Course:KIN366/ConceptLibrary/Leukemia

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KIN 366
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Instructor: Dr. Shannon S.D. Bredin
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Leukemia is a form of cancer that originates from mutations in blood stem cells within bone marrow (Canadian Cancer Society, 2015). It develops when these mutated cells begin to grow irregularly and prevent normal blood cells from properly functioning. Although the exact causes of these mutations have yet to be identified, several genetic and environmental factors have been proven to increase the risk of developing this disease (American Cancer Society, 2014). Early signs and symptoms of leukemia include increased frequency of infections, bruising and bleeding while diagnoses are usually confirmed via bone marrow biopsy and complete blood counts (Canadian Cancer Society, 2015). Although treatments vary depending on the type of leukemia, treatment methods often include chemotherapy, radiation therapy or bone marrow transplants. Leukemia is substantially more common within the developed world and amongst men (The Leukemia and Lymphoma Society, 2014). Additionally, it is the most common form of cancer amongst children and has been shown to influence motor development while the child is undergoing cancer treatment as well as several years after the treatment is complete. (Wright, Halton, Martin & Barr, 1998; De Luca et al., 2013).

Overview and Classifications

Overview

Leukemia begins with stem cells, which are basic cells that develop into different more specific types of cells, within the blood. Healthy blood stem cells either develop into lymphoid or myeloid stem cells (Canadian Cancer Society, 2015). Lymphoid stem cells eventually become lymphocytes, a type of white blood cells used to combat infections and produce antibodies. Myeloid stem cells generally develop into red blood cells, used to carry oxygen throughout the body, or platelets that are utilized to form clots in damaged blood vessels. However, sometimes these blood stem cells will develop abnormally, reproduce faster than most cells and begin to crowd out the other normal cells inhibiting them from functioning properly (Canadian Cancer Society, 2015).

Classifications

There are 4 different types of leukemia, which are classified based on their rate of development as well as the blood stem cells they originated from (Canadian Cancer Society, 2015).

1. Acute Myelogenous Leukemia (AML) develops from abnormal myeloid stem cells and replicate quickly within days or weeks. It accounts for approximately 75% of all leukemia diagnoses in children (Canadian Cancer Society, 2015).

2. Chronic Myelogenous Leukemia (CML) develops from abnormal myeloid stem cells and replicate slowly over months or years.

3. Acute Lymphocytic Leukemia (ALL) develops from abnormal lymphocyte stem cells and replicate quickly within days or weeks.

4. Chronic Lymphocytic Leukemia (CLL) develops from abnormal lymphocyte stem cells and replicate slowly over months or years (Canadian Cancer Society, 2015).

Causes

Although leukemia results from mutations in the DNA, a specific cause for these mutations has yet to be discovered. Nevertheless, scientists have identified several risk factors, which have been empirically proven to increase the risk of developing leukemia. A risk factor can be defined as anything that influences one’s likelihood of acquiring a disease. Some risk factors are more within our control such as lifestyle-related factors like smoking cigarettes or being physically inactive while others are inherited such as type 1 diabetes or Down syndrome (American Cancer Society, 2014). However, most researchers agree that since lifestyle risk factors take many years to influence cancer risk, the largest risk factors within childhood leukemia are genetically determined.

Genetic Risk Factors

This refers to any factor, which is a part of our DNA and inherited by our parents. Although the cause of leukemia is not purely genetic, many genetic risk factors have been heavily associated with increased likelihood of developing the disease (American Cancer Society, 2014).

Inherited Syndromes

Down Syndrome

Children born with an extra (third) copy of chromosome 21 are diagnosed as having Down syndrome, which causes mental retardation and a distinct facial appearance. Children with Down are significantly more likely to develop ALL and AML than other children. In fact, 2%-3% of all children with Down will develop leukemia (American Cancer Society, 2014).

Klinefelter Syndrome

This disease arises when male children are born with an extra “X” chromosome and has been deeply correlated with infertility and prevention of normal male developmental features such as body hair, deep voice, etc. This syndrome has also been proven to increase the risk of developing leukemia (American Cancer Society, 2014).

