What are leukemias?

Related conditions:
Myelodysplastic syndrome (MDS)

Definition:

Leukemias are cancers of the blood that result in abnormally high numbers of white cells, called leukocytes, in the blood and bone marrow. There are some rare forms of leukemia, but the main ones are acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Leukemias are named for the type of malfunctioning blood cell and the intensity of how the cancer progresses. Acute leukemia occurs suddenly and usually involves large numbers of abnormal cells. Chronic leukemia grows more slowly and may go undetected until the disease progresses. AML is a fast-growing leukemia that involves mature white cells. CML is slow growing, has a disease marker called the Philadelphia chromosome, and affects mature white cells. ALL affects mature lymphocytes and grows rapidly. CLL also affects mature lymphocytes but grows slowly.

Risk factors: Exposure to certain chemicals, such as benzene, is a risk factor for leukemia. Chemicals, solvents, and ionizing radiation can alter deoxyribonucleic acid (DNA), one of the acids found within the nucleus of cells. The damaged DNA causes chromosomal abnormalities linked to cancer. Another risk factor is prior treatment with chemotherapy, or cytotoxic drugs. Leukemia emerging after treatment of another cancer is known as a secondary leukemia.

Etiology and the disease process: The cause of leukemia is unknown, but it is thought that substances that damage DNA lead to the development of leukemia. The proliferation of abnormal white blood cells crowds out red blood cells, platelets, and healthy white cells. The different types of white blood cells are neutrophil, eosinophil, basophil, monocyte, and lymphocyte, and each has a specific role in fighting infection. Red blood cells carry oxygen to the body, and platelets enable blood to clot. Normal white cells, which help the body fight infection by keeping blood and tissues free of contaminants such as bacteria, viruses, and fungi, cannot function properly in the presence of leukemia. White blood cells, as well as red blood cells and platelets, originate from stem cells that mature, or differentiate, into specific types of cells inside the bone marrow. Immature white cells are called blasts, and increased numbers are found in the bone marrow, and sometimes blood, of people with AML and ALL. The presence of leukemic cells leaves less room for the normal white cells, compromising and suppressing the immune system. Myelodysplastic syndrome (MDS) is a disease that affects the normal maturation process of blood cells and may evolve into AML.

Incidence: Leukemia makes up about 3 percent of cancers, according to the National Cancer Institute (NCI). New cases of leukemia, estimated by theNCI, were expected to number 52,380 in 2014. The incidence is much higher for the elderly, with CLL, AML, and CML being most prevalent in people aged seventy and up, according to the Leukemia and Lymphoma Society of America (LLS). Leukemias account for about 32 percent of all cancers in children up to the age of fourteen. The most common form of leukemia among children under the age of fifteen is ALL. The incidence of all leukemias is higher for men than women, and the LLS predicted that, in 2014, males would account for about 57 percent of new leukemia cases. Leukemia is not a hereditary disease, because most people with leukemia report no family history of the disease.

Symptoms: The early signs of leukemia may manifest as generalized symptoms such as fatigue and shortness of breath that result from a lack of oxygen in the body because of reduced numbers of red blood cells. Pale skin, infection, and wounds that heal slowly are other symptoms. Bruising or bleeding may result when platelets are reduced by the abnormally high white cell counts. Enlarged lymph nodes and joint pain may also be noticed. A complete workup is necessary to determine the cause of the symptoms. There are multiple medical conditions that cause the same symptoms, and therefore these symptoms should not be assumed to be caused by leukemia. However, as leukemia is potentially fatal and early intervention is critical, particularly with acute leukemia, symptoms should be reported promptly to a health care provider.

Screening and diagnosis: Routine blood tests such as a complete blood count (CBC) are used to screen for abnormalities in white and red blood cells and platelets. Diagnosis is made by testing blood and bone marrow in conjunction with a thorough review of medical history and a physical examination. Bone marrow is obtained though a procedure called a biopsy. A small sample of bone marrow is obtained by inserting a needle into bone, typically near the hip. The sample is examined under a microscope to look for malignant cells and through testing called immunophenotyping. White blood cells can be identified by their size and by the way they look when stains are applied. Staining allows visualization of the different cell lines and makes it easier to quantify or estimate the number of each present in the sample. The number of blast cells found in bone marrow or blood is used to diagnosis leukemia versus myelodysplastic syndrome. An increase in the number of blasts may be indicative of conversion from myelodysplastic syndrome to AML.

