Acute Myelocytic Leukemia (AML)

Acute myelocytic leukemia is a myeloproliferative disorder characterized by the accumulation of abnormal myeloid precursors in the bone marrow. The disease may be associated with end organ dysfunction resulting from an infiltration with leukemic cells, but mortality is most commonly due to the consequences of bone marrow failure.

Acute Myelocytic Leukemia originates from the following process: neoplastic.

Presentation

AML is associated with progressive bone marrow failure. Accordingly, patients usually present with symptoms related to anemia, granulocytopenia/neutropenia, and thrombocytopenia.

Of note, leukocytosis is not uncommon in AML patients. In the case of hyperleukocytosis (>100 x 109/l), symptoms of leukostasis may manifest. Such symptoms comprise ocular and cerebrovascular hemorrhages and dysfunction [10].

On the other hand, leukemic cells may infiltrate distinct end organs, interfere with their function and cause discomfort or pain. Findings like hepatosplenomegaly (early satiety and abdominal fullness), leukemia cutis (multiple, indolent cutaneous nodules), granulocytic sarcoma (isolated mass of leukemic blasts), and bone pain may thus also indicate AML.

Jaw & Teeth
  • Bleeding Gums Patients may present with bleeding gums and multiple ecchymoses. [source] Symptoms can include: pale skin tiredness breathlessness frequent infections unusual and frequent bleeding, such as bleeding gums or nosebleeds In more advanced cases, AML can make you extremely vulnerable to life-threatening infections or serious internal [source] Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. [source]
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Liver, Gall & Pancreas
  • Hepatosplenomegaly The major clinical manifestations of malaise, hepatosplenomegaly, anemia, and leukocytosis are related to abnormal, excessive, unrestrained overgrowth of granulocytes in the bone marrow. [source] Called also promyelocytic leukemia . adult T-cell leukemia ( adult T-cell leukemia/lymphoma ) a form of leukemia with onset in adulthood, leukemic cells with T-cell properties, frequent dermal involvement, lymphadenopathy and hepatosplenomegaly, and a [source] Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, granulocytopenia with bacterial infections, bone pain, lymphadenopathy, hepatosplenomegaly, and sometimes spread to the central nervous system ( meningism ) or to other organs [source]
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Entire body system
  • Anemia The most common symptom of anemia is fatigue. [source] Symptoms of bone marrow failure Symptoms of bone marrow failure are related to anemia, neutropenia, and thrombocytopenia. [source] Other symptoms of anemia include dyspnea upon exertion, dizziness, and, in patients with coronary artery disease, anginal chest pain. [source]
  • Ecchymosis Low numbers of platelets can lead to petechiae, gingival bleeding, ecchymosis, epistaxis, or menorrhagia. [source]
  • Fatigue The most common symptom of anemia is fatigue[source] Others have a longer course, with fatigue or other symptoms lasting from weeks to months. [source] Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections. [source]
  • Fever Patients generally present with fever, which may occur with or without specific documentation of an infection. [source] Although infections can be of any type, typical symptoms include: Fever Runny nose Cough Chest pain or shortness of breath Pain with urinating Diarrhea, occasionally Infections of the bloodstream, called sepsis, and pneumonia are the most dangerous Reviewed [source] Symptoms of AML include: Fever Shortness of breath Easy bruising or bleeding Bleeding under the skin Weakness or feeling tired Weight loss or loss of appetite Tests that examine the blood and bone marrow diagnose AML. [source]
  • Malaise The major clinical manifestations of malaise, hepatosplenomegaly, anemia, and leukocytosis are related to abnormal, excessive, unrestrained overgrowth of granulocytes in the bone marrow. [source] AML Male gender [5] Systemic Involvement Patients with AML can develop a variety of systemic complications including: - Headache/disorientation - due to abnormal white blood cells infiltrating the CNS - Anemia which is accompanied by pallor, fatigue, malaise [source]
  • Pain Abdominal pain[source] Bone and joint pain[source] This is often mistaken for "growing pains." [source]
  • Pallor Leukemia cutis (multiple purplish papules or diffuse rash) Splenomegaly occurs in 50% of patients Bone discomfort (especially in ribs, sternum, and tibia) Older adults may experience delirium, progressive weakness, and pallor. [2] Associated Co-morbidities [source] close relative with AML Male gender [5] Systemic Involvement Patients with AML can develop a variety of systemic complications including: - Headache/disorientation - due to abnormal white blood cells infiltrating the CNS - Anemia which is accompanied by pallor [source] inhibiting formation of erythrocytes and thrombocytes. - Infections (pneumonia) and mouth/throat ulcerations- Caused by increased numbers of immature or abnormal leukocytes which are unable to fight off infections - Increased metabolic rate with weakness, pallor [source]
