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Encyclopedia > Acute lymphoblastic leukemia
Acute lymphoblastic leukemia
Classification & external resources
ICD-10 C91.0
ICD-9 204.0
ICD-O: 9821/3
DiseasesDB 195
eMedicine med/3146  ped/2587
MeSH D015447

Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a form of leukemia, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (also known as lymphoblasts) in the bone marrow. It is a hematological malignancy. It could be fatal if left untreated as ALL spreads into the bloodstream and other vital organs quickly. ALL is most common in childhood with a peak incidence of 4-5 years of age.12-16 die more easily from it than others. Now at least 80% of childhood ALL are considered curable. Acute refers to the undifferentiated, immature state of the circulating lymphocytes ("blasts"), and that the disease progresses rapidly with life expectancy of weeks to months if left untreated. Image File history File links Acute_leukemia-ALL.jpg‎ A Wrights stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ... In medicine, malignant is a clinical term that means to be severe and become progressively worse, as in malignant hypertension. ... Lymphoblasts are interferons produced predominantly by leucocyte cells. ... Grays Anatomy illustration of cells in bone marrow. ... Although hematological malignancies are a form of cancer, they are generally treated by specialists in hematology, although in many hospitals oncology specialists also manage these diseases. ...

Contents

Symptoms

Initial symptoms are not specific to ALL, but worsen to the point that medical help is sought. The signs and symptoms of ALL are variable but follow from bone marrow replacement and / or organ infiltration.

The signs and symptoms of ALL result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature leukocytes (white blood cells). Therefore, people with ALL experience symptoms from malfunctioning of their erythrocytes (red blood cells), leukocytes, and platelets not functioning properly. Laboratory tests which might show abnormalities include blood count tests, renal function tests, electrolyte tests and liver enzyme tests. The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... Anemia (AmE) or anæmia (BrE), from the Greek () meaning without blood, is a deficiency of red blood cells (RBCs) and/or hemoglobin. ... An analogue medical thermometer showing the temperature of 38. ... An infection is the detrimental colonization of a host organism by a foreign species. ... A bruise or contusion or ecchymoses is a kind of injury, usually caused by blunt impact, in which the capillaries are damaged, allowing blood to seep into the surrounding tissue. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... A nosebleed or nosebleedage, medically known as epistaxis, is the relatively common occurrence of hemorrhage (bleeding) from the nose, usually noticed when it drains out through the nostrils. ... Petechiae are pinpoint-sized hemorrhages of small capillaries in the skin or mucous membranes. ... Bone Pain- Bone pain is generally referred to as having pain within the affected bone. ... In medicine, arthralgia (literally: joint pain, from arthros = joint and -algia denoting pain) is the presence of painful joints in the absence of frank arthritis. ... Dyspnea (Latin dyspnoea, emphysema, COPD, broken ribs, lung cancer, malignant hypertension, and so forth. ... Lymph nodes are components of the lymphatic system. ... The liver is an organ present in vertebrates and some other animals. ... The spleen is an organ located the abdomen, where it functions in the destruction of old white blood cells and holding a reservoir of blood. ... The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: A symptom can be a physical condition which shows that one has a particular illness or disorder (see e. ... White Blood Cells is also the name of a White Stripes album. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... A full blood count (FBC) or complete blood count (CBC) is a test requested by a doctor or other medical professional that gives information about the cells in a patients blood. ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... An electrolyte is a substance containing free ions that behaves as an electrically conductive medium. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ...


Diagnosis

Diagnosing leukemia usually begins with a medical history and physical examination. If there is a suspicion of leukemia, the patient will then proceed to undergo a number of tests to establish the presence of leukemia and its type. Patients with this constellation of symptoms will generally have had blood tests, such as a full blood count. In general, a diagnosis (plural diagnoses) has two distinct dictionary definitions. ... In medicine, the physical examination or clinical examination is the process by which the physician investigates the body of a patient for signs of disease. ... Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... A full blood count (FBC) or complete blood count (CBC) is a test requested by a doctor or other medical professional that gives information about the cells in a patients blood. ...


These tests may include complete blood count (blasts on the blood film generally lead to the suspicion of ALL being raised). Nevertheless, 10% have a normal blood film, and clinical suspicion alone may be the only reason to perform a bone marrow biopsy, which is the next step in the diagnostic process. A full blood count (FBC) or complete blood count (CBC) is a test requested by a doctor or other medical professional that gives information about the cells in a patients blood. ... Blood films, Giemsa stained A blood film or peripheral blood smear is a slide made from a drop of blood, that allows the cells to be examined. ... A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ...


