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| | __NOTOC__ |
| | {{Acute myeloid leukemia}} |
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| '''For patient information click [[Leukemia (patient information)|here]]''' | | '''For patient information click [[Leukemia (patient information)|here]]''' |
| {{DiseaseDisorder infobox |
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| Name = Acute myeloid leukemia |
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| ICD10 = {{ICD10|C|92|0|c|81}} |
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| ICD9 = {{ICD9|205.0}} |
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| ICDO = {{ICDO|9861|3}} |
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| Image = Auer_rods.PNG |
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| Caption = Bone marrow aspirate showing acute myeloid leukemia. Arrows indicate [[Auer rods]].|
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| OMIM = 602439 |
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| MedlinePlus = |
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| DiseasesDB = 203 |
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| }}
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| {{SI}}
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| {{CMG}}
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| {{Editor Help}}
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| ==Overview==
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| '''Acute myeloid leukemia''' ('''AML'''), also known as '''acute myelogenous leukemia''', is a [[cancer]] of the [[myeloid]] line of [[white blood cell]]s, characterized by the rapid proliferation of abnormal cells which accumulate in the [[bone marrow]] and interfere with [[haematopoiesis|the production of normal blood cells]]. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer deaths in the United States,<ref name="cancerstats">Jemal A, Thomas A, Murray T, Thun M. Cancer statistics 2002. ''CA Cancer J Clin'' 52:23, 2002. PMID 11814064</ref> its incidence is expected to increase as the population ages.
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| The symptoms of '''AML''' are caused by replacement of normal bone marrow with leukemic cells, resulting in a drop in [[red blood cell]]s, [[platelet]]s, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Although several risk factors for AML have been identified, the specific cause of AML remains unclear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.
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| Acute myeloid leukemia is a potentially curable disease; but only a minority of patients are cured with current therapy. AML is treated initially with [[chemotherapy]] aimed at inducing a [[remission (medicine)|remission]]; some patients may go on to receive a [[stem cell transplant|hematopoietic stem cell transplant]].
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| Areas of active research in acute myeloid leukemia include further elucidation of the cause of AML, identification of better [[prognosis|prognostic indicators]], development of new methods of detecting residual disease after treatment, and the development of new drugs and [[targeted therapy|targeted therapies]].
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| ==History==
| | {{CMG}}; {{AE}} {{RT}} {{CLG}} {{shyam}}; {{GRR}} {{Nat}} |
| The first published description of a case of leukemia in medical literature dates to 1827, when a French physician named [[Alfred-Armand-Louis-Marie Velpeau]] described a 63-year-old florist who developed an illness characterized by fever, weakness, [[nephrolithiasis|urinary stones]], and substantial [[hepatosplenomegaly|enlargement of the liver and spleen]]. Velpeau noted that the blood of this patient had a consistency "like gruel", and speculated that the appearance of the blood was due to white corpuscles.<ref>
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| {{cite book |last = Hoffman |first = Ronald ''et al.'' |title= Hematology: Basic Principles and Practice |year= 2005 |publisher= Elsevier Churchill Livingstone |location= St. Louis, Mo. |edition = 4th. ed. |pages = p. 1071 |id= ISBN 0-443-06629-9}}</ref> In 1845, a series of patients who died with enlarged spleens and changes in the "colors and consistencies of their blood" was reported by the Edinburgh-based [[pathologist]] J.H. Bennett; he used the term "leucocythemia" to describe this pathological condition.<ref>Bennett JH. Two cases of hypertrophy of the spleen and liver, in which death took place from suppuration of blood. ''Edinburgh Med Surg J.'' (1845)64:413.</ref> | |
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| The term "leukemia" was coined by [[Rudolf Virchow]], the renowned German [[pathologist]], in 1856. As a pioneer in the use of the [[light microscope]] in pathology, Virchow was the first to describe the abnormal excess of white blood cells in patients with the clinical syndrome described by Velpeau and Bennett. As Virchow was uncertain of the [[etiology|cause]] of the white blood cell excess, he used the purely descriptive term "leukemia" (Greek: "white blood") to refer to the condition.<ref>Virchow R: Die Leukämie. In Virchow R (ed): Gesammelte Abhandlungen zur Wissenschaftlichen Medizin. Frankfurt, Meidinger, 1856, p 190.</ref>
| | {{SK}} AML; acute granulocytic leukaemia; acute myeloblastic leukemia; acute myelogenous leukemia; acute nonlymphocytic leukemia; M7; megakaryocytic leukemia; Acute monocytic leukemia; AMoL; AML-M5 |
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| Further advances in the understanding of acute myeloid leukemia occurred rapidly with the development of new technology. In 1877, Paul Ehrlich developed a technique of [[staining (biology)|staining]] blood films which allowed him to describe in detail normal and abnormal white blood cells. [[Wilhelm Ebstein]] introduced the term ''"acute leukemia"'' in 1889 to differentiate rapidly progressive and fatal leukemias from the more indolent [[chronic leukemia]]s.<ref>Ebstein W. Ueber die acute Leukämie und Pseudoleukämie. ''Deutsch Arch Klin Med''. (1889)44:343.</ref> The term "myeloid" was coined by Neumann in 1869, as he was the first to recognize that white blood cells were made in the bone marrow (Greek: µυєλός, ''myelos'' = (bone) marrow) as opposed to the [[spleen]]. The technique of [[bone marrow examination]] to diagnose leukemia was first described in 1879 by Mosler.<ref>Mosler F. Klinische Symptome und Therapie der medullären Leukämie. ''Berl Klin Wochenschr''. (1876)13:702. </ref> Finally, in 1900 the [[myeloblast]], which is the malignant cell in AML, was characterized by Naegeli, who divided the leukemias into ''myeloid'' and ''lymphocytic''.<ref>Naegeli O. Über rothes Knochenmark und Myeloblasten. ''Deutsch Med Wochenschr''. (1900) 26:287.</ref>
| | ==[[Acute myeloid leukemia overview|Overview]]== |
| <ref>{{cite journal | author = Zhen-yi, Wang |title = Ham-Wasserman Lecture: Treatment of Acute Leukemia by Inducing Differentiation and Apoptosis | year=2003 | journal = Hematology | pmid = 14633774}}</ref>
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| ==Signs and symptoms== | | ==[[Acute myeloid leukemia historical perspective|Historical Perspective]]== |
| Most signs and symptoms of AML are due to an increased number of malignant white blood cells displacing or otherwise interfering with [[haematopoiesis|production of normal blood cells]] in the [[bone marrow]]. A lack of normal white blood cell production makes the patient susceptible to infections (while the leukemic cells themselves are derived from white blood cell precursors, they have no infection-fighting capacity).<ref name="symptoms">Hoffman, Ronald et al. (2005), pp. 1074–75.</ref> A lack of red blood cells ([[anemia]]) can cause fatigue, paleness, and shortness of breath. A lack of [[platelet]]s can lead to easy bruising or bleeding with minor trauma.
