1.2Incidence

•Thirty-three percent of all cancers in children are leukemias

•Annually 45 of each million children less than 16 years of age are newly diagnosed as having leukemia

•Incidence peaks at 2–5 years

•Occurrence in all age-groups during childhood, grouped by type of leukemia:

–75% acute lymphoblastic leukemia

–20% acute myelogenous leukemia

–5% undifferentiated acute leukemia and chronic myelogenous leukemia

1.3Etiology and Predisposing Factors

•The cause of human leukemia is unknown

•Predisposing factors in the pathogenesis of leukemia and other malignant disorders in childhood are described in the “Pathogenesis”

•There is a 2–4 times higher incidence of leukemia in siblings within the age of 1–7 years

1.3.1Genetics

•In a monocytic twin, there is a 20% increased risk of leukemia within months after the co-twin develops leukemia

•Higher risk in congenital disorders. Examples:

–Trisomy 21 (14 times higher)

–Monosomy 7

–Neurofibromatosis type 1

–Fanconi anemia (high fragility of chromosomes)

–Bloom syndrome

–Kostmann syndrome

–Poland syndrome (absence of pectoralis major muscle and variable ipsilateral upper-extremity defects)

–Congenital agammaglobulinemia

–Ataxia-telangiectasia (high fragility of chromosomes)

–Other bone marrow failure syndromes along with inherited translocation syndromes and inherited CEBPa

1.3.2Ionizing Radiation

Atomic bomb survivors (from Hiroshima and Nagasaki) developed leukemia with an incidence of 1:60, within a radius of 1,000 m of the epicenter, occurring after 1–2 years (peak incidence after 4–8 years). There was a predominance of ALL in children and of AML in adults, which may reflect the different pathogenesis in the various age-groups.

1.3.3Chemicals and Drugs

•Benzene (related to AML)

•Chloramphenicol (usually related to ALL)

•Chemical warfare agent, i.e., nitrogen-Lost (related to AML)

•Cytotoxic agents, e.g., correlation between alkylating agents and Hodgkin disease and other malignancies – especially after irradiation, there is a higher incidence of leukemia (usually AML), ovarian carcinoma, and other solid tumors

1.3.4Infection

•Correlation between viruses and development of leukemia has been observed, especially after RNA virus infection in mice, cats, chicken, and cows

•Human T-cell leukemia virus (HTLV) has been demonstrated in adults to be linked to T-cell lymphoma in some geographical areas

•Association between Epstein–Barr virus (EBV) and occurrence of Burkitt lymphoma

•Human immunodeficiency virus (HIV): HIV infection and/or immunodeficiency causes a higher incidence of malignancy, and, particularly, NHL

•In humans vertical or horizontal transmission of human leukemia has not been demonstrated except in rare cases of a mother with leukemia to her newborn or in identical twins with prenatal leukemia

1.3.5Immunodeficiency

There is correlation between immunodeficiency and development of lymphomas and lymphoic leukemias (i.e., congenital hypogammaglobulinemia, Wiskott– Aldrich syndrome, HIV infection).

1.3.6Socioeconomic Situation

•Higher incidence of neoplasia may be seen in higher socioeconomic groups

•Similar frequencies in urban and nonurban areas

•Multivariate analyses are needed to confirm the socio economic differences

1.4Pathogenesis (Fig. 1.1)

The etiology and/or predisposition (see above) indicates a correlation between leukemogenesis and different risk factors:

•Chromosome instability/fragility

•Immunodeficiency

•Environmental exposures (ionizing radiation, chemicals, viruses)