Leukemia in Children
Background
The disease condition that is termed as Leukemia was first discovered by a German pathologist named Rudolf Virchow in 1887. The term leukemia was coined by Virchow from the Greek words: “leukos” meaning white, and “haima” which is a term for blood(“Leukemia”).
Leukemia is a form of cancer that makes up twenty-five percent of the cancers affecting children. In Canada, this disease condition is a primary fatal disease of children (Statistics). This is a cancer of the blood that usually occurs as Acute Lymphoblastic Leukemia which is 80 percent of the cases of Leukemia in children (NCLF ). In United States of America, Acute Lymphoblastic Leukemia (ALL) is the most common and is 70 percent of leukemia cases in children. Other forms of leukemia that affects the children in U.S. are: Acute Myeloid Leukemia (AML) approximately 20 percent of the cases, Chronic Myeloid Leukemia (CML) that is roughly 5 percent, and Juvenile Myelomonocytic Leukemia (JMML) that is estimated to be also 5 percent of the occurrence of Leukemia in children(Clinic).
Leukemia is a disease condition wherein there is an abnormality in the production of blood cells. The occurrence of this disease frequently involves the white blood cells production in the bone marrow but it can also involve other types of cells in the blood. Leukemia is a cancerous disease condition of the malignant form thus the disease progresses into the other organs of the body such as the lymph nodes, liver, central nervous system, and spleen after affecting the bone marrow(Byrd).
This disease is not only occurs in humans but to other animal species as well such as cats, cattle, and guinea pigs. In humans, leukemia is widespread in older people but at present there is an increasing occurrence in children. Factors that cause the occurrence of leukemia are: chromosomal abnormalities like Down syndrome, chemicals such as benzene, chemotherapeutic drugs such as alkylating agents, ionizing radiation, and viral infection due to retrovirus like HTLV-I. Alterations or mutations in the normal synthesis and development of blood cells are brought about by these factors(“Leukemia”).
Diagnosis of the type of leukemia is based on the kind of blood cells that is affected. The common types of leukemia are: Lymphocytic, affecting the formation of lymphocytes; and myelogenous, alterations in the myelocyte synthesis(Rogers). Leukemia of the myeloid type affects the stem cells of granulocytes or phagocytic white blood cells. The Lymphocytic Leukemia involves white blood cells that are stem cells of lymphocytes(“Leukemia”). The common types and forms of leukemia are the following: Acute Lymphocytic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), and Chronic myelogenous leukemia (CML). The diagnosis of this disease condition according to the type of cells affected is accompanied with the identification of the form of the condition either acute or chronic. The progression of the disease is slower in chronic form but in a longer time, while, in the acute form the progression is in a short span of time(Rogers).
The Acute Lymphocytic Leukemia (Lymphoblastic Leukemia or Lymphoid) is the most common form of leukemia in children. The cell line of the lymphocytes is the ones involved in this condition. In this disease, there is the over production of lymphocytes in the bone marrow that do not mature accordingly. The duration of this illness is from a few days to a couple of weeks. In most of the patients with ALL there is the existence of abnormalities in the chromosome wherein extra chromosomal numbers and alterations in the morphology of the chromosome material is present(Byrd).
The Acute Myelogenous Leukemia (AML) which is also termed as granulocytic, myeloblastic, myeloid, or myelocytic is 19 percent of the diagnosed children leukemia. There is hyper-proliferation of the white blood cells in the bone marrow which do not attain the necessary maturity status in order to fight infectious agents. The duration of AML is also from a few days to a couple of weeks. Children afflicted with genetic disorders like Bloom syndrome, Kostman syndrome, Fanconi Anemia, and Down syndrome are of increased risk of having the disease(Byrd).