  • Recurrent Infection Symptoms of imminent bone marrow failure may be anemia, recurrent infections with opportunistic pathogens and a propensity to bleed. [source] A blood count will show thrombocytopenia, a decreased number of platelets. recurrent infections – Although there may be an unusually high number of white blood cells on your child’s blood count, these white blood cells are immature and do not fight infection [source] In occasional cases symptoms like lymphadenopathy, enlarged tonsils, shifting lameness in legs, ocular tumors and recurrent infections are also seen. [source]
  • Refractory Anemia 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. [source] Blood Disorders : Patients with myelodysplasia (or refractory anemia), polycythemia vera, or essential thrombocythemia have a higher risk of developing AML. [source] The risk of the disease is increased among people who have been exposed to massive doses of radiation and who have certain blood dyscrasias, such as polycythemia, primary thrombocytopenia, and refractory anemia[source]
  • Weakness Symptoms of AML include: Fever Shortness of breath Easy bruising or bleeding Bleeding under the skin Weakness or feeling tired Weight loss or loss of appetite Tests that examine the blood and bone marrow diagnose AML. [source] Immunosuppression : A weak immune system, resulting from an organ transplant, can increase risk. [source] Fatigue, Weakness or Lethargy Skin Lesion or Rash Shortness of Breath : This may also worsen with exercise. [source]
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Face, Head & Neck
  • Epistaxis Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. [source] Low numbers of platelets can lead to petechiae, gingival bleeding, ecchymosis, epistaxis, or menorrhagia. [source]
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neurologic
  • Altered Mental Status Patients with markedly elevated WBC counts ( 100,000 cells/µL) can present with symptoms of leukostasis (ie, respiratory distress and altered mental status). [source]
  • Asthenia Symptoms of Acute myelocytic leukemia Asthenia Pallor Fever Dizziness Respiratory symptoms more symptoms...» [source]
  • Dizziness Other symptoms of anemia include dyspnea upon exertion, dizziness, and, in patients with coronary artery disease, anginal chest pain. [source] These include: anaemia due to a lack of red cells; causing persistent tiredness, dizziness, paleness, or shortness of breath when physically active; frequent or repeated infections and slow healing, due to a lack of normal white cells, especially neutrophils [source] Symptoms of Acute myelocytic leukemia Asthenia Pallor Fever Dizziness Respiratory symptoms more symptoms...» [source]
  • Headache skin bruising easily slurred speech swollen liver swollen lymph nodes (glands) swollen spleen unexplained regular bleeding, of perhaps the nose or gums unexplained weight loss If the affected cells enter the central nervous system (CNS) there may be headaches [source] The symptoms of the anemia may include fatigue, dizziness, headache, paleness of the skin, or, infrequently, congestive heart failure. [source] A patient may experience all or some of the following symptoms: weakness or chronic fatigue fever of unknown origin shortness of breath weight loss that is not due to dieting or exercise frequent bacterial or viral infections headaches skin rash non-specific [source]
  • Lethargy Fatigue, Weakness or Lethargy Skin Lesion or Rash Shortness of Breath : This may also worsen with exercise. [source] Symptoms – The clinical signs may include lethargy, inappetance (lack of appetite), weight loss, emaciation (become extremely thin), pallor (unnatural paleness), petechiation (condition in which there is a purplish spot on the surface), persistent fever [source] CNS leukemia, although less common in AML, can manifest with patient complaints of headache, lethargy, or cranial nerve signs. [source]
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Immune System
  • Splenomegaly Patients with splenomegaly note fullness in the left upper quadrant and early satiety. [source] Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. [source] Symptoms include splenomegaly, monocytosis with granulocytosis, and thrombocytopenia. leukemia cu tis leukemia with leukocytic invasion of the skin marked by pink, reddish brown, or purple macules, papules, and tumors. eosinophilic leukemia a form of [source]
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Skin
  • Night Sweats Night sweats[source] However, the symptoms of all types of leukemia are generally the same and include: fatigue (tiredness) and weakness swollen lymph nodes infections (like bronchitis or tonsillitis ) that keep coming back fever night sweats easy bruising or petechiae (tiny [source]
