Leukaemia Classification and external resources
A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.
ICD-10	C91.-C95.
ICD-9	208.9
ICD-O:	9800-9940
DiseasesDB	7431
MeSH	D007938

Leukemia or leukaemia (Greek leukos λευκός, "white"; aima αίμα, "blood") 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). 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. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products 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 The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases called hematological neoplasms. Hematological malignancies are the types of Cancer that affect Blood, Bone marrow, and Lymph nodes As the three are intimately connected through

Contents 1 Classification 2 Symptoms 3 Diagnosis 4 Causes and risk factors 5 Treatment options for leukemia by type 5.1 Acute lymphoblastic leukemia (ALL) 5.2 Chronic lymphocytic leukemia (CLL) 5.3 Acute myelogenous leukemia (AML) 5.4 Chronic myelogenous leukemia (CML) 5.5 Hairy cell leukemia (HCL) 6 Research 7 Epidemiology 8 See also 9 References 10 External links

Classification

Leukemia is clinically and pathologically subdivided into several large groups. The first division is between its acute and chronic forms:

• Acute leukemia is characterized by the rapid increase of immature blood cells. In Medicine, an acute disease is a disease with either or both of a rapid onset a short course (as opposed to a chronic course In Medicine, a chronic disease is a Disease that is long-lasting or recurrent This crowding makes the bone marrow unable to produce healthy blood cells. Acute forms of leukemia can occur in children and young adults. (In fact, it is a more common cause of death for children in the US than any other type of malignant disease). The United States of America —commonly referred to as the Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Central nervous system (CNS) involvement is uncommon, although the disease can occasionally cause cranial nerve palsies.
• Chronic leukemia is distinguished by the excessive build up of relatively mature, but still abnormal, blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.

Additionally, the diseases are subdivided according to which kind of blood cell is affected. This split divides lekemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:

• In lymphoblastic or lymphocytic leukemias, the cancerous change took place in a type of marrow cell that normally goes on to form lymphocytes. Lymphoid leukemia (or lymphocytic leukemia) is a type of Leukemia affecting circulating cells of Lymphoid origin Myeloid leukemia is a type of Leukemia affecting Myeloid tissue (bone marrow Lymphoid leukemia (or lymphocytic leukemia) is a type of Leukemia affecting circulating cells of Lymphoid origin A lymphocyte is a type of White blood cell in the Vertebrate Immune system.
• In myeloid or myelogenous leukemias, the cancerous change took place in a type of marrow cell that normally goes on to form red cells, some types of white cells, and platelets. Myeloid leukemia is a type of Leukemia affecting Myeloid tissue (bone marrow A myelocyte is a young cell of the granulocytic series occurring normally in Bone marrow, but not in circulating Blood (except when caused by Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved

Combining these two classifications provides a total of four main categories:

Four major kinds of leukemia

Cell type	Acute	Chronic
Lymphocytic leukemia (or "lymphoblastic")	Acute lymphocytic leukemia (ALL)	Chronic lymphocytic leukemia (CLL)
Myelogenous leukemia (also "myeloid" or "nonlymphocytic")	Acute myelogenous leukemia (AML)	Chronic myelogenous leukemia (CML)

Within these main categories, there are typically several subcategories. Acute lymphoblastic leukemia ( ALL) is a form of Leukemia, or cancer of the white blood cells. Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL" is a type of Leukemia, or cancer of the white blood cells ( Lymphocytes Acute myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized Chronic myelogenous (or myeloid leukemia ( CML) is a form of Leukemia characterized by the increased and unregulated growth of predominantly Myeloid cells Finally, hairy cell leukemia is usually considered to be outside of this classification scheme. Hairy cell leukemia is a mature B cell Neoplasm. It is usually classified as a sub-type of Chronic lymphoid leukemia for convenience

• Acute lymphoblastc leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Standard treatments involve chemotherapy and radiation. The survival rates vary by age: 85% in children and 50% in adults. ^[1]

• Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 75%. ^[2] It is incurable, but there are many effective treatments.

• Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The five-year survival rate is 40%. ^[3]

• Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease. Treatment is with imatinib (Gleevec) or other drugs. Imatinib is a drug used to treat certain types of Cancer. It is currently marketed by Novartis as Gleevec ( USA) or Glivec The five-year survival rate is 90%. ^[4][5]

• Hairy cell leukemia (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern. About 80% of affected people are adult men. There are no reported cases in young children. HCL is incurable, but easily treatable. Survival is 96% to 100% at ten years. ^[6]

Symptoms

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby This means people with leukemia may become bruised, bleed excessively, or develop pinprick bleeds (petechiae). Purpura (from the Latin purpura, meaning "purple" is the appearance of red or purple discolorations on the Skin, caused by Bleeding underneath Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from A petechia (pɨˈtiːkiə plural petechiae (pɨˈtiːkɪiː is a small (1-2mm red or purple spot on the body caused by a minor Hemorrhage (broken Capillary

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells.

Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from All symptoms can be attributed to other diseases.

Some other related symptoms:

The word leukemia, which means 'white blood', is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted 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 An infection is the detrimental Colonization of a host Organism by a foreign Species. For the structure in the Cerebellum, see Cerebellar tonsil. The tonsils are areas In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Malaise is a feeling of general discomfort or uneasiness an "out of sorts" feeling often the first indication of an infection or other disease Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing a harmful imbalance in the blood count.

Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells. However, the leukemic cells are staying in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia. Hairy cell leukemia is a mature B cell Neoplasm. It is usually classified as a sub-type of Chronic lymphoid leukemia for convenience

Diagnosis

Diagnosis requires blood tests to look for an abnormal number of white blood cells, and a bone marrow examination to look for abnormal numbers or forms of cells in the bone marrow. Diagnosis is the identification by Process of elimination, of the nature of anything A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via Bone marrow examination refers to the pathologic analysis of samples of Bone marrow obtained by bone marrow biopsy (often called a Trephine biopsy

Causes and risk factors

There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes, and very little is certain about what causes them. Researchers have strong suspicions about four possible causes:

• natural or artificial ionizing radiation
• certain kinds of chemicals
• some viruses
• genetic predispositions

Leukemia, like other cancers, results from somatic mutations in the DNA which activate oncogenes or deactivate tumor suppressor genes, and disrupt the regulation of cell death, differentiation or division. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances and are likely to be influenced by genetic factors. Image talkNew_radiation_symbol_ISO_21482svg for details --> Ionizing radiation The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation Cohort and case-control studies have linked exposure to petrochemicals, such as benzene, and hair dyes to the development of some forms of leukemia. Petrochemicals are chemical products made from raw materials of Petroleum or other Hydrocarbon origin Benzene, or benzol, is an organic Chemical compound and a known Carcinogen with the molecular formula C 6 H 6 Hair coloring is a process used to color human Hair. It is used for a variety of purposes most commonly to return gray hair to its previous color to change hair color

Viruses have also been linked to some forms of leukemia. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable For example, certain cases of ALL are associated with viral infections by either the human immunodeficiency virus or human T-lymphotropic virus (HTLV-1 and -2, causing adult T-cell leukemia/lymphoma). Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Human T-lymphotropic virus (HTLV is a Human, single-stranded RNA Retrovirus that causes T-cell Leukemia and T-cell Lymphoma Adult T cell leukemia ( ATL) is a rare Cancer of the immune system's own T-cells Human T cell leukemia/lymphotropic virus type 1 ( HTLV-1) is believed However, a CNN Health report says children may be offered limited protection against leukemia by exposure to certain germs.

Fanconi anemia is also a risk factor for developing acute myelogenous leukemia. Fanconi anemia (FA is a genetic disease that affects children and adults from all ethnic backgrounds Acute myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized

Until the cause or causes of leukemia are found, there is no way to prevent the disease. Even when the causes become known, they may not be readily controllable, such as naturally occurring background radiation, and therefore not especially helpful for prevention purposes.