Chronic Myeloblastic Leukemia (CML) is a rare form in children. The bone marrow is producing too many abnormal granulocytes that alter the function of the normal granulocytes. This form of disease progresses within months to years. There is a substitution of the genetic material of the chromosome number 9 and 22. A component of the chromosome number 9 is chipped off and adheres into chromosome number 22. The swapping of the components of the two chromosomes results into the abnormal increased production of granulocytes(Byrd).
Natural History
Symptoms of leukemia are linked with the blood function because the initial pathogenesis of the disease in on the bone marrow. The following are the common manifestations of leukemia: anemia, bleeding or bruising, bone and joint pains, recurrent infections, swollen lymph nodes, abdominal distress, and breathing difficulty. The anemia occurs due to the incapacity of the bone marrow to produce red blood cells in association with the overcrowding of the bone marrow with the proliferating cancerous cells. Manifestations of this symptom include the tiredness of the child, faster breathing, and paleness. Recurrent infections that can be viral or bacterial and occurs over the past weeks are brought about by the disrupted capacity of the immune system to mount an immune response due to the presence of immature white blood cells. Bleeding and bruising are due to the decreased number of platelets that are produced in the bone marrow as a result of the crowding in the area with cancerous cells. The multitudes of cells present in the bone marrow results to pain in joint and bone. Abdominal distress is an outcome of the pooling of leukemia cells in the liver, spleen, and kidney which causes the swelling of these organs. A child with leukemia may express pain of the abdomen by the loss of appetite and consequently decrease in body weight. Pooling of the leukemia cells also occurs in lymph nodes in the groin, neck, chest, and under the arms hence swelling of these areas arise. In T-cell Acute Lymphocytic Leukemia (T-cell ALL), the thymus is adhered by the leukemic cells resulting to pain in this area and difficulty in breathing(Byrd).
The symptoms of ALL or AML are manifested within days or weeks but in cases of Chronic Myelogenous Leukemia (CML) the clinical signs progresses over months to years. The symptoms of Leukemia are similar with blood disorders and other medical problems hence appropriate diagnostic modalities must be employed so as to reach the right diagnosis. Different individuals have varied manifestations of leukemia so diagnosis must be done with caution(Byrd).
Staging in Leukemia cases is not necessary because the disease progresses from the bone marrow and usually has metastasized to the other organs upon diagnosis. Cytologic classification systems are used in replacement of staging in this type of cancer. These system diagnoses the type and subtype of leukemia as well as aide in making prognosis or the outcome of the disease with or without therapy(oncologychannel).
The French-American-British (FAB) system is the widely used modality for leukemia. In this classification there are: three subtypes of Acute Lymphocytic Leukemia (ALL) and eight subtypes of Acute Myelogenous Leukemia (AML). The previous basis of FAB was the microscopic appearance of leukemia cells only but at this present time the cellular characteristics like the genetic composition and numbers of specific cell types are incorporated for better prediction of the outcome of the disease(oncologychannel).
In Acute Lymphocytic Leukemia there are two systems of Cytologic staging that can be employed. These are the Rai Classification and Binet Staging. The Rai classification have three categories of leukemia with corresponding stages: Low category with stage 0; Intermediate category with stage I and II; and, High- Risk category with stage III and IV. Patients that belongs to the stage 0 (Low Risk Category) have lymphocytosis which is increased quantities of lymphocytes that is above 15,000 lymphocytes per cubic millimeter. Enlargement of the lymph nodes in addition to lymphocytosis is the characteristic of Rai stage 1 (Intermediate Risk category). Aside from the lymphocytosis and enlarged liver (hepatomegaly) or spleen (splenomegaly), in Rai stage 2 (Intermediate Risk category) lympadenopathy may or may not be observed. In Rai stage 3 (High-Risk), anemia accompanies the lymphocytosis either in the presence or absence of lymphadenopathy, splenomegaly, and hepatomegaly. The patients that are also classified as High-Risk category but with stage 4 Leukemia have thrombocytopenia or decreased in number of platelets in the blood that is lower than 100-103 per deciliter in addition to lymphocytosis(oncologychannel).
