Leukemias

ALSO KNOWN AS: Hematologic malignancy, liquid tumor

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. Damaged DNA causes chromosomal abnormalities linked to cancer. Another risk factor is prior treatment with chemotherapy or cytotoxic drugs, called secondary leukemia.

Etiology and the disease process: The cause of leukemia is unknown, but substances that damage DNA may lead to the development of leukemia. The proliferation of abnormal white blood cells crowds out red blood cells, platelets, and healthy white cells. Types of white blood cells include neutrophils, eosinophils, basophils, monocytes, and lymphocytes. 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 leukemia. White blood cells, 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. Leukemic cells leave 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 4.1 percent of all cancer deaths, according to the National Cancer Institute (NCI). The incidence is much higher for older adults, with CLL, AML, and CML being most prevalent in people aged seventy and up, according to the Leukemia and Lymphoma Society of America (LLS). The most common form of leukemia among children and those under twenty is ALL. The incidence of all leukemias is higher for males than females. 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 if abnormally high white cell counts reduce platelets. Enlarged lymph nodes and joint pain may also be noticed. A complete workup is necessary to determine the cause of the symptoms. Multiple medical conditions cause the same symptoms, which 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 healthcare provider.

Screening and diagnosis: Routine blood tests such as a complete blood count (CBC) 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 through a procedure called a biopsy. A small sample of bone marrow is obtained by inserting a needle into the bone, typically near the hip. The sample is examined under a microscope to look for malignant cells and through testing called immunophenotyping. When stains are applied, white blood cells can be identified by their size and appearance. Staining allows visualization of the different cell lines and makes quantifying or estimating the number of each present in the sample easier. The number of blast cells found in bone marrow or blood helps diagnose 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 it. Chromosome testing, which reveals important genetic information about the type and aggressiveness of the leukemia, is used to guide treatment. Immunophenotyping is a process that enables the 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 reveals additional information about the chromosomes' genetic features, confirming a leukemia diagnosis and identifying its subtype. The type of genetic abnormality must be determined before treatment begins to ensure the 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 a translocation abnormality that confirms the CML diagnosis. 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 in normal karyotyping. Some abnormalities are indicative of a more favorable prognosis. The Philadelphia chromosome is present in approximately one-third of ALL cases. The information about the leukemia cells gained through cytogenetic testing aids oncologists and hematologists in helping patients weigh the chances of recovery against the risks of 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. Based on how far the disease has progressed, CML is diagnosed according to chronic, accelerated, and aggressive phases. CLL is diagnosed and monitored by examining lymphocytes, a type of white blood cell.

Treatment and therapy: Treatment options depend on the type and aggressiveness of the leukemia, 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 the mechanisms that cause and arrest the disease are better understood. Targeted therapies show promise in the treatment of some leukemias. The development of imatinib mesylate (Gleevec) has been important for treating CML. This drug works by depressing an enzyme that causes CML to grow.

Normal cells may be affected when leukemia cells are killed, causing side effects that must be closely monitored and treated in a healthcare 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 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 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 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 replaces 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 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 before the transplant. A person diagnosed with leukemia often needs transfusions of whole blood and platelets and other supportive care while undergoing treatment for leukemia.

Drugs that have shown promise in the laboratory and preliminary human clinical trials may be an option for treating leukemia. These drugs are considered investigational and are available only through clinical trial participation. Oncologists and physicians who treat leukemia can help patients learn if a clinical trial option is 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 the type of leukemia, availability of treatment options, age, and overall state of health. Survival rates are excellent for children with ALL under fifteen, with almost all cases cured. Treatment for older adults can be limited by the toxic effects of some chemotherapy regimens that these individuals poorly tolerate. The prognosis after treatment for ALL is less favorable in patients with the Philadelphia chromosome. Acute leukemia that goes into remission after treatment is considered cured after five years.

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