  • Petechiae They include black-and-blue marks or bruises occurring for no reason or because of a minor injury, the appearance of pin-head sized spots under the skin, called petechiae, or prolonged bleeding from minor cuts. [source] However, the symptoms of all types of leukemia are generally the same and include: fatigue (tiredness) and weakness swollen lymph nodes infections (like bronchitis or tonsillitis ) that keep coming back fever night sweats easy bruising or petechiae (tiny [source] Cutaneous hemorrhages ranging from petechiae to extensive ecchymoses may be noted. [source]
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respiratoric
  • Dyspnea Other symptoms of anemia include dyspnea upon exertion, dizziness, and, in patients with coronary artery disease, anginal chest pain. [source] Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. [source] Acute leukemia is characterized by fatigue, headache, sore throat, and dyspnea, followed by symptoms of acute tonsillitis, stomatitis, bleeding from the mucous membranes of the mouth, alimentary canal, and rectum, and pain in the bones and joints. [source]
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gastrointestinal
  • Abdominal Fullness Findings like hepatosplenomegaly (early satiety and abdominal fullness), leukemia cutis (multiple, indolent cutaneous nodules), granulocytic sarcoma (isolated mass of leukemic blasts), and bone pain may thus also indicate AML. [source] fullness A small minority of patients with AML have a tumor of leukemic cells at diagnosis. [source] shortness of breath weight loss that is not due to dieting or exercise frequent bacterial or viral infections headaches skin rash non-specific bone pain easy bruising bleeding from gums or nose blood in urine or stools enlarged lymph nodes and/or spleen abdominal [source]
  • Diarrhea Although infections can be of any type, typical symptoms include: Fever Runny nose Cough Chest pain or shortness of breath Pain with urinating Diarrhea, occasionally Infections of the bloodstream, called sepsis, and pneumonia are the most dangerous Reviewed [source] They can include: hair loss nausea diarrhea severe infections With intensive chemotherapy, admitting the patient to the hospital for around a week can help manage the side effects. [source] At the completion of induction I chemotherapy, patients were discharged regardless of the neutrophil counts or platelet counts if patients appeared clinically stable and well without fever and had no severe nausea/vomiting, diarrhea, abdominal pain, or [source]
  • Early Satiety Patients with splenomegaly note fullness in the left upper quadrant and early satiety[source] Findings like hepatosplenomegaly (early satiety and abdominal fullness), leukemia cutis (multiple, indolent cutaneous nodules), granulocytic sarcoma (isolated mass of leukemic blasts), and bone pain may thus also indicate AML. [source]
  • Hematochezia Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. [source]
  • Loss of Appetite Symptoms of AML include: Fever Shortness of breath Easy bruising or bleeding Bleeding under the skin Weakness or feeling tired Weight loss or loss of appetite Tests that examine the blood and bone marrow diagnose AML. [source] This pain may lead to loss of appetite and weight loss. [source] Symptoms of AML include: Fever Shortness of breath Easy bruising or bleeding Bleeding under the skin Weakness or feeling tired Weight loss or loss of appetite Tests that examine the blood and bone marrow diagnose AML. [source]
  • Melena Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. [source]
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musculoskeletal
  • Back Pain In addition, the physician may examine the teeth and look for dental abscesses, and may explore whether back pain is present. [source]
  • Bone Pain Patients with a high leukemic cell burden may present with bone pain caused by increased pressure in the bone marrow. [source] Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. [source] Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, granulocytopenia with bacterial infections, bone pain, lymphadenopathy, hepatosplenomegaly, and sometimes spread to the central nervous system ( meningism ) or to other organs [source]
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cardiovascular
  • Chest Pain Other symptoms of anemia include dyspnea upon exertion, dizziness, and, in patients with coronary artery disease, anginal chest pain[source] Although infections can be of any type, typical symptoms include: Fever Runny nose Cough Chest pain or shortness of breath Pain with urinating Diarrhea, occasionally Infections of the bloodstream, called sepsis, and pneumonia are the most dangerous Reviewed [source] Other symptoms may include bone pain, swollen lymph nodes, swollen gums, chest pain and abdominal discomfort due to a swollen spleen or liver. [source]
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urogenital
  • Hematuria Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria[source]
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Ears

