Acute Leukemia: A rapidly progressive malignant disease of the bone marrow and blood that results in the accumulation of immature, functionless cells called blast T-cells in the marrow and blood. The accumulation of blast T-cells in the marrow blocks normal blood cell development. As a result, red cells, white cells and platelets are not produced in sufficient numbers. When the disease originates in a marrow lymphocyte progenitor cell, it results in acute lymphoblastic leukemia and when the disease originates in a myeloid progenitor, it results in acute myelogenous leukemia. AML has the greatest incidence of leukemia in adults, with an estimated 10,000 new cases per year in all age groups. ALL is the most common type of childhood leukemia, with 3,000 new cases per year in all age groups.
Acute Myelogenous Leukemia (AML): A progressive cancer that starts by the malignant transformation of an immature cell in the bone marrow. This affected cell usually is a primitive multipotential cell, meaning that its normal counterpart can give rise to a variety of blood cells. The transformed cell multiplies and accumulates in the marrow as leukemic myeloblasts. AML can occur at any age but increases exponentially in incidence after age 45 years. This leukemia can have a myriad of genetic alterations and the appearance of the leukemic cells can be represented by many different subtypes. Although several genetic changes, especially translocations of chromosomes, are relatively common, a large proportion of patients has uncommon or rare genetic changes. Other terms that are synonyms for AML include acute non-lymphocytic leukemia, acute myeloid leukemia, and acute myelocytic leukemia.
Acute Promyelocytic Leukemia: One of many subtypes of acute myelogenous leukemia, so named because the leukemic cells are "frozen" at a stage that mimics the appearance of normal promyelocytes in the marrow. The latter cell type is an early stage in the development of mature neutrophils. Virtually all cases have a translocation involving chromosomes 15 and 17. The break on chromosome 17 is through the gene for the retinoic acid receptor. Retinoic acid is a derivative of vitamin A. Thus, the mutation that leads to this type of acute leukemia involves a disturbance of vitamin A metabolism in the cell nucleus. Administration of all-trans retinoic acid, a derivative of vitamin A, results in a repair of the alteration. This effect leads to maturation of the leukemic promyelocytes to neutrophils and releases the block of normal hematopoietic stem cells. They make normal blood cells that result in a remission restoring normal cells to the blood. The leukemic cells, however, will regrow and result in a relapse unless chemotherapy is used in parallel. An anthracycline antibiotic is the preferred drug in this situation. Remission rates are high and cures are possible.
Age-Adjusted Rate: An incidence or mortality rate that has been adjusted to reduce the effects of differences in the age distribution of the populations being compared. Since many diseases have a different frequency in children, adolescents, younger and older adults, this figure allows a composite number correcting for the effect of age.
Alkylating Agents: Drugs that interact with and injure DNA in such a way as to prevent T-cell growth. Drugs of this type include mechlorethamine, chlorambucil, cyclophosphamide, melphalan, carmustine, and others. They are used principally to treat cancers of lymphocytes such as Chronic Lymphocytic Leukemia, lymphomas, and myeloma. Nitrogen mustard was the first alkylating agent and first chemotherapeutic drug applied to cancer therapy at the end of World War II. It has now been largely supplanted by other alkylating agents.
Allogeneic Stem Cell Transplantation: The transfer of stem cells from one person, the donor, to another, the recipient who is not an identical twin. In practice one makes an effort to find a donor who is very similar in tissue type to the recipient by matching their HLA types. The closer the similarity the higher the probability that the transplant will be a success and that harmful immune reactions will be minimized. Siblings are the most likely to be closely matched, but other family members and unrelated matched donors can be similar enough to achieve a successful transplant if the optimal match is not available and the severity of the illness justifies the risk. In the treatment of leukemia, lymphoma, and myeloma, the cells to be transplanted are pluripotential stem cells, but they are admixed with other marrow or blood cells when infused.
Allograft: A contraction for the phrase allogeneic transplant.
Alloreactivity: The reaction between the immune cells of one individual and the cells of another individual. In hematopoietic stem cell transplantation, this immune reaction can occur in two directions because unlike solid organ transplant, the donor "organ" contains many lymphocytes (immunocytes) and, after engraftment, the donor stem cells will eventually make donor-type lymphocytes in the recipient. The classical alloreactive direction is that of the host T-lymphocytes attacking the transplanted donor cells, the so called "host versus graft reaction", which can lead to "graft rejection". The opposite direction of alloreactivity is the "graft versus host reaction" in which the lymphocytes admixed with the other donor cells that are infused, attack the recipient's tissues. (See Graft Verses host Disease)
Alopecia: The loss of hair. A side effect of some forms of intensive chemotherapy. Radiotherapy that involves the scalp also results in hair loss. In most cases, hair grows as soon as treatment is stopped or decreased in intensity.
Amyloidosis: Amyloidosis is the term for a group of conditions in which an abnormal substance called amyloid is deposited throughout the body. The term means "starch-like." In one form of amyloid, malignant plasma cells, sometimes in association with other manifestations of multiple myeloma, deposit portions of immunoglobulin molecules referred to as light chains, in tissues. These light chain deposits are the amyloid in this circumstance. In the type of amyloid that occurs in myeloma or closely related diseases, organ failure can occur as a result of amyloid deposits in the heart, gastrointestinal tract, and other systems.
Anemia: A decrease in the red blood cells and, therefore, the hemoglobin concentration of the blood. This results in a decreased capacity of the blood to carry oxygen. If severe, anemia can cause a pale complexion, weakness, fatigue, and shortness of breath on exertion.
