ACUTE LYMPHOBLASTIC LEUKEMIA FULL & REVISED STUDY GUIDE.

ACUTE LYMPHOBLASTIC LEUKEMIA FULL & REVISED STUDY GUIDE. Definition − Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. Classification Histologic Findings − According to the French-American-British (FAB) classification system, acute lymphoblastic leukemia is classified into 3 groups based on morphology.  L1: Cells are usually small, with scant cytoplasm and inconspicuous nucleoli. L1 accounts for 85% of all cases of childhood acute lymphoblastic leukemia.  L2: Cells are larger than in L1. The cells demonstrate considerable heterogeneity in size, with prominent nucleoli, and abundant cytoplasm. L2 accounts for 14% of all childhood ALL.  L3: Cells are large and notable for their deep cytoplasmic basophilia. They frequently have prominent cytoplasmic vacuolation and are morphologically identical to Burkitt lymphoma cells. L3 accounts for 1% of childhood acute lymphoblasticleukemia cases. Epidemiology: − Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children − Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood, representing nearly one third of all pediatric cancers with a peak incidence in patients aged 2-5 years. − Acute lymphoblastic leukemia (ALL) is five times more common than acute myeloid leukemia (AML) − United States has an incidence of 2.8 cases per 100,000 − International: The highest incidence of acute lymphoblastic leukemia (ALL) occurs in Italy, the United States, Switzerland, and Costa Rica. − Race: ALL occurs more frequently in whites than in black. − Sex: ALL occurs slightly more frequently in males than in females. Risk factors − Environmental factors  Exposure to ionizing radiation  Exposure to electromagnetic fields  Parental use of alcohol and tobacco − Inherited genetic syndromes  Down syndrome  Bloom syndrome  Fanconi anemia − Acute lymphoblastic leukemia may also occur in children with various congenital immunodeficiencies (i.e. Wiskott-Aldrich syndrome, congenital hypogammaglobulinemia, ataxia-telangiectasia) that have an increased predisposition to develop lymphoid malignancies. − Siblings, especially twins, of children with leukemia − Hereditary or acquired mutations in the p53 gene Pathophysiology: − The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (i.e. lymphoblasts) that are arrested in an early stage of development. − This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations. − In ALL, a lymphoid progenitor cell becomes genetically altered and subsequently undergoes dysregulated proliferation and clonal expansion. − The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. − Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. − The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes.