Acute Leukemia (Mixed Phenotype Acute Leukemia)

Both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are an acute form of leukemia characterized by proliferation of early lymphoid/myeloid precursor cells which replace the normal hematopoietic cells of the bone marrow.

Acute Leukemia originates from this process: neoplastic.

Presentation

Patients with ALL and AML may present with symptoms related to either infiltration of the bone marrow with leukemic cells or symptoms related to infiltration of leukemic cells in extramedullary organs. Fever is a universal complaint even in the absence of any infection. Any fever in a leukemia patient should be considered to be from an infection until proven otherwise. Infections remain the most common cause of death in these patients and should not be taken lightly.

Symptoms of anemia may include palpitations, general malaise, dizziness, shortness of breath and even fatigue. Signs of bleeding may include presence of petechiae, ecchymosis and swollen gums.

Some individuals with ALL and AML may develop localized or generalized lymphadenopathy, or even shortness of breath as a result of enlarged mediastinal nodes. Infiltration of the marrow by leukemic cells can also present with moderate to severe bone pain. If splenomegaly is present, the individual may have early satiety and complain of left upper quadrant fullness.

In advanced cases, patients may even present with altered mental status and renal failure (due to hyperuricemia). Some AML patients may complain of severe bone pain due to the pain caused by pressure from the expanding pool of cells. In such scenarios, urgent bone marrow decompression is required for pain relief.

Physical examination

Common features in a patient with ALL or AML may include fever, signs of anemia (eg. pallor, tachycardia), petechiae, ecchymosis and adenopathy. Rarely a red rash may be seen due to infiltration of leukemic cells under the skin.

