Myeloblastic leukemia


Myeloblastic leukemia

Description, Causes and Risk Factors:

Alternative Name: Leukemic myelosis, acute granulocytic leukemia, acute non-lymphocytic leukemia, acute myelogenous leukemia, acute myeloblastic leukemia.

The cells that make up blood are produced in the bone marrow and the lymph system.

    The bone marrow is the spongy tissue found in the large bones of the body.

  • The lymph system includes the spleen, the thymus, and the tonsils. In addition, the lymph vessels and lymph nodes are also part of the lymph system. The lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest.

The main types of cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play a part in the clotting of the blood.

The white blood cells can be further subdivided into three main types:

    Granulocytes. A mature granular leukocyte, including neutrophilic, acidophilic, and basophilic types of polymorphonuclear leukocytes, i.e., respectively, neutrophils, eosinophils, and basophils.

  • Monocytes: A relatively large mononuclear leukocyte (16-22 ?m in diameter), that normally constitutes 3-7% of the leukocytes of the circulating blood, and is normally found in lymph nodes, spleen, bone marrow, and loose connective tissue. When treated with the usual dyes, monocytes manifest an abundant pale blue or blue-gray cytoplasm that contains numerous, fine, dustlike, red-blue granules; vacuoles are frequently present; the nucleus is usually indented, or slightly folded, and has a stringy chromatin structure that seems more condensed where the delicate strands are in contact. They are also important in defending the body against pathogens.

  • Lymphocytes: A white blood cell formed in lymphatic tissue throughout the body (e.g., lymph nodes, spleen, thymus, tonsils, Peyer patches, and sometimes in bone marrow) and in normal adults making up approximately 22-28% of the total number of leukocytes in the circulating blood. Lymphocytes are generally small (7-8 ?m), but larger forms are frequent (10-20 ?m); with Wright (or a similar) stain, the nucleus is deeply colored (purple-blue), and is composed of dense aggregates of chromatin within a sharply defined nuclear membrane; the nucleus is usually round, but may be slightly indented, and is eccentrically situated within a relatively small amount of light blue cytoplasm that ordinarily contains no granules; especially in larger forms, the cytoplasm may be fairly abundant and include several bright red-violet fine granules; in contrast to granules of the myeloid series of cells, those in lymphocytes do not yield a positive oxidase or peroxidase reaction. Lymphocytes are divided into 2 principal groups, termed T and B cells, based on their surface molecules as well as function. Natural killer cells, which are large granular lymphocytes, represent a small percentage of the lymphocyte population.

Myeloblastic leukemia is the cancer of the white blood cells (WBCs). In most cases of myeloblastic leukemia, the body makes many immature WBCs called myeloblasts, which crowd the bone marrow and prevent it from making normal blood cells. Because the bone marrow cannot function properly, it cannot produces adequate number of red blood cells (RBCs), normal white blood cells (WBCs), and platelets. This make people with myeloblastic leukemia more susceptible to anemia, recurrent infection, and to bruising and bleeding easily. This abnormal blast cells eventually spill out into the blood stream and can accumulate in various organs like the spleen and liver.

Phases:

    Chronic phase: In this phase there are few blasts (fewer than 5%) in the blood and bone marrow. There may be no symptoms or symptoms may be mild. This phase can last for a few months to several years. Most cases of are diagnosed at this phase.

  • Accelerated phase: The number of blast cells increases to about 15%. This phase can last weeks to months.

  • Blastic phase or blast crisis: More than 30% of cells are blasts. Sometimes blast cells will form tumors outside of the bone marrow in the bone or lymph nodes.

There are no known causes of myeloblastic leukemia. There certain factors that may put some people at a higher risk of developing myeloblastic leukemia. They may include:

    Radiation: People exposed to large doses of radiation are more likely to develop ML. People who have received large doses of radiation therapy for the treatment of cancers also have an increased risk of developing ML.

