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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]
  • Splenomegaly can cause fullness in the left upper quadrant and early satiety. If WBC count is extremely high ( 100 x 10 9 /L), it can cause leukostasis with respiratory distress and altered mental status.[patient.info]
  • Myelofibrosis Typically splenomegaly is present. Blood film shows teardrop RBCs and a leukoerythroblastic film. Bone marrow biopsy shows reticulin fibrosis.[online.epocrates.com]
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]
  • 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]
  • 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]
  • Abstract 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[ncbi.nlm.nih.gov]
  • Aplastic anemia May have history of medications that cause aplastic anemia, such as chloramphenicol and nonsteroidal anti-inflammatory drugs. Bone marrow aspiration and peripheral blood smear are helpful in differentiating diagnosis.[online.epocrates.com]
Fever
  • Abstract A patient with acute nonlymphocytic leukemia developed progressive lung infiltrates and unremitting fevers during a profound neutropenic state.[ncbi.nlm.nih.gov]
  • Acute leukemias affect immature cells; the disease develops rapidly, with symptoms including anemia, fever, bleeding, and swelling of the lymph nodes. Immature leukemia cells Read More[britannica.com]
  • […] 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]
  • 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]
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]
  • Effects of a walking intervention on fatigue-related experiences of hospitalized acute myelogenous leukemia patients undergoing chemotherapy: a randomized controlled trial. J Pain Symptom Manage. 2008;35(5):524-34.[physio-pedia.com]
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]
  • Joint pain Enlargement of the liver and spleen Swelling, pain, and bleeding of the gums Painless lumps in the neck, underarms, stomach, or groin Diagnosis Your doctor will ask about your symptoms and medical history.[web.archive.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]
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]
  • 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.[medlineplus.gov]
  • Immunosuppression : A weak immune system, resulting from an organ transplant, can increase risk.[knowcancer.com]
  • […] polycythemia vera , essential thrombocythemia , and myelodysplasia Certain chemicals (for example, benzene) Certain chemotherapy drugs, including etoposide and drugs known as alkylating agents Exposure to certain chemicals and harmful substances Radiation Weak[medlineplus.gov]
Cough
  • 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]
  • During the treatment period, blood cultures are administered to patients who develop symptoms, most commonly fever or cough. These blood cultures occasionally lead to the diagnosis of invasive aspergillosis.[hematologyandoncology.net]
  • Any wheezing, coughing and/or labored or painful breathing requires immediate medical attention.[chop.edu]
  • Your child may have had several viral or bacterial infections over the past few weeks and may show symptoms of an infection such as fever, runny nose and cough. bone and joint pain – Your child may also experience pain in his bones and joints.[danafarberbostonchildrens.org]
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]
  • In 2 of them, with WBC counts of 186,000/μL and 38,000/μL upon admission, respectively, dyspnea, hypoxia, and pulmonary infiltrates were already present, before the onset of ATRA. Worsening of those signs occurred within hours on ATRA onset.[bloodjournal.hematologylibrary.org]
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]
  • Hepatomegaly and splenomegaly may be found. Lymphadenopathy is less common. Leukaemia cutis is an uncommon condition due to infiltration of the skin. [ 10 ] Gingivitis is common, with swollen, bleeding gums.[patient.info]
  • 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]
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
  • Common side effects of Mylotarg include fever (pyrexia), nausea, infection, vomiting, bleeding, low levels of platelets in the blood (thrombocytopenia), swelling and sores in the mouth (stomatitis), constipation, rash, headache, elevated liver function[fda.gov]
  • Four episodes of severe toxic effects (infection, hepatotoxicity, headache, and hypertriglyceridemia) occurred in 3 of the 105 patients assigned to observation. Disease-Free Survival Effect of Induction Treatment Figure 1. Figure 1.[doi.org]
  • […] 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]
  • […] 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
  • Anemia manifests in the form of pallor, fatigue, weakness, dizziness, dyspnea on exertion, and possibly chest pain.[symptoma.com]
  • Dizziness and shortness of breath on exertion may present in older people and, if there is coronary heart disease, it may present with angina or myocardial infarction.[patient.info]
  • […] 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]
