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Overview of Leukemia

by Michael E. Rytting, MD

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-lymphotropic virus 1 and 2, Epstein-Barr virus)

  • Chromosomal translocations

  • Preexisting conditions, including immunodeficiency disorders, chronic myeloproliferative disorders, and chromosomal disorders (eg, Fanconi 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.

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 myelogenous 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 occasionally, in kidney and gonadal involvement. Meningeal infiltration results in clinical features associated with increasing intracranial pressure (eg, cranial nerve palsies).

Findings at Diagnosis in the Most Common Leukemias

Feature

Acute Lymphocytic

Acute Myelogenous

Chronic Lymphocytic

Chronic Myelogenous

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.

Acute leukemias

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

Chronic leukemias

Chronic leukemias have more mature cells than do acute leukemias. They usually manifest as abnormal leukocytosis with or without cytopenia in an otherwise asymptomatic person. Findings and management differ significantly between chronic lymphocytic leukemia (CLL—see Chronic Lymphocytic Leukemia (CLL)) and chronic myelogenous leukemia (CML—see Chronic Myelogenous Leukemia (CML)).

Myelodysplastic syndromes

Myelodysplastic syndromes (see Myelodysplastic Syndrome) 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.

Leukemoid reaction

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 Chronic Myelogenous Leukemia (CML)).

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • VUMON
  • CYTOXAN (LYOPHILIZED)
  • ALKERAN
  • ETOPOPHOS
  • MATULANE

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