Workup

Laboratory analyses of blood samples including a complete cell count with differential count are generally the first step towards the diagnosis of AML. Indeed, the incidental detection of hematological anomalies that precede the onset of clinical symptoms is not uncommon in older patients undergoing routine screenings and may allow for an early diagnosis of leukemia and a timely initiation of treatment. Pancytopenia or any combination of anemia, granulocytopenia, and thrombocytopenia are often observed and may indicate imminent or existing bone marrow failure. As has been mentioned above, leukocytosis and even hyperleukocytosis may also be observed.

Subsequently, an aspiration of bone marrow needs to be performed. Immunohistochemical staining for myeloperoxidase expression or immunophenotyping of bone marrow blasts should be performed to confirm the involvement of the myeloid lineage. In general, the presence of more than 20% leukemic blasts in bone marrow specimens is required for the diagnosis of AML [11]. Furthermore, samples should be analyzed regarding their cytogenetic and molecular features. A detailed characterization of blasts is necessary for prognostic and therapeutic reasons.

In order to prevent and identify possible complications of AML, a comprehensive metabolic profile, as well as coagulation studies, should be ordered. Diagnostic imaging may be indicated to assess the condition of the patient's heart, lungs and possible central nervous system involvement.

Pathology

Biopsy

Laboratory

Serum
  • Decreased Platelet Count platelet count, and anemia due to decreased erythrocyte count. [source] Of primary concern are those symptoms attendant to suppression of normal bone marrow function, particularly susceptibility to infection due to the predominance of immature and abnormally functioning white blood cells, bleeding tendency owing to decreased [source]
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Urine
Cerebrospinal Fluid

Imaging

X-ray

Treatment

Cytotoxic chemotherapy and hematopoietic stem cell transplantation are the mainstays of therapy. Distinct chemotherapeutic regimens have been used in AML patients, but the standard induction therapy consists of anthracyclines (e.g., daunorubicin at a minimum dose of 60 mg/m², idarubicin at a dose of approximately 10 mg/m², for three days) and cytarabine (at a dose of up to 200 mg/m², for seven days) [11]. Such treatment should be initiated as soon as possible and leads to complete remission in the majority of adults aged less than 60 years. Older patients known to have adverse cytogenetics may be considered for alternative approaches, e.g., investigational regimens or mild cytoreductive therapy.

Post-remission strategies include intense chemotherapy with high-dose cytarabine, prolonged maintenance treatment, as well as autologous and allogeneic stem cell transplantation. Precise recommendations depend on prior risk assessment and genetic features displayed by clonal tumor cells. For instance, allogeneic stem cell transplantation is associated with the lowest rates of recurrence, but also with high treatment-related mortality. Thus, it is typically considered for high-risk AML patients if a matched donor is available.

Patients presenting with bone marrow failure should be stabilized before further therapeutic measures are undertaken. Here, medical care may include the transfusion of blood products, antimicrobial therapy, and leukapheresis, as needed. AML treatment may be restricted to palliative measures in patients suffering from severe comorbidities.

It is beyond the scope of this article to discuss target-oriented therapy for individual types of AML, but excellent reviews on this topic are available elsewhere [12].

Prognosis

AML is generally associated with an unfavorable prognosis; if left untreated, it is uniformly fatal. Despite the provision of optimum medical care, most patients die from bone marrow failure. Five years after diagnosis, only 21% of AML patients remain alive, but this value is highly age-dependent: More than half of AML patients aged less than 45 years survive for more than five years, in contrast to less than 10% of those aged 65 years and older [7].

It is important to note that median survival times observed in patients diagnosed with distinct subtypes of AML vary largely [8]:

  • Translocations t(8;21)(q22;q22), t(15;17)(q24;q21), and inv(16)(p13;q22) are associated with a favorable prognosis and a 5-year-survival rate of 55%.
  • Patients with AML and normal cytogenetics constitute the largest subgroup and are usually assigned an intermediate prognosis; their 5-year-survival rates range between 24 and 42%. Here, the identification of genetic abnormalities of malignant cells may allow for a more reliable prognosis. The interested reader is referred to an extensive review on this topic [9].
  • Monosomy 5 or 7, 11q23 rearrangements and complex chromosomal aberrations are related to a poor prognosis; the respective 5-year-survival rate is only 11%.