Altered Mental Status
  • If WBC count is extremely high ( 100 x 10 9 /L), it can cause leukostasis with respiratory distress and altered mental status. Leukostasis is a medical emergency that requires immediate intervention. There can also be bone pain.[patient.info]
  • 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]
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]
  • The causes for discontinuation or early termination were neutropenia (n 3), asthenia, polyarthritis, acute congestive heart failure, bronchospasm, venous thrombosis/renal-cell cancer, hepatobiliary disorder, hypersensitivity with local reaction/flush,[doi.org]
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]
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.[medlineplus.gov]
  • […] 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]
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[ucsfhealth.org]
  • , 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]
  • 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]
  • Splenomegaly can cause fullness in the left upper quadrant and early satiety. If WBC count is extremely high ( 100 x 10 9 /L), it can cause leukostasis with respiratory distress and altered mental status.[patient.info]
  • 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]
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]
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]
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]
  • Leukaemia cutis is an uncommon condition due to infiltration of the skin. [ 10 ] Gingivitis is common, with swollen, bleeding gums. This may lead to initial presentation at the dentist.[patient.info]
Chest Pain
  • 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]
  • 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]
  • 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
  • When erythrocytes are affected (the most common situation), patients present with signs of anemia, including pallor, pale conjunctiva, tachycardia, hypotension, fatigue, headache, and exercise intolerance, or with signs and symptoms of a worsening underlying[doi.org]
Bone Pain
  • It can also be used to treat bone pain that comes from bone affected by the leukemia. Chemotherapy With Stem Cell Transplant Chemotherapy is followed by a transplantation of stem cells (immature blood cells).[web.archive.org]
  • […] 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]
  • 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]
  • 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]
  • 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]
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]
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]
Photophobia
  • However, one dose of high-dose cytarabine or 20 percent of the dose of the 24-hour infusions of cytarabine was subtracted in the event that marrow recovery required more than 28 days; a confluent maculopapular eruption or drug-induced desquamation; photophobia[doi.org]
Petechiae
  • Thrombocytopenia often causes petechiae on the lower limbs. DIC may aggravate the situation and cause larger lesions. Petechiae are small dots, purpura is larger and ecchymoses are larger bruises. Hepatomegaly and splenomegaly may be found.[patient.info]
  • […] 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]
Purpura
  • Petechiae are small dots, purpura is larger and ecchymoses are larger bruises. Hepatomegaly and splenomegaly may be found. Lymphadenopathy is less common.[patient.info]
  • 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]
  • [PUBMED Abstract] Ghauri RI, Naveed M, Mannan J: Congenital amegakaryocytic thrombocytopenic purpura (CAMT). J Coll Physicians Surg Pak 24 (4): 285-7, 2014.[cancer.gov]
Papule
  • 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[medical-dictionary.thefreedictionary.com]
  • 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[physio-pedia.com]
  • Skin manifestations of disease caused by infiltration of myeloblasts (termed leukemia cutis) have a broad possible range of appearances but are most often manifested as purplish or violaceous nodules or papules.[clinicaladvisor.com]
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),[cancer.gov]
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]
  • Fewer than 20% of patients present with symptoms of isolated thrombocytopenia such as minor bleeding (eg, mucosal bleeding, petechiae, easy bruising, epistaxis) or major bleeding (eg, gastrointestinal bleeding, intracranial hemorrhage) or of isolated[doi.org]

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]
  • In particular, the histologic distinction between the “prefibrotic” stage of PMF (a stage often associated with marked thrombocytosis in the PB and granulocytic and atypical megakaryocytic proliferation with minimal, if any, fibrosis in the BM) and ET[doi.org]
  • [PUBMED Abstract] Jubinsky PT: Megakaryopoiesis and thrombocytosis. Pediatr Blood Cancer 44 (1): 45-6, 2005.[cancer.gov]
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]

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