicin (Casciato & Territo, 2009).
3.1. Cytarabine
3.1.1. Mechanism of action and Pharmacodynamics of Cytarabine
The action of cytarabine occurs directly through incorporation into DNA as well as by DNA
damage. Various proliferating mammalian cells are affected by the drugs cytotoxicity as well as
its specificity to cell phase (Kester, Karpa, & Vrana, 2011). Basically, all cells in the S-phase
(DNA synthesis) are killed by the drug. Additionally, it may block the G1 phase to S-phase
progression of cells under some conditions. As such, inhibition of DNA polymerase is the main
mode of action for cytarabine.
Cytarabine is an anti-metabolite antineoplastic drug. Intercellular metabolism of the drug
transforms it into its triphosphate active form. The metabolite formed then employs multiple
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mechanisms to damage the DNA of AML cells. Some of the mechanisms are; effect on beta-
DNA polymerase to inhibit DNA repair, inhibiting polymerase of alpha-DNA as well as
incorporation into the DNA (Rudek, Chau, Figg, & McLeod, 2014).
3.1.2. Pharmacokinetics
Upon introduction into the body through various modes of administration, the drug undergoes
metabolism into its triphosphate form. Hepatic metabolism occurs in the liver giving rise to
cytosine arabinoside triphosphate (Rudek, Chau, Figg, & McLeod, 2014). The drug is later
eliminated through urinary excretion where kidneys play a significant role. It has an elimination
half-life of 1-3 hours
3.1.3. Route of administration
Cytarabine may be administered through an infusion into the vein (IV). It can also be
administered through intrathecal infusion. This method is particularly used when the drug is
targeted to reach the cerebrospinal fluid. Here, the drug is directly infused into the spinal fluid
(Chemocare, 2017). It is worth noting that there is no pill form of the drug.
3.1.4. Indications
In combination with other anticancer drugs, Cytarabine is indicated for remission induction of
Acute Myeloid Leukemia, acute lymphocytic leukemia, acute non-lymphocytic leukemia as well
as the blast phase of chronic myelocytic leukemia (Chemocare, 2017).
3.1.5. Contraindications
There are several circumstances when this drug cannot be used. First, the drug cannot be
administered to a pregnant patient during the first phase of pregnancy. Additionally, it cannot be
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used if the following had been recently administered; cholera vaccine, rotavirus vaccine, typhoid
vaccine, yellow fever vaccine, varicella vaccine, and zoster vaccine (Epocrates, 2019).
3.1.6. Precautions
Females are to avoid pregnancy during the period of use. Breastfeeding should be avoided for the
period within 24-48 hours after administration. Infectious people or places are to be highly
avoided. Upon noticing any bruising, bleeding, pinpoint red spots or blood in stool or urine, the
doctor should be consulted immediately (Chemocare, 2017).
3.1.7. Side effects
Due to its nature as a bone marrow suppressant, it is expected that cytarabine will cause
thrombocytopenia, reduced reticulocytes, anemia, megaloblastosis, and leukopenia. Vomiting,
nausea, loss of appetite, diarrhea, skin rash, temporal hair loss, and headaches are also common
side effects (Chemocare, 2017). Additionally, a patient using this drug may experience a
temporal decrease in platelets, red and white blood cells. Some patients have testified to having
witnessed confusion, dizziness, and loss of balance.
4. Relevance to Nursing Practice
Knowledge of acute myeloid leukemia is of high relevance to practitioners of the nursing
profession. First, it will aid nurses actively participate in pre-operative surgery planning
whenever it becomes necessary for AML patients to undergo surgical procedures (Wilkes &
Barton-Burke, 2016). Nurses also play a significant role in planning for pre-treatment as well as
actual treatment for newly diagnosed patients. Additionally, the quality of care from oncology
nurses is boosted by knowledge on AML. This is because nurses efficiently take part in the
development and implementation of cancer rehabilitation programs for cancer survivors after
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treatment. Lastly, the relevance of the topic is evidenced by the crucial role that nurses lay in
aiding patients to avoid barriers to treatment as well as screening them for physical impairments
and distress emanating from cancer (Wilkes & Barton-Burke, 2016).
5. Conclusion
In conclusion, it has been stated that Acute Myeloid Leukemia (AML) originates from the inner
soft part of bones, commonly known as bone marrow, responsible for the production of new
blood cells. Normally, the blood, bone marrow and lymph tissue are involved in the
multiplication and growth of new cells with no deformity. Genetic alterations during the
formation of new cells in the bone marrow lead to AML. FLT3, RAS, and c-KIT have been
identified as some of the genes that mainly undergo mutations resulting in AML. Induction and
consolidation are the two phases of chemotherapy treatment of AML. Cytarabine has been
identified and comprehensively discussed as a major drug used in AML treatment. The
inscription ends with a brief discussion of the relevance of this topic to nursing practice.
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6. References
Acton, Q. A. (2013). Acute Myeloid Leukemia: New Insights for the Healthcare Professional:
2013 Edition. ScholarlyEditions.
Casciato, D. A., & Territo, M. (2009). Manual of Clinical Oncology (abridged, illustrated ed.).
Lippincott Williams & Wilkins.
Chemocare. (2017). Cytarabine. Retrieved from CHEMOCARE:
http://chemocare.com/chemotherapy/drug-info/cytarabine.aspx
Ciesla, B. (2011). Hematology in Practice. F.A. Davis Publisher.
Coleman, W. B., & Tsongalis, G. J. (2016). The Molecular Basis of Human Cancer (2, illustrated
ed.). Humana Press.
Epocrates. (2019). Cytarabine:Monograph. Retrieved from Epocrates:
https://online.epocrates.com/drugs/381710/cytarabine/Monograph
Faderl, S., & Kantarjian, H. (2011). Leukemias: Principles and Practice of Therapy. John Wiley
& Sons.
Karp, J. E. (2009). Acute Myelogenous Leukemia (Illustrated ed.). Springer Science & Business
Media.
Kester, M., Karpa, K., & Vrana, K. (2011). Elsevier's Integrated Review Pharmacology E-Book:
With STUDENT CONSULT Online Access (2 ed.). Elsevier Health Sciences.
Lanza, R., Gearhart, J., Hogan, B., Melton, D., Pedersen, R., Thomson, J., & Wilmut, I. (2009).
Essentials of Stem Cell Biology. Academic Press.
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Liotta, L. (2012). Influence of Tumor Development on the Host (Illustrated ed.). Springer Science
& Business Media.
Muggia, F. M. (2012). Cancer Chemotherapy 1 (illustrated ed.). Springer Science & Business
Media.
Nagarajan, L. (2010). Acute Myelogenous Leukemia: Genetics, Biology and Therapy (Illustrated
ed.). Springer Science & Business Media.
Orkin, S. H., Fisher, D., Look, T., Lux, S., Ginsburg, D., & Nathan, D. (2009). Oncology of
Infancy and Childhood E-Book. Elsevier Health Sciences.
Rudek, M. A., Chau, C., Figg, W., & McLeod, H. (2014). Handbook of Anticancer
Pharmacokinetics and Pharmacodynamics (2, illustrated, revised ed.). Springer Science
& Business Media.
Wilkes, & Barton-Burke, M. (2016). 2016 Oncology Nursing Drug Handbook. Jones & Bartlett
Publishers.
Woolley, P. V. (2010). Cancer Management in Man: Biological Response Modifiers,
Chemotherapy, Antibiotics, Hyperthermia, Supporting Measures. Springer Science &
Business Media.
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