Skin
Petechiae
  • Symptoms and Types Generalized illness, no specific symptoms Tiny, non-raised purple spots on the skin, from hemorrhages beneath the skin ( petechia ), or dark red-purple spots on the gums, from ruptured blood vessels under the skin (ecchymotic) Inconstant[petmd.com]
  • The early symptoms and signs of acute leukemia may be similar to the flu, and include fatigue, fever, dyspnea, weight loss, bony pain and petechiae (flat pinpoint spots under the skin caused by bleeding).[secure.ssa.gov]
  • Fatigue Pale complexion (due to low red blood cells) Bruises or black-and-blue marks occurring for little or no reason Prolonged bleeding from minor cuts Small red spots on the skin (due to low platelet count) called petechiae Mild fever Infection (due[parkview.com]
  • The symptoms of ALL may include: paleness, or pallor bleeding from the gums a fever bruises, purpura, or bleeding within the skin petechiae, which are red or purple spots on the body lymphadenopathy, which is characterized by enlarged lymph nodes in the[healthline.com]
  • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity.[merckmanuals.com]
Purpura
  • The symptoms of ALL may include: paleness, or pallor bleeding from the gums a fever bruises, purpura, or bleeding within the skin petechiae, which are red or purple spots on the body lymphadenopathy, which is characterized by enlarged lymph nodes in the[healthline.com]
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  • Eyes
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  • hematological
    Easy Bruising
    • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[nlm.nih.gov]
    • Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections.[medical-dictionary.thefreedictionary.com]
    • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity.[merckmanuals.com]
    • bruising or bleeding because of a low number of platelets AML is usually found in the blood and bone marrow, the spongy, red tissue in the inner part of the large bones.[cancer.net]
    • Easy bruising or bleeding.[my.clevelandclinic.org]
    Hemophilia A
    • Here, five people speak about living with hemophilia.[nytimes.com]
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  • cardiovascular
    Tachycardia
    • Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state.[merckmanuals.com]
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  • musculoskeletal
    Bone Pain
    • pain, sometimes associated with swelling of the joints The signs and symptoms of ALL can be the same as more common children’s illnesses and many children are treated for those other illnesses before leukemia is diagnosed.[childrensoncologygroup.org]
    • They’ll likely ask about bone pain, which is one of the first symptoms of ALL.[healthline.com]
    • A high number of leukemia cells can cause bone pain and swelling of the joints .[stbaldricks.org]
    • pain, sometimes associated with swelling of the joints Weight loss or loss of appetite Enlarged lymph nodes The signs and symptoms of ALL can be the same as more common children’s illnesses and some children are treated for those other illnesses before[curesearch.org]
    • 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[medical-dictionary.thefreedictionary.com]
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  • Face, Head & Neck
    Epistaxis
    • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity.[merckmanuals.com]
    • Low numbers of platelets can lead to petechiae, gingival bleeding, ecchymosis, epistaxis, or menorrhagia.[clevelandclinicmeded.com]
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  • Entire body system
    Fever
    • In prospective clinical trials at centers where gram-positive infections are prevalent, vancomycin therapy begun empirically at the time of first infectious fever results in prompt resolution of fever, rapid clearance of local and/or disseminated gram-positive[cancernetwork.com]
    • The cause of fever often is not found, although granulocytopenia may lead to a rapidly progressing and potentially life-threatening bacterial infection.[merckmanuals.com]
    • It is the decrease in normal cells that produces many of the symptoms of ALL Fatigue and being pale results from a decreased number of red blood cells, known as anemia Fever due to the disease itself or from infection because there are a decreased number[childrensoncologygroup.org]
    • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[nlm.nih.gov]
    • For example, when a child with symptoms like unexplained fevers or bruises on the skin is taken to a pediatrician, the doctor will do a blood count test and may found very high white blood cells, which suggest the child might have leukemia.[livescience.com]
    Anemia
    • Common to all leukemias are the tendency to bleed and the resultant anemia and increased susceptibility to infection.[medical-dictionary.thefreedictionary.com]
    • Anemia (Hb 8 g/dL) is treated with transfusions of packed RBCs.[merckmanuals.com]
    • The anemia is severe in acute MPDs.[wearethecure.org]
    • These blast cells disrupt the normal balance of cells in the blood leading to shortage of red blood cells causing anemia and platelets causing bleeding tendencies.[news-medical.net]
    • The leukocytopenic forms are the most difficult to differentiate from aplastic anemias, pancytopenias, and the myelodysplastic syndromes.[meds.com]
    Fatigue
    • Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections.[medical-dictionary.thefreedictionary.com]
    • It is the decrease in normal cells that produces many of the symptoms of ALL Fatigue and being pale results from a decreased number of red blood cells, known as anemia Fever due to the disease itself or from infection because there are a decreased number[childrensoncologygroup.org]
