Leukemia - types, symptoms and treatment

What is Leukemia and Definition

A type of CANCER that affects the BONE marrow’s production of leukocytes (white BLOOD cells). Doctors classify leukemia as either myeloid (sometimes called myelocytic) or lymphocytic (sometimes called lymphoblastic), depending on the type of leukocytes affected. Within either classification leukemia can be acute or chronic.

The four most common types of leukemia are

• acute lymphocytic leukemia (ALL)
• chronic lymphocytic leukemia (CLL)
• acute myeloid leukemia (AML)
• chronic myeloid leukemia (CML)

LEUKEMIA VS. LYMPHOMA

LYMPHOMA is another type of cancer that can affect the lymphocytes. However, lymphoma is a cancer of the lymphatic tissues that produce and store lymphocytes. Leukemia is a cancer of the BONE MARROW that alters the development and proliferation of the lymphocytes that enter the BLOOD circulation.

There are a number of subtypes within these classifications, usually identified according to the affected cell type or its developmental stage. Though common perception is that leukemia primarily affects children, 10 times as many adults as children develop this type of cancer. Children are more likely to develop acute leukemia and adults over age 60 to develop chronic leukemia, though either form can occur at any age. Some forms of childhood leukemia are fully curable and some forms of adult leukemia are highly manageable. GENETIC PREDISPOSITION and certain environmental factors, such as exposure to industrial chemicals, pesticides, and RADIATION THERAPY or CHEMOTHERAPY, appear to increase an individual’s risk for developing leukemia. However, most of the time doctors do not know what causes this leukemia to develop.

How Leukemia Develops

All blood cells arise from pluripotent BLOOD STEM CELLS, “parent” cells within the BONE MARROW that have the ability to form into several different kinds of blood cells. A complex interaction of genetic encoding, chemicals, proteins, molecular functions, and physiologic needs determines the manner in which blood stem cells differentiate (become specific kinds of cells) and proliferate (reproduce themselves). At the first level of differentiation, a blood stem cell establishes its lineage as lymphoid or myeloid. Myeloid stem cells give rise to erythrocytes, platelets, granulocytes, and monocytes. Lymphoid stem cells give rise to lymphocytes. In leukemia, the stem cells are normal though something goes awry at the first stage of differentiation, and one of the lines-lymphoid or myeloid-produces abnormal cells.

In acute forms of leukemia the bone marrow accelerates LEUKOCYTE production and releases immature leukocytes not yet capable of functioning as leukocytes. In relatively short time the immature cells flood the bone marrow, crowding out other cells. The onset of symptoms with acute leukemia is generally rapid because the immature cells the bone marrow releases cannot function yet are entering the circulation at a rate that causes them to quickly become dominant in the blood. In chronic leukemia the bone marrow’s rate of production is normal and the leukocytes the marrow releases into the circulation are mature but defective. The onset of symptoms in chronic leukemia is usually gradual because these cells, though defective, can function to some extent and enter the blood circulation at the normal rate. In all types of leukemia, the defective cells also block the bone marrow from producing platelets and erythrocytes, resulting in dysfunctional COAGULATION (clotting) and ANEMIA.

Acute lymphatic leukemia (ALL)

The most common leukemia of childhood, ALL arises when a genetically damaged lymphoid clone cell in the bone marrow proliferates, causing immature lymphocytes, called lymphoblasts or leukemic blasts, to replace healthy lymphocytes in the bone marrow and the blood circulation. The accumulation prevents normal HEMATOPOIESIS, resulting in anemia, coagulation dysfunction, and vulnerability to INFECTION. About 85 percent of ALL involves B-cell lymphocytes and the remaining 15 percent involves T-cell lymphocytes. Doctors diagnose about 4,000 people a year with ALL in the United States.

Chronic lymphatic leukemia (CLL)

Doctors diagnose about 8,000 people a year with CLL in the United States, more than 75 percent of them being over the age of 60. In CLL, the proliferating defective lymphocytes function normally. CLL may generate no symptoms or ill effects, in which case doctors generally opt for watchful waiting as the treatment approach. As CLL progresses, however, it causes dysfunctional IMMUNE RESPONSE. Defective lymphocytes that accumulate in the bone marrow eventually suppress bone marrow function.

Acute myeloid leukemia (AML)

The most common leukemia among people over age 40, AML arises through the proliferation of a defective myeloid clone cell and manifests in one of seven forms. Doctors designate these forms as subtypes M1 through M7, according to the cells involved. The subtype determines the course of treatment and likelihood for REMISSION. As with ALL, the proliferation of the defective clone prevents normal hematopoiesis with consequent THROMBOCYTOPENIA, anemia, and often NEUTROPENIA. Doctors diagnose about 12,000 people a year with AML in the United States.