Treatment options for leukemia by type

Acute lymphoblastic leukemia (ALL)

Further information: Acute lymphoblastic leukemia#Treatment

Management of ALL focuses on control of bone marrow and systemic (whole-body) disease. Acute lymphoblastic leukemia ( ALL) is a form of Leukemia, or cancer of the white blood cells. Additionally, treatment must prevent leukemic cells from spreading to other sites, particularly the central nervous system (CNS). In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. In general, ALL treatment is divided into several phases:

• Induction chemotherapy to bring about bone marrow remission. For adults, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. Prednisone is a synthetic Corticosteroid drug that is usually taken orally but can be delivered by Intramuscular injection and can be used for a great number Vincristine (brand name Oncovin also known as leurocristine, is a vinca Alkaloid from the Madagascar periwinkle ( Catharanthus roseus, Anthracyclines (or anthracycline antibiotics) are a class of drugs used in cancer chemotherapy. Asparaginase ( is an Enzyme that catalyzes the Hydrolysis of Asparagine to Aspartic acid. Cyclophosphamide (the generic name for Cytoxan Neosar Revimmune also known as cytophosphane is a Nitrogen mustard alkylating agent, from the oxazophorines group For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment.

• Consolidation therapy to eliminate any remaining leukemia cells. This typically requires one to three months in adults and four to eight months in children. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). An antimetabolite is a chemical with a similar structure to a substance (a Metabolite) required for normal biochemical reactions yet different enough to interfere with the normal Mercaptopurine (also called 6-Mercaptopurine 6-MP or its brand name Purinethol) is an Immunosuppressive drug used to treat Leukemia. High-risk patients receive higher drug doses of these drugs, plus additional drugs.

• CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system. Standard prophylaxis may include radiation of the head and/or drugs delivered directly into the spine. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose

• Maintenance treatments with chemotherapeutic drugs to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves lower drug doses, and may continue for two years.

• Alternatively, allogeneic bone marrow transplantation may be appropriate for high-risk or relapsed patients. Allogeneic bone marrow transplantation is a procedure in which a person receives Stem cells (cells from which all Blood cells develop from a Genetically

Chronic lymphocytic leukemia (CLL)

Further information: Chronic lymphocytic leukemia#Treatment

Decision to treat
Hematologists base CLL treatment upon both the stage and symptoms of the individual patient. Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL" is a type of Leukemia, or cancer of the white blood cells ( Lymphocytes Hematology ( American English) or haematology ( British English) is the branch of biology (physiology Pathology, Clinical laboratory A large group of CLL patients have low-grade disease, which does not benefit from treatment. Individuals with CLL-related complications or more advanced disease often benefit from treatment. In general, the indications for treatment are:

• falling hemoglobin or platelet count
• progression to a later stage of disease
• painful, disease-related overgrowth of lymph nodes or spleen
• an increase in the rate of lymphocyte production

Typical treatment approach
CLL is probably incurable by present treatments. Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. 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 lymphocyte is a type of White blood cell in the Vertebrate Immune system. The primary chemotherapeutic plan is combination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The term polypharmacy generally refers to the use of multiple Medications by a patient Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a Chemotherapy drug that has been mainly used in the treatment of Chronic lymphocytic Cyclophosphamide (the generic name for Cytoxan Neosar Revimmune also known as cytophosphane is a Nitrogen mustard alkylating agent, from the oxazophorines group Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. Prednisone is a synthetic Corticosteroid drug that is usually taken orally but can be delivered by Intramuscular injection and can be used for a great number Prednisolone is the active metabolite of Prednisone. Uses It is a Corticosteroid drug with predominantly Glucocorticoid and low Mineralocorticoid The use of a corticosteroid has the additional benefit of suppressing some related autoimmune diseases, such as immunohemolytic anemia or immune-mediated thrombocytopenia. Warm Antibody Autoimmune Hemolytic Anemia (AIHA is the most common of the autoimmune hemolytic diseases Idiopathic thrombocytopenic purpura (ITP is the condition of having a low Platelet count ( Thrombocytopenia) of no known cause ( Idiopathic) In resistant cases, single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine may be successful. Monotherapy refers to a therapy which is taken by itself It can be applied to any therapeutic approach but it is most commonly used to describe the use of a single Medication Fludarabine (marketed as fludarabine phosphate under the trade name Fludara) is a Chemotherapy drug used in the treatment of hematological malignancies Pentostatin (Deoxycoformycin is an anticancer Chemotherapeutic drug Cladribine is a drug commonly used to treat Hairy cell leukemia (leukemic reticuloendotheliosis Younger patients may consider allogeneic or autologous bone marrow transplantation. An allograft or allogeneic transplant or homograft is a transplant in which transplanted cells, tissues, or organs are sourced from In Biology, autologous refers to cells, tissues or even Proteins that are reimplanted in the same individual as they come from