Complications

  • Acute Leukemia AML is the most common type of acute leukemia in adults. [source] , Leukemia, Myelogenous, Acute , Leukemias, Acute Myeloblastic , Myelocytic Leukemias, Acute , Myeloid Leukemia, Acute , Leukemia, Acute Myeloblastic , Leukemia, Nonlymphoblastic, Acute , Leukemia, Myeloid, Acute , Myeloblastic Leukemia, Acute , Myelocytic [source] , leukemia; granulocytic, acute , leukemia; myelocytic, acute , leukemia; myeloid, acute , myelocytic; leukemia, acute , myeloid; leukemia, acute , Acute Myelogenous Leukemias , Acute Nonlymphocytic Leukemia , Acute Myeloblastic Leukemia , Acute Myelocytic [source]
  • Agranulocytosis considerations for patients with AML: Acute Lymphoblastic Leukemia (ALL) Agnogenic Myeloid Metaplasia with Myelofibrosis Anemia Aplastic Anemia Bone Marrow Failure Chronic Myelogenous Leukemia Lymphoma, B-cell Lymphoma, Lymphoblastic Myelodysplastic Syndrome Agranulocytosis [source]
  • Aleukemic Leukemia This is referred to as aleukemic leukemia[source]
  • Basophilia Blasts were smaller, with a predominance of small cells, scanty cytoplasm, moderate cytoplasmic basophilia, and variable cytoplasmic vacuolation. [source] In contrast to the previous neoplasm, the blasts in the current specimen were smaller, with a predominance of small cells, scanty cytoplasm, moderate cytoplasmic basophilia, and variable cytoplasmic vacuolation (Figure 3 ), along with the immunophenotype [source] Alsabeh R, Brynes RK, Slovak ML, et al.: Acute myeloid leukemia with t(6;9) (p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype. [source]
  • Bleeding Diathesis A general bleeding diathesis may be the result of thrombocytopenia. [source]
  • Disseminated Intravascular Coagulation Bleeding may be caused by thrombocytopenia, coagulopathy that results from disseminated intravascular coagulation (DIC), or both. [source] In APL and some other cases of AML, disseminated intravascular coagulation (DIC) may be present when leukemia is diagnosed and may worsen as leukemic cell lysis releases procoagulant. [source] Bleeding and blood clotting problems, such as disseminated intravascular coagulation (DIC), are commonly seen with this form of leukemia. [source]
  • Eosinophilia Good responses are observed after treatment with retinoids, which are drugs chemically related to vitamin A. myelomonocytic leukemia (M4 or M4 variant with eosinophilia [M4E] )—The bone marrow and circulating blood have variable amounts of differentiated [source] Whilst the majority of inv(16)(p13q22) have been identified as AML M4EO, this abnormality may occasionally been seen in other myeloid malignancies, including AML M2, M4 without eosinophilia, M5 and MDS. [source] leukemia with maturation 25% t(8;21) (called 8 21 translocation) M3 Acute promyelocytic leukemia 10% t(15;17) (called 15 17 translocation) t(11;17) t(5;17) M4 Acute myelomonocytic leukemia 20% Inversion 16 t(6;11) M4eos Acute myelomonocytic leukemia with eosinophilia [source]
  • Gingivitis Gingivitis due to neutropenia can cause swollen gums, and thrombocytopenia can cause the gums to bleed. [source] Upper respiratory infection or pneumonia and gingivitis/stomatitis are most frequently reported. [source] Low numbers of platelets can lead to petechiae, gingival bleeding, ecchymosis, epistaxis, or menorrhagia. [source]
  • Hyperuricemia leukocytes which are unable to fight off infections - Increased metabolic rate with weakness, pallor, and weight loss- Caused by increased leukocyte production which require increased nutrient production; destruction of cells also increases metabolic waste - Hyperuricemia [source]
  • Leukocytosis Of note, leukocytosis is not uncommon in AML patients. [source] As has been mentioned above, leukocytosis and even hyperleukocytosis may also be observed. [source] Diagnostic methods Diagnosis relies on laboratory findings showing anemia, thrombocytopenia and leucopenia or leukocytosis which result from disturbed hematopoietic function due to bone marrow and peripheral blood infiltration by immature blast cells. [source]
  • Leukostasis Leukostasis is a medical emergency that calls for immediate intervention. [source] Patients with markedly elevated WBC counts ( 100,000 cells/µL) can present with symptoms of leukostasis (ie, respiratory distress and altered mental status). [source] In the case of hyperleukocytosis (>100 x 109/l), symptoms of leukostasis may manifest. [source]
  • Stomatitis Acute leukemia is characterized by fatigue, headache, sore throat, and dyspnea, followed by symptoms of acute tonsillitis, stomatitis, bleeding from the mucous membranes of the mouth, alimentary canal, and rectum, and pain in the bones and joints. [source] Upper respiratory infection or pneumonia and gingivitis/stomatitis are most frequently reported. [source]
  • Thrombocytopenia Gingivitis due to neutropenia can cause swollen gums, and thrombocytopenia can cause the gums to bleed. [source] Symptoms of bone marrow failure Symptoms of bone marrow failure are related to anemia, neutropenia, and thrombocytopenia[source] Bleeding may be caused by thrombocytopenia, coagulopathy that results from disseminated intravascular coagulation (DIC), or both. [source]
  • Thrombocytosis Evidence Based Medicine Research for Acute myelocytic leukemia Medical research articles related to Acute myelocytic leukemia include: Thrombocytosis (Overview) Thrombocytosis (Treatment) Hematopoietic Stem Cell Transplantation (Overview) Acute Myeloid [source] In a more recent report a dog was diagnosed with primary thrombocytosis[source] Essential Thrombocythemia Hydroxyurea is the drug of choice for treating thrombocytosis[source]
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Etiology