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| The early signs of AML are often non-specific, and may be similar to those of [[influenza]] or other common illnesses. Some generalized symptoms include [[fever]], [[Fatigue (physical)|fatigue]], [[weight loss]] or [[loss of appetite]], [[dyspnea|shortness of breath]] with exertion, [[anemia]], easy [[bruising]] or [[bleeding]], [[petechia]]e (flat, pin-head sized spots under the skin caused by bleeding), [[bone pain]] and [[joint pain]] and persistent or frequent [[infections]].<ref name = "symptoms"/>
| | ==[[Acute myeloid leukemia classification|Classification]]== |
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| [[Splenomegaly|Enlargement of the spleen]] may occur in AML, but it is typically mild and [[asymptomatic]]. [[lymphadenopathy|Lymph node swelling]] is rare in AML, in contrast to [[acute lymphoblastic leukemia]]. The skin is involved about 10% of the time in the form of [[chloroma|leukemia cutis]]. Rarely, [[Sweet syndrome|Sweet's syndrome]], a [[paraneoplastic syndrome|paraneoplastic]] inflammation of the skin, can occur with AML.<ref name = "symptoms"/> | | ==[[Acute myeloid leukemia pathophysiology|Pathophysiology]]== |
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| Some patients with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the [[bone marrow]], called a [[chloroma]]. Occasionally, a person may show [[asymptomatic|no symptoms]], and the leukemia may be discovered incidentally during a routine blood test.<ref>
| | ==[[Acute myeloid leukemia causes|Causes]]== |
| {{cite book |last = Abeloff |first = Martin ''et al.'' |title= Clinical Oncology |year= 2004 |publisher= Elsevier Churchill Livingstone |location= St. Louis, Mo. |edition = 3rd. edition |pages = p. 2834 |id= ISBN 0-443-06629-9}}</ref>
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| ==Causes== | | ==[[Acute myeloid leukemia differential diagnosis|Differentiating Acute Myeloid Leukemia from Other Diseases]]== |
| A number of risk factors for developing AML have been identified, including:
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| *"Pre-leukemic" blood disorders such as [[myelodysplastic syndrome|myelodysplastic]] or [[myeloproliferative syndrome|myeloproliferative]] syndromes can evolve into AML; the exact risk depends on the type of MDS/MPS.<ref>{{cite journal | author = Sanz G, Sanz M, Vallespí T, Cañizo M, Torrabadella M, García S, Irriguible D, San Miguel J | title = Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. | journal = Blood | volume = 74 | issue = 1 | pages = 395–408 | year = 1989 | pmid = 2752119}}</ref>
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| *Exposure to [[chemotherapy|anti-cancer chemotherapy]], in particular [[alkylating antineoplastic agent|alkylating agents]], can increase the risk for the subsequent development of AML. The risk is highest about 3–5 years after chemotherapy.<ref>{{cite journal | author = Le Beau M, Albain K, Larson R, Vardiman J, Davis E, Blough R, Golomb H, Rowley J | title = Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7 | journal = J Clin Oncol | volume = 4 | issue = 3 | pages = 325-45 | year = 1986 | pmid = 3950675}}</ref> Other chemotherapy agents, specifically [[Podophyllotoxin|epipodophyllotoxins]] and [[anthracycline]]s, have also been associated with treatment-related leukemia. These treatment-related leukemias are often associated with specific chromosomal abnormalities in the leukemic cells.<ref>{{cite journal | author = Thirman M, Gill H, Burnett R, Mbangkollo D, McCabe N, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg A | title = Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations | journal = N Engl J Med | volume = 329 | issue = 13 | pages = 909-14 | year = 1993 | pmid = 8361504}}</ref>
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| *[[Ionizing radiation]] exposure can increase the risk of AML. Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML,<ref>{{cite journal | author = Bizzozero O, Johnson K, Ciocco A | title = Radiation-related leukemia in Hiroshima and Nagasaki, 1946–1964. I. Distribution, incidence and appearance time | journal = N Engl J Med | volume = 274 | issue = 20 | pages = 1095-101 | year = 1966 | pmid = 5932020}}</ref> as did [[radiologist]]s exposed to high levels of [[X-ray]]s prior to the adoption of modern radiation safety practices.<ref>{{cite journal | author = Yoshinaga S, Mabuchi K, Sigurdson A, Doody M, Ron E | title = Cancer risks among radiologists and radiologic technologists: review of epidemiologic studies | journal = Radiology | volume = 233 | issue = 2 | pages = 313-21 | year = 2004 | pmid = 15375227}}</ref>
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| *Occupational chemical exposure to [[benzene]] and other [[organic solvent|aromatic organic solvents]] is controversial as a cause of AML. Benzene and many of its derivatives are known to be [[carcinogenic]] ''in vitro''. While some studies have suggested a link between occupational exposure to benzene and increased risk of AML,<ref>{{cite journal | author = Austin H, Delzell E, Cole P | title = Benzene and leukemia. A review of the literature and a risk assessment. | journal = Am J Epidemiol | volume = 127 | issue = 3 | pages = 419-39 | year = 1988 | pmid = 3277397}}</ref> others have suggested that the attributable risk, if any, is slight.<ref>Linet, MS. The Leukemias: Epidemiologic Aspects. Oxford University Press, New York 1985.</ref>