    • By LISA FOGARTY Photo Credit Patient Voices: Hepatitis Fatigue, liver disease and the stigma of a contagious disease: six men and women speak about living with hepatitis.[nytimes.com]
    • The early symptoms and signs of acute leukemia may be similar to the flu, and include fatigue, fever, dyspnea, weight loss, bony pain and petechiae (flat pinpoint spots under the skin caused by bleeding).[secure.ssa.gov]
    • The decrease in normal cells causes the symptoms of leukemia, which may include: Fatigue and being pale results from a decreased number of red blood cells , known as anemia Fever due to the disease itself or from infection because there are a decreased[curesearch.org]
    Down Syndrome
    • […] in Down syndrome children with ALL.[haematologica.org]
    • syndrome Being male Although there is no way to completely prevent AML, you may lower your risk by not smoking and avoiding exposure to chemicals.[webmd.com]
    • Michel Zwaan and Marry M. van den Heuvel-Eibrink Chapter 11 Pediatric Natural Killer Cell Malignancy by Yoshiko Hashii Chapter 12 Leukemogenesis in Down Syndrome by Lílian Barros Queiroz, Íris Ferrari, Cezar Martins de Sá, Juliana Forte Mazzeu, Isis[intechopen.com]
    • Risk is also increased in children with Down Syndrome (trisomy 21).[oncolink.org]
    • syndrome Read more about the causes of AML .[nhs.uk]
    Pallor
    • The symptoms of ALL may include: paleness, or pallor bleeding from the gums a fever bruises, purpura, or bleeding within the skin petechiae, which are red or purple spots on the body lymphadenopathy, which is characterized by enlarged lymph nodes in the[healthline.com]
    • Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state.[merckmanuals.com]
    • 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[wearethecure.org]
    • Case presentation A 4-year-old Mexican Mestizo (Hispanic) male was admitted to the Hospital Infantil de México Federico Gómez presenting a 30-day history of fever, pallor, and enlarged cervical lymph nodes.[casesjournal.biomedcentral.com]
    • Pallor is a common finding on physical examination.[clevelandclinicmeded.com]
    Malaise
    • 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]
    • The clinical picture is marked by the effects of anemia, which is usually severe (fatigue, malaise), an absence of functioning granulocytes (proneness to infection and inflammation), and thrombocytopenia (hemorrhagic diathesis).[meds.com]
    • Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state.[merckmanuals.com]
    Infectious Mononucleosis
    • Epstein-Barr virus, which is usually responsible for infectious mononucleosis, has been linked to ALL and Burkitt’s lymphoma.[healthline.com]
    • Aplastic anemia, viral infections such as infectious mononucleosis, and vitamin B 12 and folate deficiencies should be considered in the differential diagnosis of severe pancytopenia.[merckmanuals.com]
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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.[medical-dictionary.thefreedictionary.com]
    • In addition, patients with leukemia may have hepatosplenomegaly, an enlargement of the liver and spleen.[encyclopedia.com]
    • […] 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, polydipsia (increased thirst), hepatosplenomegaly[wearethecure.org]
    • Palpable lymphadenopathy and hepatosplenomegaly are rare findings in AML.[clevelandclinicmeded.com]
    Hepatomegaly
    • […] pallor bleeding from the gums a fever bruises, purpura, or bleeding within the skin petechiae, which are red or purple spots on the body lymphadenopathy, which is characterized by enlarged lymph nodes in the neck, under the arms, or in the groin region hepatomegaly[healthline.com]
    • Extramedullary infiltration by leukemic cells may cause lymphadenopathy, splenomegaly, hepatomegaly, and leukemia cutis (a raised, nonpruritic rash).[merckmanuals.com]
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  • Jaw & Teeth
    Bleeding Gums
    • 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]
    • Signs and symptoms may include: excessive sweating fatigue frequent unexplained bleeding, such as nosebleeds or bleeding gums high fever painful joints and/or bones panting several infections over a short period swollen glands (lymph nodes) swollen liver[medicalnewstoday.com]
    • They include: Swollen lymph nodes that usually don't hurt (especially lymph nodes in the neck or armpit) Fevers or night sweats Frequent infections or poor healing of minor cuts Feeling weak or tired Bleeding and bruising easily (bleeding gums, purplish[roswellpark.org]
    • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity.[merckmanuals.com]
    • Frequent or severe nosebleeds and bleeding gums Swollen lymph nodes Lymph nodes are responsible for filtering the blood and leukemia cells may collect in the lymph nodes, causing swelling.[stlouischildrens.org]
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  • Immune System
    Splenomegaly
    • 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]
    • CT, MRI, or abdominal ultrasonography may help assess splenomegaly or leukemic infiltration of other organs.[merckmanuals.com]
    • , purpura, or bleeding within the skin petechiae, which are red or purple spots on the body lymphadenopathy, which is characterized by enlarged lymph nodes in the neck, under the arms, or in the groin region hepatomegaly, or enlargement of the liver splenomegaly[healthline.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.[healthcommunities.com]
    • Other conditions included splenomegaly, gastrointestinal bleeding and elevated number of circulating basophils. [wearethecure.org]
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  • Course
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  • Workup

