Download ACUTE LYMPHOBLASTIC LEUKEMIA Running head: ACUTE

ACUTE LYMPHOBLASTIC LEUKEMIA
1
Running head: ACUTE LYMPHOBLASTIC LEUKEMIA
Acute Lymphoblastic Leukemia
Insert Name Here
Insert Affiliation Here
ACUTE LYMPHOBLASTIC LEUKEMIA
2
Acute lymphoblastic leukemia (ALL) is the one of the more prevalent forms of leukemia
seen in the United States and the rest of the Western world, and is usually characterized by the
presence and spread of malignant B-cells, which are leukocytes normally responsible for the
creation and activation of antibodies, although a form with malignant T-cells also exists
(Geyeregger et al., 2009). ALL can begin in childhood or adulthood, and it is the most common
leukemia seen in children, while the adult form is somewhat rare (Leukemia- Acute
Lymphocytic, 2010). This disease begins in the bone marrow, where leukocytes are produced,
and spreads to other parts of the body integral to the immune system, including the lymph nodes,
spleen, liver, nervous system, and, in males, the testicles; this disease is distinguished from
lymphomas by the fact that lymphomas normally start in the lymph nodes, and spread to the
bone marrow (Leukemia- Acute Lymphocytic, 2010). Unlike many forms of cancer, which are
difficult to treat, ALL has an excellent survival rate, especially in children.
There are genetic differences in the two forms of ALL, but phenotypical differences
present as well. Childhood-onset ALL tends to exhibit a greater degree of cancerous T-cells,
higher levels of hemoglobin, and fewer lymphomatous components (Nachman, 2005). Adults
with ALL tend to display more heterogenous features, such as the rapid metastasis of the cancer
to multiple tissues, and tend to have comorbidity with other diseases, which are both factors that
complicate the treatment outlook (Nachman, 2005). Adult onset ALL usually involves
uncontrolled reproduction of T-cells, instead of the more common B-cell variety, and is also
characterized by extramedullary symptoms, and a propensity to affect men more often than
women (Acute Lymphoblastic Leukemia, 2005).
ACUTE LYMPHOBLASTIC LEUKEMIA
3
Diagnosis of ALL involves more than just the cataloguing of symptoms. The symptoms
presented by this cancer are non-specific, and could signal the onset of any number of diseases.
These symptoms can include fever, sweating, fatigue, weakness, loss of appetite, weight loss,
susceptibility to infection, and a tendency to bruise or bleed easily (Leukemia- Acute
Lymphocytic, 2010). Most of these symptoms are the result of a lack of blood cells, as the
cancerous bone marrow cells deny space to cells producing normal platelets, erythrocytes, and
leukocytes (Leukemia- Acute Lymphocytic, 2010).
The way in which ALL affects other body systems can cause other symptoms, as well as
reveal opportunities for diagnosis. If ALL manages to spread to the lymph nodes, it normally
results in swelling, which can be palpated near the surface of the skin, or detected with MRI or
CT scans if they are located deep within the abdomen (Leukemia- Acute Lymphocytic, 2010). If
affected leukocytes accrete near the spinal cord, they can create central nervous system-related
symptoms including seizures, vomiting, weakness, blurred vision, and balance problems. The 20
percent of ALL cases that affect T-cells usually spread to the thymus gland, causing swelling that
can create pressure on the trachea, leading to wheezing and breathing difficulties (LeukemiaAcute Lymphocytic, 2010).
Diagnosis can be obtained through a variety of methods. Bone marrow is obtained both
by aspiration and biopsy, and is used to screen for the presence of cancerous cells (LeukemiaAcute Lymphocytic, 2010). Blood samples may also be drawn to check for cancerous
leukocytes, and cerebrospinal fluid may be tapped in order to determine if the cancer has spread
to the central nervous system. Generally, these tests look for an abundance of lymphoblasts, or
immature leukocytes, and a lack of platelets and erythrocytes (Leukemia- Acute Lymphocytic,
2010). Lymphoblasts are also searched for in bone marrow tests; the presence of 20 to 30 percent
ACUTE LYMPHOBLASTIC LEUKEMIA
4
lymphoblasts is required for a diagnosis of ALL; normally, lymphoblasts only account for
around 5 percent of white blood cells in bone marrow (Leukemia- Acute Lymphocytic,
2010).While lymph node biopsies are often performed for other forms of cancers, they are only
performed if the physician suspects that the ALL has spread to the lymph nodes (LeukemiaAcute Lymphocytic, 2010). In order to confirm that the cells discovered are cancerous, screening
for certain chromosomal or genetic patterns may be performed by in-situ hybridization, or
specific antigen patterns may be detected by immunochemistry (Leukemia- Acute Lymphocytic,
2010).