Bone marrow is examined for blasts, cell counts and other signs of disease. Pathological examination, cytogenetics (e.g. presence of the Philadelphia chromosome) and immunophenotyping establish whether the "blast" cells began from the B lymphocytes or T lymphocytes. Histopathology is a field of pathology which specialises in the histologic study of diseased tissue. ... A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... Immunophenotyping involves the labelling of white blood cells with antibodies directed against surface proteins on their membrane. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... T cells are a subset of lymphocytes that play a large role in the immune response. ...


If ALL has been established as a diagnosis, a lumbar puncture is generally required to determine whether the malignant cells have invaded the central nervous system (CNS). A patient undergoes a lumbar puncture at the hands of a neurologist. ... A diagram showing the CNS: 1. ...


Lab tests (mentioned above) and clinical information may also be used to determine whether other medical imaging (such as ultrasound or CT scanning) may be required to find invasion of other organs such as the lungs or liver. Medical imaging designates the ensemble of techniques and processes used to create images of the human body (or parts thereof) for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and function). ... Medical ultrasonography (sonography) is an ultrasound-based diagnostic imaging technique used to visualize muscles and internal organs, their size, structures and possible pathologies or lesions. ... CAT apparatus in a hospital Computed axial tomography (CAT), computer-assisted tomography, computed tomography, CT, or body section roentgenography is the process of using digital processing to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around... In biology, an organ (Latin: organum, instrument, tool) is a group of tissues that perform a specific function or group of functions. ... Human respiratory system The lungs flank the heart and great vessels in the chest cavity. ...


Pathophysiology

The etiology of ALL remains uncertain, although some doctors believe that ALL develops from a combination of genetic and environmental factors. However, there is no definite way of determining the cause of leukemia. Etiology (alternately aetiology, aitiology) is the study of causation. ... DNA, the molecular basis for inheritance. ...


Scientific research has shown that the malignancies are due to subtle or less subtle changes in DNA that lead to unimpaired cell division and breakdown of inhibitory processes. In leukemias, including ALL, chromosomal translocations occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger oncogenes to "turn on", causing unregulated mitosis where cells divide too quickly and abnormally, resulting in leukemia. There is little indication that propensity for ALL is passed on from parents to children. DNA replication Deoxyribonucleic acid (DNA) is a nucleic acid which carries genetic instructions for the biological development of all cellular forms of life and many viruses. ... Chromosomal translocation of the 4th and 20th chromosome. ... An oncogene is a modified gene that increases the malignancy of a tumor cell. ... Mitosis is the process in which a cell duplicates its chromosomes to generate two identical cells. ...


There have been indications that excessive exposure to high doses of radiation (such as that of nuclear reactors, notably Chernobyl, and the atomic bombs in Nagasaki and Hiroshima, Japan 1945) increases the risk of developing acute leukemia. There has also been inconclusive evidence suggesting that exposure to chemicals such as benzene can cause an increased risk for developing acute leukemia. Radiation hazard symbol. ... Core of a small nuclear reactor used for research. ... Chernobyl area. ... The mushroom cloud of the atomic bombing of Nagasaki, Japan, 1945, rose some 18 km (11 mi) above the epicenter. ... This article does not cite any references or sources. ... Benzene, also known as benzol, is an organic chemical compound with the formula C6H6. ...


Cytogenetics

Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, has been increasingly recognized as an important predictor of outcome in ALL.[1] A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... This article is about the biological chromosome. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... A cell is a single unit or compartment, enclosed by a border or wall. ...

Cytogenetic change Risk category
Philadelphia chromosome Poor prognosis
t(4;11)(q21;q23) Poor prognosis
t(8;14)(q24.1;q32) Poor prognosis
Complex karyotype (more than four abnormalities) Poor prognosis
Low hypodiploidy or near triploidy Poor prognosis
High hypodiploidy Good prognosis
del(9p) Good prognosis

Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... Karyogram of human male using Giemsa staining. ... Polyploid (in Greek: πολλαπλόν - multiple) cells or organisms contain more than two copies (ploidy) of their chromosomes. ...

