|Acute lymphoblastic leukemia|
Classification and external resources
Acute lymphoblastic leukemia (ALL), is a form of leukemia, or cancer of the white blood cells. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases 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 The Diseases Database 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 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood Hematological malignancies are the types of Cancer that affect Blood, Bone marrow, and Lymph nodes As the three are intimately connected through
Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. Malignant (from the Latin roots mal- = "bad" and -genus = "born" is a medical term used to describe a severe and progressively worsening disease Lymphoblasts are immature cells which typically differentiate to form mature Lymphocytes Normally lymphoblasts are found in the bone marrow but in Acute lymphoblastic Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (metastasizing) to other organs. Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, ALL is most common in childhood and young adulthood with a peak incidence at 4-5 years of age, and another peak in old age. The overall cure rate in children is 85%, and about 50% of adults have long-term disease-free survival.  'Acute' refers to the undifferentiated, immature state of the circulating lymphocytes ("blasts"), and to the rapid progression of disease, which can be fatal in weeks to months if left untreated.
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). Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris An infection is the detrimental Colonization of a host Organism by a foreign Species. The term ' Bone pain' (or Ostealgia, or Osteodynia) generally is used to refer to Pain felt within a bone Arthralgia (from Greek arthro-, joint + -algos, pain literally means joint pain; it is a symptom of injury infection illnesses -- in particular Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. The liver is a vital organ in the human body and is present in Vertebrates and some other animals The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Therefore, people with ALL experience symptoms from malfunctioning of their erythrocytes (red blood cells), leukocytes, and platelets not functioning properly. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Laboratory tests which might show abnormalities include blood count tests, renal function tests, electrolyte tests and liver enzyme tests. A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. An electrolyte is any substance containing free Ions that behaves as an electrically conductive medium Liver function tests (LFTs or LFs which include liver enzymes, are groups of Clinical biochemistry laboratory blood assays designed to give information about the
Diagnosing ALL begins with a medical history and physical examination, complete blood count, and blood smears. Diagnosis is the identification by Process of elimination, of the nature of anything Physical examination or clinical examination is the process by which a Health care provider investigates the body of a Patient for signs A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is Because the symptoms are so general, many other diseases with similar symptoms must be excluded. Typically, the higher the white blood cell count, the worse the prognosis.  Blast cells are seen on blood films in 90% of cases. A bone marrow biopsy is conclusive proof of ALL. Bone marrow examination refers to the pathologic analysis of samples of Bone marrow obtained by bone marrow biopsy (often called a Trephine biopsy  A spinal tap will tell if the spinal column and brain has been invaded. In Medicine, a lumbar puncture (colloquially known as a spinal tap) is a Diagnostic and at times therapeutic procedure that is performed in order In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges.
Pathological examination, cytogenetics (particularly the presence of Philadelphia chromosome) and immunophenotyping, establish whether the "blast" cells began from the B lymphocytes or T lymphocytes. Histopathology (from the Greek histos (tissue and pathos (suffering refers to the microscopic examination of tissue in order to study the manifestations Cytogenetics is a branch of Genetics that is concerned with the study of chromosomes and cell division Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with Chronic myelogenous leukemia (CML Immunophenotyping is a technique used to study the protein expressed by cells B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. DNA testing can establish how aggressive the disease is; different mutations have been associated with shorter or longer survival.
Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys and reproductive organs. Medical imaging refers to the techniques and processes used to create Images of the human body (or parts thereof for clinical purposes ( Medical procedures seeking to Computed tomography (CT is a Medical imaging method employing Tomography. In Biology, an organ ( Latin: organum, "instrument tool" from Greek όργανον - organon "organ instrument lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive
The cause of most ALL is not known. In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth, or interrupting chemical signals that control growth. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Damage can be caused through the formation of fusion genes, as well as the dysregulation of a proto-oncogene via juxtaposition of it to the promotor of another gene, e. An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. g. the T-cell receptor gene. The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound This damage may be caused by environmental factors such as chemicals, drugs or radiation.
ALL is associated with exposure to radiation and chemicals in animals and humans. Image talkNew_radiation_symbol_ISO_21482svg for details --> Ionizing radiation The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl nuclear reactor and atom bombs in Hiroshima and Nagasaki. Chernobyl (as transliterated from the Чернобыль) or Chornobyl (as transliterated from Чорнобиль tʃɔrˈnɔbɪlʲ was a city in northern A nuclear weapon is an explosive device that derives its destructive force from Nuclear reactions either fission or a combination of fission and fusion. The Japanese city of ( is the capital of Hiroshima Prefecture, and the largest city in the Chūgoku region of western Honshū, the largest of Japan 's ( is the Capital and the largest city of Nagasaki Prefecture in Japan. In animals, exposure to benzene and other chemicals can cause leukemia. Benzene, or benzol, is an organic Chemical compound and a known Carcinogen with the molecular formula C 6 H 6 Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Patients who are treated for other cancers with radiation and chemotherapy often develop leukemias as a result of that treatment.