  • Genetic Factors: Although myeloblastic leukemia is not inherited, genetic factors may play a role in its development. Some congenital disorders associated with the development of ML. These include Down's syndrome, Bloom's syndrome, and Fanconi's anemia. In very rare cases, myeloblastic leukemia develops because of abnormal gene is passed down from one generation to the next.

  • Chemicals: Exposures to high level of benzene over a long period of time may increases the risk of some blood disorder like ML.

  • Smoking: Exposure to cancer-causing substance such as tobacco smoke increases the risk of developing ML. About 20% cases of myeloblastic leukemia are linked to smoking.

  • Preexisting blood disorders: People with preexisting blood disorders include myelodysplastic disorder, myelofibrosis, aplastic anemia, paroxysmal nocturnal hemoglobinuria have an increased risk of developing ML.

Ongoing Research Data:

    Heterozygous mutations in exon 12 of the nucleophosmin member 1 (NPM1) gene, resulting in abnormal cytoplasmic expression of its protein product, nucleophosmin, have recently been reported in 46% to 62% of AML (acute myeloblastic leukemia) patients with a normal karyotype, thus becoming the most frequent genetic alterations in this cytogenetic group of AML.

  • Mutations of CEBPA, a gene encoding a myeloid transcription factor that plays an important role in normal granulopoiesis, have been detected in 15% to 20% of AML patients with normal cytogenetics.

  • MLL-PTD was the first molecular alteration shown to impact on clinical outcome of cytogenetically normal adults with de novo AML. It is detected in approximately 5% to 10% of the patients and usually involves exons 5 through 11 or, less frequently, exons 5 through 12. In 30% to 40% of patients with the MLL-PTD a FLT3-ITD is also found, whereas CEBPA or NPM1 mutations are rarely found together with MLL-PTD.

  • Overexpression of the ETS-related gene (ERG) is a recently identified molecular marker predicting adverse outcome in karyotypically normal AML patients. ERG overexpression was also detected in a subset of cytogenetically normal AML, raising the possibility that it might also be associated with poor prognosis in this cytogenetic subgroup of AML.

  • Gene-expression profiling: Relatively little information on the clinical usefulness of gene-expression profiling in AML is available at present.

Symptoms:

The symptoms of acute myeloid leukemiausually come on quickly, within daysor weeks. Myeloblastic leukemia makes people sick byinterfering with normal bone marrowfunction. The leukemia cells replace andcrowd the normal bone marrow cells,resulting in low blood cell counts. Thelack of red blood cells results in anemia,which is a condition that causes a personto be tired and pale. Other symptoms may include:

    Weight loss or lack of appetite.

  • Fatigue.

  • Fever.

  • Bone or joint pain.

  • Swelling in the abdomen.

  • Lumps or rashes on the skin.

  • Swollen and bleeding gums.

  • Night sweats.

Diagnosis:

Other malignancies that should be differentiated from myeloblastic leukemia may include acute lymphocytic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, tumor such as neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma, bone marrow invasion by NHL (non-Hodgkin lymphoma), juvenile chronic arthritis, myeloproliferative syndrome, aplastic anemia, and autoimmune cytopenia.

A doctor who suspects leukemia may start by obtaining a thorough medical history. The doctor may then conduct a very thorough physical examination to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, enlarged liver or spleen, bruises, or pinpoint red rashes all over the body are among the signs of the disease. In addition, the physician may examine the teeth and look for dental abscesses, and may explore whether back pain is present.

Tests:

    Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count. This count will give the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia. Patients suffering from myelocytic leukemia may have high leukocyte counts and typically have low counts of both red blood cells and platelets. Many patients with myelocytic leukemia have low counts of all of the major components of the blood.

  • A microscopic exploration of the blood will usually show that leukemic blast cells are present. However, the diagnosis has to be confirmed by more specific tests.