In contrast to the classification of Chronic Lymphocytic Leukemia (CLL) by Rai classification according to the lymphocyte quantity and organ enlargement, the Binet Staging grade CLL based on the number of involved lymphoid tissue (lymph nodes and spleen); and, existence of decreased quantity of red blood cell (anemia) and decreased number of platelets in the blood (thrombocytopenia). The three Binet stages are: stage A, wherein there are lower than three lymphoid tissue section that are engorged; Stage 2 involves greater than three areas of lymphoid tissue enlargement; and Stage 3, wherein the patients in this stage have thrombocytopenia in addition to anemia(oncologychannel).
Diagnosis of leukemia is done with various modalities and these include the following: complete blood cell count (CBC) which consists of total White blood Cell (WBC) count, Differential White blood Cell count, and Packed Cell Volume; Bone marrow aspiration or biopsy, wherein a sample of the bone marrow fluid is aspirated from the hip bones to assess the bone marrow cell size, quantity, ratio of normal to abnormal cells, and maturity of the cells; blood chemistry examinations such as Serum Glutamic Pyruvic Transaminase (SGPT) for the liver and Creatine test for the kidney; Computed Tomography or CT scan, an imaging modality that utilizes computer and x-ray to generate a three dimensional image; x-ray, an imaging modality that uses electromagnetic energy rays to visualize the internal organs; and, lymph node biopsy, examines the cells of the lymph node(Byrd).
Agent-Host Environment
The primary etiologic agent of the development of Leukemia is not known though it is established that this disease condition occurs due to the damage of DNA of blood cells (Department of Environmental Health). Various factors are associated with the development of leukemia in children. Among these causes are toxins, viral infections, radiation, benzene, and chemotherapeutic agents. Pesticides and electromagnetic fields are also a predisposing factor to the occurrence of Leukemia. Ionizing radiation exposure that can be because of x-ray examinations of the mother during pregnancy predisposes a child to the development of Leukemia.
The children patients afflicted with leukemia have no specific characteristics that can serve as a cause of the disease. Exposure to various factors is the only explanation that can be related to the occurrence of leukemia in children. Examples of such factors are x-rays which involves ionizing radiation in the procedure that causes genetic mutations leading to the development of leukemia(Tower).
Mode of Acquisition
The development of leukemia in an individual is not a result of a specific etiologic agent but rather due to the exposure of the individual to factors that catalyze the mutation of the bone marrow cells resulting to the synthesis and proliferation of leukemia cells. Leukemia also is associated to the following factors: air pollution, socioeconomic status, electromagnetic fields, infections, genetics, and living near nuclear power plants(Tower).
The incidence of cancer such as leukemia in well developed countries is explained to be attributed to exposure to various environmental factors including the following: water and food contaminants; air pollution; chemicals like pesticides, mercury, and lead; and physical causes such as ultraviolet radiation. The cells of children are very vulnerable to mutations caused by environmental factors because there is still an ongoing development in their bodies(Kheifets ).
Children with genetic disorders such as trisonomy 21 or down syndrome are very susceptible to leukemia due to the congenital defects that is present in their genes. The genes which encode for the hematopoietic transcription factor GATA1 have mutations that result to the development of leukemia. There is 10 to 20 fold raise in incidence of acute leukemia cases in children that are affected with Down syndrome. There are two forms of leukemia found to occur in children with Trisonomy 21: the Transient Leukemia and the Acute megakaryoblastic leukemia(Hitzler).