AML is the result of anomalies in hematopoietic cell differentiation and proliferation. These are essentially due to chromosomal aberrations that are discussed in detail below. Both endogenous and exogenous factors may contribute to the malignant transformation of myeloid precursors. In this context, the following risk factors have been identified [2]:

Causes

  • Myocardial Infarction In fact, myocardial infarction may be the first presenting symptom of acute leukemia in an older patient. [source] Due to the high prevalence of atherosclerosis in the older population, myocardial infarction because of leukemia-related anemia is not uncommon. [source]
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Epidemiology

AML is the most common acute leukemia in adults, and about 20,000 cases are diagnosed each year in the United States alone [3]. The latter corresponds to an annual incidence of about 1 in 15,000 inhabitants, and similarly, high incidence rates have only been reported in Europe and Australia [4]. Age-specific incidence rates follow a bimodal distribution: Infants and young children are more likely to develop AML than older children and young adults, while highest incidence rates are observed in the elderly population. Accordingly, the patients' median age at symptom onset is 65 years. People age 65 years and older have a tenfold increased risk of developing AML when compared with young adults [2]. Moreover, incidence rates depend on race and gender. For instance, Caucasians are more prone to develop AML at very young ages compared to patients of African descent, while the disease is more frequently diagnosed in older black children and adolescents. Males are affected slightly more often than females.

Sex distribution
Age distribution

Pathophysiology

Only a minor proportion of cases can unequivocally be related to either of the above -mentioned risk factors. Indeed, AML is most likely not the result of a single event or gene defect, but the consequence of a susceptible myeloid precursor being subjected to additional influences that induce leukemogenesis. According to the so-called "2-hit-hypothesis", a first mutation confers a proliferative and survival advantage to the respective cell. Only subsequent rearrangements provoke the onset of leukemia: They result in a maturation arrest and reduced apoptosis [5]. The molecular mechanisms underlying this development vary depending on the precise chromosomal aberration(s) and environmental factor(s). The heterogeneity of leukemogenesis is best illustrated by the diversity of acquired cytogenetic anomalies that may be detected in bone marrow specimens obtained from AML patients:

  • Partial or complete loss of chromosomes 5 or 7
  • Trisomy 8 or 21
  • Translocations t(8;21)(q22;q22), t(15;17)(q24;q21), t(16;16)(p13;q22), inv(16)(p13;q22)
  • 11q23 rearrangements

As the presence of genetic features is of prognostic and therapeutic relevance, the identification of recurrent genetic abnormalities constitutes the basis of modern AML classification [6]. Furthermore, AML may be related to Down syndrome, myelodysplasia or prior chemotherapy. It is important to note that the current World Health Organization classification of myeloid neoplasms and acute leukemia additionally lists AML, not otherwise specified, as a subtype of AML.