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| *Several [[congenital]] conditions may increase the risk of leukemia; the most common is probably [[Down syndrome]], which is associated with a 10- to 18-fold increase in the risk of AML.<ref>{{cite journal | author = Evans D, Steward J | title = Down's syndrome and leukaemia | journal = Lancet | volume = 2 | issue = 7790 | pages = 1322 | year = 1972 | pmid = 4117858}}</ref>
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| ==Epidemiology== | | ==[[Acute myeloid leukemia epidemiology and demographics|Epidemiology and Demographics]]== |
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| Acute myeloid leukemia is a relatively rare cancer. There are approximately 10,500 new cases each year in the United States, and the [[incidence (epidemiology)|incidence]] rate has remained stable from 1995 through 2005. AML accounts for 1.2% of all cancer deaths in the United States.<ref name="cancerstats"/> | | ==[[Acute myeloid leukemia risk factors|Risk Factors]]== |
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| The incidence of AML increases with age; the median age at diagnosis is 63 years. AML accounts for about 90% of all acute leukemias in adults, but is rare in children.<ref name="cancerstats"/> The rate of ''therapy-related AML'' (that is, AML caused by previous chemotherapy) is rising; therapy-related disease currently accounts for about 10–20% of all cases of AML.<ref>Leone G, Mele L, Pulsoni A, et al: The incidence of secondary leukemias. ''Haematologica'' 84:937, 1999. PMID 10509043 </ref> AML is slightly more common in men, with a male-to-female ratio of 1.3:1.<ref>Greenlee RT, Hill-Harmon MB, Murray T, et al: Cancer statistics, 2001 erratum appears in CA Cancer J Clin 2001 Mar-Apr;51(2):144. ''CA Cancer J Clin'' 2001;51:15–36. PMID 11577478</ref>
| | ==[[Acute myeloid leukemia screening|Screening]]== |
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| There is some geographic variation in the incidence of AML. In adults, the highest rates are seen in North America, Europe, and Oceania, while adult AML is rarer in Asia and Latin America.<ref>Linet MS: The leukemias: Epidemiologic aspects. In Lilienfeld AM (ed): Monographs in Epidemiology and Biostatistics. New York, Oxford University Press, 1985, p I.</ref><ref>Aoki K, Kurihars M, Hayakawa N, et al: Death Rates for Malignant Neoplasms for Selected Sites by Sex and Five-Year Age Group in 33 Countries 1953–57 to 1983–87. Nagoya, Japan, University of Nagoya Press, International Union Against Cancer, 1992.</ref> In contrast, childhood AML is less common in North America and India than in other parts of Asia.<ref>Bhatia S, Neglia JP: Epidemiology of childhood acute myelogenous leukemia. ''J Pediatr Hematol Oncol'' 17:94, 1995. PMID 7749772</ref> These differences may be due to population genetics, environmental factors, or a combination of the two.
| | ==[[Acute myeloid leukemia natural history|Natural History, Complications and Prognosis]]== |
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| A hereditary risk for AML appears to exist. There are numerous reports of multiple cases of AML developing in a family at a rate higher than predicted by chance alone.<ref>Taylor GM, Birch JM: The hereditary basis of human leukemia. In Henderson ES, Lister TA, Greaves MF (eds): Leukemia, 6th ed. Philadelphia, WB Saunders, 1996, p 210.</ref><ref>Horwitz M, Goode EL, Jarvik GP: Anticipation in familial leukemia. ''Am J Hum Genet'' 59:990, 1996. PMID 8900225</ref><ref>Crittenden LB: An interpretation of familial aggregation based on multiple genetic and environmental factors. ''Ann N Y Acad Sci'' 91:764, 1978. PMID 13696504</ref><ref>Horowitz M: The genetics of familial leukemia. Leukemia 11:1345, 1997</ref> The risk of developing AML is increased threefold in [[first degree relative|first-degree relatives]] of patients with AML.<ref>Gunz FW, Veale AM: Leukemia in close relatives: Accident or predisposition. ''J Natl Cancer Inst'' 42:517, 1969. PMID 4180615</ref>
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| ==Pathophysiology== | |
| The malignant cell in AML is the [[myeloblast]]. In normal [[haematopoiesis|hematopoiesis]], the myeloblast is an immature precursor of [[myeloid]] white blood cells; a normal myeloblast will gradually mature into a mature white blood cell. However, in AML, a single myeloblast accumulates genetic changes which "freeze" the cell in its immature state and prevent [[cellular differentiation|differentiation]].<ref>Fialkow PJ: Clonal origin of human tumors. ''Biochim Biophys Acta'' 1976;458:283–321. PMID 1067873 </ref> Such a mutation alone does not cause leukemia; however, when such a "differentiation arrest" is [[Knudson hypothesis|combined with other mutations]] which disrupt genes controlling [[cell growth|proliferation]], the result is the uncontrolled growth of an immature clone of cells, leading to the clinical entity of AML.<ref>Fialkow PJ, Janssen JW, Bartram CR: Clonal remissions in acute nonlymphocytic leukemia: Evidence for a multistep pathogenesis of the malignancy. ''Blood'' 1991;77:1415–1517. PMID 2009365</ref>
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| Much of the diversity and heterogeneity of AML stems from the fact that leukemic transformation can occur at a number of different steps along the differentiation pathway.<ref>Bonnet D, Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. ''Nat Med'' 1997;3:730–737. PMID 9212098</ref> Modern classification schemes for AML recognize that the characteristics and behavior of the leukemic cell (and the leukemia) may depend on the stage at which differentiation was halted.
