Acute leukemias in children

Essence of the disease and classification principles

Leukemia, or leukemia, is a malignant transformation of the body's hematopoietic system. The fundamental basis of the pathology is that healthy bone marrow hematopoiesis is gradually replaced by the pathological proliferation of the least mature (poorly differentiated) cells. Historically, this term was proposed by researcher V. Ellermann back in 1921.

In modern clinical practice, acute leukemias are typically divided into three main groups. The primary criterion for this division is the lineage of the initial cell in which the tumor mutation occurred.

Acute lymphoblastic and myeloblastic leukemias

Among pediatric acute leukemias, acute lymphoblastic leukemia (ALL) is unconditionally dominant. The tumor substrate in this form is represented by lymphoblasts — lymphocyte progenitor cells with a specific set of genetic and immunophenotypic markers. This is the most common form of cancer in pediatrics: approximately 3.5–4 cases per 100,000 children are registered annually. A pronounced age pattern is characteristic: the so-called "infant peak" occurs between the ages of 2 and 5 years. Boys are affected more often than girls, with the gender bias varying depending on the ALL type: for the T-cell variant, the ratio is 4:1, and for the B-cell variant, 1.6:1.

The second major form is acute myeloid leukemia (AML). The substrate here consists of myeloblasts. This group of diseases is extremely heterogeneous and radically different from ALL in its formation mechanisms, clinical presentation, and response to therapy. AML occurs in children about five times less frequently. Depending on the degree of maturation and the type of initial progenitor cell, this form is further subdivided into 8 different variants.

Etiology and predisposing factors

A reliable and sole cause of the disease has not yet been established. It is believed that the pathology is triggered by a combination of a complex of risk factors:

• Maternal factors: the risk increases with advanced maternal age and a burdened obstetric history (past cases of fetal demise). This may indirectly indicate exposure to genetic or environmental mutagens.
• Child-related factors: macrosomia, i.e., a newborn birth weight exceeding 4000 grams.
• Exogenous exposures: ionizing radiation has a proven impact.
• Genetics and heredity: a family history of cancer (leukemia in siblings is especially dangerous), the presence of congenital immunodeficiency states, and chromosomal abnormalities (e.g., Down syndrome).

Pathogenesis: from mutation to systemic dissemination

The central modern hypothesis of pathogenesis states that the starting point is a spontaneous mutation in a single normal hematopoietic cell. The logic of disease development represents a sequential chain of disorders:

1. Cellular level: the mutated cell completely loses the ability to undergo normal differentiation and maturation.
2. Immune failure: a healthy immune system should timely eliminate (destroy) such elements. Leukemia starts when immune surveillance weakens, and the defective cell forms an uncontrollably dividing malignant clone.
3. Bone marrow level: a massive hyperproduction of cells of one specific lineage is triggered. Development arrests at the blast stage (partial or abortive differentiation occurs). Massive expansion of the tumor clone leads to a sharp suppression of all other normal hematopoietic lineages.
4. Systemic dissemination: blast cells migrate beyond the bone marrow into the systemic circulation. They infiltrate various organs, penetrate the nerve sheaths and vascular adventitia.

Disease manifestation has no single pattern. It can begin either gradually (with the appearance of general, non-specific complaints) or quite suddenly (acutely), with the rapid development of specific clinical syndromes.

Class and exam questions

What else to study on this topic

• Three clinical stages of the course of acute leukemia
• Specific clinical syndromes during disease manifestation
• Immunophenotypic and genetic markers of lymphoblasts
• Eight variants of acute myeloid leukemia (typing)
• Mechanisms of infiltration of nerve sheaths and other organs by blasts

Other topics in "Chapter 10. Diseases of the Blood and Blood-Forming Organs"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.