Myelogenous leukemia


Myelogenous leukemia

Description, Causes and Risk Factors:

Myelogenous leukemia is a fast-growing cancer of the blood and bone marrow. In myelogenous leukemia, the bone marrow makes many unformed cells called blasts. Blasts normally develop into white blood cells [WBCs] that fight infection. However, the blasts are abnormal in myelogenous leukemia. They do not develop and cannot fight infections. The bone marrow may also make abnormal red blood cells [RBCs] and platelets. The number of abnormal cells (or leukemia cells) grows quickly. They crowd out the normal red blood cells, white blood cells and platelets the body needs.

More than 25000 new cases occur in The United States each year, mostly in elderly people. The average age of a person with myelogenous leukemia is 65 years. Fewer than 10% of people with myelogenous leukemia are children.

Hematopoiesis in normal cells involves the differentiation of a stem cell into myelocytes, lymphocytes, and megakaryocytes. In myelogenous leukemia, this process of cell differentiation is interrupted in those cells committed to the myeloid lineage. Some reports have supported the concept of a single transformed hematopoietic stem cell, whereas others have contended that transformation can occur at any point from stem cell to lineage-committed progenitor cell. This transformation can occur either as a de novo event or associated with previous therapy.

Several molecular and genetic lesions have been identified in myelogenous leukemia, leading to advances in defining its pathogenesis. The most familiar of these is the t(15;17) translocation, resulting in myelogenous leukemia with abnormal promyelocytes, known as acute promyelocytic leukemia (APL). Translocation of these chromosomes results in the fusion of the retinoic acid receptor gene alpha on chromosome 15, with the PML gene on chromosome 17, giving rise to a fusion product that prevents differentiation to mature granulocytes. This block in differentiation can be overcome with all-trans retinoic acid (ATRA), a vitamin A derivative. The DNA-binding subunit core-binding factor b (CBFb) produces a transcription factor that regulates numerous hematopoietic-specific genes. The genetic translocations t(8;21), inv(16), and t(16;16) have all been associated with this transcription factor. Myelogenous leukemia patients with these genetic disorders have a better prognosis. Six percent to 8% of patients with myelogenous leukemia have structural alterations of 11q23, leading to the MLL rearrangement. The MLL gene rearrangement, also known as mixed lineage leukemia, may lead to myelogenous leukemia composed of both myeloid and lymphoid cells. The MLL gene rearrangement portends a worse outcome in patients with acute myelogenous leukemia.

Causes & Risk Factors:

    Chromosomal instability in several autosomal dominant conditions can lead to acute myelogenous leukemia, including Fanconi's anemia, ataxia-telangiectasia, neurofibromatosis, and Bloom's syndrome.

  • Germline mutations in the AML-1 gene are known to be associated with an increased risk of the development of acute myelogenous leukemia. Additionally, congenital immunodeficiency disorders. including infantile X-linked agammaglobulinemia and Down syndrome, have also been associated with an increased incidence of acute myelogenous leukemia.

  • Several studies demonstrate a relationship between radiation exposure and acute myelogenous leukemia. Early radiologists (before the use of appropriate shielding) were found to have an increased likelihood of developing leukemia. Patients receiving therapeutic irradiation for ankylosing spondylitis were at increased risk of acute myelogenous leukemia. Survivors of the atomic bomb explosions in Japan were at a markedly increased risk for the development of leukemia. Persons who smoke have a small but statistically significant (odds ratio, 1.5) increased risk of developing acute myelogenous leukemia. In several studies, the risk of myelogenous leukemia was slightly increased in people who smoked compared with those who did not smoke. Exposure to benzene is associated with aplastic anemia and pancytopenia. These patients often develop acute myelogenous leukemia. Many of these patients demonstrate M6 morphology.

  • Myelogenous leukemia can affect both children and adults.

Myelogenous leukemia is more commonly diagnosed in developed countries, and it is more common in Whites mainly (Americans, Australians, & Europeans) than in other populations.

Symptoms:

The symptoms of myelogenous leukemia are caused by low numbers of healthy blood cells and high numbers of leukemia cells.

    White blood cells [WBCs] fight infection. Low numbers of WBCs can lead to fever and frequent infections.

  • Red blood cells [RBCs] carry oxygen throughout the body. Low numbers of RBCs can lead to anemia — feeling tired or weak, being short of breath and looking pale are the most common symptoms.

  • Platelets control bleeding. Low numbers platelets can lead to easy bleeding or bruising and tiny red spots under the skin (petechiae).

  • High numbers of leukemia cells may cause pain in the bones or joints.

Other General Symptoms:

    A high fever.

  • A large number of infections over a short period.

  • Breathlessness (shortness of breath).

  • Fatigue.

  • Hyperhidrosis (sweating a lot).

  • Pallor.

  • Easy skin bruising.

  • Swollen liver.

  • Swollen lymph nodes (glands).

  • Swollen spleen.

  • Unexplained regular bleeding, of perhaps the nose or gums.

  • Unexplained weightloss.

  • If the affected cells get into the central nervous system (CNS) there may be headaches, blurred vision, dizziness, fits (seizures) and vomiting.

Diagnosis:

Blood studies: Which generally may include, but not limited to,

    Complete blood count (CBC).

  • Coagulation studies.

  • Peripheral blood smear.

  • Blood chemistry profile.

  • Blood culture.Appropriate cultures should be obtained in patients with fever or signs of infection, even in the absence of fever.

Other Tests:

    Bone marrow aspiration & biopsy.

  • Perform human leukocyte antigen (HLA) or DNA typing in patients who are potential candidates for allogeneic transplantation.

  • Flow cytometry.

Imaging studies: Imaging studies generally needed as precautionary measures, which may include chest radiograph, electrocardiography, MUGA scanning, etc.

Treatment:

Myelogenous leukemia treatment has two phases, Induction Therapy and Post-remission Therapy (continuation therapy). Treatment will be done under supervision of Multidisciplinary Approach especially Hematologist and Oncologist.

    Induction Therapy - the aim is to destroy as many leukemia cells as possible and achieve remission. The following drugs may be used: idarubicin, daunorubicin, or mitoxantrone +cytarabine & thioguanine. As soon as all signs of leukemia are gone (remission), the patient enters the second phase.

  • Post-Remission Therapy - the aim is to destroy any leukemic cells that may still linger. This involves high doses of chemotherapy, with a combination of the following medications: cytarabine, cyclophosphamide, idarubicin, etoposide, daunorubicin, mitoxantrone, or cytarabine.

Patients should limit their activity to what is tolerable. They should refrain from strenuous activities (eg, lifting, exercise).

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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