    Workup of a patient with suspected ALL and AML includes the following:

    • Blood cultures need to be done in patients with a fever.
    • Bone marrow aspiration and biopsy is the definitive diagnostic test to confirm the diagnosis of leukemia. Cells obtained should be sent for flow cytometry and immunophenotyping to determine the subtype. Cytogenetic studies can help determine presence of the Philadelphia chromosome and other chromosomal abnormalities.
    • Chest X-ray may reveal presence of an infiltrative process or a prominent mediastinal mass.
    • Chest CT scan is often used to further evaluate a mediastinal mass or hilar adenopathy.
    • Complete blood count may reveal neutropenia. When the neutrophil count is < 500/ul, the risk of infection is high.
    • Coagulation profile is necessary as it may reveal abnormalities in prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation products, which is suggestive of concomitant disseminated intravascular coagulation (DIC).
    • A chemistry profile as well as uric acid and lactic dehydrogenase levels are recommended. In addition, liver function and renal function tests are necessary before the initiation of chemotherapy.
    • A baseline ECG is recommended before initiation of chemotherapy.
    • Because of cardiotoxicity of some chemotherapeutic drugs, it is important to perform some type of cardiac stress test to determine presence of ischemia.
    • Peripheral blood smear can help confirm results of the CBC and also reveals presence of blasts. If DIC is present, schistocytes will be present.

    National Comprehensive Cancer Network (NCCN) guidelines to make a diagnosis of ALL include the following [2]:

    • Presence of ≥20% lymphoblasts in bone marrow
    • Morphologic presence of blasts cells on stained bone marrow aspirate smears
    • Stained bone marrow core biopsy and clot sections
    • Complete immunophenotyping, cytogenetic and flow cytometric studies

    In the older literature, ALL was classified by the French-American-British (FAB) classification. Today, the newer World Health Organization (WHO) classification is utilized.

    Pathology

    Biopsy
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  • Laboratory

    Cerebrospinal Fluid
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  • Serum
    Decreased Platelet Count
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  • Imaging

    X-ray
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  • Test Results

    Skin Test
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  • Treatment

    Both AML and ALL treatment requires considerable expertise in oncology and hematology. Because of the need for blood products, patient should receive care where both leukapheresis and excellence in blood banking is available. These individuals require frequent hospital admissions and need to be looked after a team of healthcare professionals [8] [9] [10]. Overall less than 1/3rd of patients with ALL are cured with conventional chemotherapy regimens [1] [2].

    The treatment of ALL has 4 basic components that include:

    1. Induction
    2. Consolidation
    3. Maintenance
    4. CNS prophylaxis

    Hospital admission is required for treatment and for the management of adverse effects from chemotherapy [11]. Most patients need a semi-permanent IV line like a triple lumen or a Hickman catheter for administration of chemotherapy.

    Induction chemotherapy usually involves the use of a 4-5- drug regimen which include prednisone, vincristine, cyclophosphamide and anthracycline, or L-asparaginase [6]. The treatment is administered over a course of 4-6 weeks. Complete remission occurs in about 60-85% of patients. Those patients who rapidly enter remission within 4 weeks tend to have good outcomes compared to those who remission occurs later.

    CNS prophylaxis

    Patients with ALL frequently develop leukemic meningitis following relapse. As a result intrathecal chemotherapy is required. The number of intrathecal treatment varies depending on severity but most individuals require a minimum of 4-6 treatments [1] [2] [9].

    Newer induction approaches

    In the past there were fewer antibiotics available and transfusion medicine was still not well developed. With advances in blood baking and availability of newer antibiotics, more aggressive chemotherapeutic regimens are being used to treat ALL and AML. Today there are several chemotherapy protocols for treatment of ALL and AML including the use of protein based therapies like imatinib and dastinib [13][14] [15].

    Treatment of Ph chromosome–positive ALL

    Today, patients with Philadelphia chromosome–positive (Ph+) ALL are treated with tyrosine kinase inhibitors like nilotinib and dasatinib in combination of standard chemotherapy regimens. Unfortunately the tyrosine kinase inhibitors also have serious adverse effects like liver dysfunction, pleural effusion, pulmonary artery hypertension and prolonged QT interval. Their use requires clinical judgment and the benefits must outweigh the adverse effects [7].

    Transplantation

    Allogeneic transplantation is now performed for young patients who have high risk features whose ALL and AML is in the first remission. In patients without high risk features allogeneic transplantation is reserved for those who relapse [16] [17].

