Description
Leukemia is cancer of the blood and the blood-forming bone marrow, characterized by an uncontrolled growth of bone marrow stem cells. There are four major types of leukemia: acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Myelogenous and lymphocytic refer to the type of cell affected.
Acute leukemia progresses much more quickly than the chronic disease. In acute leukemia, genetic mutations in the blood-forming cells result in an excess of immature, useless blood cells in the bone marrow and blood, essentially crowding out the production of healthy marrow cells. As a result, the marrow cannot produce enough red blood cells, many types of white blood cells and blood-clotting platelets, leaving individuals anemic and susceptible to infection and bleeding. In chronic leukemia, greater numbers of more mature, working cells are made.
ALL and AML are marked by the accumulation of immature, non-infection-fighting white blood cells called blasts, which fail to function as normal blood cells. CLL is characterized by an overproduction of a type of mature white blood cell called a B lymphocyte.
CML (and some cases of ALL) is caused by a genetic anomaly in the blood-forming cells known as a translocation, in which part of one chromosome breaks off and attaches to another chromosome. In this case, a section of chromosome 9 tears away and connects onto a section of chromosome 22, resulting in the fusion of two normally separate genes, BCR and ABL. The new BCR-ABL gene produces an abnormal enzyme that results in the uncontrolled growth of white blood cells – and cancer.
There are several symptoms common to individuals with leukemia, including fatigue, weight loss, infections and fever. Many individuals bruise easily, and have nosebleeds and other types of bleeding. Symptoms of the acute leukemias may progress rapidly. In chronic leukemia, which develops more slowly, symptoms may hardly appear at all.
Statistics
Survival of patients with leukemia has improved dramatically over the years. From 1960 to 1963, an individual with leukemia, when compared to a healthy person, had a 14 percent chance of living five years. By 1995 to 2000, the number had jumped to 46 percent.
While the incidence of leukemia has decreased overall by 1.1 percent per year since 1995, an estimated 34,810 new cases of leukemia are expected in 2005. Of these, acute cases (15,930) will slightly outnumber chronic (14,330).
Leukemia in general is 10 times more common in adults than in children, with the notable exception of ALL, which accounts for approximately 78 percent of expected leukemia cases among children. AML and CLL are the most common adult leukemias (approximately 10,980 and approximately 8,900 expected cases, respectively, in 2005). The incidence of AML, CLL and CML increases dramatically after age 40, and is highest in those 60 years of age and older.
Approximately 22,570 individuals are expected to die of leukemia in 2005, a drop of about 0.5 percent per year since 1991.
The statistics regarding how long individuals live with leukemia vary according to the type of disease. Only about 20 percent of those with AML, for example, live for five years. Yet some 73 percent of individuals who have CLL live that long. The survival numbers have risen dramatically for those with ALL in the past several decades, largely due to advances in therapies for children. In the 1970s, the five-year relative survival rate was 38 percent. By the late 1990s, it had reached 65 percent. In children with ALL, the survival rate in that period went from 53 percent to 85 percent.
The vast majority of cases of CML occur in adults, and its frequency escalates with age. It is estimated that only one in one million children up to age 10 develop CML, rising to one in 100,000 by age 50 and to one in 10,000 by age 80. The five-year relative survival rate between 1995 and 2000 was approximately 37 percent.
Early Detection, Diagnosis
Leukemia in general can be difficult to detect early, since many associated symptoms are non-specific and could be from other conditions such as the flu. Abnormal red blood cell and white blood cell counts frequently trigger a search for the cause, often leading to a definitive examination in which a piece of bone marrow is removed and examined under a microscope for signs of cancer. Further tests might look for damage to the chromosomes.
Once leukemia is diagnosed, tests are done to determine if the cancer has spread beyond the blood and bone marrow.
Minimizing Risk/Prevention
The causes for the majority of cases of leukemia are not known. There are no known ways to prevent leukemia and there are few known risk factors for developing the disease. Exposure to industrial chemicals such as benzene, pesticides and solvents may increase an individual’s risk of developing leukemia. Some genetic disorders such as Down syndrome increase the risk of leukemia. Certain chemotherapy drugs may be connected with the development of leukemia years later.
Scientists continue to study potential lifestyle and environmental influences in the development of leukemia.
Latest Research
One of the most promising areas of research centers on the development of new agents that target particular proteins. As researchers continue to better understand the molecular events leading to leukemia, they will be able to design more specific drugs to halt the disease’s progression. Approximately 30 percent of AML patients, for example, have mutations in a protein called FLT3, which causes the cancer to grow more aggressively and become unresponsive to treatment. Drugs that block FLT3 mutations currently are in development. FLT3 inhibitors are now being tested in clinical trials in combination with traditional chemotherapy drugs.
Another type of drug called a farnesyl transferase inhibitor is in clinical testing. It blocks an enzyme that is potentially important to the development of some types of leukemia. Previously untreated older patients with AML have responded well to the drug to date.
Immune-based therapy has also shown some promise. Rituximab, a monoclonal antibody that binds to certain CLL B cells, is under evaluation alone and in combination with chemotherapy. Preliminary results suggest that rituximab given in combination with the chemotherapy drug Fludarabine leads to a high rate of remission. There currently (August 2005) are studies underway to evaluate the effectiveness of combination chemotherapy using Fludarabine.
The most striking example of a targeted therapy’s effectiveness in treating cancer is the use of Imatinib mesylate (Gleevec®) for patients with CML. Imatinib binds to the ABL protein and blocks the activity of the BCR-ABL enzyme. Patients who have received the drug, especially early in the course of the disease, have shown a high rate of positive response, with nearly every one experiencing a return to normal blood counts. Only time will tell what the long-term survival results will be.
Current Treatment
Chemotherapy is the mainstay of treatment for the majority of the leukemias, with the exception of CML. Chemotherapy for acute leukemias is commonly given in two or three phases. The first phase entails the administration of drugs to put the patient into a prolonged remission. This induction therapy typically achieves complete remission – meaning no evidence of the disease, and normal blood and marrow cells – in about 75 percent of younger adults and half of those older than 50. The disease nearly always returns, however, without further treatment with chemotherapy. Then a second chemotherapy regimen is given, with the goal of killing all of the remaining leukemia cells, which otherwise could begin to regrow and cause disease again. If this treatment fails to achieve or maintain remission, or if patients are at high risk for relapse, they may be given a hematopoietic stem cell transplant. This is a somewhat risky procedure in which the patient’s bone marrow – and leukemia, it is hoped – is destroyed, and the body’s blood-forming system is built again from scratch.
In the case of CML, the introduction of the targeted agent Imatinib mesylate (Gleevec®) has dramatically changed the treatment of the disease. Newer agents are now in development to overcome the resistance to Gleevec® that some patients develop.
Because CLL can progress slowly, some patients may not require treatment for years, if not decades. Doctors continue to monitor symptoms in such individuals. When treatment is necessary, one of the first chemotherapy drugs used is Fludarabine.
Resources
National Cancer Institute
1-800-4-CANCER
www.cancer.gov
American Cancer Society
1-800-ACS-2345
www.cancer.org
The Leukemia & Lymphoma Society
800-955-4572
www.leukemia-lymphoma.org