Cytogenetic translocations associated with specific molecular genetic abnormalities in ALL
|Cytogenetic translocation||Molecular genetic abnormality|
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. Cytogenetics is a branch of Genetics that is concerned with the study of chromosomes and cell division A chromosome is an organized structure of DNA and Protein that is found in cells. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled 
Some cytogenetic subtypes have a worse prognosis than others. These include:
|Cytogenetic change||Risk category|
|Philadelphia chromosome||Poor prognosis|
|t(8;14)(q24. Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with Chronic myelogenous leukemia (CML 1;q32)||Poor prognosis|
|Complex karyotype (more than four abnormalities)||Poor prognosis|
|Low hypodiploidy or near triploidy||Poor prognosis|
|High hyperdiploidy||Good prognosis|
As ALL is not a solid tumour, the TxNxMx notation as used in solid cancers is of little use. A karyotype is the characteristic Chromosome complement of a Eukaryote Species. Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes. The TNM Classification of Malignant Tumours ( TNM) is a Cancer staging system that describes the extent of Cancer in a patient’s body
Subtyping of the various forms of ALL used to be done according to the French-American-British (FAB) classification, which was used for all acute leukemias (including acute myelogenous leukemia, AML). 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 myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized
Each subtype is then further classified by determining the surface markers of the abnormal lymphocytes, called immunophenotyping. In general vacuole functions include Removing unwanted structural debris Isolating materials that might be harmful or a threat to the cell Containing There are 2 main immunologic types: pre-B cell and pre-T cell. The mature B-cell ALL (L3) is now classified as Burkitt's lymphoma/leukemia. Burkitt lymphoma (or "Burkitt's tumor" or "Malignant lymphoma Burkitt's type" is a cancer of the lymphatic system (in particular B lymphocytes Subtyping helps determine the prognosis and most appropriate treatment in treating ALL.
The recent WHO International panel on ALL recommends that the FAB classification be abandoned, since the morphological classification has no clinical or prognostic relevance. It instead advocates the use of the immunophenotypic classification mentioned below.
1- Acute lymphoblastic leukemia/lymphoma Synonyms:Former Fab L1/L2
2- Burkitt's leukemia/lymphoma Synonyms:Former FAB L3
The use of a TdT assay and a panel of monoclonal antibodies (MoAbs) to T cell and B cell associated antigens will identify almost all cases of ALL. Precursor T acute lymphoblastic leukemia/lymphoma is a form of Lymphoid leukemia. Burkitt lymphoma (or "Burkitt's tumor" or "Malignant lymphoma Burkitt's type" is a cancer of the lymphatic system (in particular B lymphocytes Acute biphenotypic leukaemia is a form of Leukaemia where the lineage is of both lymphoid and myeloid origin
Immunophenotypic categories of acute lymphoblastic leukemia (ALL)
|Types||FAB Class||Tdt||T cell associate antigen||B cell associate antigen||c Ig||s Ig|
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).
Treatment for acute leukemia can include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), and growth factors. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Stem cells are cells found in most if not all multi-cellular Organisms.
Chemotherapy is the initial treatment of choice. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. 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. Malignant (from the Latin roots mal- = "bad" and -genus = "born" is a medical term used to describe a severe and progressively worsening disease
A newly developed study for the treatment of Acute Lymphoblastic leukemia, known as COALL 03-07 is underway. It is started in European region and has Hamburg as its center. This new study compares between the chemotherapeutic medications. Finally it shall be revealed that which chemotherapy better suits for the patients with ALL.
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). Chemotherapy regimens are often identified with acronyms identifying the agents used in combination Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. In Medicine, a central venous catheter ( CVC or central venous line or central venous access catheter) is a Catheter placed into a A Hickman line is an Intravenous catheter most often used for the administration of Chemotherapy or other medications as well as for the withdrawal of In Medicine, a port (or portacath) is a small medical appliance that is installed beneath the skin 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.
Radiation therapy (or radiotherapy) 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 therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant 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.
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. Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood 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 anemia, Bloom syndrome, Ataxia telangiectasia, X-linked agammaglobulinemia and Severe combined immunodeficiency. Down syndrome, Down's syndrome, or trisomy 21 is a Chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. Fanconi anemia (FA is a genetic disease that affects children and adults from all ethnic backgrounds Bloom syndrome (BLM is a rare Autosomal Recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's Ataxia-telangiectasia (AT ( Boder-Sedgwick syndrome or Louis-Bar syndrome) is a rare neurodegerative inherited disease which affects many parts of the body X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia XLA, Bruton type agammaglobulinemia) is a rare X-linked genetic disorder Severe combined immunodeficiency ( SCID) or Boy in the Bubble Syndrome is a genetic disorder in which both "arms" ( B cells and T cells
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 defined as Human activity based on Intellectual application in the investigation of Matter. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices Hematopoietic stem cell transplantation (HSCT or bone marrow transplantation is a medical procedure in the field of Hematology and Oncology that involves
It is worth noting that medical advances in recent 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:
Correlation of prognosis with bone marrow cytogenetic finding in acute lymphoblastic leukemia
|Favorable||Hyperdiploidy > 50 ; t (12;21)|
|Intermediate||Hyperdioloidy 47 -50; Normal(diploidy); del (6q); Rearrangements of 8q24|
|Unfavorable||Hypodiploidy-near haploidy; Near tetraploidy; del (17p); t (9;22); t (11q23)|
acute lymphoblastic leukemia (ALL), peripheral blood of a child, Pappenheim stain, magnification x100
bone marrow smear (large magnification) from a patient with acute lymphoblastic leukemia
bone marrow smear from a patient with acute lymphoblastic leukemia