Acute myelogenous leukemia (AML)

Further information: Acute myeloid leukemia#Treatment

Many different anti-cancer drugs are effective for the treatment of AML. Acute myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized Treatments vary somewhat according to the age of the patient and according to the specific subtype of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease, while offering specific treatment for the central nervous system (CNS), if involved.

In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission and a lower risk of disease resistance. Remission is the state of absence of Disease activity in patients with known Chronic illness. Consolidation and maintenance treatments are intended to prevent disease recurrence. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

Chronic myelogenous leukemia (CML)

Further information: Chronic myelogenous leukemia#Treatment

There are many possible treatments for CML, but the standard of care for newly diagnosed patients is imatinib (Gleevec) therapy. Chronic myelogenous (or myeloid leukemia ( CML) is a form of Leukemia characterized by the increased and unregulated growth of predominantly Myeloid cells Imatinib is a drug used to treat certain types of Cancer. It is currently marketed by Novartis as Gleevec ( USA) or Glivec ^[7] Compared to most anti-cancer drugs, it has relatively few side effects and can be taken orally at home. With this drug, more than 90% of patients will be able to keep the disease in check for at least five years,^[7] so that CML becomes a chronic, manageable condition.

In a more advanced, uncontrolled state, when the patient cannot tolerate imatinib, or if the patient wishes to attempt a permanent cure, then an allogeneic bone marrow transplantation may be performed. This procedure involves high-dose chemotherapy and radiation followed by infusion of bone marrow from a compatible donor. Approximately 30% of patients die from this procedure. ^[7]

Hairy cell leukemia (HCL)

Further information: Hairy cell leukemia#Treatment

Decision to treat
Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. Hairy cell leukemia is a mature B cell Neoplasm. It is usually classified as a sub-type of Chronic lymphoid leukemia for convenience Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e. g. , infection-fighting neutrophil count below 1. 0 K/µL), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.

Typical treatment approach
Patients who need treatment usually receive either one week of cladribine, given daily by intravenous infusion or a simple injection under the skin, or six months of pentostatin, given every four weeks by intravenous infusion. Cladribine is a drug commonly used to treat Hairy cell leukemia (leukemic reticuloendotheliosis Pentostatin (Deoxycoformycin is an anticancer Chemotherapeutic drug In most cases, one round of treatment will produce a prolonged remission.

Other treatments include rituximab infusion or self-injection with Interferon-alpha. Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20 Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents In limited cases, the patient may benefit from splenectomy (removal of the spleen). A splenectomy is a procedure that involves the removal of the Spleen by operative means These treatments are not typically given as the first treatment because their success rates are lower than cladribine or pentostatin.

Research

Significant research into the causes, diagnosis, treatment, and prognosis of leukemia is being done. Hundreds of clinical trials are being planned or conducted at any given time. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures.

Epidemiology

As of 1998, it is estimated that each year, approximately 30,800 individuals will be diagnosed with leukemia in the United States and 21,700 individuals will die of the disease. ^[8]

See also

• Hematologic diseases

References

External links

Images of leukemias

• UVA Healthsystem -- Images of acute leukemias by stage

Research organizations

• The Therapeutic Advances in Childhood Leukemia (TACL) Consortium -- US research group

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