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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.

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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.

Splenomegaly
  • Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. AML occurs most frequently in adolescents and young adults.[medical-dictionary.thefreedictionary.com]
  • […] blood progenitor cell mobilization and collection are bone pain, pyrexia, increased blood alkaline phosphatase, and headache with severe chronic neutropenia are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly[neupogenhcp.com]
  • Laboratory and physical findings include enlarged spleen (splenomegaly), a high white blood cell count, and absent or low amounts of the white blood cell enzyme alkaline phosphatase. Like other forms of leukemia, CML is not "staged."[healthcommunities.com]
  • It is characterized by the absence of hepatomegaly and splenomegaly. Their involvement suggests the origin of AML as a result of a complication of a pre-existing myeloproliferative disorder.[lecturio.com]
Dyspnea
  • Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. AML occurs most frequently in adolescents and young adults.[medical-dictionary.thefreedictionary.com]
  • Anemia manifests in the form of pallor, fatigue, weakness, dizziness, dyspnea on exertion, and possibly chest pain.[symptoma.com]
  • Other symptoms of anemia include dyspnea on exertion; dizziness; and, in patients with coronary artery disease, anginal chest pain. In fact, myocardial infarction may be the first presenting symptom of acute leukemia in an older patient.[emedicine.medscape.com]
  • Patients presenting with symptoms due to the failure of other cell lines often appear with symptomatic anemia (fatigue, dyspnea on exertion, and/or weakness) or petechiae and mucosal bleeding from thrombocytopenia.[clinicaladvisor.com]
Fever
  • A patient with acute nonlymphocytic leukemia developed progressive lung infiltrates and unremitting fevers during a profound neutropenic state.[ncbi.nlm.nih.gov]
  • […] administration of NEUPOGEN Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture Acute Respiratory Distress Syndrome (ARDS) ARDS has been reported in patients receiving NEUPOGEN Evaluate patients who develop fever[neupogenhcp.com]
  • Review Topic QID: 106506 M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.ON.49) A 62-year-old female presents to your office with a sore throat, low-grade fever, and bleeding gums.[step1.medbullets.com]
  • Symptoms include fatigue, pallor, easy bruising and bleeding, fever, and infection; symptoms of extramedullary leukemic infiltration are present in only about 5% of patients (often as skin manifestations).[msdmanuals.com]
  • Recurrent fevers/infections. The child with leukemia often shows non-specific symptoms of infection such as fever and fatigue.[chop.edu]
Anemia
  • However, it is not clear whether this autoantibody in AML patients induces frank hemolysis (autoimmune hemolytic anemia, AIHA), as seen in lymphoid neoplasms.[ncbi.nlm.nih.gov]
  • Pirofsky B (1968) Autoimmune hemolytic anemia and neoplasia of the reticuloendothelium. Ann Intern Med 68:109–121 Google Scholar 13. Pirofsky B (1969) Autoimmunization and the autoimmune hemolytic anemias.[link.springer.com]
  • Cytogenetic investigation of the bone marrow cells of an 88-year-old woman with refractory anemia with an excess of blasts in transformation with progression to acute myelocytic leukemia (AML), FAB classification M4, revealed a deleted chromosome #8 with[ncbi.nlm.nih.gov]
  • Accordingly, patients usually present with symptoms related to anemia, granulocytopenia/neutropenia, and thrombocytopenia. Anemia manifests in the form of pallor, fatigue, weakness, dizziness, dyspnea on exertion, and possibly chest pain.[symptoma.com]
  • This leads to a loss of normal bone marrow function and associated complications of bleeding, anemia, and infection. The incidence of AML increases with age, peaking in the sixth decade of life.[ncbi.nlm.nih.gov]
Pain
  • […] severe chronic neutropenia are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary tract infection, epistaxis, chest pain, diarrhea, hypoesthesia,[neupogenhcp.com]
  • Bone and joint pain. Pain in bones and joints is usually a result of the bone marrow being crowded with leukemic blasts. This is often mistaken for "growing pains." Recurrent fevers/infections.[chop.edu]
  • Additionally, the patient will need relief from pain and discomfort arising from enlargement of the lymph nodes and distention of the liver and spleen.[medical-dictionary.thefreedictionary.com]
  • Joint Pain Joint pain occurs due to the presence of increased deposition of uric acid in the joints resulting in gout . There is also a feasibility of the joint synovial infiltration by the neoplastic cells, resulting in the joint pain.[lecturio.com]
Fatigue
  • Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections.[medical-dictionary.thefreedictionary.com]
  • Review Topic QID: 106974 M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.ON.72) A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months.[step1.medbullets.com]