    Another newer option is use of stem cell transplant in patients with ALL and AML who have poor prognostic features such as age less than 6 months and poor repose to steroids or a high level of leukocytes. Some studies indicate that in high risk patients allogeneic bone marrow transplant may be superior to chemotherapy in achieving long term remissions.

    Treatment of relapsed ALL & AML

    ALL patients who relapse tend to have a poor prognosis and most of them are referred only for investigational treatments.

    Blood broducts

    Since ALL and AML patients regularly develop an inability make normal blood cells, they constantly need blood replacement products. All blood products given to leukemic patients must be irradiated to prevent transfusion-related graft versus host disease, which is frequently fatal.

    Therapy and prophylaxis for infection

    Febrile patients with ALL and AML are routinely given antibiotics including antifungal agents. Steroids should be given with great care to leukemic patients as they may mask any signs of infections. The role of antibiotics in afebrile patients is controversial.

    Growth factors

    The use of granulocyte colony stimulating factors is now routine during induction chemotherapy. These factors help prevent the abrupt decline in white cells and decrease the risk of infections. While many studies indicate that CSF reduces febrile neutropenia, the survival of ALL and AML patients is not altered.

    Hyperuricemia and tumor lysis syndrome

    A potentially life threating complication of chemotherapy is tumor lysis syndrome. The syndrome is characterized by elevated levels of potassium, uric acid and phosphate. In addition the patient may develop depressed levels of calcium and acute renal failure. Allopurinol is recommended during chemotherapy and some patients with infiltration of the kidneys by leukemic cells may benefit from rasburicase.

    Long-term monitoring

    All patients with ALL or AML need close monitoring on an outpatient basis. Maintenance therapy is usually administered in an outpatient setting. Further patients are also treated with trimethoprim-sulfamethoxazole to prevent pneumocystis jiroveci pneumonia. To reduce the development of candida, patients should be prescribed am antifungal drug like oral nystatin or clotrimazole troches. Patients who are severely neutropenic and at a high risk of relapse may require supplemental antifungal therapy with agents like amphotericin or itraconazole.

    Prognosis

    Overall only 20-40 percent of individuals with ALL are cured with current treatment protocols [5] [6]. The prognosis of patients is based on risk assessment as follows:

    Good risk

    • Age less than 30
    • Complete remission within 4 weeks
    • No adverse cytogenetics findings
    • WBC count of < 30,000/ul

    Intermediate risk includes those patients who do not fall into the good or poor risk criteria.

    Poor risk

    • Age 60 years
    • Failing to achieve complete remission within 4 weeks of therapy
    • Presence of chromosomal aberrations like translocations t(9;22), t(4;11)
    • Presence of precursor B-cells
    • WBC count > 100,000/μL
    • Failure to achieve complete remission within 4 weeks

    Despite autologous transplantation or conventional chemotherapy, individuals who have precursor B-cell ALL tend to have the worst prognosis. Several studies indicate the expression of myeloid antigens may be associated with a decreased survival.

    In patients who survive ALL, other impairments include decreased physical performance, neuromuscular deficits and vision loss. These neurological deficits have been linked to intrathecal use of drugs like methotrexate and vincristine.

    The prognosis for patients with AML depends on several factors such as advanced age, any comorbid condition and prior myelodysplastic syndrome. The best prognosis is in patients with t(15;17) or t(8:21) with long term survival rates of about 60%. Patients with normal cytogenetic studies have a survival rate of 15% and patients with poor cytogenetic findings like FLT3 mutation have the worst survival of only 10%. Overall, about 1/3rd of AML patients less than 60 years survive 5 years. Less than 10% of patients older than 60 survive long term [7].

    Death in patients with ALL and AML is usually due to uncontrolled sepsis or hemorrhage.

