Atlas of pathophysiology, 2 Edition

Part II - Disorders

Hematologic Disorders

Leukemia

Leukemia is a group of diseases caused by malignant proliferation of white blood cells (WBCs); each is classified by the dominant cell type. The course of a leukemia may be acute or chronic.

·   Acute—large numbers of immature leukocytes; rapid onset and progression

·   Chronic—excessive mature leukocytes in the periphery and bone marrow; slower onset and progression.

Age Alert

Leukemias are the most common malignancies in children. Each specific type has its own prognosis, but generally, the prognosis in children is better than in adults.

Causes

No definitive cause identified

Possible risk factors

·   Genetic predisposition

·   Immunologic factors

·   Environmental exposure to chemicals, radiation

·   Predisposing disease

Chronic myeloid leukemia (CML)

·   In almost 90% of patients, Philadelphia, or Ph1 chromosome; translocated long arm of chromosome 22, usually to chromosome 9

Pathophysiology

Acute leukemia is characterized by malignant proliferation of WBC precursors (blasts) in bone marrow or lymph tissue and their accumulation in peripheral blood, bone marrow, and body tissues. Leukemic cells inhibit normal bone marrow production of erythrocytes, platelets, and immune function. Its most common forms and the characteristic cells include:

·   acute lymphoblastic (or lymphocytic) leukemia (ALL)—lymphocyte precursors (lymphoblasts)

·   acute myeloid leukemias (AMLs), known collectively as acute non-lymphocytic leukemia:

§  acute myeloblastic (or myelogenous) leukemia—myeloid precursors (myeloblasts)

§  acute monoblastic (monocytic) leukemia—monocyte precursors (monoblasts)

§  other types—acute myelomonocytic leukemia, acute erythroleukemia.

·   CML proceeds in two distinct phases:

§  insidious chronic phase—anemia and bleeding disorders

§  blastic crisis or acute phase—rapid proliferation of myeloblasts, the most primitive granulocyte precursors.

·   Chronic lymphocytic leukemia (CLL)—abnormal small lymphocytes in lymphoid tissue, blood, and bone marrow.

Signs and symptoms

Acute leukemias

·   Sudden high fever, thrombocytopenia, abnormal bleeding

·   Nonspecific signs and symptoms, including weakness, pallor, chills

·   Also, in ALL, AML, and acute monoblastic leukemia: possible dyspnea, anemia, fatigue, malaise, tachycardia, palpitations, systolic ejection murmur, abdominal and bone pain

CML

·   Anemia, thrombocytopenia

·   Hepatosplenomegaly

·   Sternal and rib tenderness

·   Low-grade fever

·   Anorexia, weight loss

·   Renal calculi or gouty arthritis

·   Prolonged infection

·   Ankle edema

CLL

·   Early stages: fatigue, malaise, fever, nodular enlargement

·   Late stages: severe fatigue, weight loss, liver or spleen enlargement, bone tenderness

·   With disease progression and bone marrow involvement: anemia; pallor; weakness; dyspnea; tachycardia; palpitations; bleeding; opportunistic fungal, viral, and bacterial infections

Diagnostic test results

Acute leukemia

·   Laboratory studies show thrombocytopenia and neutropenia. WBC differential shows cell type.

·   Computed tomography (CT) scan shows affected organs.

·   Bone marrow biopsy shows proliferation of immature WBCs.

CML

·   Chromosomal studies of peripheral blood or bone marrow show the Philadelphia chromosome.

·   Laboratory studies reveal low leukocyte alkaline phosphate, leukocytosis, leukopenia, neutropenia, decreased hemoglobin (Hb) and hematocrit, increased circulating myeloblasts, thrombocytosis, and increased serum uric acid level.

·   CT scan shows affected organs.

·   Bone marrow biopsy is hypercellular showing bone marrow infiltration by increased number of myeloid elements.

CLL

·   Laboratory studies show increased WBC, granulocytopenia, decreased Hb, neutropenia, lymphocytosis, and thrombocytopenia.

·   CT scan shows affected organs.

·   Bone marrow biopsy shows lymphocytic invasion.

·   Serum protein electrophoresis shows hypogammaglobulinemia.

Treatment

·   Antibiotic, antifungal, antiviral drugs

·   Systemic chemotherapy

·   Granulocyte injections

·   Transfusion of blood and blood products

·   Bone marrow transplantation

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HISTOLOGIC FINDINGS OF LEUKEMIAS

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