Genetic testing is the key to diagnosing leukemia because it identifies the cell defect causing the leukemia. Chromosome testing, which reveals important genetic information about type and aggressiveness of the leukemia, is used to guide treatment. Immunophenotyping is a process that enables examination of individual cells in a sample of blood or bone to determine the types of proteins and antigens on their surface. This process helps determine the percentage of abnormal markers on cells, which determines leukemia type. The specific abnormalities found through this testing give a picture of the genetic defect and prognosis for the leukemia.

Karyotyping is done to gain additional information about the genetic features of the chromosomes and thereby confirm a diagnosis of leukemia and identify its subtype. The type of genetic abnormality needs to be determined before treatment begins to ensure utilization of the correct regimen. The abnormality may be a deletion, addition, or translocation of a segment of DNA that controls cell replication and function. The Philadelphia chromosome describes the abnormality of a translocation that confirms the diagnosis of CML. It is the switch of part of chromosome 9 to chromosome 22 and part of chromosome 22 to chromosome 9.

Fluorescence in situ hybridization (FISH) is another genetic test that can confirm or rule out a diagnosis. This test detects abnormalities that may be missed on normal karyotyping. Some abnormalities are more favorable than others in terms of prognosis. The Philadelphia chromosome is also found in approximately a third of the cases of ALL. The information about the leukemia cells gained through cytogenetic testing aids oncologists and hematologists in helping patients weigh the chances of recovery against potential risks inherent in chemotherapy. Radiographs, such as X rays, computed tomography (CT) scans, and magnetic resonance images (MRI), may be needed to rule out other conditions or medical problems.

The staging of leukemia differs for each type. For example, a common staging system for AML is the French-American-British (FAB) system, which uses eight subtypes labeled MO to M7. The World Health Organization’s classification is another system used to identify the extent of disease.

CML may cause few or no symptoms initially and may be discovered during a routine doctor visit when blood samples are obtained. CML is diagnosed according to chronic, accelerated, and aggressive phases based on how far the disease has progressed. CLL is diagnosed and monitored through examination of lymphocytes, a type of white blood cell.

Treatment and therapy: Treatment options depend on the type and aggressiveness of the leukemia as well as the patient’s age and other health considerations. Severe symptoms, associated with acute leukemia, require immediate hospitalization and treatment. Chemotherapy, radiation, and bone marrow or stem cell transplantation are possible modes of therapy. chemotherapy is most frequently used and may involve multiple drugs in different combinations, called regimens. Treatments evolve with ongoing research as more is learned about the mechanisms that cause and arrest the disease. Targeted therapies show promise in the treatment of cancer, including some leukemias. The development of imatinib mesylate (Gleevec) has been important for the treatment of CML. This drug works by depressing an enzyme that causes CML to grow.

In the process of killing leukemia cells, normal cells may be affected, causing side effects that must be closely monitored and treated in a health care setting. In acute leukemia, the white cell count may be dangerously high, requiring treatment with hydroxyurea to reduce the number of white cells before treatment for the leukemia begins.

The initial treatment phase of leukemia is called induction and is designed to put the leukemia into remission. When testing shows improvement in the leukemia but diseased cells remain, it is regarded as a partial remission and the patient may be given a second induction. Consolidation or intensification therapy is another treatment step that increases or improves the chance of a cure. It is given after a remission is achieved with induction therapy. Patients may continue to get other drugs during a maintenance phase of treatment that is given to reinforce remission.

A stem cell or bone marrow transplant is the process of replacing diseased cells with normal or disease-free cells and may be an option after remission to prolong survival. An autologous transplant uses an individual’s own cells, and an allogeneic transplant involves cells from another person, called a donor. Chemotherapy and sometimes total body irradiation (TBI) are used to clear as much of the disease as possible prior to the transplant. A person diagnosed with leukemia often needs transfusions of whole blood and platelets and other supportive care while undergoing treatment for the leukemia.

Drugs that have shown promise in the laboratory and in preliminary clinical trials with humans may be an option for the treatment of leukemia. These drugs are considered investigational and are available only through participation in a clinical trial. Oncologists and other physicians who treat leukemia can help patients learn if there is a clinical trial option appropriate for a particular diagnosis.

Prognosis, prevention, and outcomes: Preventive strategies include undergoing routine health screenings to check blood counts and avoiding prolonged exposure to chemicals. Outcomes depend on type of leukemia, availability of treatment options, age, and overall state of health. Survival rates are excellent for children with ALL under the age of fifteen, with almost all cases cured. Treatment for the elderly can be limited by the toxic effects of some chemotherapy regimens that are poorly tolerated by individuals in this age group. The prognosis after treatment for ALL is less favorable in patients who have the Philadelphia chromosome. Acute leukemia that goes into remission after treatment is considered cured after five years.

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