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leukemia (lo͞okēˈmēə), cancerous disorder of the blood-forming tissues (bone marrow, lymphatics, liver, spleen) characterized by excessive production of immature or mature leukocytes (white blood cells; see blood) and consequently a crowding-out of red blood cells and platelets. It was first named by Rudolf Virchow in 1887.
See also cancer.
Incidence and Cause
Leukemias are classified as either lymphocytic or myeloid, depending on the type of leukocyte affected. In addition, leukemias are classified as either acute, referring to a rapidly progressing disease that involves immature leukocytes, or chronic, referring to a slower proliferation involving mature white cells. In acute leukemias, immature nonfunctioning leukocytes called blast cells proliferate.
The myeloid leukemias affect white blood cells (myelocytes) that give rise to granulocytes (phagocytic white blood cells that mount an inflammatory immune response). They include chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), also called acute nonlymphocytic leukemia (ANLL). The lymphocytic leukemias affect the white blood cells that give rise to various types of lymphocytes. They include acute lymphocytic leukemia (ALL); chronic lymphocytic leukemia (CLL), also called chronic granulocytic leukemia; and hairy cell leukemia (HCL), a chronic leukemia named for the cells' tiny hairlike projections. The lymphocytic leukemias are sometimes referred to as B cell leukemias or T cell leukemias depending upon whether they arise in antibody-producing B cells (HCL, CLL, and some cases of ALL) or in the T cell lymphocytes involved in cell-mediated immunity (some cases of ALL). (See immunity for a further explanation of the cells of the immune system.) Each of these types may be further classified into subtypes. Most childhood leukemias are of the acute lymphocytic type; acute myeloid leukemia is the most common type of adult leukemia.
Many of the symptoms of acute leukemia can be attributed to anemia, which results from the attrition of red blood cells as they are crowded out by the leukemic cells. Frequent infections result from a dearth of functioning white blood cells. Bone tenderness may also be present. Hemorrhaging may develop because blood-clotting elements are scarce. Blasts may congregate in the lymph nodes, spleen, and liver, causing enlargement and pain, or they may invade the central nervous system, causing dizziness, headache, or fever. If untreated, death can supervene rapidly in acute leukemia.
Patients with chronic leukemias often have no symptoms and may be hard to diagnose, but less virulent versions of the symptoms seen in the acute leukemias may be present. Death from chronic leukemia is usually from infection.
The diagnosis of leukemia is confirmed by finding a disproportionate number of leukocytes in tissue obtained from a bone marrow biopsy. The course of treatment is based upon the type of cell affected, the progression of the disease, and the age of the patient. Some slowly progressing forms may require no treatment. Improved treatments have increased survival from some types of leukemia considerably.
Treatment may include chemotherapy with anticancer drugs, radiation therapy, blood and plasma transfusions, and bone marrow transplantation. In bone marrow transplantation, healthy bone marrow (either donated by a closely matched donor or treated marrow from the patient) is infused into the patient after the patient has undergone a course of marrow-destroying very high dose chemotherapy. Recent studies have indicated that blood from a newborn infant's umbilical cord and placenta (called cord blood) can be used effectively instead of marrow transplants in some leukemias. Biological therapy (sometimes called immunotherapy) is also used. Biological therapies include monoclonal antibodies; interferons; maturation drugs, such as all-trans retinoic acid; and tyrosine kinase inhibtors, such as imantinib mesylate (also known as STI-571 and Gleevec). These therapies may enhance the body's natural reaction to leukemia by bolstering the immune response, may inhibit the gene that drives cell proliferation, or may encourage maturation of immature leukemic cells or reproduction of needed healthy blood elements.
a tumorous systemic disease of hematopoietic tissue in which the impairment of hematopoiesis is manifested by a proliferation of immature pathological cellular elements, both in the hematopoietic organs proper and in other organs (the kidneys, vascular walls, neural pathways, skin, and so forth). The disease is rare (one case per 50,000 population).
Leukemias are grouped into the spontaneous leukemias, the causes of which have not been determined; radiation leukemias, caused by ionizing radiation; and leukemias caused by certain chemical (leukemogenic, or blastomogenic) substances. Leukemogenic viruses have been isolated from a number of animals suffering from leukemia (chickens, mice, rats, dogs, cats, cattle). A viral etiology has not been proved for human leukemia. Leukemias are divided into reticulosis, hemocytoblastosis, myeloid leukemia, erythromyelosis, and megakaryocytic leukemia, depending on cellular morphology (the predominance of particular elements).
Depending on the extent of the increase in the total number of leukocytes and the “flooding” of the blood with immature, pathological cells (normally not found in the blood), leukemias are classified as leukemic, in which the number of pathological leukocytes found in 1 cu mm of blood totals tens of thousands, hundreds of thousands, and even millions, instead of the normal 6,000–10,000; subleukemic, in which the number of pathological leukocytes does not exceed 15,000–25,000 per cu mm; leukopenic, in which the number of leukocytes in the blood decreases but with which pathological, “leukemic” cells may also be present; and aleukemic, in which the number of leukocytes in the blood does not increase and no immature, pathological forms are present. Aleukemic leukemias that progress at a pronouncedly malignant rate are usually called reticuloses.