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| Specific [[cytogenetics|cytogenetic]] abnormalities can be found in many patients with AML; the types of chromosomal abnormalities often have [[prognosis|prognostic]] significance.<ref>Abeloff, Martin et al. (2004), pp. 2831–32.</ref> The chromosomal [[translocations]] encode abnormal fusion [[proteins]], usually [[transcription factors]] whose altered properties may cause the "differentiation arrest."<ref>Greer, John P., et al. ''Wintrobe's Clinical Hematology'', 11th ed. Philadelphia: Lippincott, Williams, and Wilkins, 2004. p. 2045–2062</ref> For example, in [[acute promyelocytic leukemia]], the t(15;17) translocation produces a PML-RARα [[fusion protein]] which binds to the [[retinoic acid]] receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.<ref>Melnick A, Licht JD. Deconstructing a disease: RARα its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. ''Blood'' 1999;93:3167–3215. PMID 10233871</ref>
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| The clinical signs and symptoms of AML result from the fact that, as the leukemic clone of cells grows, it tends to displace or interfere with the development of normal blood cells in the bone marrow.<ref>
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| Abeloff, Martin et al. (2004), p. 2828.</ref> This leads to [[neutropenia]], [[anemia]], and [[thrombocytopenia]]. The symptoms of AML are in turn often due to the low numbers of these normal blood elements. In rare cases, patients can develop a ''[[chloroma]]'', or solid tumor of leukemic cells outside the bone marrow, which can cause various symptoms depending on its location.<ref name="symptoms"/>
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| ==Diagnosis== | | ==Diagnosis== |
| The first clue to a diagnosis of AML is typically an abnormal result on a [[complete blood count]]. While an excess of abnormal white blood cells ([[leukocytosis]]) is a common finding, and leukemic blasts are sometimes seen, AML can also present with isolated decreases in [[platelet]]s, [[red blood cell]]s, or even with a ''low'' white blood cell count ([[leukopenia]]).<ref>Abeloff, Martin et al. (2004), p. 2834.</ref> While a presumptive diagnosis of AML can be made via examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy
| | [[Acute myeloid leukemia diagnostic study of choice|Diagnostic Study of Choice]] | [[Acute myeloid leukemia history and symptoms|History and Symptoms]] | [[Acute myeloid leukemia physical examination|Physical Examination]] | [[Acute myeloid leukemia laboratory tests|Laboratory Findings]] | [[Acute myeloid leukemia electrocardiogram|Electrocardigram]] | [[Acute myeloid leukemia chest x ray|Chest X Ray]] | [[Acute myeloid leukemia echocardiograph and ultrasound|Echocardiograph and Ultrasound]] | [[Acute myeloid leukemia CT|CT]] | [[Acute myeloid leukemia mri|MRI]] | [[Acute myeloid leukemia other imaging findings|Other Imaging Findings]] | [[Acute myeloid leukemia other diagnostic studies|Other Diagnostic Studies]] |
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| A [[bone marrow examination]] is often performed to identify the type of abnormal blood cells; however, if there are many leukemic cells circulating in the peripheral blood, a bone marrow [[biopsy]] may not be necessary. Marrow or blood is examined via [[light microscopy]] as well as [[flow cytometry]] to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. [[acute lymphoblastic leukemia]]), and to classify the subtype of disease (see below). A sample of marrow or blood is typically also tested for [[chromosomal translocation]]s by routine [[cytogenetics]] or [[fluorescent in situ hybridization]].
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| The diagnosis and classification of AML can be challenging, and should be performed by a qualified [[hematopathologist]] or [[hematologist]]. In straightforward cases, the presence of certain morphologic features (such as [[Auer rods]]) or specific flow cytometry results can distinguish AML from other leukemias; however, in the absence of such features, diagnosis may be more difficult.<ref>Abeloff, Martin et al. (2004), p. 2835.</ref>
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| According to the widely used [[WHO]] criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic [[myeloblast]]s.<ref>{{cite journal | author = Harris N, Jaffe E, Diebold J, Flandrin G, Muller-Hermelink H, Vardiman J, Lister T, Bloomfield C | title = The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997 | journal = Ann Oncol | volume = 10 | issue = 12 | pages = 1419–32 | year = 1999 | pmid = 10643532}}</ref> AML must be carefully differentiated from "pre-leukemic" conditions such as [[myelodysplastic syndrome|myelodysplastic]] or [[myeloproliferative syndrome|myeloproliferative]] syndromes, which are treated differently.
