The leukemias are cancers of the WBCs involving bone marrow, circulating WBCs, and organs such as the spleen and lymph nodes.

Etiology

Risk of developing leukemia is increased in patients with

• History of exposure to ionizing radiation (eg, post–atom bomb in Nagasaki and Hiroshima) or to chemicals (eg, benzene)
• Prior treatment with certain antineoplastic drugs, particularly procarbazine, nitrosureas (cyclophosphamide, melphalan), and epipodophyllotoxins (etoposide, teniposide)
• Infection with a virus (eg, human T-lymphotrophic virus 1 and 2, Epstein-Barr virus)
• Chromosomal translocations
• Preexisting conditions, including immunodeficiency disorders, chronic myeloproliferative disorders, and chromosomal disorders (eg, Fanconi's anemia, Bloom syndrome, ataxia-telangiectasia, Down syndrome, infantile X-linked agammaglobulinemia)

Pathophysiology

Malignant transformation usually occurs at the pluripotent stem cell level, although it sometimes involves a committed stem cell with more limited capacity for differentiation. Abnormal proliferation, clonal expansion, and diminished apoptosis (programmed cell death) lead to replacement of normal blood elements with malignant cells.

Table 1
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French-American-British (FAB) Classification of Acute Leukemias FAB Classification Description Acute lymphocytic leukemia L1 Lymphoblasts with uniform, round nuclei and scant cytoplasm L2 More variability of lymphoblasts Sometimes irregular nuclei with more cytoplasm than L1 L3 Lymphoblasts with finer nuclear chromatin and blue to deep blue cytoplasm that contains vacuoles Acute myelocytic leukemia M1 Undifferentiated myeloblastic No cytoplasmic granulation M2 Differentiated myeloblastic Sparse granulation in few to many cells M3 Promyelocytic Granulation typical of promyelocytic morphology M4 Myelomonoblastic Mixed myeloblastic and monocytoid morphology M5 Monoblastic Pure monoblastic morphology M6 Erythroleukemic Predominantly immature erythroblastic morphology, sometimes megaloblastic appearance M7 Megakaryoblastic Cells with shaggy borders that may show some budding French-American-British (FAB) Classification of Acute Leukemias FAB Classification Description Acute lymphocytic leukemia L1 Lymphoblasts with uniform, round nuclei and scant cytoplasm L2 More variability of lymphoblasts Sometimes irregular nuclei with more cytoplasm than L1 L3 Lymphoblasts with finer nuclear chromatin and blue to deep blue cytoplasm that contains vacuoles Acute myelocytic leukemia M1 Undifferentiated myeloblastic No cytoplasmic granulation M2 Differentiated myeloblastic Sparse granulation in few to many cells M3 Promyelocytic Granulation typical of promyelocytic morphology M4 Myelomonoblastic Mixed myeloblastic and monocytoid morphology M5 Monoblastic Pure monoblastic morphology M6 Erythroleukemic Predominantly immature erythroblastic morphology, sometimes megaloblastic appearance M7 Megakaryoblastic Cells with shaggy borders that may show some budding

Manifestations of leukemia are due to suppression of normal blood cell formation and organ infiltration by leukemic cells. Inhibitory factors produced by leukemic cells and replacement of marrow space may suppress normal hematopoiesis, with ensuing anemia, thrombocytopenia, and granulocytopenia. Organ infiltration results in enlargement of the liver, spleen, and lymph nodes, and occasional kidney and gonadal involvement. Meningeal infiltration results in clinical features associated with increasing intracranial pressure (eg, cranial nerve palsies).

Table 2
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Findings at Diagnosis in the Most Common Leukemias Feature Acute Lymphocytic Acute Myelocytic Chronic Lymphocytic Chronic Myelocytic Peak age of incidence Childhood Any age Middle and old age Young adulthood WBC count High in 50% Normal or low in 50% High in 60% Normal or low in 40% High in 98% Normal or low in 2% High in 100% Differential WBC count Many lymphoblasts Many myeloblasts Small lymphocytes Entire myeloid series Anemia Severe in > 90% Severe in > 90% Mild in about 50% Mild in 80% Platelets Low in > 80% Low in > 90% Low in 20 to 30% High in 60% Low in 10% Lymphadenopathy Common Occasional Common Infrequent Splenomegaly In 60% In 50% Usual and moderate Usual and severe Other features Without prophylaxis, CNS commonly involved CNS rarely involved Sometimes Auer rods in myeloblasts Occasionally hemolytic anemia and hypogammaglobulinemia Low leukocyte alkaline phosphatase level Philadelphia chromosome–positive in > 90% Findings at Diagnosis in the Most Common Leukemias Feature Acute Lymphocytic Acute Myelocytic Chronic Lymphocytic Chronic Myelocytic Peak age of incidence Childhood Any age Middle and old age Young adulthood WBC count High in 50% Normal or low in 50% High in 60% Normal or low in 40% High in 98% Normal or low in 2% High in 100% Differential WBC count Many lymphoblasts Many myeloblasts Small lymphocytes Entire myeloid series Anemia Severe in > 90% Severe in > 90% Mild in about 50% Mild in 80% Platelets Low in > 80% Low in > 90% Low in 20 to 30% High in 60% Low in 10% Lymphadenopathy Common Occasional Common Infrequent Splenomegaly In 60% In 50% Usual and moderate Usual and severe Other features Without prophylaxis, CNS commonly involved CNS rarely involved Sometimes Auer rods in myeloblasts Occasionally hemolytic anemia and hypogammaglobulinemia Low leukocyte alkaline phosphatase level Philadelphia chromosome–positive in > 90%

Classification

Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity.

Peripheral Blood Blast Cell

Acute Promyelocytic Leukemia

Acute Myeloid Leukemia Without Maturation

Acute Lymphocytic Leukemia FAB Class L1

Acute Lymphocytic Leukemia FAB Class L2

Acute Lymphocytic Leukemia FAB Class L3

Blasts With Monocytic Differentiation

Acute leukemias consist of predominantly immature, poorly differentiated cells (usually blast forms). Acute leukemias are divided into lymphocytic (ALL) and myelocytic (AML) types, which may be further subdivided by the French-American-British (FAB) classification (see Table 1: Leukemias: French-American-British (FAB) Classification of Acute Leukemias).

Chronic leukemias have more mature cells than do acute leukemias. Chronic leukemias are described as lymphocytic (CLL) or myelocytic (CML—see Table 2: Leukemias: Findings at Diagnosis in the Most Common Leukemias).

Myelodysplastic syndromes involve progressive bone marrow failure but with an insufficient proportion of blast cells (< 30%) for making a definite diagnosis of AML; 40 to 60% of cases evolve into AML.

A leukemoid reaction is marked granulocytic leukocytosis (ie, WBC > 30,000/μL) produced by normal bone marrow in response to systemic infection or cancer. Although not a neoplastic disorder, a leukemoid reaction with a very high WBC count may require testing to distinguish it from CML (see Leukemias: Chronic Myelocytic Leukemia (CML)).

Last full review/revision July 2012 by Michael E. Rytting