Acute myelogenous leukemia (AML) is a malignant disease of the bone marrow in which hematopoietic precursors are arrested in an early

stage of development. Most AML subtypes are distinguished from other related blood disorders by the presence of more than 20% blasts in the bone marrow. The underlying pathophysiology in AML consists of a maturational arrest of bone marrow cells in the earliest stages of development. (See Pathophysiology.) Several factors have been implicated in the causation of AML, including antecedent hematologic disorders, familial syndromes, environmental exposures, and drug exposures. However, most patients who present with de novo AML have no identifiable risk factor. (See Etiology.) Patients with AML present with symptoms resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells, or both. The time course is variable. (See Clinical.) Workup for AML includes blood tests, bone marrow aspiration and biopsy (the definitive diagnostic tests), analysis of genetic abnormalities, and diagnostic imaging. (See Workup.) Current standard chemotherapy regimens cure only a minority of patients with AML. As a result, all patients should be evaluated for entry into well-designed clinical trials. If a clinical trial is not available, the patient can be treated with standard therapy. (See Treatment.) For consolidation chemotherapy or for the management of toxic effects of chemotherapy, readmission is required. Pathophtsio: The underlying pathophysiology in AML consists of a maturational arrest of bone marrow cells in the earliest stages of development. The mechanism of this arrest is under study, but in many cases, it involves the activation of abnormal genes through chromosomal translocations and other genetic abnormalities.[1, 2] This developmental arrest results in 2 disease processes. First, the production of normal blood cells markedly decreases, which results in varying degrees of anemia, thrombocytopenia, and neutropenia. Second, the rapid proliferation of these cells, along with a reduction in their ability to undergo programmed cell death (apoptosis), results in their accumulation in the bone marrow, the blood, and, frequently, the spleen and liver. Ethiology: Several factors have been implicated in the causation of AML, including antecedent hematologic disorders, familial syndromes, environmental exposures, and drug exposures. However, most patients who present with de novo AML have no identifiable risk factor. Antecedent hematologic disorders The most common risk factor for AML is the presence of an antecedent hematologic disorder, the most common of which is myelodysplastic syndrome (MDS). MDS is a bone marrow disease of unknown etiology that occurs most often in older patients and manifests as progressive cytopenias that occur over months to years. Patients with low-risk MDS (eg, refractory anemia with normal cytogenetics findings) generally do not develop AML, whereas patients with high-risk MDS (eg, refractory anemia with excess blasts-type 2) frequently do. Other antecedent hematologic disorders that predispose patients to AML include aplastic anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, and polycythemia vera.

Down syndrome. Early radiologists (before the use of appropriate shielding) were found to have an increased likelihood of developing leukemia. rarely. including polymorphisms of enzymes that metabolize carcinogens. in multivariable analysis. Previous exposure to chemotherapeutic agents .[5] Mutation of CEBPA (the gene encoding CCAAT/enhancer binding protein alpha. Environmental exposures Several studies demonstrate a relationship between radiation exposure and leukemia. CBFA2) occur in the familial platelet disorder with predisposition for AML. 7. Usually.[6] Taskesen et al evaluated concurrent gene mutations. These patients often develop AML. Likewise. However. the risk of AML was slightly increased in people who smoked compared with those who did not smoke. 63% and 56% versus 39%. 1. congenital neutropenia. Patients receiving therapeutic irradiation for ankylosing spondylitis were at increased risk of leukemia. P < . Fanconi anemia. Persons who smoke have a small but statistically significant (odds ratio. such as Li-Fraumeni syndrome. cases of leukemia are less common than the solid tumors that generally characterize these syndromes. Survivors of the atomic bomb explosions in Japan were at a markedly increased risk for the development of leukemia.[8] In several studies. and neurofibromatosis. an enzyme that metabolizes benzene derivatives.Congenital disorders Some congenital disorders that predispose patients to AML include Bloom syndrome. some may present in young adulthood. Some hereditary cancer syndromes. For example. or both. these patients develop AML during childhood. polymorphisms in glutathione S -transferase are associated with secondary AML after chemotherapy for other malignancies. only double=mutated CEBPA was a prognostic factor for favorable outcome. an autosomal dominant disorder characterized by moderate thrombocytopenia.05. also predispose patients to AML. However. Exposure to benzene is associated with aplastic anemia and pancytopenia. a defect in platelet function.0001 and P=. a granulocytic differentiation factor and member of the bZIP family) was described in a family with 3 members affected by AML. More subtle genetic disorders. and gene expression signatures of CEBPA double versus single mutations in 1182 patients with cytogenetically-normal AML (CN-AML) (aged 16-60 y).5) increased risk of developing AML. Many of these patients demonstrate M6 morphology. are associated with an increased risk of AML.[3] Particularly increased risk exists for AML that occurs after chemotherapy for another disease or for de novo AML with an abnormality of chromosomes 5. and propensity to develop AML. clinical outcome. polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1).[4] Familial syndromes Germline mutations in the gene AML1 (RUNX1. can manifest as leukemia. respectively).[7] Both double-mutated CEBPA and single-mutated CEBPA were associated with favorable outcome compared with wild type CEBPA (5-year overall survival (OS).