Descriptive Studies
The most common type of leukemia that affects children is the Acute Lymphocytic Leukemia (ALL) which is 73 percent of the diagnosed cases of leukemia in United States. Children of ages 2-3 years old are the ones most commonly afflicted with ALL. The second widespread type of leukemia is Acute Myelogenous Leukemia (AML). This disease condition occurs in children 10 years old and above; and those whom are 2 years of age. This form of leukemia though only the second widespread form in children is the most frequent form in adults. Leukemia in children is rarely of chronic form(Byrd). The occurrence of leukemia is greatest in ages 0-4, intermediate in 5-9, and unapparent in 10-14.There is a noticeable difference in the incidence of ALL and AML in different ages. The peak ages for the occurrence of ALL are among 2 to 5 years old with 75 cases per million children. AML on the other hand peaks during infancy and occurs in a uniform manner in older children (Tower).
In U.S. and Canada, leukemia is the widespread type of cancer that afflicts children which are 0-14 years of age. The occurrence of ALL is five-fold greater than the incidence of AML though these two are the common forms of leukemia that badly affects children. Despite the intensive study and improvements in the modalities used for treatment of acute leukemia, it still lingers as the primary causative disease in morbidities and mortalities among children(Tower).
Among different countries, the incidence of leukemia in children is varied. On a yearly basis the incidence of Acute Lymphocytic Leukemia (ALL) in children is within 19 to 56 for every million of males and 12 to 43 for every million of females. The highest incidence among countries for ALL is in Costa Rica, Canada, and Finland. India and China has the lowest incidence of ALL in children. Canada averages 41.0 for both male and female; 44.8 for males; and 36.9 for females in the incidence of ALL in children. The annual standard rate for Acute Myeloid Leukemia (AML) in children is highest in New Zealand, Costa Rica, and Australia. Canada has an intermediate rate of 6.3 for both male and female; 6.9 for males; and 5.6 for females. In the period 1997-2002, the rate of occurrence of ALL is 32.3 cases per million and AML is 6.8 cases per million among 0-19 years old children in Canada(Tower).
Males are slightly diagnosed more with ALL and AML in different ages though the females have greater incidence of having ALL and AML in their first year of existence. White people are more afflicted with ALL when compared to the blacks. The ratio of the incidence is 2:0 between the whites and the blacks. In contrast AML occurrence is equal in both races(Tower).
Epidemiology journal published that in Canada the incidence of Leukemia occurrence is so much greater in children belonging to the richest families than that of the poorest population(Statistics). The association of increased occurrence of leukemia to the socioeconomic status can be noticed in the study of Tower et al. (2007) wherein the economically developed Denmark has the highest incidence while the economically challenged nation- Nigeria has the lowest rate of ALL(Tower). The explanation given was that the poor children are more exposed to etiologic factors such as infectious agents hence the development of antibodies against these agents at an earlier age compared to the rich children (Statistics). The constant exposure of the poor children to etiologic factors that cause leukemia enhance their immune system’s ability to combat the adverse effects of these agents through the production of antibodies that have specific immune response to an etiologic agent.
Children living near a fuel station are found out to be of greater risk in developing Acute Leukemia. There is a four-fold increase in the risk of the development of the acute form of leukemia in children who reside near vehicle-repair garage and fuel stations(Sahelian). Nuclear power plants also pose as a risk to acquiring leukemia in children. Those children which are nine years old and below who reside near nuclear power plants have 21 percent increase in the risk of mortality due to leukemia. The study which was conducted in Canada, United Kingdom, USA, Germany, France, Spain, and Japan was published in the European Journal of Cancer Care. The study was able to overcome the natural variables because the said study was conducted before and after the establishment of the nuclear power plants. Aside from children 9 years of age and below, the young adults that are 25 years old and younger are also found out to be with 18 percent increase in risk if they live near nuclear power plants(“Power Plant Risk “).
Analytic Studies
In a study of Noshchenko et al. (2002) it was indicated that there were significant amplification in the cases of acute leukemia in children in relation to the exposure to ionizing radiation. The exposure due to residence near nuclear test sites also causes considerable raise in the leukemia cases of children. There is also a significant increase in the number of leukemia disease cases when the mother was exposed to atomic bombing during the course of her pregnancy. The survivors of atomic bombing which were pregnant are associated to leukemia cases in the data of the Oxford Survey of Childhood Cancers and related X-ray exposures(Russ).