Li-Fraumeni Syndrome

This is an extremely rare condition caused by mutation in the tumor suppressing gene, TP53. Children with this illness are at substantially higher risk of developing several kinds of cancer, in particular leukemia (American Cancer Society, 2014).

Inherited Immune-Deficient Diseases

These illnesses have been shown to significantly increase risk of developing serous infections from reduced immune defenses and also increase likelihood of developing leukemia (American Cancer Society, 2014). Some of these immune system diseases include Ataxia Telangiectasia, Wiskott-Aldrich syndrome and Bloom syndrome.

Immediate Family With Leukemia

Siblings of children with leukemia are 2 to 4 times more likely to develop leukemia than a child without siblings with leukemia. However, the risk amongst identical twins is substantially higher. If an identical twin develops leukemia, the other twin has a 20% chance of also developing leukemia (American Cancer Society, 2014). Inversely, there appears to be no correlation between an adult who had leukemia and their child developing the disease (American Cancer Society, 2014).

Lifestyle-Related Risk Factors

Since most lifestyle-related risk factors take many years to develop, it is unlikely that they would play a role in most childhood cancers (American Cancer Society, 2014). Nevertheless, several recent studies are beginning to show that the lifestyle of the mother may play a role in the child’s risk of developing leukemia. While alcohol consumption by a pregnant woman, in particular, has been suggested to influence leukemia likelihood within her child, not all studies have found this link (American Cancer Society, 2014).

Environmental Risk Factors

Radiation Exposure

6-8 years after their radioactive exposure, Japanese atomic bomb survivors had a significantly higher risk of developing AML. This lead to much research that has concluded that radiation exposure is a major risk factor for childhood leukemia (American Cancer Society, 2014). As a result most doctors recommend that pregnant women and children not get x-ray or CT scans unless they are absolutely necessary (American Cancer Society, 2014).

Chemotherapy Exposure

Children treated for other cancers via chemotherapeutic drugs have a higher risk of developing a secondary cancer form of cancer, most commonly AML (American Cancer Society, 2014). This form of leukemia generally develops 5-10 years after the original chemotherapy treatment and are generally very difficult to treat. The specific drugs associated with increased risks of leukemia include Cyclophosphamide, Chlorobucil, Etoposide and Teniposide (American Cancer Society, 2014).

Immune System Suppression

Doctors will often prescribe to patients undergoing organ transplants, intensive treatment to inhibit their immune system so that the body will successfully accept the foreign organ (American Cancer Society, 2014). Unfortunately, this treatment has also been linked with increased risks of lymphoma and ALL (American Cancer Society, 2014).

Potential Risk Factors

Many other factors are currently being examined for a possible association with childhood leukemia. These potential yet unproven factors include (American Cancer Society, 2014):

  • Living near a nuclear power plant
  • Infections early in life
  • Mother’s age when child is born
  • Parent’s smoking history
  • Contamination of ground water
  • Air pollution
  • Fetal exposure to birth control pills

Signs and Symptoms

A sign is something which a health professional can observe and recognize (i.e. inflammation) while a symptom is something that is undetectable based on observations and can only be identified by the individual who is experiencing it (i.e. fatigue) (Canadian Cancer Society, 2015).

Signs

Signs of Leukemia include (Canadian Cancer Society, 2015):

  • Fever
  • Paleness
  • Widespread bruising
  • Frequent bleeding of nose or gums
  • Heavy menstrual flow
  • Frequent infections in lungs, urinary tract, gums and anus.
  • Vomiting
  • Enlarged lymph nodes

Symptoms

Symptoms of Leukemia include (Canadian Cancer Society, 2015):

  • Malaise (general feeling of being ill)
  • Loss of appetite
  • Headache
  • Night sweats
  • Bone or joint pain
  • Abdominal discomfort
  • Vision problems
  • Fatigue

