Section 14. Blood Disorders

Chapter 176. Leukemias

Topics: Introduction | Acute Lymphocytic Leukemia | Acute Myelocytic Leukemia | Chronic Lymphocytic Leukemia | Chronic Myelocytic Leukemia

Acute Lymphocytic Leukemia

Acute lymphocytic (lymphoblastic) leukemia is a life-threatening disease in which the cells that normally develop into lymphocytes become cancerous and rapidly replace normal cells in the bone marrow.

Acute lymphocytic leukemia (ALL) occurs in people of all ages but is the most common cancer in children, accounting for 25% of all cancers in children younger than 15 years. ALL most often affects young children between the ages of 2 and 5 years. Among adults, it is somewhat more common in those older than 65.

In ALL, very immature leukemia cells accumulate in the bone marrow, destroying and replacing cells that produce normal blood cells. The leukemia cells are also carried in the bloodstream to the liver, spleen, lymph nodes, brain, and testes, where they may continue to grow and divide. They can irritate the layers of tissue covering the brain and spinal cord, causing inflammation (meningitis), and can cause anemia, liver and kidney failure, and other organ damage.

Symptoms and Diagnosis

Early symptoms result from the inability of the bone marrow to produce enough normal blood cells. Fever and excessive sweating, which may indicate infection, result from too few normal white blood cells. Weakness, fatigue, and paleness, which indicate anemia, result from too few red blood cells. Easy bruising and bleeding, sometimes in the form of nosebleeds or bleeding gums, result from too few platelets. Leukemia cells in the brain may cause headaches, vomiting, and irritability, and those in the bone marrow may cause bone and joint pain. A sense of fullness in the abdomen and sometimes pain can result when leukemia cells enlarge the liver and spleen.

Blood tests, such as a complete blood count (see Section 14, Chapter 170), can provide the first evidence that a person has ALL. The total number of white blood cells may be decreased, normal, or increased, but the number of red blood cells and platelets is almost always decreased. In addition, very immature white blood cells (blasts) are seen in blood samples examined under a microscope. A bone marrow biopsy (see Section 14, Chapter 170) is almost always performed to confirm the diagnosis and to distinguish ALL from other types of leukemia.

Prognosis and Treatment

Before treatment was available, most people who had ALL died within 4 months of the diagnosis. Now, nearly 80% of children and 30 to 40% of adults with ALL are cured. For most people, the first course of chemotherapy brings the disease under control (complete remission). Children between the ages of 3 and 7 have the best prognosis; children younger than 2 and older adults fare the least well. The white blood cell count and particular chromosome abnormalities in the leukemia cells also influence outcome.

Chemotherapy is highly effective and is administered in phases. The goal of initial treatment (induction chemotherapy) is to achieve remission by destroying leukemia cells so that normal cells can once again grow in the bone marrow. The person may need to stay in the hospital for a few days or weeks, depending on how quickly the bone marrow recovers. Blood and platelet transfusions may be necessary to treat anemia and to prevent bleeding, and antibiotics may be needed to treat infections. Intravenous fluids and therapy with a drug called allopurinol may also be used to help rid the body of harmful substances, such as uric acid, that are released when leukemia cells are destroyed.

One of several combinations of chemotherapy drugs is used, and doses are repeated for several days or weeks. One combination consists of prednisone taken by mouth and weekly doses of vincristine given with an anthracycline drug (usually daunorubicin), asparaginase, and sometimes cyclophosphamide, given intravenously. Other drugs are being investigated.

For treatment of leukemia cells in the meninges (the layers of tissue covering the brain and spinal cord), methotrexate, cytosine arabinoside, or both is usually injected directly into the cerebrospinal fluid. This chemotherapy may be given in combination with radiation therapy to the brain. Even when there is little evidence that the leukemia has spread to the brain, a similar type of treatment is usually given as a preventive measure because of the high likelihood of spread to the meninges.

A few weeks after the initial, intensive treatment, additional treatment (consolidation chemotherapy) is given to destroy any remaining leukemia cells. Additional chemotherapy drugs, or the same drugs as were used during the induction phase, may be used a few times over a period of several weeks. Further treatment (maintenance chemotherapy), which usually consists of fewer drugs, sometimes at lower doses, may continue for 2 to 3 years. For some people who are at high risk of relapse because of particular chromosomal changes found in their cells, stem cell transplantation (see Section 16, Chapter 187) during the first remission is often recommended.

Leukemia cells may begin to appear again (a condition termed relapse), often in the blood, bone marrow, brain, or testes. Reappearance in the bone marrow is particularly serious. Chemotherapy is given again, and although most people respond to treatment, the disease has a strong tendency to come back, especially in children younger than 2 and in adults. When leukemia cells reappear in the brain, chemotherapy drugs are injected into the cerebrospinal fluid 1 or 2 times a week. When leukemia cells reappear in the testes, radiation therapy is given along with chemotherapy.

For people who have relapsed, high-dose chemotherapy along with allogeneic stem cell transplantation offers the best chance of cure, but this procedure can be performed only if stem cells can be obtained from a person who has a compatible tissue type (HLA-matched). The donor is usually a sibling, but cells from matched, unrelated donors (or occasionally partially matched cells from family members or unrelated donors, as well as umbilical stem cells) are sometimes used. Stem cell transplantation is rarely used for people older than 65, because it is much less likely to be successful and side effects are much more likely to be fatal.

After relapse, additional treatment for a person who is unable to undergo stem cell transplantation is often poorly tolerated and ineffective, frequently causing the person to feel much sicker. However, remissions can occur. End-of-life care should be considered for people who do not respond to treatment (see Section 1, Chapter 8).