Classification

Subtyping of the various forms of ALL is done according to the French-American-British (FAB) classification, which is used for all acute leukemias (including acute myelogenous leukemia, AML). As ALL is not a solid tumour, the TxNxMx notation used in those cancers is of little use. There are at least three French-American-British (FAB) classification systems; they are used to describe different sets of hematologic diseases: FAB classification of acute lymphoblastic leukemias FAB classification of acute myeloid leukemias FAB classification of myelodysplastic syndromes Categories: | ... Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of blood cells. ... TNM Classification of Malignant Tumours (TNM) is the system developed and maintained by the International Union Against Cancer (UICC) to maintain consensus on one globally recognised standard for categorising cancer. ...


The FAB classification is:

  • ALL-L1: small uniform cells
  • ALL-L2: large varied cells
  • ALL-L3: large varied cells with vacuoles (bubble-like features)

Note: The recent WHO International panel on ALL recommends that this classification be abandoned, since the morphological classification has no clinical or prognostic relevance. It instead advocates the use of the immunophenotypic classification mentioned below. Schematic of typical animal cell, showing subcellular components. ...


Each subtype is then further classified by determining the surface markers of the abnormal lymphocytes, called immunophenotyping. There are three main immunologic types: B-cell, pre-B cell and T-cell. Subtyping helps determine the prognosis and most appropriate treatment in treating ALL. The abbreviation B comes from bursa of Fabricius that is an organ in birds in which avian B cells mature. ... T cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. ...


Some cytogenetic subtypes have a worse prognosis than others. These include:

  • A translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, occurs in about 20% of adult and 5% in pediatric cases of ALL.
  • A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.
  • Not all translocations of chromosomes carry a poorer prognosis. Some translocations are relatively favorable. For example, Hyperdiploidy (>50 chromosomes) is a good prognostic factor.

Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ...

Treatment

The earlier acute lymphocytic leukemia is detected, the more effective the treatment. The aim is to induce a lasting remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells on the bone marrow). Remission is the state of absence of disease activity in patients with known chronic illness. ...


Treatment for acute leukemia can include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), and growth factors. Chemotherapy is the use of chemical substances to treat disease. ... Steroid skeleton of lanosterol. ... Clinac 2100 C100 accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...


Chemotherapy

Chemotherapy is the initial treatment of choice. Most ALL patients end up receiving a combination of different treatments. There are no surgical options, due to the body-wide distribution of the malignant cells.


As the chemotherapy regimens can be intensive and protracted (often about 2 years in case of the GMALL UKALL, HyperCVAD or CALGB protocols; about 3 years for males on COG protocols), many patients have an intravenous catheter inserted into a large vein (termed a central venous catheter or a Hickman line), or a Portacath (a cone-shaped port with a silicone nose that is surgically planted under the skin, usually near the collar bone, and the most effective product available, due to low infection risks and the long-term viability of a portacath). Since ALL cells sometimes penetrate the Central Nervous System CNS, most protocols include delivery of chemotherapy into the CNS fluid. More advanced centers deliver the drug through Ommaya reservoir (a device surgically placed under the scalp and used to deliver drugs to the CNS fluid and to extract CNS fluid for various tests). More traditional centers would perform multiple lumbar punctures as needed for testing and treatment delivery. Chemotherapy regimens are often identified with acronyms, identifying the agents used in combination. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... In medicine, a central venous catheter (CVC or central (venous) line) is a catheter placed into a large vein in the chest or groin. ... A Hickman line in a leukemia patient. ... Port-a-Cath device. ... CNS can refer to: in air traffic control, Communication, Navigation, Surveillance often associated with the acronym ATM (Air Traffic Management) as CNS/ATM. the central nervous system the title granted to a Clinical Nurse Specialist the mnemonic for the demogroup Conspiracy the IATA code for Cairns International Airport This is...


Radiation therapy

Radiation therapy is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant (total body irradiation). Radiation in the form of whole brain radiation is also used for central nervous system prophylaxis, to prevent recurrence of leukemia in the brain. Whole brain prophylaxis radiation used to be a common method in treatment of children’s ALL. Recent studies showed that CNS chemotherapy provided results as favorable but with less developmental side effects. As a result, the use of whole brain radiation has been more limited. Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...