Children whom were born with fathers that are radiation workers are found out to likely develop leukemia and non-Hodgkin lymphoma. In the cohort study of Dickinson and Parker (2002), it was learned that there is a considerable 200 percent increase of Leukemia and non-Hodgkin Lymphoma risk in radiation workers children. These studies serve as evidences that indeed father whom are exposed to rather will increase the likelihood of having a child that is afflicted with leukemia. Exposure to ionizing radiation during preconception, pregnancy, and post pregnancy of the mother serve as risk factors for the development of leukemia in children(Russ).
Treatment
Various factors are considered before the planning of treatment program to be used in leukemia cases. These factors are: age, health, and medical history of the child; the capacity of the child patient to tolerate medication, medical procedures, and therapies; the degree of the disease condition; and the opinion of the parents or guardians of the child. Symptomatic treatments are employed for conditions like bleeding, anemia, and infection(Byrd).
The treatment regimen for Leukemia at present involves the following approaches: chemotherapy which aims to kill the proliferating leukemia cells with anti-cancer drugs; radiation therapy that destroys the leukemia cells through high-energy radiation exposure; interferon therapy which aims to increase the time for the proliferation of leukemia cells and at the same time enhance the capacity of the immune system to destroy the leukemia cells; surgery that includes either the installation of catheters to serve as passage way for medications or resection of enlarged spleen; and stem cell transplantation (SCT) so that high doses chemotherapy and radiation therapy can be employed as a treatment regimen(oncologychannel).
The aforementioned treatment modality can be used either alone or in various combinations. These modalities of therapy though have disadvantages that accompany the advantages they offer. Prior to undergoing therapy programs a second opinion is needed so as to lessen the chances of wasting resources on a therapy program that will have no effect at all for the betterment of the patient’s condition(oncologychannel).
Interferon therapy is a treatment modality in utilized in leukemia patients to aide the patient’s body in reducing the proliferation of leukemia cells and at the same time enhances the immune system of the leukemic patient to mount the proper immune response. The most widely employed type of interferon for this purpose is the Interferon-alpha (INFa). The expected length of survival of the patient can be predicted by the physician through using this treatment modality. Interferon-alpha is administered through intravenous, intramuscular, and subcutaneous injection. The frequently used route though is the subcutaneous injection. Disadvantages of using this drug are development of the following: fever, muscle aches, headaches, bone pain, fatigue, flu-like symptoms and chills, difficulty in concentration, vomiting, and nausea. The duration of the side effects range from 1 to 2 weeks but can be managed by acetaminophen administration(oncologychannel).
Treatment of leukemia involves various stages and these are: induction stage, intensification stage, maintenance stage, and relapse stage. The induction stage includes a mixture of various treatment modalities like chemotherapy, radiation, and medications so as to end the synthesis of abnormal cells in the bone marrow. The primary aim of this stage is for remission or the ending of the production of leukemia cells to occur. The duration of this stage is one month and repeated after rest period if the goal is not attained. The next stage of treatment therapy is the intensification wherein the treatments are continued until the leukemia cells do not longer exist as per diagnostic blood test or bone marrow examination is concerned. The leukemia cells though may still exist in the body. The maintenance stage is when the leukemia-free bone marrow is preserved through a continuous chemotherapy of lower intensity but longer in duration (months to years). Constant visits to the health care provider are necessary so that the patient’s response to the treatment will be assessed, recurrence of the disease will be diagnosed, and side effects of the treatment employed can be controlled. The relapse stage is a period wherein the aggressive therapy is not able to stop the synthesis of leukemia cells in the bone marrow. The relapse stage can happen in the duration of the treatment in various stages or months to years after the end of the treatment(Byrd).