  • Symptoms include fatigue, pallor, easy bruising and bleeding, fever, and infection; symptoms of extramedullary leukemic infiltration are present in only about 5% of patients (often as skin manifestations).[msdmanuals.com]
  • Symptoms include: Unexplained and persistent fever Marked fatigue and weakness Unexpected weight loss with poor appetite Easy bruising or bleeding.[drugs.com]
Weakness
  • Review Topic QID: 106974 M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.ON.72) A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months.[step1.medbullets.com]
  • Immunosuppression : A weak immune system, resulting from an organ transplant, can increase risk.[knowcancer.com]
  • Symptoms include: Unexplained and persistent fever Marked fatigue and weakness Unexpected weight loss with poor appetite Easy bruising or bleeding.[drugs.com]
  • The symptoms of all types of leukemia are generally the same and include: being very tired and weak swollen gums swollen lymph glands (or nodes) infections (like bronchitis or tonsillitis ) that keep coming back a fever night sweats easy bruising or petechiae[kidshealth.org]
Loss of Appetite
  • […] of appetite Frequent infections, because the body’s normal immune system cells are crowded out by cancer cells The signs and symptoms of leukemia are the same as more common childhood illnesses, such as colds or flu, and many children are treated for[curesearch.org]
  • This pain may lead to loss of appetite and weight loss. Swollen lymph nodes. Lymph nodes filter the blood. Leukemia cells often collect in the nodes, causing swelling.[chop.edu]
  • This may include fever, tiredness, loss of appetite and shortness of breath.[aamds.org]
  • […] of appetite Unexplained weight loss Pain or aches in your bones or joints Swollen abdomen Swollen lymph nodes in your neck, underarm, groin or stomach Headaches, dizziness Vomiting Diagnosing AML If your doctor suspects you may have leukemia, they will[seattlecca.org]
Diarrhea
  • , oropharyngeal pain, and alopecia with AML are epistaxis, back pain, pain in extremity, erythema, ras h maculo-papular, diarrhea, constipation, and transfusion reaction with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT[neupogenhcp.com]
  • Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4).[ascopost.com]
  • Adverse events were as expected and included nausea, diarrhea and vomiting, febrile neutropenia, and hypokalemia.[aacr.org]
  • 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[ucsfhealth.org]
  • After an episode of fever, abdominal pain, and diarrhea, antibiotic therapy was conducted. As the bone marrow examination showed persisting infiltration, we indicated cycle 1 and 2 to myeloid leukemia (described above).[casesjournal.biomedcentral.com]
Early Satiety
  • 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.[symptoma.com]
  • Patients with splenomegaly note fullness in the left upper quadrant and early satiety. Patients with gum infiltration often present to their dentist first.[emedicine.medscape.com]
  • satiety (splenomegaly) Family history of AML (Fanconi, Bloom or Kostmann syndromes or ataxia telangiectasia) History of cancer (exposure to alkylating agents, radiation, topoisomerase II inhibitors) Occupational exposures (radiation, benzene, petroleum[slideshare.net]
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.[symptoma.com]
  • fullness A small minority of patients with AML have a tumor of leukemic cells at diagnosis.[encyclopedia.com]
Melena
  • Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. Cutaneous hemorrhages ranging from petechiae to extensive ecchymoses may be noted. Of note, leukocytosis is not uncommon in AML patients.[symptoma.com]
  • Pot apare hemoragii severe ce pot pune viata pacientului in pericol : hemoptizii, hematemeza, melena, hemoragii la nivelul SNC. 2.[clinicaoncologieseverin.ro]
Bleeding Gums
  • Review Topic QID: 106506 M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.ON.49) A 62-year-old female presents to your office with a sore throat, low-grade fever, and bleeding gums.[step1.medbullets.com]
  • Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. AML occurs most frequently in adolescents and young adults.[medical-dictionary.thefreedictionary.com]
  • Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. Cutaneous hemorrhages ranging from petechiae to extensive ecchymoses may be noted. Of note, leukocytosis is not uncommon in AML patients.[symptoma.com]
  • 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[nhs.uk]
Chest Pain
  • pain, diarrhea, hypoesthesia, and alopecia Please see the full Prescribing Information for NEUPOGEN .[neupogenhcp.com]
  • Anemia manifests in the form of pallor, fatigue, weakness, dizziness, dyspnea on exertion, and possibly chest pain.[symptoma.com]
  • 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[ucsfhealth.org]
  • Other symptoms of anemia include dyspnea on exertion; dizziness; and, in patients with coronary artery disease, anginal chest pain. In fact, myocardial infarction may be the first presenting symptom of acute leukemia in an older patient.[emedicine.medscape.com]
Tachycardia