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| Because [[acute promyelocytic leukemia]] (APL) has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. [[Fluorescent in situ hybridization]] performed on blood or bone marrow is often used for this purpose, as it readily identifies the [[chromosomal translocation]] (t[15;17]) that characterizes APL.<ref>{{cite journal | author = Grimwade D, Howe K, Langabeer S, Davies L, Oliver F, Walker H, Swirsky D, Wheatley K, Goldstone A, Burnett A, Solomon E | title = Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia: cytogenetic, molecular and PML immunofluorescence assessment of patients entered into the M.R.C. ATRA trial. M.R.C. Adult Leukaemia Working Party. | journal = Br J Haematol | volume = 94 | issue = 3 | pages = 557-73 | year = 1996 | pmid = 8790159}}</ref>
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| ===Pathology===
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:AML.jpg|AML - Auer Rods, DIC<ref>http://picasaweb.google.com/mcmumbi/USMLEIIImages</ref>
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| Image:AML (with Auer Rods).jpg|AML (with Auer Rods)<ref>http://picasaweb.google.com/mcmumbi/USMLEIIImages</ref>
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| </gallery>
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| (Images shown below are courtesy of Melih Aktan MD., Istanbul Medical Faculty - Turkey, and Kyoto University - Japan)
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| Image:AML-M0 0001.jpg|AML-M0
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| Image:AML-M1 peroxidase 0001.jpg|AML-M1 peroxidase
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| Image:AML-M2 0002.jpg|AML-M2
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| Image:AML-M2 0004.jpg|AML-M2
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| Image:AML-M3 0006.jpg|AML-M3
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| Image:AML-M3 0002.jpg|AML-M3
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| Image:AML-M3 Auer bodies 0005.jpg|AML-M3 Auer bodies
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| Image:AML-M3 Auer bodies 0003.jpg|AML-M3 Auer bodies
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| Image:AML-M3 variation 0007.jpg|AML-M3 variation
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| Image:AML-M4 0001.jpg|AML-M4
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| Image:AML-M5a 0003.jpg|AML-M5a
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| Image:AML-M5a 0001.jpg|AML-M5a
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| Image:AML-M5a alpha naphtyle acetat 0002.jpg|AML-M5a (alpha naphtyle acetat)
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| Image:AML-M5b 0001.jpg|AML-M5b
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| Image:AML-M5b 0002.jpg|AML-M5b
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| Image:AML-M7 0001.jpg|AML-M7
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| Image:AML-M7 CD41 0001.jpg|AML-M7
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| </gallery>
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| ==Classification==
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| The two most commonly used classification schemata for AML, as of 2006, are the older French-American-British (FAB) system and the newer [[World Health Organization]] (WHO) system.
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| ===French-American-British classification===
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| The [[French-American-British classification | French-American-British (FAB) classification]] system divided AML into 8 subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. This is done by examining the appearance of the malignant cells under [[light microscopy]] and/or by using [[cytogenetics]] to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy. Although the WHO classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.
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| The eight FAB subtypes are:<ref>{{cite journal | author = Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C | title = Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group | journal = Br J Haematol | volume = 33 | issue = 4 | pages = 451-8 | year = 1976 | pmid = 188440}}</ref>
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| * M0 ([[undifferentiated]] AML)
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| * M1 (myeloblastic, without maturation)
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| * [[M2 AML|M2]] (myeloblastic, with maturation)
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| * M3 (promyelocytic), or [[acute promyelocytic leukemia]] (APL)
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| * M4 (myelomonocytic)
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| * M4eo (myelomonocytic together with bone marrow [[eosinophil]]ia)
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| * M5 [[monoblastic leukemia]] (M5a) or [[monocytic leukemia]] (M5b)
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| * M6 (erythrocytic), or [[erythroleukemia]]
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| * M7 (megakaryoblastic)
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| ===World Health Organization classification ===
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| The [[World Health Organization]] (WHO) classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. Each of the WHO categories contains numerous descriptive sub-categories of interest to the [[hematopathologist]] and [[oncologist]]; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five subtypes listed below.
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| The WHO subtypes of AML are:<ref>{{cite journal | author = Vardiman J, Harris N, Brunning R | title = The World Health Organization (WHO) classification of the myeloid neoplasms | journal = Blood | volume = 100 | issue = 7 | pages = 2292-302 | year = 2002 | pmid = 12239137}}'' [http://www.bloodjournal.org/cgi/content/full/100/7/2292 Full text]''.</ref>
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| * '''AML with characteristic genetic abnormalities''', which includes AML with translocations between chromosome 8 and 21 [t(8;21)], inversions in chromosome 16 [inv(16)], or translocations between chromosome 15 and 17 [t(15;17)]. Patients with AML in this category generally have a high rate of remission and a better prognosis compared to other types of AML.
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| * '''AML with multilineage dysplasia'''. This category includes patients who have had a prior [[myelodysplastic syndrome]] (MDS) or [[myeloproliferative disease]] (MPD) that transforms into AML. This category of AML occurs most often in elderly patients and often has a worse prognosis.
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| * '''AML and MDS, therapy-related'''. This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop AML or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis.
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| * '''AML not otherwise categorized'''. Includes subtypes of AML that do not fall into the above categories.
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| * '''Acute leukemias of ambiguous lineage'''. Acute leukemias of ambiguous lineage (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells, or where both types of cells are present.
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| ==Prognosis==
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| [[Image:9;11.rhyax.jpg|thumb|125px|right|Chromosomal translocation (9;11), associated with AML]]
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| Acute myeloid leukemia is a curable disease; the chance of cure for a specific patient depends on a number of prognostic factors.<ref name="prog">{{cite journal | author = Estey E | title = Prognostic factors in acute myelogenous leukemia | journal = Leukemia | volume = 15 | issue = 4 | pages = 670-2 | year = 2001 | pmid = 11368376}}</ref>