    Complications

    Fever
    • In prospective clinical trials at centers where gram-positive infections are prevalent, vancomycin therapy begun empirically at the time of first infectious fever results in prompt resolution of fever, rapid clearance of local and/or disseminated gram-positive[cancernetwork.com]
    • The cause of fever often is not found, although granulocytopenia may lead to a rapidly progressing and potentially life-threatening bacterial infection.[merckmanuals.com]
    • It is the decrease in normal cells that produces many of the symptoms of ALL Fatigue and being pale results from a decreased number of red blood cells, known as anemia Fever due to the disease itself or from infection because there are a decreased number[childrensoncologygroup.org]
    • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[nlm.nih.gov]
    • For example, when a child with symptoms like unexplained fevers or bruises on the skin is taken to a pediatrician, the doctor will do a blood count test and may found very high white blood cells, which suggest the child might have leukemia.[livescience.com]
    Thrombocytopenia
    • Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections.[medical-dictionary.thefreedictionary.com]
    • Other conditions may include anemia and thrombocytopenia.[wearethecure.org]
    • […] a decreased number 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[childrensoncologygroup.org]
    • […] a decreased number 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[curesearch.org]
    • Thrombocytopenia is a condition when there is a low number of platelets which can cause bleeding and easy bruising with no apparent cause.[lls.org]
    Infection
    • Infection 19:73-80, 1991. 11.[cancernetwork.com]
    • In patients with refractory pneumonitis, Pneumocystis jirovecii infection or a viral infection should be suspected and confirmed by bronchoscopy and bronchoalveolar lavage and treated appropriately.[merckmanuals.com]
    • B cells particularly help prevent germs from infecting the body while T cells destroy the infected cells.[cancercenter.com]
    • Most infections are just infections and not leukemia, so treating a suspected infection is appropriate and this short delay in diagnosis is not likely to affect the course of the disease.[oncolink.org]
    • Infection Prevention Both chemotherapy and transplantation increase the risk for infection.[umm.edu]
    Anemia
    • Common to all leukemias are the tendency to bleed and the resultant anemia and increased susceptibility to infection.[medical-dictionary.thefreedictionary.com]
    • Anemia (Hb 8 g/dL) is treated with transfusions of packed RBCs.[merckmanuals.com]
    • The anemia is severe in acute MPDs.[wearethecure.org]
    • These blast cells disrupt the normal balance of cells in the blood leading to shortage of red blood cells causing anemia and platelets causing bleeding tendencies.[news-medical.net]
    • The leukocytopenic forms are the most difficult to differentiate from aplastic anemias, pancytopenias, and the myelodysplastic syndromes.[meds.com]
    Epistaxis
    • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity.[merckmanuals.com]
    • Low numbers of platelets can lead to petechiae, gingival bleeding, ecchymosis, epistaxis, or menorrhagia.[clevelandclinicmeded.com]
    Disseminated Intravascular Coagulation
    • Prophylactic platelet transfusion is done when platelets fall to 10,000/ μ L; a higher threshold (20,000/ μ L) is used for patients with the triad of fever, disseminated intravascular coagulation, and mucositis secondary to chemotherapy.[merckmanuals.com]
    • Bleeding and blood clotting problems, such as disseminated intravascular coagulation (DIC), are commonly seen with this form of leukemia.[healthcommunities.com]
    • APML is often associated with a condition of abnormal bleeding and blood clotting called DIC (disseminated intravascular coagulation).[oncolink.org]
    • APL is a distinct entity of AML that often manifests with hemorrhagic complications, including disseminated intravascular coagulation.[clevelandclinicmeded.com]
    Hyperuricemia
    • Other laboratory findings may include hyperuricemia, hyperphosphatemia, hyperkalemia or hypokalemia, hypocalcemia, elevated serum hepatic transaminases or LDH, hypoglycemia, and hypoxia.[merckmanuals.com]
    • […] system (CNS) prophylaxis Supportive care (eg, blood products, antibiotics, growth factors) Special considerations apply to the treatment of the following: Mature B-cell ALL Ph ALL ALL in older children and younger adults Relapsed ALL ALL in patients with hyperuricemia[emedicine.medscape.com]
    Pancytopenia
    • Aplastic anemia, viral infections such as infectious mononucleosis, and vitamin B 12 and folate deficiencies should be considered in the differential diagnosis of severe pancytopenia.[merckmanuals.com]
    • Low numbers of all three blood cell counts is called pancytopenia.[lls.org]
    • However, extramedullary hematopoiesis (formation of blood cellular components outside the medulla of the bone) fails to arrest pancytopenia (reduction of red blood cells, white blood cells and platelets) which develops eventually.[wearethecure.org]
    • The leukocytopenic forms are the most difficult to differentiate from aplastic anemias, pancytopenias, and the myelodysplastic syndromes.[meds.com]
    • Back to Top Signs and Symptoms AML often manifests with clinical sequelae attributable to pancytopenia.[clevelandclinicmeded.com]
    Infectious Mononucleosis
    • Epstein-Barr virus, which is usually responsible for infectious mononucleosis, has been linked to ALL and Burkitt’s lymphoma.[healthline.com]
    • Aplastic anemia, viral infections such as infectious mononucleosis, and vitamin B 12 and folate deficiencies should be considered in the differential diagnosis of severe pancytopenia.[merckmanuals.com]
    Tumor Lysis Syndrome
    • Hydration (twice the daily maintenance volume), urine alkalinization (pH 7 to 8), and electrolyte monitoring can prevent the hyperuricemia, hyperphosphatemia, hypocalcemia, and hyperkalemia (ie, tumor lysis syndrome ) caused by the rapid lysis of leukemic[merckmanuals.com]
    • Additionally, metabolic abnormalities, including tumor lysis syndrome, can occur spontaneously because of high tumor burden or as a result of cytotoxic chemotherapy.[clevelandclinicmeded.com]
    • lysis syndrome See Treatment and Medication for more detail.[emedicine.medscape.com]
    • After that, the patient had infectious complications, followed by development of tumor lysis syndrome and septic shock.[casesjournal.biomedcentral.com]
    Varicella
    • ., varicella, influenza, or rubella) ( 2 , 39 ), as well as postnatal Mycoplasma pneumoniae ( 40 ).[jnci.oxfordjournals.org]
    Down Syndrome
    • […] in Down syndrome children with ALL.[haematologica.org]
    • syndrome Being male Although there is no way to completely prevent AML, you may lower your risk by not smoking and avoiding exposure to chemicals.[webmd.com]
    • Michel Zwaan and Marry M. van den Heuvel-Eibrink Chapter 11 Pediatric Natural Killer Cell Malignancy by Yoshiko Hashii Chapter 12 Leukemogenesis in Down Syndrome by Lílian Barros Queiroz, Íris Ferrari, Cezar Martins de Sá, Juliana Forte Mazzeu, Isis[intechopen.com]
    • Risk is also increased in children with Down Syndrome (trisomy 21).[oncolink.org]
    • syndrome Read more about the causes of AML .[nhs.uk]