They arise in the bone marrows but infiltrate the spleen. often have a myelodysplastic phase before the development of AML. Less commonly. For example. y Leukemia is malignant neoplasms of the cells derived from either the myeloid or lymphoid line of the hematopoietic stem cells in the bone marrow. with peak incidence between ages 2 and 9. but it is only 9-12 months for topoisomerase inhibitors. ALL is the most common cancer in children. Acute leukemias are characterized by rapid progression of symptoms. The median age of onset is approximately 70 years. Prognosis> It was estimated that 13. Approximately 85 % of acute leukemias in adults are AML. lymph nodes. and it is more common in whites than in other populations. and thrombocytes. Patients with a previous exposure to alkylating agents. including intracranial hemorrhage. This is likely because MDS is more common in men. Lymphocytic leukemias involve immature lymphocytes and their progenitors. and other tissues. Approximately half of new leukemias are acute. AML affects all age groups. and other tissue. the number of patients with AML increases because of exposure to chemotherapeutic agents. and advanced MDS frequently evolves into AML. 12] AML is more common in men than in women.As more patients with cancer survive their primary malignancy and more patients receive intensive chemotherapy (including bone marrow transplantation [BMT]). patients developed leukemia with other balanced translocations. Patients with a previous exposure to topoisomerase-II inhibitors do not have a myelodysplastic phase. interfere with the maturation of granulocytes. Proliferating abnormal and immature cells (blast) spill out into the blood and infiltrate the spleen. However.[10] The typical latency period between drug exposure and acute leukemia is approximately 3-5 years for alkylating agents/radiation exposure. the prevalence of AML increases with age. 6350 in women) would occur in the United States in 2007.[11. Cytogenetics testing frequently reveals -5 and/or -7 (5q.[9] Patients with previous exposure to chemotherapeutic agents can be divided into 2 groups: (1) those with previous exposure to alkylating agents and (2) those with exposure to topoisomerase-II inhibitors. the cumulative incidence of acute leukemia in patients with breast cancer who were treated with doxorubicin and cyclophosphamide as adjuvant therapy was 0. with high risk for rupture and bleeding. High numbers (greater than 50.0% at 5 years. such as inversion 16 or t(15. thus.410 new cases of AML (7060 in men. central nervous system (CNS).000/mm3) of circulating blast weaken blood vessel walls. and incidence of AML increases with age.or monosomy 7). with or without radiation. Acute myelogenous leukemias (AML) and acute lymphatic leukemia (ALL) have similar presentations and courses. The difference is even more apparent in older patients. lymph nodes. Some have proposed that the increased prevalence of AML in men may be related to occupational exposures (see Etiology). erythrocytes.2-1. AML is more commonly diagnosed in developed countries.17). Cytogenetics testing reveals a translocation that involves band 11q23. . Myelogenous leukemias involve the pluripotent myeloid stem cells and.

usually from infection or bleeding.17])  Acute myeloid leukemia with multilineage dysplasia  Acute myeloid leukemia and myelodysplasia syndromes secondary to therapy (eg. those following alkylating agents) . leukostasis leading to hemorrhage.  Acute myeloid leukemia consists of a group of malignant disorders characterized by the replacement of normal bone marrow with abnormal. the disorder uniformly results in death. If untreated. for general purposes.   The World Health Organization (WHO) has classified acute myeloid leukemias into groups. Complications include infection.   The long-term survival rate for pediatric patients with acute myeloid leukemia is nearly 60%.Although the cause of leukemias is unknown. Fanconi s anemia). Mortality is a consequence of resistant progressive disease or treatment-related toxicity. The French-American-British classification system recognizes 7 primary types of acute myeloid leukemia (M1-M7). note the following:   Acute myeloid leukemia with characteristic cytogenetic translocations (eg. tumor lysis syndrome. and disseminating intravascular coagulation. predisposing factors include genetic susceptibility.  Classification of acute myeloid leukemia   Acute myeloid leukemia can be divided into subtypes on the basis of marrow findings.   See Acute Myelogenous Leukemia and Pediatric Acute Lymphoblastic Leukemia for complete information on these topics. Some of these subtypes have characteristic clinical pictures. and human T-cell leukemia-lymphoma virus. treatments are associated with notable morbidity and mortality. although this classification is rarely used in pediatrics. some genetic disorder (Down syndromes. exposure to ionizing radiation or certain chemicals and toxins. However. Although the cure rate has improved. Acute myeloid leukemia accounts for about 35% of childhood deaths from leukemia. renal failure. which can usually be established by morphology and additional marrow studies. primitive hematopoietic cells. promyelocytic leukemia with typical t[15.