There is a strong genetic component to this disease, with the Philadelphia chromosome
serving as a predictor for adult onset ALL, which has a poorer outcome, regardless of the type of
treatment used (Nachman, 2005). Pieces of chromosomes that have been duplicated or
transposed are quite common in childhood ALL, whereas they are less frequently seen in the
adult-onset form (Mullighan, 2009). In the adult form of ALL, instead, the genetic changes often
seen involve the Philadelphia chromosome and deletions and lesions on genes, some of which
seem to occur regularly enough to predict the way that ALL will manifest in patients (Mullighan,
2009). These changes, however, are not the entire cause of this leukemia; in animal models, the
presence of these characteristic alterations do not create cases of leukemia, so there must be other
environmental or biological events necessary to trigger the development of ALL (Mullighan ,
2009). Some researchers have guessed that at least one of the gene alterations codes for a
mutation or reduction in expression of a tumor suppressor gene, which would certainly
contribute to the spread of ALL without being its origin (Mullighan, 2009). Other affected genes
have been found to be involved in apoptosis, cell cycle control, and development of lymphoid
cells.
ACUTE LYMPHOBLASTIC LEUKEMIA
5
Although acute lymphoblastic leukemia was once extremely fatal, survival rates have
improved in the last few decades, and medical advances have succeeded in about 75 percent of
people with ALL obtaining long-term event-free survival rates (Moricke et al., 2008). Due to the
diffuse nature of ALL, where cancer cells are not localized to a particular part of the body as
they may be with other cancers, chemotherapy is the preferred form of treatment, with radiation
therapy and surgery being used only under special circumstances (Leukemia- Acute
Lymphocytic, 2010). Chemotherapy differs for children and adults with this disease; due to
studies showing that the anticancer agents vincristine and L-asparaginase are toxic to older
patients, they are generally only used in children, as a form of continuous therapy with steroids
(Nachman, 2005). Chemotherapy is usually intensified in the pediatric treatment regimen shortly
after the beginning of therapy, and at the end, which has been reported to yield more optimal
results (Nachman, 2005). Older adults, on the other hand, have intermittent high-dose
chemotherapy with myelosuppressive medications (Nachman, 2005). These medications often
include tyrosine kinase inhibitors, which seem to have the best treatment results, and giving the
patient the best chance for bone marrow transplant success after chemotherapy (Vitale,
Grammatico, Capria, Fiocchi, Foa, & Meloni, 2009). Studies performed on young adults that
could be treated via either method showed increased recovery rates when treated using the
pediatric method of continuous chemotherapy, which could be part of the reason that the survival
rate for ALL favors the childhood form over the adult form.
The success of chemotherapy can be predicted by a test measuring prednisone response; a
“good response” can predict a positive treatment outcome around 90 percent of the time, other
responses to the test predict only a 50 percent chance of being cured (Moricke et al., 2008).
Combinations of different chemotherapy drugs are being tested to try and reduce relapse rate in
ACUTE LYMPHOBLASTIC LEUKEMIA
6
at-risk groups with ALL, and interleukin-based therapy may soon be employed for this purpose
as well (Geyeregger et al., 2009). If the cancer has spread to bone, radiation therapy may be
given as an adjunct to chemotherapy. Additionally, in adults, antibiotics may be given in
conjunction with, or following, chemotherapy, since the person’s weakened immune system is
less able to cope with infection; newer studies have shown that certain hormones like
granulocyte stimulating factors can accomplish the same purpose of boosting the counts of
certain immune system cells, specifically, neutrophils (Welte et al., 1996).