Prevention

According to the information given above, avoidance of risk factors may be of help to prevent AML. Corresponding measures may include refraining from tobacco consumption and reducing the exposure to radiation and chemical carcinogens, inter alia by implementing occupational safety standards.

Summary

The term acute myelocytic leukemia (AML), possibly also referred to as acute myeloid leukemia or acute myelogenous leukemia, describes a group of myeloproliferative disorders. In all types of AML, malignant transformation of myeloid precursor cells is associated with a maturation arrest and impaired apoptosis. This may affect precursors of granulocytes, monocytes, mast cells, erythrocytes or platelets. With regards to the prevailing stage of degenerated blasts, the following subtypes of AML may be distinguished (French-American-British classification, [1]):

  • Acute myeloblastic leukemia
  • Acute promyelocytic leukemia
  • Acute myelomonocytic leukemia
  • Acute monoblastic leukemia
  • Acute monocytic leukemia
  • Acute erythroid leukemia
  • Acute megakaryoblastic leukemia
  • Mixed lineage leukemia (both myeloproliferative and lymphoproliferative features)

In any case, the clonal population of tumor cells interferes with bone marrow function and hematopoiesis. Affected individuals thus tend to develop pancytopenia and present with symptoms consistent with anemia, immunodeficiency and a propensity to bleed. To date, treatment of AML mainly consists of non-specific measures like cytotoxic chemotherapy and hematopoietic stem cell transplantation. Unfortunately, this approach continues to be related to poor survival rates.

Recent studies shed more light on the molecular mechanisms underlying leukemogenesis in single types of AML and emphasize the need for a personalized, target-oriented therapy. Treatment recommendations are thus to be expected to change in the near future.

Patient Information

Acute myelocytic leukemia (AML), sometimes also referred to as acute myeloid leukemia, is a myeloproliferative disorder and hematological malignancy. It is characterized by an excess proliferation of myeloid precursors in the bone marrow. These cells originate from hematopoietic stem cells and are supposed to differentiate into red blood cells, white blood cells and platelets. Because the development of these cell populations involves distinct intermediate stages, patients may suffer from different subtypes of AML. Acute promyelocytic leukemia, for instance, is defined as an accumulation of abnormal promyelocytes, which are granulocyte precursors. In any case, the presence of abundant tumor cells in the bone marrow interferes with this organ's function and hematopoiesis. Eventually, this condition may lead to bone marrow failure. Symptoms of imminent bone marrow failure may be anemia, recurrent infections with opportunistic pathogens and a propensity to bleed.

Although several endogenous and exogenous factors have been related to the onset of AML, the etiology of this type of blood cancer remains poorly understood. Few cases are related to Down syndrome, Klinefelter syndrome, myelodysplasia, prior cytotoxic chemotherapy, as well as exposure to chemical carcinogens and radiation, but in the majority of patients, causes cannot be identified. In order to diagnose AML, bone marrow specimens have to be analyzed. A detailed characterization of tumor cells is necessary for prognostic and therapeutic reasons. To date, treatment primarily consists of cytotoxic chemotherapy and hematopoietic stem cell transplantation, but more specific approaches may be feasible in certain types of AML. To summarize, an individual patient's prognosis depends on the type of AML, on the genetic features displayed by degenerated myeloid precursors, on the patient's age and overall condition, and the involvement of extramedullary sites.

Self-assessment

References

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  3. De Kouchkovsky I, Abdul-Hay M. 'Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016; 6(7):e441.
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  5. Müller AM, Duque J, Shizuru JA, Lubbert M. Complementing mutations in core binding factor leukemias: from mouse models to clinical applications. Oncogene. 2008; 27(44):5759-5773.
  6. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20):2391-2405.
  7. Pulte D, Gondos A, Brenner H. Expected long-term survival of patients diagnosed with acute myeloblastic leukemia during 2006-2010. Ann Oncol. 2010; 21(2):335-341.
  8. Riva L, Luzi L, Pelicci PG. Genomics of acute myeloid leukemia: the next generation. Front Oncol. 2012; 2:40.
  9. Gregory TK, Wald D, Chen Y, Vermaat JM, Xiong Y, Tse W. Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics. J Hematol Oncol. 2009; 2:23.
  10. Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med. 1999; 341(14):1051-1062.
  11. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010; 115(3):453-474.
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