Pharmacology For Acute Lymphoblastic Leukemia

Diagnosis

Discuss about the Pharmacology for Acute Lymphoblastic Leukemia.

The acute lymphoblastic leukemia refers to a malignant disease which mostly affects the bone marrow, a region where the early lymphoid precursors grow (Inaba et al., 2013). This disease leads to the replacement of the normal hematopoietic cells in the bone marrow. The acute lymphoblastic leukemia is so far the most common form of leukemia cancer in the children. More specifically, acute lymphoblastic leukemia refers to a condition in which the tissues which make the white blood cells produce too many of the white blood cells which are underdeveloped in the lymphocytes (Harrison and Johansson, 2015). The immature white blood cells then accumulate in the lymph tissues making these tissues to swell and make it difficult for the bone marrow to produce other blood cells. For instance, if the bone marrow is not able to make the red blood cells, the patient develops anemia, which in most cases makes one appear pale, as presented in Jenny’s case on her skin (Ribera, 2016). The bone marrow also becomes unable to make enough platelets that are important in the formation of clots, which means that in the case of bruises or injuries, the body bleeds severely.

It is also a common occurrence in acute lymphoblastic leukemia, for the lymphocytes to invade other neighboring tissues and impair their functions as well. The leukemic cells in acute lymphoblastic leukemia commence in either the T or B cell lymphocytes (McNeer et al., 2017). The acute lymphoblastic leukemia is associated with the cancer cases which are common in old men, indicating that their treatment in children requires high doses of chemotherapy. There are multiple types of leukemia which are affecting the children in the modern world (Brentjens et al., 2013). In reference to Jenny’s case, the acute lymphoblastic leukemia affects children of between three to seven years. This paper addresses the pathophysiology and pharmacology of acute lymphoblastic leukemia in reference to Jenny’s case.

Chromosomes have been linked with an early and accurate diagnosis of acute lymphoblastic leukemia. For instance, TEL-AML 1 fused genes are indicative of the leukemia of B-cell origin and favorable disease prognosis. Moreover, in performing of the acute lymphoblastic leukemia diagnosis, it is important to take the patient history in order to understand the possibility of the disease being hereditary or not. It is a common practice, just like in the case of Jenny for the blood sample to be taken for blood tests such as platelets, hemoglobin, and white blood cell counts. The lumbar puncture can also be done so that cerebral spinal fluid is tested for the possible spread of the disease to the spinal cord and the brain. Other tests include the peripheral blood smear, complete differential blood count, chest x-ray, computed tomography, electrocardiography, liver function tests (uric acid), and immunohistochemistry and polymerase chain reaction among others.

Signs and Symptoms

Other common signs include fatigue, pale skin, pain in the bones, weakness, headache due to cranial pressure and pallor. Some other common signs and symptoms include pain in the bones, possible infections like pneumonia, and rashes of the skin as a result of the infiltration of the leukemia cells, low neutrophil counts, bleeding, fever and leukostasis. 

In patients who have been diagnosed with acute lymphoblastic leukemia, the white blood cells which are found in the lymphoid precursor cells are those which that have been arrested in the course of their growth and development (Pui et al., 2014). This makes them unable to fight any infections in the body s a result of the viral, parasitic, fungal and bacterial pathogens which might enter the body via the blood stream. It is believed that most of these cases are caused by genetic factors a situation in which there is an abnormal expression of the genetic structure of a physiological process which leads to the arresting of the growth as well as the development of the white blood cells. In the process of this arresting of the lymphoid precursor cells, the elements of the normal bone marrow are replaced by immature precursor cells (Papaemmanuil et al., 2014).

The accumulation of the immature precursor cells causes the increased efficiency in the spread of the abnormal cells in the blood. These abnormal cells accumulate in the spin cord and the brain of the patient and in other few cases, the spread to the reproductive organs (Inaba et al., 2013). The patients are also reported to have a low concentration of the platelets and red blood cells, just like in people suffering from anemia. The low production of red blood cells is associated with the bleeding in these patients as compared to healthy individuals (McNeer et al., 2017). However, if the acute lymphoblastic leukemia has spread to the spinal cord and the brain, it requires care and attention by the doctors when offering treatment. It is recommended that when a patient is diagnosed with acute lymphoblastic leukemia, chemotherapy treatment should begin immediately.

In case there are some abnormal chromosomes noted during the diagnosis, the doctors need to make a careful decision on when to begin the treatment. In some other cases, the doctors may use the induction therapy, a situation in which a patient receives more than one drug for every dosage. This helps to strengthen the drugs for a better effectiveness. For chemotherapy, it can be carried out either through the oral administration or by putting a catheter in the chest on the upper part of the chest. During acute lymphoblastic leukemia infections, some patients may accumulate so much of the uric acid in the blood which leads to the development of painful kidney stones. Other possible cause of this disease condition could be exposure to radiations, chemicals as well as viral infections. The viral related cases of acute lymphoblastic leukemia are quite common in the Carribean region as well as Japan. An example is the Epstein Barr virus which is associated with mononucleosis and can possible cause acute lymphoblastic leukemia.