  • Physical Examination Ecchymosis and oozing from IV sites (DIC, possible acute promyelocytic leukemia) Fever and tachycardia (signs of infection) Papilledema, retinal infiltrates, cranial nerve abnormalities (CNS leukemia) Poor dentition, dental abscesses[slideshare.net]
Hepatosplenomegaly
  • In all three patients, radionuclide imaging with technetium-99m sulfur colloid showed hepatosplenomegaly, decreased liver uptake, and increased splenic activity.[ncbi.nlm.nih.gov]
  • The major clinical manifestations of malaise, hepatosplenomegaly, anemia, and leukocytosis are related to abnormal, excessive, unrestrained overgrowth of granulocytes in the bone marrow.[medical-dictionary.thefreedictionary.com]
  • On exam, he has bilateral submandibular lymphadenopathy and hepatosplenomegaly. CBC demonstrates decreased RBCs and mature WBCs.[step1.medbullets.com]
  • 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.[symptoma.com]
Hepatomegaly
  • Multivariate analysis showed that grades 1 or 2 GVHD (P .008) and no hepatomegaly at diagnosis (P .014) were associated with improved relapse-free survival (RFS).[ncbi.nlm.nih.gov]
  • The clinical presentation was similar in all three, with acute onset of hepatomegaly and thrombocytopenia in the absence of significant transaminasemia or icterus.[ncbi.nlm.nih.gov]
  • It is characterized by the absence of hepatomegaly and splenomegaly. Their involvement suggests the origin of AML as a result of a complication of a pre-existing myeloproliferative disorder.[lecturio.com]
  • Liver failure or jaundice with hepatomegaly and/or splenomegaly is also possible from leukemic invasion of the organs, though hepatomegaly and splenomegaly are much less common with AML than with other hematologic malignancies.[clinicaladvisor.com]
  • Datorita infiltratiei organelor cu celule leucemice pot apre splenomegalie, hepatomegalie si mai rar adenopatii. Rar pacientii pot prezenta rash tegumentar datorita infiltratiei tegumentului cu celule leucemice.[clinicaoncologieseverin.ro]
Bone Pain
  • pain, pyrexia, increased blood alkaline phosphatase, and headache with severe chronic neutropenia are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary[neupogenhcp.com]
  • […] there are a decreased number of healthy white blood cells , known as neutropenia Bruising or bleeding from decreased platelets, known as thrombocytopenia Petechiae , a rash of tiny red spots caused by low platelet levels (platelets help stop bleeding) Bone[curesearch.org]
  • Typical symptoms are spongy and bleeding gums, anemia, fatigue, fever, dyspnea, moderate splenomegaly, joint and bone pain, and repeated infections. AML occurs most frequently in adolescents and young adults.[medical-dictionary.thefreedictionary.com]
  • Signs and symptoms of acute myelogenous leukemia include: Fever Bone pain Lethargy and fatigue Shortness of breath Pale skin Frequent infections Easy bruising Unusual bleeding, such as frequent nosebleeds and bleeding from the gums When to see a doctor[mayoclinic.org]
  • Bone Pain or Tenderness Gum Swelling : This symptom is rare Acute Myeloid Leukemia Diagnosis If symptoms for acute myeloid leukemia persist, a doctor may recommend several tests: Physical Exam : A swollen liver, spleen or lymph nodes may be indicative[knowcancer.com]
Back Pain
  • , sepsis, bronchitis, and insomnia undergoing peripheral blood progenitor cell mobilization and collection are bone pain, pyrexia, increased blood alkaline phosphatase, and headache with severe chronic neutropenia are arthralgia, bone pain, back pain,[neupogenhcp.com]
  • The presence of back pain indicates sarcomatous changes in the spine. Pancytopenia This is the predominant cause of the majority of the symptoms in AML.[lecturio.com]
  • In addition, the physician may examine the teeth and look for dental abscesses, and may explore whether back pain is present.[encyclopedia.com]
  • pain, lower extremity weakness [spinal granulocytic sarcoma, most likely in t(8;21) patients] 17.[slideshare.net]
Arthralgia
  • […] thrombocytopenia, anemia, hypertension, sepsis, bronchitis, and insomnia undergoing peripheral blood progenitor cell mobilization and collection are bone pain, pyrexia, increased blood alkaline phosphatase, and headache with severe chronic neutropenia are arthralgia[neupogenhcp.com]
Petechiae
  • […] of red blood cells , known as anemia Fever due to the disease itself or from infection because there are a decreased number of healthy white blood cells , known as neutropenia Bruising or bleeding from decreased platelets, known as thrombocytopenia Petechiae[curesearch.org]
  • 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.[diagnose-me.com]
  • […] include: A pale complexion from anemia caused by a low red cell count Prolonged bleeding and easy bruising caused by a very low platelet count called thrombocytopenia , which may also include the appearance of pinhead-size red spots on the skin called petechiae[aamds.org]
  • The symptoms of all types of leukemia are generally the same and include: being very tired and weak swollen gums swollen lymph glands (or nodes) infections (like bronchitis or tonsillitis ) that keep coming back a fever night sweats easy bruising or petechiae[kidshealth.org]
Purpura