 Bleeding   Bleeding is the second most common cause of death in acute myeloid leukemia. Signs of serious infections in children with leukemia are often subtle.  . and treatment with broad-spectrum antibiotics.   Sepsis and pneumonia are particularly common. Causative agents cover the entire gamut of bacterial. Fever at any time must be taken seriously.                         Acute myeloid leukemia not otherwise categorized (eg. or intracranial hemorrhage is frequently observed. antibiotic-resistant bacterial. The risk of sepsis is greatest when the absolute granulocyte count is less than 200 cells/ L.   Septic shock is most commonly secondary to gram-negative bacteria. pulmonary.   The predisposition to infection is a consequence of granulocytopenia and immunosuppression. common causes of death are fungal. viral. and other opportunistic infections. fungal. erythroid leukemias. immunosuppression. and appropriate cultures and investigations must be ordered to diagnose and treat it early.   Severe GI. Staphylococcus aureus. and other pathogens. and group A Streptococcus bacteria and is often lethal. monocytic leukemias) Complications Immediate and short-term complications include the following: Serious infections Alopecia Emesis GI erosions and bleeding Hemorrhage Malnutrition Nausea Death Long-term or delayed complications include the following: Congestive heart failure and arrhythmia (rare) Growth and other endocrine disorders Second malignancies Death Infection Infection is a major cause of morbidity and mortality in acute myeloid leukemia.   Because of prolonged neutropenia.

APL accounts for about five to 10 percent of all cases of AML and is most likely to affect young adults. hyperuricemia. We offer state-of-the-art chemotherapy protocols for leukemia and Stanford hematologists have helped develop the National . Acute myelogenous leukemia (AML). in those with other acute myelocytic leukemia subtypes. In addition to crowding out other important cells. with leukemic cell infiltration. which normally fight infection. can cause devastating complications or death. and pulmonary complications are common problems patients and clinicians face. and their conditions must be treated as true emergencies. In AML the bone marrow makes too many granulocytes. These patients are at greater risk of intracranial hemorrhage.  Central nervous system complications   Central nervous system (CNS) involvement. hemorrhage. Acute promyelocytic leukemia (APL) is a form of AML that is caused when part of chromosome 15 and chromosome 17 are swapped in an action called a translocation.   This condition is often characterized by pronounced metabolic abnormalities. to some extent. myelocytic.  Effects of chemotherapy   The aggressive chemotherapy necessary to cure the patient also results in a great deal of morbidity. It can occur in association with thrombosis and hemorrhage.   Profound myelosuppression due to high-dose.   Mucositis and typhlitis in association with intestinal perforation. or myeloid leukemia. also called granulocytic.   The risk is particularly high for patients with hyperleukocytosis and white blood cell (WBC) counts of more than 200 X 109/L (>200. are produced in the bone marrow. hypocalcemia. Stanford Expertise Patients with leukemia are evaluated and treated in Stanford's Hematology and Bone Marrow Transplant clinics by a team of world-renowned faculty. Disseminated intravascular coagulation is a serious potential problem in all patients with acute promyelocytic leukemia (APL) and. myeloblastic. including hyperkalemia. or infection. intensive treatment regimens contribute to a high risk of infection and bleeding. Information about childhood AML can be found at Lucile Packard Children s Hospital which has excellent programs and physicians. it can also occur in children.000/ L). is a cancer of the blood in which too many granulocytes. AML accounts for about threequarters of all leukemias in adults. renal.  Tumor lysis syndrome   Patients with high leukemic cell counts or massive organomegaly are at significant risk for tumor lysis syndrome. these over-produced granulocytes do not mature correctly. Although AML typically occurs in adults. and renal failure. a type of white blood cell.

Our goal is to improve the survival and quality of life of patients. .Comprehensive Cancer Network (NCCN) guidelines for the management of hematologic malignancies.