Diagnosis

Although many people with leukemia experience no symptoms, early detection can still occur via a routine medical examination. Common warning signs for leukemia that a doctor may detect include an enlarged lymph node or spleen as well as an abnormality on a routine blood test (Cleveland Clinic, 2014). If the doctor suspects that one may have leukemia he/she will conduct a complete blood count (CBC) test, in which the primary sign of concern is abnormally high or low white blood cell counts although abnormalities in red blood cells and platelets may also be good indicators (Cleveland Clinic, 2014). The diagnosis of leukemia is generally confirmed by a biopsy of the bone marrow, in which a pathologist and hematologist will work together to determine the type of cell that has become cancerous and whether it is acute or chronic (Cleveland Clinic, 2014). In recent years it has become very common to also conduct a cytogenetic study, which examines the genetic material in cells, to provide additional information on each individual’s specific cancer cells. Unlike many other cancers, leukemia is not staged numerically based on its severity, but rather through its classification as acute or chronic. The one exception is a rare form of leukemia called Chronic Lymphocytic Leukemia (Cleveland Clinic, 2014).

Treatment

Chemotherapy

Chemotherapy is the insertion of cytoxic (anti-cancer) drugs into the bloodstream, which circulates throughout the entire body and destroys cancer cells (Canadian Cancer Society, 2015). It has been proven to be quite effective at eradicating leukemia cells while returning blood cell production to normal rates. Chemotherapy is the main treatment for leukemia particularly within children. Inversely, in eliminating cancer cells many healthy cells are often damaged, leading to numerous severe side effects (Canadian Cancer Society, 2015).

Chemotherapy Side Effects

Potential Chemotherapy side effects include (Canadian Cancer Society, 2015):

  • Nausea and vomiting
  • Hair loss
  • Vein inflammation
  • Diarrhea
  • Muscle and joint pain
  • Organ damage
  • Bone marrow suppression
  • Second cancers

Radiation Therapy

Radiation therapy is another common treatment used for leukemia, in which high-energy rays are used to destroy cancer cells (Cleveland Clinic, 2014). In addition to preventing the spread of cancer cells, radiation is also used to relieve bone pain, shrink tumors and as a vital part of the preparatory process for a stem cell transplant (Cleveland Clinic, 2014). However, it also leads to several side effects.

Radiation Therapy Side Effects

Potential Radiation therapy side effects include (Canadian Cancer Society, 2015):

  • Fatigue
  • Hair loss
  • Skin reactions
  • Bone marrow suppression
  • Lethargy (lack of energy)
  • Balance problems
  • Coordination problems

Physical Activity as Treatment

Aznar et al. (2006) noted that during treatment, children with ALL experienced significantly lower levels of physical activity than regular children. Additionally, even when the children wanted to play they were often discouraged from participating in physical forms of activity out of fear of them getting hurt. The irrationality of this fear can be best described through the findings of Battaglini et al. (2009), in which 10 patients recently diagnosed with ALL and undergoing chemotherapy treatment underwent an individualized in-hospital exercise program for 3-5 weeks. The exercise program comprised of aerobic resistance and core exercises as well as light stretches. Battaglini et al. (2009) noted that during this trial these patients experienced significantly lower fatigue and depression scores. Moreover, even after the trial the patients experienced improved cardiorespiratory and muscular endurance relative to their baseline measurements. This study demonstrated that not only is exercise programs feasible for patients undergoing chemotherapy but it also very beneficial.

Leukemia Effects on Motor Development

Some leukemia or treatment-related side effects may occur during the cancer treatment and discontinue once the treatment has ended while others may last for weeks, months or even years after the cancer is no longer present. Moreover, if these side effects take place during critical years of growth and motor development, the effects many last decades or even a lifetime (Canadian Cancer Society, 2015).

Fine Motor Development

Hockenberry et al. (2007) examined the fine motor and sensor perceptual performances of 82 children recently (last 6 months) diagnosed with ALL over a 2 year span. They identified unusually decreased fine motor speed and dexterity for the dominant and non-dominant hand as well as when both hands were used simultaneously. Additionally, these children experienced substantial and persistent visual-motor integration problems throughout cancer treatment. The delayed development of these skills has been proven to increase the likelihood of many more developmental issues both cognitively and physically.