  • Purpura is characterized by flat bruises that are larger than petechiae but smaller than ecchymoses. Signs relating to organ infiltration with leukemic cells include hepatosplenomegaly and, to a lesser degree, lymphadenopathy.[emedicine.medscape.com]
  • Extensive purpura is present on the soles of a patient with acute promyelocytic leukemia and DIC 47.[slideshare.net]
  • Ghauri RI, Naveed M, Mannan J: Congenital amegakaryocytic thrombocytopenic purpura (CAMT). J Coll Physicians Surg Pak 24 (4): 285-7, 2014.[northshore.org]
Night Sweats
  • The symptoms of all types of leukemia are generally the same and include: being very tired and weak swollen gums swollen lymph glands (or nodes) infections (like bronchitis or tonsillitis ) that keep coming back a fever night sweats easy bruising or petechiae[kidshealth.org]
  • Symptoms of chronic myelogenous leukemia include fever, night sweats, and feeling tired. Sometimes chronic myelogenous leukemia does not cause any symptoms.[cdc.gov]
  • Chronic phase, which lasts for approximately 3 years if untreated, usually presents with symptoms secondary to hyperleukocytosis such as weakness, fever, night sweats, bone pain, respiratory distress, priapism, left upper quadrant pain (splenomegaly),[northshore.org]
Epistaxis
  • […] blood alkaline phosphatase, and headache with severe chronic neutropenia are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary tract infection, epistaxis[neupogenhcp.com]
  • Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. Cutaneous hemorrhages ranging from petechiae to extensive ecchymoses may be noted. Of note, leukocytosis is not uncommon in AML patients.[symptoma.com]
  • The symptoms include general weakness, increased infections and episodes of bleeding, especially from the gums and epistaxis. Increased fatigue and weakness is attributed to anemia and usually precedes AML.[lecturio.com]
Hematuria
  • […] fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim products Discontinue NEUPOGEN if sickle cell crisis occurs Glomerulonephritis Has occurred in patients receiving NEUPOGEN Diagnoses were based on azotemia, hematuria[neupogenhcp.com]
  • Patients may claim a propensity for epistaxis, bleeding gums, melena and hematochezia, and hematuria. Cutaneous hemorrhages ranging from petechiae to extensive ecchymoses may be noted. Of note, leukocytosis is not uncommon in AML patients.[symptoma.com]
Headache
  • […] followed by BMT are rash, hypersensitivity, thrombocytopenia, anemia, hypertension, sepsis, bronchitis, and insomnia undergoing peripheral blood progenitor cell mobilization and collection are bone pain, pyrexia, increased blood alkaline phosphatase, and headache[neupogenhcp.com]
  • If AML spreads to the brain and its meninges, patients may suffer from headache, visual disturbances, nausea, vomiting, and other central nervous system impairments.[kinderkrebsinfo.de]
  • The symptoms of the anemia may include fatigue, dizziness, headache, paleness of the skin, or, infrequently, congestive heart failure. Easy bruising, bleeding gums, and nosebleeds may be present, as may fever.[encyclopedia.com]
  • […] bruising or prolonged bleeding from cuts Frequent or severe nosebleeds Other general symptoms: Loss of appetite Unexplained weight loss Pain or aches in your bones or joints Swollen abdomen Swollen lymph nodes in your neck, underarm, groin or stomach Headaches[seattlecca.org]
Dizziness
  • […] prolonged bleeding from cuts Frequent or severe nosebleeds Other general symptoms: Loss of appetite Unexplained weight loss Pain or aches in your bones or joints Swollen abdomen Swollen lymph nodes in your neck, underarm, groin or stomach Headaches, dizziness[seattlecca.org]
  • Anemia manifests in the form of pallor, fatigue, weakness, dizziness, dyspnea on exertion, and possibly chest pain.[symptoma.com]
  • The symptoms of the anemia may include fatigue, dizziness, headache, paleness of the skin, or, infrequently, congestive heart failure. Easy bruising, bleeding gums, and nosebleeds may be present, as may fever.[encyclopedia.com]
Altered Mental Status
  • Signs relating to leukostasis include respiratory distress and altered mental status. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al.[emedicine.medscape.com]
  • Altered mental status may suggest developing leukostasis, and ideally a fundoscopic exam should be performed to look for signs of retinal hemorrhages or congestion that could be harbingers of incipient leukostatic complications.[clinicaladvisor.com]
Lethargy
  • Signs and symptoms of acute myelogenous leukemia include: Fever Bone pain Lethargy and fatigue Shortness of breath Pale skin Frequent infections Easy bruising Unusual bleeding, such as frequent nosebleeds and bleeding from the gums When to see a doctor[mayoclinic.org]
  • Fatigue, Weakness or Lethargy Skin Lesion or Rash Shortness of Breath : This may also worsen with exercise.[knowcancer.com]
Asthenia
  • The most common adverse reactions in patients: with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs are anemia, constipation, diarrhea, oral pain, vomiting, asthenia, malaise, edema peripheral, hemoglobin decreased, decreased appetite[neupogenhcp.com]

