Discuss the Epidemiology of Pediatric Leukemia

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The Answer is Approximately 11% of all cases of leukemia are diagnosed in children and adolescents under the age of 20 years. Acute lymphocytic leukemia accounts for more than 80% of cases for children younger than 10 years of age. The incidence of acute lymphocytic leukemia peaks in 2-year-olds at 83 per million.
In developed nations, the annual death rate from leukemia in children has fallen by more than 50% in the past three decades. This favorable downward trend in mortality has occurred even though the incidence of childhood leukemia has increased more than 30% over the same time period. The falling leukemia mortality in children of developed nations reflects a marked increase in survival due to rapid detection coupled with improved therapy. Despite the obvious benefit of early detection and effective therapy in some parts of the world, survival remains poor for the children who develop leukemia in less-developed nations.
Leukemia is the most common cancer in children and has been intensively investigated using molecular, genetic, clinical, and epidemiologic techniques. Nevertheless, with the exception of ionizing radiation, rare genetic syndromes, and certain chemotherapeutic drugs that are implicated in a small fraction of cases, causal factors for most cases are obscure, and the etiology remains enigmatic. Infectious and allergenic agents have also been implicated, but causal associations with specific agents remain unproven.
Radiation exposure has been found to increase the risk of developing acute lymphocytic leukemia in children. The Life Span Study was initiated in 1950 to monitor the impact of radiation exposure among survivors of the atomic bomb explosions in Japan during World War II. As of the year 2000, 204 leukemia deaths had occurred among 49,204 survivors who received a bone marrow radiation dose of at least 0.005 Gy, constituting an excess of 94 cases (46%) attributable to radiation from the atomic bomb explosions.
Marked gender and ethnic differences have been noted in the incidence rates of pediatric acute lymphocytic leukemia. For children under 15 years of age, boys have about 1.2 times higher risk than girls, and Caucasians have about 2 times higher risk than African Americans. Reasons for these gender and ethnic differences are speculative. The recently proposed "adrenal hypothesis" relates the higher leukemia risk in children of higher socioeconomic classes to their relatively low exposure to infectious viruses and bacteria during the early years of life. Presumably, the risk of acute lymphocytic leukemia is reduced when childhood infections during infancy induce the hypothalamic-pituitary-adrenal axis to secrete high levels of plasma cortisol. Corticosteroids are known to regulate the maturation and proliferation of B lymphocytes by stimulating apoptosis, and high levels may eliminate leukemic cells and/or progenitor B lymphocytes with leukemogenic potential.
Some studies have noted an association between childhood leukemia and the presence of autoimmune conditions among relatives. These results suggest that a family history of autoimmune thyroid disease may be associated with childhood acute leukemia. Genetic polymorphisms of the P-450 enzyme system have been found that appear to increase the risk.
The risk of developing acute lymphocytic leukemia is increased in subjects with certain rare genetic syndromes and conditions. These include Down syndrome, Bloom syndrome, Shwachman syndrome, ataxia telangiectasia, neurofibromatosis, and Fanconi anemia.
Certain chemotherapeutic agents have been found to heighten the risk of leukemia development in children and adults. For example, the compound epipodophyllotoxin (etoposide and teniposide) has been linked to the development of acute myeloid leukemia. This compound interferes with the function of topoisomerases, enzymes that unwind and wind DNA for transcription and replication.
Acute lymphocytic leukemia is characterized by quick onset with rapid transition from good health to life-threatening disease, particularly in children. In a US study, the pattern of onset showed peaks in winter, spring, and summer, coinciding with seasonal elevations in the rates of allergenic and infectious diseases that are capable of promoting lymphocytic proliferation and transformation.
Cytogenetic abnormalities and reciprocal chromosomal translocations are characteristic of pediatric acute lymphocytic leukemia. Reciprocal translocations are the most common structural chromosomal aberrations found in acute lymphocytic leukemia. The first translocation discovered in pediatric acute lymphocytic leukemia was t(9;22), a reciprocal translocation involving juxtaposition of the BCR gene on chromosome 9 to the promoter region of the ABL gene on chromosome 22. The altered chromosome 22 produced by this translocation is called the "Philadelphia Chromosome," which is the defining element of chronic myelocytic (granulocytic) leukemia in adults.

Discuss the Epidemiology of Pediatric Leukemia

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