Acute Myelogenous Leukemia
Acute Myelogenous Leukemia (AML) is a cancer of the blood. It is a rapidly progressing disease that results in the accumulation of immature cells in the marrow and blood.
“There is no level of benzene exposure that does not raise the risk of developing AML.”
Egilman, D.
Because it is a disease of the blood cells, AML does not usually form a solid mass or tumor. Click here to see frequently asked questions about blood and marrow.
Although AML starts in the bone marrow, it can spread to the blood, lymph nodes, spleen, liver, central nervous system and other organs.
AML Etiology - Causes of the Disease [Top]
Acute myelogenous leukemia (AML) is the acquired (not inherited) genetic damage to the DNA of developing cells in the bone marrow.AML is also known as an acute non-lymphocytic leukemia (ANLL).
Exogenous toxicants like benzene, irradiation (radiation), cytotoxic (chemotherapy) drugs, and cigarette smoking are known causes of AML that have been established within the biological and epidemiological communities.
Epidemiological studies done during the 1970’s clearly established benzene as cause of AML. Dr. Martyn Smith
Occupational exposure to benzene.
AML begins in the bone marrow when abnormalities develop in the blast cells (immature cells) to form granulocytes, the small particles or granules found in the white blood cells.
Uncontrolled, exaggerated growth and accumulation of cells called "leukemic blasts," which fail to function as normal blood cells.
This causes an obstruction of the production of normal marrow cells, leading to a deficiency of red cells (anemia), platelets (thrombocytopenia) and normal white cells (especially neutrophils, i.e. neutropenia) in the blood.
Signs and Symptoms [Top]
Most patients diagnosed with AML report the following symptoms:
- Feeling a loss of well-being;
- General lack of energy, complaints of being tired;
- Shortness of breath when physically active;
- Pale complexion due to anemia;
- Unexplained appearance of black and blue marks;
- Bruises occurring for no reason or from a minor injury;
- Petechiae, pin-head-sized purple or brownish red discoloration or spots under the skin;
- Prolonged or excessive bleeding from minor cuts or after surgery;
- Mild fever;
- Swollen and bleeding gums, or rare excessive gum tissue growth;
- Swollen ankles;
- Bleeding with urination, opening the bowel, or heavy menstrual periods;
- Frequent minor infections like pustules or lesions, tonsillitis, sinusitis or pneumonia;
- Slow healing of cuts;
- Swelling of liver, spleen or lymph nodes;
- Discomfort in bones or joints (normally considered to be arthritis).
What Diseases May Precede the Diagnosis of AML? [Top]
Myelodysplastic syndromes (MDS)
- MDS includes a group of diseases which are blood-cell related cancers that originate in the bone marrow’s immature blood-forming cells;
- The use of the suffix “dysphasia” is misleading because they are really “neoplastic diseases” (the abnormal and rapid new growth of similar cells);
- The disorders found in the multi-potent bone marrow stem cells are too few red blood cells, white blood cells and often platelets;
- With approximately 50% of patients being asymptomatic, diagnosis is usually found during a routine medical examination;
- Most common in adults over 50 years of age with a history of benzene exposure, radiation therapy , or exposure to alkylating agents (chemotherapy drugs) within 8 years;
- Drugs that stimulate the production of blood cells may be useful in treatment;
- Some severe cases may require chemotherapy;
- Constant medical surveillance is required due to the potential manifestation of bone marrow myeloblasts increasing the risk of evolution to AML;
- Curative therapy and prognosis is poor if patient is elderly and bone marrow transplantation treatment is unavailable;
- The most common treatment option uses immunosuppresion techniques. Click here for more information.