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| ===Cytogenetics and prognosis in AML===
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| The single most important prognostic factor in AML is [[cytogenetics]], or the chromosomal structure of the leukemic cell. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in [[acute promyelocytic leukemia]]). About half of AML patients have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.<ref>{{cite journal | author = Wheatley K, Burnett A, Goldstone A, Gray R, Hann I, Harrison C, Rees J, Stevens R, Walker H | title = A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. | journal = Br J Haematol | volume = 107 | issue = 1 | pages = 69–79 | year = 1999 | pmid = 10520026}}</ref><ref>{{cite journal | author = Slovak M, Kopecky K, Cassileth P, Harrington D, Theil K, Mohamed A, Paietta E, Willman C, Head D, Rowe J, Forman S, Appelbaum F | title = Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. | journal = Blood | volume = 96 | issue = 13 | pages = 4075–83 | year = 2000 | pmid = 11110676}}</ref><ref>{{cite journal | author = Byrd J, Mrózek K, Dodge R, Carroll A, Edwards C, Arthur D, Pettenati M, Patil S, Rao K, Watson M, Koduru P, Moore J, Stone R, Mayer R, Feldman E, Davey F, Schiffer C, Larson R, Bloomfield C | title = Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). | journal = Blood | volume = 100 | issue = 13 | pages = 4325–36 | year = 2002 | pmid = 12393746}}</ref>
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| The first publication to address cytogenetics and prognosis was the MRC trial of 1998:<ref>Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood. 1998 Oct 1;92(7):2322–33.</ref>
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| {| class="wikitable"
| |
| |-
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| !Risk Category
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| !Abnormality
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| !5-year survival
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| !Relapse rate
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| |-
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| |Favorable
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| |t(8;21), t(15;17), inv(16)
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| |70%
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| |33%
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| |-
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| |Intermediate
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| |Normal, +8, +21, +22, del(7q), del(9q), Abnormal 11q23, all other structural or numerical changes
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| |48%
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| |50%
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| |-
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| |Adverse
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| | -5, -7, del(5q), Abnormal 3q, Complex cytogenetics
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| |15%
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| |78%
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| |-
| |
| |}
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| Later, the [[Southwest Oncology Group]] and [[Eastern Cooperative Oncology Group]],<ref>Slovak ML; Kopecky KJ; Cassileth PA; Harrington DH; Theil KS; Mohamed A; Paietta E; Willman CL; Head DR; Rowe JM; Forman SJ; Appelbaum FR Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000 Dec 15;96(13):4075–83.</ref> and later still, [[Cancer and Leukemia Group B]] published other, mostly overlapping lists of cytogenetics prognostication in leukemia<ref>{{cite journal | author = Byrd J, Mrózek K, Dodge R, Carroll A, Edwards C, Arthur D, Pettenati M, Patil S, Rao K, Watson M, Koduru P, Moore J, Stone R, Mayer R, Feldman E, Davey F, Schiffer C, Larson R, Bloomfield C | title = Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). | journal = Blood | volume = 100 | issue = 13 | pages = 4325–36 | year = 2002 | pmid = 12393746}}</ref>
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| ===Antecedent MDS and prognosis===
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| AML which arises from a pre-existing [[myelodysplastic syndrome]] or [[myeloproliferative disease]] (so-called ''secondary AML'') has a worse [[prognosis]], as does ''treatment-related AML'' arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unfavorable cytogenetic abnormalities.<ref>{{cite journal | author = Thirman M, Larson R | title = Therapy-related myeloid leukemia. | journal = Hematol Oncol Clin North Am | volume = 10 | issue = 2 | pages = 293–320 | year = 1996 | pmid = 8707757}}</ref><ref>{{cite journal | author = Rowley J, Golomb H, Vardiman J | title = Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. | journal = Blood | volume = 58 | issue = 4 | pages = 759-67 | year = 1981 | pmid = 7272506}}</ref><ref>{{cite journal | author = Pedersen-Bjergaard J, Andersen M, Christiansen D, Nerlov C | title = Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. | journal = Blood | volume = 99 | issue = 6 | pages = 1909–12 | year = 2002 | pmid = 11877259}}</ref>
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| ===Other prognostic markers===
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| In some studies, age >60 years and elevated [[lactate dehydrogenase]] level were also associated with poorer outcomes.<ref>{{cite journal | author = Haferlach T, Schoch C, Löffler H, Gassmann W, Kern W, Schnittger S, Fonatsch C, Ludwig W, Wuchter C, Schlegelberger B, Staib P, Reichle A, Kubica U, Eimermacher H, Balleisen L, Grüneisen A, Haase D, Aul C, Karow J, Lengfelder E, Wörmann B, Heinecke A, Sauerland M, Büchner T, Hiddemann W | title = Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies. | journal = J Clin Oncol | volume = 21 | issue = 2 | pages = 256–65 | year = 2003 | pmid = 12525517}}</ref> As with most forms of cancer, performance status (i.e. the general physical condition and activity level of the patient) plays a major role in prognosis as well.
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| [[FLT3]] internal tandem duplications (ITDs) have been shown to confer a poorer prognosis in AML.<ref>{{cite journal |author=Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, Löffler H, Sauerland C, Serve H, Büchner T, Haferlach T, Hiddemann W |title=Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease |journal=Blood |volume=100 |issue=1 |pages=59–66 |year=2002 |pmid=12070009}}</ref> Treating these patients with more aggressive therapy, such as stem-cell transplantation in first remission, has not been shown to enhance long-term survival, so this prognostic feature is of uncertain clinical significance at this point.<ref>{{cite journal |author=Gale R, Hills R, Kottaridis P, Srirangan S, Wheatley K, Burnett A, Linch D |title=No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials |journal=Blood |volume=106 |issue=10 |pages=3658–65 |year=2005 |pmid=16076872}}</ref> | |
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| Researchers are investigating the clinical significance of [[c-KIT]] mutations<ref>{{cite journal | author = Paschka P, Marcucci G, Ruppert A, Mrózek K, Chen H, Kittles R, Vukosavljevic T, Perrotti D, Vardiman J, Carroll A, Kolitz J, Larson R, Bloomfield C | title = Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study | journal = J Clin Oncol | volume = 24 | issue = 24 | pages = 3904–11 | year = 2006 | pmid = 16921041}}</ref> in AML. These are prevalent, and clinically relevant because of the availability of [[tyrosine kinase inhibitors]], such as [[sunitinib]] and [[imatinib]] that can block the activity of [[c-KIT]] pharmacologically.
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| Other genes being investigated as prognostic factors or therapeutic targets include CEBPA, BAALC, ERG, and NPM1.