The formulation of the prognosis of leukemia will need to consider the following : degree of the disease condition; genetics; treatment response; age and general health of the child; recent medication developments; and, the child patient’s capacity to tolerate medications, medical procedures, and therapies(Byrd). Different forms of leukemia require dissimilar treatment programs. In Acute Lymphoblastic Leukemia (ALL), multi-agent therapy is utilized. Despite the improvements in treatment modalities though it is found out that ALL cells reach the meninges of the brain. Thus administration of prophylactic treatment for the CNS is incorporated in the treatment programs for this form of leukemia. The therapy for this disease condition is very rigorous and lasts for two to three years. Included in the treatment program are the: intrathecal chemotherapy; and radiation therapy for the brain and spinal column that is generally done to children under 1 year old ,teenagers, and those diagnosed with vast amounts of white blood cells. In Canada, it is estimated that 75 percent of the children diagnosed with this form of leukemia survive five years after the diagnosis and the bulk of them are said to be healed. Thirty percent of the patients though are estimated to have relapses thus they will undergo into another treatment program that is different from the previous one. Improvement in the survival rate of these patients is observed when bone marrow transplant is employed after succeeding remissions(Program).
In cases of Acute Nonlymphoblastic Leukemia, the treatment program utilized is more thorough when compared to that of ALL. Chemotherapy, CNS treatment, and bone marrow transplant are indicated for this disease condition. Remission occurs in 70 to 90 percent of the cases and 40 to 50 percent of these patients will be leukemia free for a long time. In Canada, there is a 40 percent survival rate for five years by these patients(Program).
Prevention
The Federal Government of Canada launched the Canadian Childhood Cancer Surveillance and Control Program in an effort to decrease the risk of development of health problems among the country’s children. As part of the programs advocacy awareness about Cancer including leukemia was promoted among children through the publication of the book entitled “This Battle Which I Must Fight: Cancer in Canada’s Children and Teenagers”(Program). The publication of the book helps people understand the disease condition and aides those children already with the disease cope up with the treatment process.
The application of pesticides is studied in Canada and was found out to be a causal factor in the development of various health problems such as cancers like leukemia. In an effort to contain then progression of leukemia in the children of Canada the use various pesticides is already banned despite the lack of efforts of other countries to ban these substances that are known to be a factor in development of cancers(AHRP).
Researches and conferences have been done in Canada in line with the advocacy against the incidence of cancers including Leukemia in children. An example of these researches is Joint study between Israel’s Weizmann Institute of Science, Toronto General Hospital, and Toronto Western Hospitals of University Health Network. With continuous research, improvement in the clinical care of Leukemia patients is established and will incessantly find ways of providing new treatment regimens that will promote survival rates. The partnership between this entities aims to improve the capability to put off and treat Leukemia(Foundation).
Future Trend
Early intervention in leukemia cases will result into increased survival rates because the cancer has not metastasized intensively into various organs of the patient’s body. It is encourage to for individuals to regularly have medical check-ups so as to diagnose diseases such as leukemia in early stages or non-metastasizing stage. The parents have this role of ensuring that their children will have regular check ups for leukemia so that prompt intervention can be employed and the remission will be assured. Early treatment of the disease condition will prevent the occurrence of damages to various other parts of the patient’s body.
In the future, much improved treatment modalities for Leukemia in children will be established. Intensive researches on the etiologic factors of Leukemia will result into the discovery of treatment modalities that will totally treat the cases of this disease condition. The formulation of a vaccine for leukemia is a start in the process of finding ways to eradicate this disease condition. The human CD40 ligand or human interleukin-2 autologous cell vaccine is a promising prophylactic treatment modality for the prevention of the occurrence of leukemia in not only in children and young adults but to the adult population as well. Gene therapy which is also widely studied will have positive results that will serve as a treatment modality in the future. The discovery of new drugs that will alter the gene of leukemia cells and spare the normal blood cells is the beginning of the exploration in gene therapy for the treatment of leukemia(Foundation).