Aplastic Anemia
- A marked deficiency of all three types of blood cells but no noticeable abnormalities in blood cell function or shape;
- Aplastic anemia requires examination of the bone marrow for diagnostic confirmation;
- Benzene-based compounds, airplane glue, insecticides, chemotherapy drugs and chloramphenicol (some oral antibiotics) have been clearly linked to aplastic anemia;
- Aplastic Anemia is considered a medical emergency and severe cases require immediate hospitalization;
- Blood transfusions can correct the deficiency of the red blood cells;
- Antibiotics are necessary to combat infection because white blood cells have an extremely short life span;
- Considered a close parallel to acute and chronic myelogenous leukemia. Progression to AML or CML increases dramatically in patients over 60 years old;
- Aplastic Anemia is immediately treated with a blood transfusion, antibiotics to fight infection, and isolation to prevent outside contact. Bone marrow transplantation and drug therapy are also commonly used to treat this blood disorder. Click here for more information.
Pancytopenia
- A marked reduction in the number of all three types of blood cells, red blood cells, white blood cells, and platelets;
- Findings of two or more “cytopenias” in a benzene-exposed individual suggests a more advanced form of toxicity.
Polycycthemia Vera
- An abnormal excess in the number of erythrocytes (red blood cells) causing an increase in blood volume. This makes the blood thicker and less able to freely flow through small blood vessels;
- A very rare disease that afflicts approximately 5 of every 1 million people. The average age of diagnosis is 60 and is more frequently found in men;
- Treatment objective is to decrease thickness of blood by removing 1 pint weekly until red blood cell levels return to their normal level;
- Polycycthemia Vera usually develops slowly, but problems can be eliminated with proper treatment;
- Side effect include an Increased risk of blood clots, strokes and heart attacks;
- Caution is necessary because other bone marrow cells may begin to grown abnormally and lead to AML.
World Health Organization [Top]
In order to diagnose and classify AML and myelodysplasic syndromes (MDS) doctors need to obtain clinical data of the morphology, cytochemistry, immunophenotype, cytogenetics and molecular nature of the leukemia blasts.
The WHO has recommended that all of the above characteristics be identified and considered when diagnosing AML. Taking measures to classify them into four (4) groups helps develop and refine treatment strategies.
- AML with “recurrent cytogenetic translocations” - Most commonly identified abnormalities are reciprocal translocations. Molecular studies show that the structural chromosomal rearrangements involve a committed precursor and high rate of complete remission.
- mAML: Multineage AML - Defined by the presence of multineage dysplasia after cytological analysis. Commonly found in elderly patients with gain or loss of major segments of chromosomes
- Secondary AML - Patients have a long standing of benzene exposure. Detailed occupational history is of the utmost importance. Patients may have a history of prolonged administration of chemotherapy agents or radiation. This classification is characterized by a short latency period that rapidly evolves into AML.
- Morphological and Immunophenotype Classification - This last group is necessary to include all other situations with blast cells and maturation of different cell lineages in the bone marrow. The diagnosing criteria is based on bone marrow aspirates.
What is the Clinical History of a Patient Diagnosed with AML? [Top]
- The average patient is 65 years of age when diagnosed with AML.
- AML affects more men than women, and is a little more common among whites than blacks.
- Smoking, especially after age 60.
- Complaints of nagging fatigue.
- A thorough medical and family history must be acquired during initial examination to rule out genetic hemoglobin abnormalities, previous chemotherapy or radiation therapy.
- Has an occupational history of benzene exposure.
- Death can occur within months if untreated.
How many Americans are diagnosed with (AML each year? [Top]
- It is estimated that 11,920 cases of AML will be diagnosed each year.
- At least 11 times as many adults as children were diagnosed.
- 56% of those cases were male and 44% were female.
- AML diagnoses comprise 36% of all leukemia cases each year.
- From 1995 to 2000, only 19.5% of adult AML patients survived.
- Approximately 8870 people with AML will die each year.
Sources [Top]
- Department of Labor, State of Michigan; www.michigan.gov
- Agency for Toxic Substances and Disease Registry; www.atsdr.cdc.gov
- Atlas of Genetics and Cytogenetics in Oncology and Hematology; www.infrobiogen.fr/services/chromcancer
- The Path Guy; www.pathguy.com
- Adam, Inc.; http://adam.about.com
- PathologyOutlines.com; http://pathologyoutlines.com
- American Society of Hematology; http://www.asheducationbook.org
- National Cancer Institute; www.nci.nih.gov
- Medical Education Information Center; http://medic.uth.tmc.edu