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| ===Overall expectation of cure===
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| Cure rates in clinical trials have ranged from 20–45%;<ref>{{cite journal | author = Cassileth P, Harrington D, Appelbaum F, Lazarus H, Rowe J, Paietta E, Willman C, Hurd D, Bennett J, Blume K, Head D, Wiernik P | title = Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. | journal = N Engl J Med | volume = 339 | issue = 23 | pages = 1649–56 | year = 1998 | pmid = 9834301}}</ref><ref>{{cite journal | author = Matthews J, Bishop J, Young G, Juneja S, Lowenthal R, Garson O, Cobcroft R, Dodds A, Enno A, Gillett E, Hermann R, Joshua D, Ma D, Szer J, Taylor K, Wolf M, Bradstock K | title = Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia. | journal = Br J Haematol | volume = 113 | issue = 3 | pages = 727-36 | year = 2001 | pmid = 11380464}}</ref> however, it should be noted that clinical trials often include only younger patients and those able to tolerate aggressive therapies. The overall cure rate for all patients with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for promyelocytic leukemia can be as high as 98%.<ref>{{cite journal | author = Sanz M, Lo Coco F, Martín G, Avvisati G, Rayón C, Barbui T, Díaz-Mediavilla J, Fioritoni G, González J, Liso V, Esteve J, Ferrara F, Bolufer P, Bernasconi C, Gonzalez M, Rodeghiero F, Colomer D, Petti M, Ribera J, Mandelli F | title = Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups | journal = Blood | volume = 96 | issue = 4 | pages = 1247–53 | year = 2000 | pmid = 10942364}}</ref>
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|
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|
| ==Treatment== | | ==Treatment== |
| Treatment of AML consists primarily of [[chemotherapy]], and is divided into two phases: ''induction'' and ''postremission'' (or ''consolidation'') therapy. The goal of ''induction'' therapy is to achieve a complete remission by reducing the amount of leukemic cells to an undetectable level; the goal of ''consolidation'' therapy is to eliminate any residual undetectable disease and achieve a cure.
| | [[Acute myeloid leukemia medical therapy|Medical Therapy]] | [[Acute myeloid leukemia surgery|Surgery]] | [[Acute myeloid leukemia primary prevention|Primary Prevention]] | [[Acute myeloid leukemia secondary prevention|Secondary Prevention]] | [[Acute myeloid leukemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Acute myeloid leukemia future or investigational therapies|Future or Investigational Therapies]] |
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| ===Induction===
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| As of 2006, all FAB subtypes except M3 are usually given induction chemotherapy with [[cytarabine]] (ara-C) and an [[anthracycline]] (such as [[daunorubicin]] or [[idarubicin]]).<ref name="treatment">Abeloff, Martin et al. (2004), pp. 2835–39.</ref> Other alternatives, including high-dose ara-C alone, may also be used.<ref>Weick JK, Kopecky KJ, Appelbaum FR, et al: A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: A Southwest Oncology Group Study. ''Blood'' 1996;88:2841–2851. PMID 8874180</ref><ref>Bishop JF, Matthews JP, Young GA, et al: A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. ''Blood'' 1996;87:1710–1717. PMID 8634416 </ref> Because of the toxic effects of therapy, including [[myelosuppression]] and an increased risk of infection, induction chemotherapy may not offered to the very elderly. Induction chemotherapy usually requires a hospitalization of about 1 month to receive the chemotherapy and recover from its side effects.
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| Induction chemotherapy is known as "7 and 3" because the [[cytarabine]] is given as a continuous IV infusion for seven consecutive days, while the [[anthracycline]] is given for three consecutive days as an IV push. Up to 70% of patients will achieve a remission with this protocol.<ref>{{cite journal |author=Bishop J |title=The treatment of adult acute myeloid leukemia |journal=Semin Oncol |volume=24 |issue=1 |pages=57–69 |year=1997 |pmid=9045305}}</ref>
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| The M3 subtype of AML, also known as [[acute promyelocytic leukemia]], is almost universally treated with the drug [[ATRA]] (all-''trans''-retinoic acid) in addition to induction chemotherapy.<ref>Huang ME, Ye YC, Chen SR, et al: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. ''Blood'' 1988;72:567–572. PMID 3165295</ref><ref>Tallman MS, Anderson JW, Schiffer CA, et al: All-trans-retinoic acid in acute promyelocytic leukemia. ''N Engl J Med'' 1997;337:1021–1028. PMID 9321529</ref><ref>Fenaux P, Chastang C, Chevret S, et al: A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. ''Blood'' 1999;94:1192–1200. PMID 10438706</ref> Care must be taken to prevent disseminated intravascular coagulation ([[Disseminated intravascular coagulation|DIC]]), complicating the treatment of [[Acute promyelocytic leukemia|APL]] when the promyelocytes release the contents of their granules into the peripheral circulation. [[APL]] is eminently curable with well-documented treatment protocols.
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| The goal of the induction phase is to reach a ''complete remission''. Complete remission does not mean that the disease has been cured; rather, it signifies that no disease can be detected with available diagnostic methods (i.e., <5% leukemic cells remain in the [[bone marrow]]).<ref name="treatment"/> Complete remission is obtained in about 50%–75% of newly diagnosed adults, although this may vary based on the prognostic factors described above.<ref>{{cite journal | author = Estey E | title = Treatment of acute myelogenous leukemia | journal = Oncology (Williston Park) | volume = 16 | issue = 3 | pages = 343–52, 355–6; discussion 357, 362, 365–6 | year = 2002 | pmid = 15046392}}</ref>
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| The durability of remission depends on the prognostic features of the original leukemia. In general, all remissions will fail without consolidation (post-remission) chemotherapy, and consolidation has become an important component of treatment.<ref>{{cite journal |author=Cassileth P, Harrington D, Hines J, Oken M, Mazza J, McGlave P, Bennett J, O'Connell M |title=Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia |journal=J Clin Oncol |volume=6 |issue=4 |pages=583–7 |year=1988 |pmid=3282032}}</ref>
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| ===Consolidation===
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| Even after complete remission is achieved, leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques. If no further ''postremission'' or consolidation therapy is given, almost all patients will eventually relapse.<ref>Cassileth PA, Hines JD, Oken MM, et al: Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia. ''J Clin Oncol'' 1988;6(4):583–587. PMID 3282032</ref> Therefore, more therapy is necessary to eliminate non-detectable disease and prevent relapse — that is, to achieve a cure.