The Canadian Federal Government with the help of various non-governmental organizations is unifying their efforts in the advocacy against leukemia. Researches which is focused in discovering ways of treating Leukemia which is widespread in Canada is an affirmative way of combating Leukemia.
Innovations in the treatment modalities though will also be accompanied by side effects due to these treatments. The costs of therapeutic programs will also be increased in the future as a result of the emergence of new diagnostic and treatment modalities.
Works Cited
AHRP, Alliance for Human Research Protection. “Comprehensive Scientific Review Concluded: All Pesticides Pose Serious Health Risks to Humans–Especially Children”. 2004. Alliance for Human Research Protection. December 2 2007. <http://www.ahrp.org/infomail/04/05/08.php>.
Byrd, Rebecca; Werner, Eric; Bevan, Herbert; Owen, William; Peg ram, Linda; & Lowe, Eric “Hematology and Blood Disorders: Leukemia”. 2007. Children’s Hospital of The King’s Daughters. December 2 2007. <http://www.chkd.org/HealthLibrary/content.aspx?pageid=P02324>.
Clinic, Mayo. “Acute Leukemia”. 2001. Mayo Foundation for Medical Education and Research. December 1 2007. <http://www.mayoclinic.org/acute-leukemia/children.html>.
Department of Environmental Health, Boston Univeristy School of Public Health. “Environmental Causes of Blood-Related Cancers in Children.” Health Effects Review (2003). <http://www.ijc.org/rel/pdf/06_blood-summer2003.pdf>.
Foundation, Toronto General & Western Hospital. “For Immediate Release: Israel and Canada Unite for Leukemia Research”. 2006. Toronto General & Western Hospital Foundation. December 2 2007. <http://www.uhn.on.ca/donate/tgwh/site/html/events/michaelbaker/news/2006_03_20.html>.
Hitzler, Johann K; and Zipursky, Alvin. “Origins of Leukaemia in Children with Down Syndrome.” Nature Reviews 5 (2005).
Kheifets, Leeka; Repacholi, Michael; Saunders, Rick; and van Deventer, Emilie. “The Sensitivity of Children to Electromagnetic Fields.” Pediatrics 116 (2005): e303-e13.
“Leukemia.” The Columbia Encyclopedia. 6th ed: Columbia University Press, 2007.
NCLF, National Children’s Leukemia Foundation “What Is Childhood Leukemia?” 2006. National Children’s Leukemia Foundation (NCLF). December 1 2007. <http://www.leukemiafoundation.org/cancer-and-leukemia-info/3.htm>.
oncologychannel. “Leukemia Treatment”. 1999. Healthcommunities.com, Inc. December 2 2007. <http://www.oncologychannel.com/leukemias/treatment.shtml>.
“Power Plant Risk “. Ecologist 37.8 (2007).
Program, Canadian Childhood Cancer Surveillance and Control. This Battle Which I Must Fight 1997. Cancer in Canada’s Children and Teenagers. December 2 <http://www.phac-aspc.gc.ca/publicat/tbwimf-mcplv/other1_e.html>.
Rogers, Miriam P. “Leukemia.” Diseases and Conditions Encyclopedia: Discovery Communications, 2007.
Russ, Abel. “Ionizing Radiation and Childhood Leukemia.” Environmental Health Perspectives 115.8 (2007).
Sahelian, Ray “A Natural Approach to Leukemia”. <http://www.raysahelian.com/leukemia.html>.
Statistics, Canada. “Study: Childhood Leukemia and Socioeconomic Status”. 2005. British Columbia Cancer Agency. December 1 2007. <http://www.statcan.ca/Daily/English/050705/d050705b.htm>.
Tower, Richard L.; and Spector, Logan G. “The Epidemiology of Childhood Leukemia with a Focus on Birth Weight and Diet.” Critical Reviews in Clinical Laboratory Sciences 44. 3 (2007): 203-42.