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.

Thrombocytosis
  • To our knowledge, this is the first report of the association of AML with thrombocytosis and Grönbland-Strandberg syndrome.[ncbi.nlm.nih.gov]
  • Risk Factors in the Development of AML Hereditary causes Trisomy 21: Down syndrome Defective DNA repair: Bloom syndrome, Fanconi anemia , and ataxia-telangiectasia Myeloproliferative syndromes: Polycythemia Vera , and essential thrombocytosis Exposure[lecturio.com]
  • Other chronic myeloproliferative syndromes, such as polycythemia vera and essential thrombocytosis, are extremely rare in children.[northshore.org]
Decreased Platelet Count
Hemoglobin Decreased
  • The most common adverse reactions in patients: with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs are anemia, constipation, diarrhea, oral pain, vomiting, asthenia, malaise, edema peripheral, hemoglobin decreased, decreased appetite[neupogenhcp.com]
Auer Rods Present
  • Prognosis Factors Favourble Unfavourable Morphology Auer rods Present Absent Eosinophils Present Absent Megaloblastic erythroid Absent Present Dysplastic Absent Present megakaryocytes FAB type M2,M3,M4 M0,M6,M7 87.[slideshare.net]

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%.

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]:

  • Genetic diseases like ataxia telangiectasia, congenital neutropenia, Down syndrome, Fanconi anemia, Klinefelter syndrome, Li-Fraumeni syndrome, Patau syndrome, Shwachman syndrome
  • Hematological disorders, e.g., myelodysplasia
  • Prior cytotoxic chemotherapy with alkylating agents, anthracyclines, taxanes and topoisomerase-II inhibitors
  • Exposure to carcinogens e.g. cigarette smoke, herbicides, pesticides, and benzene
  • Radiation exposure

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.

References

Article

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Last updated: 2018-09-04 11:08