Pathophysiology

This disease is common in children and a few cases in adults and it is characterized by a low cure rate. Analysis of prenatal cases indicates that this disease is inherited, whereby genetic abnormalities have been found in parental genes. In some instances, there are theories which argue that there might be a possibility of clustering of cases of his infection, a situation which is sometimes caused by the increased industrialization of the modern society. Increased cases of acute lymphoblastic leukemia can be as a result of exposure to pathogens as a result of mixing up of the population. In other occasions, the late exposure to a pathogen may push a hematopoietic cell prenatally upon infection thereby causing the predisposing genetic factors to form transformed leukemia cells. It has been observed that the lymphocytes which are intended for differentiation into either B or T cell lymphocyte in the early stages of life are transformed as a result of chromosome translocations and eventually end up causing acute lymphoblastic leukemia.

It is also believed that this condition is initiated by a single progenitor cell which divides at a very high rate and thus multiplies in the lymphoid tissues rapidly. The majority of these cells begin in the B or T cells, although they mostly start in the B cells which have not yet become mature (Davila et al., 2014). 

Chemotherapy is one of the treatment options for acute lymphoblastic leukemia infection. It involves the use of chemicals and drugs either singly or in combination in order to destroy the malignant cells in the blood or tissues of the patients (Kantarjian et al., 2017). The drugs for chemotherapy are administered either orally, through intravenous routes or injection into the skin or muscles. Chemotherapy is usually administered in cycles for a given period of time, then followed by a recovery period which is then followed by another treatment period and progresses in that pattern. The drugs and chemicals used during chemotherapy enter the blood stream where they kill the leukemia cells in the body (McNeer et al., 2017). A major drawback with this form of treatment is that it is not able to reach into the spinal cord and brain (Hunger and Mullighan, 2015). This is because there is an existence of a large network of blood vessels which prevents foreign materials from entering into the central nervous system.  In this case, the caregivers inject these drugs directly into the cerebrospinal fluid which then distributes into the brain.

Pharmacology

For the radiotherapy form of acute lymphoblastic leukemia treatment, ionizing radiations are used to kill malignant cells and the DNA containing the mutant genes responsible for the infection. Once the best dose for radiation is determined, a specific angle and beam are employed in order to have the high energy radiation beam targeting the exact location for some time (Vora et al., 2016). Despite the fact that the uninfected parts of the body are covered, sometimes even the normal cells might get damaged leading to the development of the sunburns on the skin and other side effects like nausea and diarrhea. The use of bone marrow transplantation is also a common method of treatment which is employed in acute lymphoblastic leukemia cases. In this case, since the bone marrow is no longer functional, it is completely destroyed by the use of chemotherapy and ionizing radiation (Topp et al., 2015). The patient is then given new healthy bone marrow from a donor so that it is perfectly compatible with their own bone marrow.

Conclusion

Once the acute lymphoblastic leukemia appears, these are the common signs and symptoms, diagnosis methods and treatment options that are available for use. However, the fact is that leukemia is a type of cancer which has a low cure rate and most patients end up losing their lives.

Reference List

Brentjens, R.J., Davila, M.L., Riviere, I., Park, J., Wang, X., Cowell, L.G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M. and Borquez-Ojeda, O., 2013. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Science translational medicine, 5(177), pp.177ra38-177ra38.

Davila, M.L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., Chung, S.S., Stefanski, J., Borquez-Ojeda, O., Olszewska, M. and Qu, J., 2014. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science translational medicine, 6(224), pp.224ra25-224ra25.

Harrison, C.J. and Johansson, B., 2015. Acute lymphoblastic leukemia. Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells, p.198.

Hunger, S.P. and Mullighan, C.G., 2015. Acute lymphoblastic leukemia in children. New England Journal of Medicine, 373(16), pp.1541-1552.

Inaba, H., Greaves, M. and Mullighan, C.G., 2013. Acute lymphoblastic leukaemia. The Lancet, 381(9881), pp.1943-1955.

Kantarjian, H., Stein, A., Gökbuget, N., Fielding, A.K., Schuh, A.C., Ribera, J.M., Wei, A., Dombret, H., Foà, R., Bassan, R. and Arslan, Ö., 2017. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine, 376(9), pp.836-847.

McNeer, J.L., Bleyer, A., Conter, V. and Stock, W., 2017. Acute lymphoblastic leukemia. In Cancer in Adolescents and Young Adults (pp. 151-175). Springer International Publishing.

Papaemmanuil, E., Rapado, I., Li, Y., Potter, N.E., Wedge, D.C., Tubio, J., Alexandrov, L.B., Van Loo, P., Cooke, S.L., Marshall, J. and Martincorena, I., 2014. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nature genetics, 46(2), pp.116-125.

Pui, C.H., Pei, D., Campana, D., Cheng, C., Sandlund, J.T., Bowman, W.P., Hudson, M.M., Ribeiro, R.C., Raimondi, S.C., Jeha, S. and Howard, S.C., 2014. A revised definition for cure of childhood acute lymphoblastic leukemia. Leukemia, 28(12), pp.2336-2343.

Ribera, J.M., 2016. Acute lymphoblastic leukemia. In HIV-associated Hematological Malignancies (pp. 145-151). Springer International Publishing.

Topp, M.S., Gökbuget, N., Stein, A.S., Zugmaier, G., O’Brien, S., Bargou, R.C., Dombret, H., Fielding, A.K., Heffner, L., Larson, R.A. and Neumann, S., 2015. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), pp.57-66.

Vora, A., Andreano, A., Pui, C.H., Hunger, S.P., Schrappe, M., Moericke, A., Biondi, A., Escherich, G., Silverman, L.B., Goulden, N. and Taskinen, M., 2016. Influence of cranial radiotherapy on outcome in children with acute lymphoblastic leukemia treated with contemporary therapy. Journal of Clinical Oncology, 34(9), pp.919-926.