    Etiology

    The cause of ALL and AML remains a mystery. However, some data from the atomic bomb in Hiroshima seems to suggest that radiation exposure may be a risk factor for both ALL and AML. Recently use of topoisomerase 11 inhibitors has resulted in ALL in some patients due to alterations in certain chromosomes. Nearly 10-15 percent of individuals with ALL have a t(9;22) translocation (ie, Philadelphia [Ph] chromosome). However, several other chromosomal abnormalities have also been identified such as t(2;8), t(4;11), and t(8;14) [1].

    Risk factors for AML include myelodysplastic syndrome (the most common), aplastic anemia, myelofibrosis toxin (benzene), chemotherapeutic drugs or environmental exposure. Congenital disorders that are linked to an increased risk of AML include Down syndrome, Bloom syndrome and Fanconi anemia. There are also some germline mutations in the AML1 gene that predispose people to AML. People who smoke tend to have a higher risk of AML than those who do not. However, the majority of patients with AML have no identifiable risk factor [3].

    Causes

    Epidemiology

    In children, ALL is the most common malignancy accounting for nearly 1/4th of all cancers in children up to age 14 and nearly 3/4rd of all cancers in infants and small children. ALL is not common in adults. Overall, ALL is slightly more common males than females. Globally the highest incidence of ALL is observed in the US, Italy, Costa Rica and Switzerland.