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|
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|
| The specific type of postremission therapy is individualized based on a patient's prognostic factors (see above) and general health. For good-prognosis leukemias (i.e. inv(16), t(8;21), and t(15;17)), patients will typically undergo an additional 3–5 courses of intensive chemotherapy, known as ''consolidation'' chemotherapy.<ref>Mayer RJ, Davis RB, Schiffer CA, et al: Intensive post-remission chemotherapy in adults with acute myeloid leukemia. ''N Engl J Med'' 1994;331:896–903. PMID 8078551</ref><ref name="nccn">O'Donnell MR, Appelbaum FR, Baer MR, et al: NCCN practice guidelines for acute myelogenous leukemia. ''Oncology NCCN Proc'' 2000;14:53–61. PMID 11195419</ref> For patients at high risk of relapse (e.g. those with high-risk cytogenetics, underlying MDS, or therapy-related AML), [[bone marrow transplant|allogeneic stem cell transplantation]] is usually recommended if the patient is able to tolerate a transplant and has a suitable donor. The best postremission therapy for intermediate-risk AML (normal cytogenetics or cytogenetic changes not falling into good-risk or high-risk groups) is less clear and depends on the specific situation, including the age and overall health of the patient, the patient's personal values, and whether a suitable stem cell donor is available.<ref name="nccn"/>
| | ==Case Studies== |
| | [[Acute myeloid leukemia case study one|Case #1]] |
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| ===Relapsed AML=== | | ==Related Chapters== |
| Despite aggressive therapy, however, only 20%–30% of patients enjoy long-term disease-free survival. For patients with relapsed AML, the only proven potentially curative therapy is a [[stem cell transplant]], if one has not already been performed.<ref name="relapse">Abeloff, Martin et al. (2004), pp. 2840–41.</ref><ref>Appelbaum FR: Who should be transplanted for AML? editorial. ''Leukemia'' 2001;15:680–682. PMID 11368380</ref><ref>Appelbaum FR: Hematopoietic cell transplantation beyond first remission keynote Address. ''Leukemia'' 2002;16:157–159. PMID 11840278</ref> In 2000, [[Mylotarg]] (gemtuzumab zogamicin) was approved in the United States for patients aged more than 60 years with relapsed AML who are not candidates for high-dose chemotherapy.<ref>Sievers EL, Larson RA, Stadmauer EA, et al: Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. ''J Clin Oncol'' 2001;19:3244–3254. PMID 11432892</ref>
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| Patients with relapsed AML who are not candidates for stem cell transplantion, or who have relapsed after a stem cell transplant, should be strongly considered for enrollment in a [[clinical trial]], as conventional treatment options are limited. Agents under investigation include cytotoxic drugs such as [[clofarabine]] as well as [[targeted therapy|targeted therapies]] such as [[farnesyltransferase inhibitor|farnesyl transferase inhibitors]], decitabine, and inhibitors of MDR1 (multidrug-resistance protein). Since treatment options for relapsed AML are so limited, another option which may be offered is [[palliative care]].
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| For relapsed acute promyelocytic leukemia (APL), [[arsenic trioxide]] has been tested in trials and approved by the [[Food and Drug Administration]]. Like ATRA, arsenic trioxide does not work with other subtypes of AML.<ref>Soignet SL, Frankel SR, Douer D, et al: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. ''J Clin Oncol'' 2001;19:3852–3860. PMID 11559723</ref>
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| ==See also==
| |
| * [[Chloroma]] | | * [[Chloroma]] |
| * [[Chronic myelogenous leukemia]] | | * [[Chronic myelogenous leukemia]] |
| * [[Acute lymphoblastic leukemia]] | | * [[Acute lymphoblastic leukemia]] |
|
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| ==Further reading==
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| * {{cite book |author = Martin Abeloff |coauthors= James Armitage, John Niederhuber, Michael Kastan, W. Gillies McKenna |title= Clinical Oncology |year= 2004 |publisher= Elsevier Churchill Livingstone |location= St. Louis, Mo. |edition = 3rd. edition |id= ISBN 0-443-06629-9}}
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| * {{cite book |author = Ronald Hoffman |coauthors= Edward Benz, Jr., Sanford Shattil, Bruce Furie, Harvey Cohen, Leslie Silberstein, Philip McGlave |title= Hematology: Basic Principles and Practice |year= 2005 |publisher= Elsevier Churchill Livingstone |location= St. Louis, Mo. |edition = 4th. edition |id= ISBN 0-443-06629-9}}
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|
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| ==References==
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| {{reflist|2}}
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|
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|
| ==External links== | | ==External links== |
|
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| * [http://www.kanbilim.com/dahiliyeatlasi.htm Atlas of Hematology]
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| * [http://www.cancer.org/docroot/CRI/CRI_2_1x.asp?rnav=criov&dt=82 American Cancer Society page on Acute Myeloid Leukemia]
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| * [http://leukemia.acor.org/ Association of Cancer Online Resource (ACOR) Leukemia Links]
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| * [http://www.leukemia-lymphoma.org/all_page?item_id=8459 Leukemia & Lymphoma Society page on Acute Myeloid Leukemia]
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| * [http://www.cchs.net/health/health-info/docs/1400/1403.asp?index=6211 Childhood Acute Myeloid Leukemia]
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| * [http://www.marrow.org National Marrow Donor Program]
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| * [http://www.bmtinfonet.org/ Blood & Marrow Transplant Information Network]
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| * [http://www.cancer.gov/cancer_information/doc.aspx?viewid=4d3f920e-87d6-4b6a-a2fe-74c6efa53398&version=1 National Cancer Institute (NCI) PDQ statement on AML for health professionals] | | * [http://www.cancer.gov/cancer_information/doc.aspx?viewid=4d3f920e-87d6-4b6a-a2fe-74c6efa53398&version=1 National Cancer Institute (NCI) PDQ statement on AML for health professionals] |
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