  • The doctor may also perform a bone marrow aspiration and biopsy to confirm the diagnosis of myelocytic leukemia. Aspiration involves the withdrawal of a liquid sample of marrow. During the biopsy, a cylindrical piece of bone and marrow is removed. The tissue is generally taken out of the hipbone. These samples are sent to the laboratory for examination.

  • Cytogenetic studies, which examine the number and shape of the chromosomes in the DNA (deoxyribonucleic acid) of individual blast cells, should be conducted in addition to the immunophenotyping of cells of the bone marrow. This procedure involves applying various stains to the marrow cells. These stains help doctors identify some of the proteins lying on the surface of the cells.

Imaging: Standard imaging tests such as x rays may be used to check whether the leukemic cells have invaded other areas of the body, such as the bones, chest, kidneys, abdomen, or brain. Other tests, such as CT scans (computed tomography scans), MIR (magnetic resonance imaging), or gallium scans, are not typical for myelocytic leukemia may also be performed.

Treatment:

The primary objective in treating patients with myeloblastic leukemia is to induce remission and thereafter prevent relapse. Remission is conventionally defined morphologically by the presence of fewer than 5 percent blasts in bone marrow together with the recovery of peripheral-blood counts. More sensitive immunologic and molecular genetic methods are now available, which should be able to characterize remission status more accurately; however, they have not yet been extensively validated clinically. Treatment is conventionally divided into two phases: induction and postinduction.

Treatment Options:

    Chemotherapy: Uses drugs to kill cancer cells. Drugs that go into the bloodstream can reach cancer cells in most part of the body. Drugs that go into the spinal fluid can reach cancer cells that spread to the brain and spinal cord.

  • Radiation Therapy: Uses high energy x-rays to kill cancer cells. Radiation therapy may be given to the patients with high-risk leukemia to treat cancer cells in the brain and spinal cord. The treatment may also keep cancer cells from spreading to those part of the body.

  • Stem cell transplantation: Replaces blood cells killed after high dose chemotherapy and radiation with stem cells that can make new blood cells.

  • Immunotherapy: Uses drugs that kill cancer cells directly or help the immune system kill those cells.

Treatment Phases:

    Phase I: For most patients, the standard first phase of myelocytic leukemia treatment is induction chemotherapy. The goal of induction chemotherapy is to bring the disease into remission. Remission is when the patient's blood counts return to normal and bone marrow samples show no sign of disease (less than 5% of cells are leukemia cells).

  • Phase II: The second phase of chemotherapy is often called consolidation chemotherapy. The goal of consolidation chemotherapy is to destroy any remaining leukemia cells. Consolidation chemotherapy is used to treat many patients with myelocytic leukemia. The second phase of treatment is based on a patient's risk factors. It is important to discuss your risk factors and your treatment options with a doctor who is experienced in treating myelocytic leukemia.

For some patients, a bone marrow or cord blood transplant may offer the best chance for a long-term remission. A transplant is a strong treatment with risks of serious side effects, so it is not used for all patients with myelocytic leukemia. A transplant is used when chemotherapy alone is unlikely to provide a long-term remission.

Types of transplants:

    Autologous transplant: An autologous transplant uses blood-forming cells collected from the patient. If an autologous transplant is a treatment option for you, you will have blood-forming cells collected from your blood stream. The cells are usually collected after one or two cycles of consolidation treatment. The cells are frozen until you are ready for transplant. You may receive an autologous transplant soon after your induction therapy is completed, or your cells may be saved as a backup option in case you relapse after receiving consolidation chemotherapy.

  • Allogeneic transplant: An allogeneic transplant replaces the abnormal cells in a patient's bone marrow with healthy blood-forming cells from a family member or unrelated donor or cord blood unit. An allogeneic transplant has a higher risk of serious side effects than consolidation chemotherapy or an autologous transplant. However, the risk of relapse is lower after an allogeneic transplant.

Side effects of treatment usually present.

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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