Epidemiology

The number of annual ALL cases in the US is roughly 4000, 3000 of which inflict children. ALL accounts for approximately 80 percent of all childhood leukemia cases, making it the most common type of childhood cancer. It has a peak incident rate of 2-5 years old, decreasing in incidence with increasing age before increasing again at around 50 years old. ALL is slightly more common in males than females. There is an increased incidence in people with Down Syndrome, Fanconi's anemia, Bloom's syndrome, ataxia-telangiectasia, X-linked agammaglobulinemia and severe combined immunodeficiency. Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ...


Prognosis

Advancements in medical technology and research over the past four decades in the treatment of ALL has improved the overall prognosis significantly from a zero to 20-75 percent survival rate, largely due to the continuous development of clinical trials and improvements in bone marrow transplantation (BMT) and stem cell transplantation (SCT) technology. Medical technology refers to the diagnostic or therapeutic application of science and technology to improve the management of health conditions. ... Research is a human activity based on intellectual investigation and aimed at discovering, interpreting, and revising human knowledge on different aspects of the world. ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is the application of the scientific method to human health. ... Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...


It is worth noting that medical advances in the last years, both through matching the best treatment to the genetic characteristics of the blast cells and through the availability of new drugs, are not fully reflected in statistics that usually refer to five-year survival rates. The prognosis for ALL differs between individuals depending on a wide variety of factors:

  • Sex: females tend to fare better than males.
  • Ethnicity: Caucasians are more likely to develop acute leukemia than African-Americans, Asians and Hispanics and tend to have a better prognosis than non-Caucasians.
  • Age at diagnosis: children between 1-10 years of age are most likely to be cured.
  • White blood cell count at diagnosis of less than 50,000/µl
  • Whether the cancer has spread to the brain or spinal cord
  • Morphological, immunological, and genetic subtypes
  • Response of patient to initial treatment
  • Genetic disorders such as Down's Syndrome

This article does not cite its references or sources. ... An African American (also Afro-American, Black American, or simply black) is a member of an ethnic group in the United States whose ancestors, usually in predominant part, were indigenous to Africa. ... An Asian American is a person of Asian ancestry or origin who was born in or is an immigrant to the United States. ... The Hispanics in the United States or Hispanic American is an American citizen or resident of Hispanic ethnicity and can identify themselves as having Hispanic Cultural heritage. ... Italic text // ahh addiing sum spiice iin hurr`` For other uses, see Brain (disambiguation). ... The Spinal cord nested in the vertebral column. ... A genetic disorder is a disease caused by abnormalities in genes or chromosomes. ...

Additional images

External links

  • The Leukemia & Lymphoma Society - provides information about leukemia and related diseases, updates on current clinical trials, and discussion forums.
  • Cancer Research UK - trains and supports scientists for cancer research, offers regional news about current research, and provides ways that individuals can become involved.
  • Children's Cancer Web - a directory of children's cancer-related resources.
  • The Centre for Cancer and Blood Disorders at Sydney Children’s Hospital provides information on cancers in children and adolescents, including Acute lymphoblastic leukemia.
  • Children's Leukemia and Cancer Research Foundation (INC) (Australia) - provides funding for children's leukemia, especially to the Princess Margaret Hospital for Children [1].
  • European LeukemiaNet
  • Ped-Onc Resource Center - provides information on childhood ALL, including disease details (MRD, phenotypes, molecular characterization), a layman's list of current and past clinical trials, a collection of articles on the possible causes of ALL, a bibliography of journal articles, and links to sources of support for parents of children with ALL.
  • Association of Cancer Online Resource (ACOR) Leukemia Links - provides links to information on leukemia, including ALL, primarily in adults.

  Results from FactBites:
 
eMedicine - Acute Lymphoblastic Leukemia : Article by Noriko Satake, MD (6041 words)
Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing nearly one third of all pediatric cancers.
Lymphoblasts with this phenotype have a distinctive morphology, with deeply basophilic cytoplasm containing prominent vacuoles.
The lymphoblasts are large and have basophilic cytoplasm with prominent vacuoles.
Childhood Acute Lymphoblastic Leukemia Treatment - National Cancer Institute (6198 words)
Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).
Childhood acute lymphoblastic leukemia (also called acute lymphocytic leukemia or ALL) is a cancer of the blood and bone marrow.
Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the bloodstream.
  More results at FactBites »

 
 

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