If doctors are successful in forcing the cancer into remission after chemotherapy, a bone
marrow transplant to replace the dead marrow cells is sometimes the next step. Bone marrow
transplants in adults are more common, and generally come from the patient themselves, from
undiseased marrow, although they can come from an outside source as well (Nachman, 2005). In
contrast, children with ALL generally only receive bone marrow transplants if they are shown to
have the presence of the Philadelphia chromosome, and, in this case, they would receive bone
marrow from a matched sibling donor (Nachman, 2005). In many cases, transplants that come
from another person are preferred, since while the new leukocytes produced by the body’s own
stem cells won’t recognize cancerous leukocytes as foreign and attack them, leukocytes from
transplanted marrow will, leading to a “graft vs. leukemia” effect (Leukemia- Acute
Lymphocytic, 2010). Bone marrow transplants are about as successful, providing a 60 percent
survival rate of more than 5 years, whether intermittent or continuous chemotherapy has
preceded it (Chang et al., 2008). Bone marrow transplants are often performed if the bone has
been exhibiting symptoms of pain, so that doctors can use radiation therapy on the area as an
adjunct without jeopardizing leukocyte production to an extreme degree (Leukemia- Acute
Lymphocytic, 2010). Although not as widespread a practice as the transplant of bone marrow,
ACUTE LYMPHOBLASTIC LEUKEMIA
7
transplant of unrelated blood cord cells have yielded survival rates that are roughly equivalent
(Jacobsohn, Hewlett, Ranalli, Seshadri, Duerst, & Kletzel, 2004).
The success seen in the combinatorial approach to acute lymphocytic leukemia involving
both chemotherapy and bone marrow or blood cord cell transplantation has led researchers to
reverse their opinion that diffuse cancers could be incurable. Although more research must be
performed in order to raise the survival rates of those that manifest this cancer in adulthood,
research made in the direction of immunotherapy may yield positive results with fewer side
effects. Acute lymphocytic leukemia has allowed researchers to delineate links between genetics
and the risk of cancer, since it shows a much stronger, and much more clearly mapped,
relationship than many other cancers. Although this disease remains difficult to treat, it is
certainly not impossible, and successes in this realm have inspired researchers of other forms of
cancer, that have revised their approach to chemotherapy in accordance with ALL treatment
methods.
ACUTE LYMPHOBLASTIC LEUKEMIA
References
Acute Lymphoblastic Leukemia. (2005). Medscape. Retrieved from
http://www.medscape.com/viewarticle/498526_2
Chang, J. E., Medlin, S.C., Kahl, B.S., Longo, W.L., Williams, E.C., Lionberger, J., . . .
kett, M.B.(2008). Augmented and standard Berlin-Frankfurt-Munster
chemotherapy for treatment of adult acute lymphoblastic leukemia. Leukemia &
Lymphoma, 49(12), 2298-2307.
Geyeregger, R., Shehata, M., Zeyda, M., Kiefer, F.W., Stuhlmeyer, K.M., Porpaczy, E.,
Zlabinger,G.J., Jager, U., & Stulnig, T.M. (2009). Liver X receptors interfere with
cytokine-induced proliferation and cell survival in normal and leukemic
lymphocytes. Journal of Leukocyte Biology, 86, 1039-1048.
Jacobsohn, D.A., Hewlett, B., Ranalli, M., Seshadri, R., Duerst, R., & Kletzel. M. (2004).
Bone Marrow Transplantation, 34, 901-907.
Leukemia, Acute Lymphocytic. (2010). American Cancer Society. Retrieved from
http://www.cancer.org/Cancer/LeukemiaAcuteLymphocyticALLinAdults/DetailedGuide/leukemia-acute-lymphocytic-whatis-all
Moricke, A., Reiter, A., Zimmerman, M., Gadner, H., Stanulla, M., Dordelmann, M., . . .
Schrappe, M. (2008). Risk-adjusted therapy of acute lymphoblastic leukemia can
decrease treatment burden and improve survival: Treatment results of 2169
Unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.
Blood, 111, 4477-4489.
Mullighan, C.G. (2009). Genomic analysis of acute leukemia. International Journal of
8
ACUTE LYMPHOBLASTIC LEUKEMIA
Laboratory Hematology, 31, 384-397.
Nachman, J. (2005). Clinical characteristics, biologic features, and outcome for young
adult patients with acute lymphoblastic leukemia. British Journal of Hematology,
130, 166-173.
Vitale, A., Grammatico, S., Capria, S., Fiocchi, C., Foa, R., & Meloni, G. (2009).
Advanced Philadelphia chromosome-positive leukemia patients relapsed after
treatment with tyrosine kinase inhibitors. Haematologica, 94(10), 1471-1473.
Welte, K., Reiter, A., Mempel, K., Pfetch, M., Schwab, G., Schrappe, M., & Riehm, H.
(1996). A randomized phase-III study of granulocyte colony stimulating factor in
children with high-risk acute lymphoblastic leukemia. Blood, 87(8), 3143-3150.
9