Chronic myeloid leukemia (CML)

Nearly always a cancer occurring in adulthood, CML results from the translocation of chromosomes 9 and 22, an acquired MUTATION commonly referred to as the Philadelphia, or Ph, CHROMOSOME. Researchers do not know what causes the abnormality, which produces the rampant proliferation of monocytes or granulocytes that function normally. Other hematopoiesis is normal as well. Doctors diagnose about 54,000 people a year with CML in the United States.

Symptoms of Leukemia and Diagnostic Path

Symptoms of leukemia develop when the cancerous cells in the blood circulation begin to outnumber the healthy cells. Early symptoms are insidious and often mimic those of common viral infections. As the leukemia progresses, symptoms become more pronounced and typically include

• unexplained low-grade FEVER
• general malaise or lethargy
• PAIN in the joints
• unintended weight loss
• sweating at night
• loss of APPETITE
• tiredness or fatigue
• easy bleeding or bruising, or the appearance of PETECHIAE (pinpoint hemorrhages beneath the SKIN)

The diagnostic path typically includes physical examination, diagnostic blood tests, and bone marrow biopsy. The physical examination may reveal SPLENOMEGALY (swollen SPLEEN) and LYMPHADENOPATHY (swollen lymph nodes). Characteristic patterns of abnormal cell counts and structures identify the different types of leukemia. In addition to abnormalities in the leukocytes, depletion of erythrocytes and platelets is common. Bone marrow biopsy confirms the diagnosis. Specialized laboratory tests, such as cytologic examination and immunophenotyping, establish the characteristics of the abnormal cells to identify the type of leukemia.

Leukemia Treatment Options and Outlook

Treatment regimens for leukemia vary with the type of leukemia, the person’s age, and the person’s general health status aside from the leukemia. Chemotherapy and RADIATION THERAPY, separately or in combination, remain the mainstay of the therapeutic arsenal, with the objective being to establish remission (a state in which there is no evidence of the leukemia and all blood counts and blood cells are normal). Oncologists use several staging systems for leukemia to identify the kinds of cells, cell lineage, and cell counts.

Chemotherapy is the treatment of choice, with blood stem cell or BONE MARROW TRANSPLANTATION sometimes an option depending on the leukemia’s characteristics and stage at the time of diagnosis. Research continues to produce new chemotherapy agents and new combinations of existing agents that appear more successful, though their ability to sustain remission over time remains unknown. The initial phase of chemotherapy typically involves cycles of chemotherapy drugs administered over a period of one to two years, with maintenance oral chemotherapy drugs for another two and a half to three years for ALL. Oncologists may use radiation therapy to treat accumulations of cancerous lymphocytes in the BRAIN, spleen, and lymph nodes such as may occur with ALL. Many people need supplemental BLOOD TRANSFUSION and ANTIBIOTIC MEDICATIONS during chemotherapy.

Across all types of leukemia, about 65 percent of people achieve initial remission with treatment. The rate of sustained remission (five years or longer) is much higher with acute than with chronic forms of leukemia, and in younger (under age 14 years) than older (over age 60) people. For children under age 14 who undergo treatment for ALL, about 80 percent achieve long-term remission such that doctors consider them cured of the leukemia. About 30 percent of adults who have ALL achieve similar long-term remission. Because successful treatment regimens are relatively new, however, doctors do not know what potential health complications, if any, may arise decades after treatment. Long-term survival rates are higher for lymphocytic leukemias than for myeloid leukemias.

Risk Factors and Preventive Measures

The causes of leukemia remain mostly unknown. Doctors do know that about 60 percent of people who have myelodysplasia syndrome eventually develop AML. As well, people who have firstdegree relatives (parent, sibling, or child) who acquire ALL are about four times more likely to develop ALL themselves. Researchers have identified a number of potential risk factors associated with leukemia, though the extent and nature of the associations remains unclear. Among them are

• exposure to high-DOSE radiation, including radiation therapy
• previous chemotherapy for other kinds of cancer
• exposure to the industrial chemicals benzene and formaldehyde and their derivative compounds
• cigarette smoking
• infection with human T-cell leukemia virus 1 (HTLV-1)
• DOWN SYNDROME and CHROMOSOMAL DISORDERS that run in families

Most people who develop leukemia do not have any history of exposure to suspected risk factors, however, making prevention recommendations difficult. There are no known methods for preventing leukemia.

See also B-CELL LYMPHOCYTE; CANCER TREATMENT OPTIONS AND DECISIONS; ENVIRONMENTAL HAZARD EXPOSURE; ERYTHROPOIETIN (EPO); LYMPHOMA; MULTIPLE MYELOMA; SIGNS AND SYMPTOMS OF CANCER; SMOKING AND HEALTH; STAGING AND GRADING OF CANCER.

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