Anorexia: An eating disorder characterized by extremely low body weight, and a loss of appetite
Anthracycline Antibiotics: Drugs derived from microorganisms, especially fungi that prevent T-cell division by disrupting the structure of DNA. Drugs of this type include daunorubicin, doxorubicin, epirubicin, and idarubicin. These drugs are used in the treatment of acute leukemia, lymphomas, and myeloma.
Anti-Emetic: A drug to prevent or alleviate nausea and vomiting. Nausea and vomiting are side effects of some chemotherapy.
Antibiotics: Drugs that kill or stop the growth of cells and that are derived from microbes, especially bacteria or fungi. They are principally used to treat infectious diseases. The classical example is penicillin. In some cases, the antibiotics may be used as anticancer agents. An example is the anthracycline agents.
Antibodies: Proteins released by plasma cells that recognize and bind to the specific foreign substances. These foreign substances are called antigens. Plasma cells are derived from B-lymphocytes. Antibodies coat, mark for destruction or inactivate foreign particles like bacteria, viruses or foreign chemicals like harmful toxins. Antibody binds specifically to its antigen. One, also, can make antibodies in the laboratory in two ways. If one injects material from one species into another, the latter will recognize it as foreign and make antibodies to it. The injection of human celles into rabbits, for example, allows one to prepare rabbit antibodies directed against the human cell that acted as the antigen. These antibodies are usually polyclonal antibodies. A technique known as a hybridoma can be used to get immune cells in a laboratory flask to generate a specific antibody called a monoclonal antibody. These antibodies can be used in several important ways. They can be used to identify and classify human leukemias and lymphomas or can be altered to make them useful in antibody-mediated immunotherapy. Antigen: A general term for a foreign substance introduced into the body that stimulates an immune response, such as a bacterium, virus, or an allergen that is ingested, inhaled or contacted. Antigens are usually proteins. Antigens stimulate plasma cells, which are derived from B-lymphocytes, to produce antibodies. Immunizations are the injection of a microbial antigen that are used to provoke plasma cells to make protective antibodies against a specific infectious agent. Immune identity is under genetic control. Thus, the cells of an identical twin do not behave as antigens when injected into the other twin. They could induce an immune reaction if injected into a non-identical sibling or unrelated individual. Thus, bacterial or viral antigens can produce potent and sometimes life-long antibody responses in humans, forming the basis for immunization therapy.
Antiglobulin Test: This laboratory procedure can identify antibodies on the surface of red cells or platelets. Patients with Chronic Lymphocytic Leukemia and other lymphocytic malignancies may make antibodies to their own red cells or platelets (auto- or self-directed antibodies). These autoantibodies may lead to anemia or low platelet counts. The antiglobulin test can be used to recognize the presence of autoantibodies on blood cells. A synonym for the test is the Coombs' test, named for one of the scientists who described it.
Antimetabolites: A group of anti-cancer drugs that prevent T-cell from growing and dividing by blocking the chemical reactions required in the cell to produce DNA. Drugs of this type include 6-mercaptopurine, azathioprine, thioguanine, methotrexate, and cytarabine. (See Chemotherapy )
Antithymocyte or Antilymphocyte Globulin: Antibodies that attach to and destroy lymphocytes. This may be used clinically by injection into a vein. These preparations are used in situations in which T-lymphocytes are participating in a deleterious immune attack against a patients tissues.
Apheresis: see hemapheresis
Aplasia: Failure of production of blood cells in the bone marrow. This condition is a consequence of intensive chemotherapy or radiation therapy, the effect of a toxic, usually longstanding exposure to benzene or another organic chemical. It may occur without apparent external cause, a disorder called aplastic anemia.
Aplastic Anemia: An uncommon disorder characterized by the failure of the bone marrow to produce blood cells. It may occur as an inherited condition (see Fanconi's anemia) or, more often, the disease develops later in life. This form is called acquired aplastic anemia. It leads to a severe shortage of all types of blood cell causing tiredness, susceptibility to infection, and potentially serious problems with bleeding as a result of a deficiency in blood platelets. The acquired disease is usually the result of an autoimmune attack of lymphocytes against blood cell progenitors preventing normal blood cell formation.
Autograft: see Autologous Stem Cell Infusion
Autoimmune Disease: Diseases caused by an individual's immune system producing antibodies to the persons own cells. These antibodies can be directed against red blood cells (autoimmune anemia), platelets (autoimmune thrombocytopenia) or other tissues. In some cases, the autoimmune disease is mediated by T-lymphocytes that attack the tissues directly.
Autologous Stem Cell Infusion: This technique, often referred to as transplantation, involves 1) harvesting the patient's stem cells from blood or marrow, 2) freezing them for later use, and 3) thawing and infusing them via an indwelling catheter after the patient has been given intensive chemotherapy or radiation therapy. The blood or marrow may be obtained from a patient with a disease of the marrow (for example, acute myelogenous leukemia) when in remission or when the marrow and blood is not overtly abnormal (for example, lymphoma). Technically, this procedure is not transplantation, which implies taking tissue from one individual (donor) and giving it to another person (recipient). The purpose of this procedure is to restore blood cell production from the preserved and reinfused stem cells after intensive therapy has severely damaged the patient's remaining marrow. This procedure can be performed using marrow or blood stem cells. The latter can be harvested by hemapheresis.