Gross Motor Development

Wright, Halton, Martin & Barr (1998) compared musculoskeletal and gross motor functions between 36 child survivors of ALL and 36 age and gender matched comparison subjects. While scores for gross motor function for standing, walking, running and jumping were practically identical within both groups, substantial deviation was observed in motor proficiency. Subjects that had survived ALL experienced significantly lower scores in strength, balance and running speed and agility. Moreover, these subjects demonstrated significantly less handgrip strength and ankle dorsiflexion than the comparison group (Wright et al., 1998). These findings allowed Wright et al. (1998) to conclude that although leukemia child survivors were able to perform basic gross motor functions at the same level as their non-cancer counterparts, their motor proficiency was significantly poorer.

De Luca et al. (2013) examined that 26% of the 37 children with ALL who participated in his study experienced general motor difficulties not only during their treatment but also when they were reassessed substantial time after their treatment. Additionally, De Luca et al. (2013) identified that time-off treatment did not affect the prevalence of motor impairments, meaning that once damaged these motor difficulties were unlikely to be corrected.

Basic Psychomotor Development

Harten et al. (1984) compared the psychomotor skills of 51 long-term child survivors of ALL to 30 patients who had recovered from other malignancies that did not require chemotherapy or cranial radiation therapy. Their study showed that while approximately 33% of all patients showed mild disturbances of psychomotor speed and motor skills, ALL survivors had slightly lower scores than those with other malignancies for nearly all tasks. However, ALL survivors showed significantly lower scores for sensory integration than the other patients, indicating a substantial increase in psychomotor disturbances due to CNS targeted radiation and chemotherapy (Harten et al.,1984).

Balance Development

Galea, Wright & Barr (2004) measured the balancing abilities of 79 ALL child survivors who were at least 1 year post-treatment and 83 age-matched controls. Although the youngest group of patients (5-7 years old) performed similarly to their healthy counterparts, ALL survivors in the 8–11, 12–15 and 16 years and older groups did significantly worst in the more difficult balance challenges. In fact, 33% of ALL survivors were unable to complete the most challenging task. These findings have lead Galea, Wright & Barr (2004) to conclude that integration and development of postural systems are compromised as a result of chemotherapy and cranial irradiation. They propose that activities promoting postural control should be included in physical therapy during and especially following treatment.

Epidemiology

United States

In 2000, an estimated 256,000 children and adults developed a type of leukemia, of which 209,000 (81.6%) died from it. this represents approximately 3% of the nearly 7 million deaths from cancer that year. in 2010, an estimated 281,500 people died of leukemia (The Leukemia and Lymphoma Society, 2014). In the US approximately 33% of all children diagnosed with cancer have a form leukemia. This form of cancer is the most common among children and the second most common among infants. Caucasian children are almost twice as likely to develop leukemia that African-American children. And boys are slightly more likely to develop leukemia than girls. For adults, more than 30% ore men are diagnosed with leukemia than women (The Leukemia and Lymphoma Society, 2014).

United Kingdom

In 2011, 8,600 people were diagnosed with leukemia, making it the 11th most common cancer in the UK. In 2012, approximately 4,800 people died of leukemia (Cancer Research UK, 2014).

Canada

In 2014, an estimated 5,900 people were diagnosed with leukemia and 2,700 died from it (Canadian Cancer Society, 2015). Every year 3,400 men and 2,600 women are diagnosed with leukemia and 1,550 men and 1,100 women will die from it. Based on 2009 estimates, 1.9% of Canadian men and 1.4 Canadian women will be diagnosed with leukemia during their lifetime (Canadian Cancer Society, 2015).

Leukemia is the most common form of cancer in children (age 0-14) (Canadian Cancer Society, 2015). In Canada between 2006-2010, 1,465 children were diagnosed with leukemia. Of this figure, 1,145 children (78%) were due to ALL and 200 children were due to AML (Canadian Cancer Society, 2015). In Canada between 2006-2009, 137 children died from leukemia, of which 56 were from ALL and 37 from AML (Canadian Cancer Society, 2015).

References

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