    AML occurs in both young people and elderly. The malignancy is more frequently seen in developed countries and is more common in Caucasians compared to other populations. The risk of AML increases with age, with the median age of diagnosis in the 7th decade of life. AML is more common in men compared to women at all ages. It is believed that AML is higher in males because of possible occupational exposure to toxins [3].

    Sex distribution
    Age distribution

    Pathophysiology

    In acute leukemia, lymphoid or myeloid precursor cells that have arrested during the phase of maturity and development become prominent in the marrow and systemic circulation. The exact cause of this malignant clonal proliferation is not known but believed to be due to some type of DNA rearrangement.

    After chromosomal rearrangement occurs, this leads to faulty regulation of oncogenes that control development of white cells. Once the abnormal cell lines proliferate, the bone marrow gets congested and starts to function poorly. There is physical replacement of bone marrow cells by immature cell. In addition, the abnormal white cells also secrete cytokines that also inhibit normal hematopoiesis in bone marrow.

    As the bone marrow becomes congested with abnormal cells, there is spillage of cells into the circulation and infiltration of other organs, such as the liver, spleen, and eye. The clinical features of ocular infiltration may be:

    1. Secondary to direct infiltration by leukemic cells
    2. A result of abnormal systemic coagulation and hematological factors
    3. Development of opportunistic infections
    4. Iatrogenic complications arising from chemotherapeutic agents [1] [2].

    Prevention

    Because the cause of ALL and AML are not known it it difficult to make any firm recommendations on prevention. Even though radiation exposure has been linked to ALL and AML, this is by no means a direct correlation. In any case, if possible, one should avoid buying a home near any major power lines or a nuclear facility.

    Summary

    Acute lymphoblastic leukemia (ALL) is a malignancy of the bone marrow which is characterized by proliferation of early lymphoid precursor cells. Over time, these abnormal cells replace the normal hematopoietic cells of the bone marrow. ALL is the most common type of cancer in children in the United States. ALL is differentiated from several other related malignancies of the bone marrow using a variety of cytochemistry, immunochemistry and cytogenetic markers. The majority of cells in ALL are premature lymphoid precursor cells that have arrested during the early stage of development.

    The exact cause of ALL is not known but there appears to be chromosomal translocations which results in an abnormal expression of certain oncogenes. As the premature lymphoblasts replace the normal bone marrow, this results in a marked decreased in production of normal blood cells. Classic features of ALL include neutropenia, anemia and thrombocytopenia. The lymphoblasts also proliferate and infiltrate other organs of the body including the liver, spleen, central nervous system (CNS), lymph nodes and eye [1] [2].

    Acute myeloid leukemia (AML) is a hematological malignancy disorder that affects the bone marrow. AML is differentiated from other related malignancies by the presence of > 20% blasts in the bone marrow. Like ALL, in AML there is arrest of maturation of certain bone marrow cells. Several factors have been associated with this malignancy include exposure to radiation, genetic mutations, environment and toxin exposure and familial syndromes. AML patients present with symptoms resulting from bone marrow failure and infiltration of organs with leukemic cells [3] [4].

    Patient Information

    Acute leukemia is a type of cancer in which the bone marrow makes abnormal blood cells. Forms of acute leukemia include acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Once ALL or AML has been diagnosed, the patient and the family must be thoroughly educated about the disease and the symptoms. The patient should be instructed to seek emergent care if there are signs of a fever or bleeding. In addition, patients who receive chemotherapy should be told to avoid exposure to other people with illness, especially children with viral infections. Even though leukemic patients can resume all activities but most do not have the physical endurance to participate in intense physical activity. Finally all ALL and AML patients should adhere to a neutropenic diet that includes the following:

    • All food must be cooked.
    • No vegetables or fresh fruit is to consumed.
    • All meals are to be cooked until well done.

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    References

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    10. Silverman LB. Balancing cure and long-term risks in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):190-7.
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    13. Carneiro BA, Altman JK, Kaplan JB, Ossenkoppele G, Swords R, Platanias LC, Giles FJ. Targeted therapy of acute myeloid leukemia. Expert Rev Anticancer Ther. 2015 Jan 26:1-15.
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