Leukemias may be acute or chronic. Acute leukemias are marked by a rapid course with a blood picture characterized by an abrupt breakdown of hematopoiesis at a given stage, resulting in the failure of the most immature forms, or blasts, to develop into mature blood cells. The hemogram is marked by some degree of “blastemia,” with an insignificant number of mature leukocytes and an absence of transitional forms. As a rule, acute leukemia occurs with fever, marked anemia, hemorrhagic diathesis, ulcerations, and necrosis in various organs.
Chronic leukemias are classified, according to the aspect of hematopoiesis disturbed, as chronic myelosis (myeloid leukemia), lymphadenosis (lymphocytic leukemia), histiomonocytic leukemia, erythromyelosis, and megakaryocytic leukemia. Chronic myelosis, the most common, is characterized by hyperplasia (proliferation) of the elements of bone-marrow, or myeloid, hematopoiesis, both in the bone marrow proper (the fat marrow of the long bones being replaced by red hematopoietic marrow) and in the spleen (which enlarges significantly), liver, and lymph nodes (where normal lymphoid tissue is replaced by pathological myeloid elements). The blood is flooded with immature, mature, and transitional granular leukocytes.
Chronic lymphadenosis usually follows a protracted but comparatively benign course. The disease develops gradually, chiefly with enlargement of the lymph nodes, although enlargement of the spleen and liver sometimes becomes predominant. Normal myeloid bone marrow is replaced by lymphoid marrow. The blood is flooded with lymphocytes (predominantly mature). Blasts appear during exacerbations. Anemia gradually develops, because lymphoid infiltrates depress the normal hematopoietic function of the bone marrow and because the pathological lymphocytes lose the function of immune competence and manufacture autoaggressive antibodies (in particular, antierythrocytic antibodies, which cause hemolysis). In some cases, the pathological lymphocytes produce antithrombocytic antibodies, which cause thrombocytopenia and hemorrhages. Exacerbations of chronic leukemia are marked by elevated temperature, sweating, wasting, bone pains, increasing general weakness, anemia, and hemorrhagic diathesis.
The pathogenesis (that is, the mechanism of development) of leukemia has not been studied adequately; however, it is believed that the disease begins with cellular mutations that appear in the body after exposure to a variety of exogenous (viral, radiation, chemical) and endogenous leukemogenic agents (in particular, agents that appear with an impairment of tryptophan metabolism). The mutagenic action of these agents disrupts the normal development of the hematopoietic cells, and anaplasia sets in (that is, the loss by the cells of their capacity for normal differentiation and development into mature leukocytes). The accumulation of immature, physiologically deficient cells, manifested in tumorlike growths and leukemic invasion of various organs, results in systemic intoxication and wasting and in dysfunction of the affected organs and systems. Because of the more or less marked decrease in the number of mature, functionally adequate leukocytes and thrombocytes (depending on the form of leukemia and the phase of its development), the course of leukemia is accompanied by a decline in systemic and local immunity. This is manifested in the development of severe infectious, septic, necrotic, ulcerative, and hemorrhagic complications. Leukemic invasion, or metaplasia, of the bone marrow usually gives rise to anemia; this is further aggravated by hemorrhages associated with the thrombocytopenia and intensified hemolysis that result from the autoimmune complications.
Acute leukemia and exacerbations of chronic leukemia are treated in a hospital (preferably one that specializes in blood diseases) where the blood and bone marrow can be monitored. Combinations of cytostatic agents and steroid hormones are used. Sometimes radiotherapy, blood transfusions, supporting and antianemic agents, and multiple vitamins are prescribed. Antibiotics are administered to prevent or control infectious complications. During remissions, acute and chronic leukemia patients receive supporting treatment in specialized hematological departments of polyclinics. In accordance with present regulations in the USSR, all leukemia patients receive all prescribed drugs free of charge.
REFERENCESDul’tsin, M. S., I. A. Kassirskii, and M. O. Raushenbakh. Leikozy. Moscow, 1965.
Kassirskii, I. A., and G. A. Alekseev. Klinicheskaia gematologiia, 4th ed. Moscow, 1970.
Avian leukosis occurs in countries with advanced poultry farming and causes great economic damage. The causative agent of the disease is a virus with a large number of strains. The disease occurs mostly in chickens more than four months of age; less commonly, it is found in turkeys, guinea hens, ducks, and geese. Cases have also been recorded in pigeons, canaries, parrots, and other birds. Diseased birds and virus carriers are the source of the causative agent. Infection takes place mainly through the eggs. There are no characteristic clinical symptoms of the disease, which is diagnosed on the basis of laboratory tests and pathomorphological examination. No treatment has been developed. Preventive measures include the building up of pedigreed flocks with animals from leukosis-free farms only, the strict isolation and good care of the young animals, proper feeding, and the breeding of fowl resistant to the disease.
REFERENCESVasil’ev, N. T., N. V. Rumiantsev, and V. Z. Cherniak. Leikozy sel’skokhoziaistvennykh zhivotnykh. Moscow, 1966.
Problemy leikozov. Moscow, 1967.
Khokhlova, M. P. “Izuchenie epidemiologii leikozov cheloveka v sravnitel’nom aspekte.” In Materialy II simpoziuma po leikozu krupnogo rogatogo skota. Tallinn, 1971. Pages 19–35.
A. M. LAKTIONOV