Signs and Symptoms of Acute Leukemia

Acute leukemia can cause many different signs and symptoms. Most of these occur in all kinds of acute leukemia, but some are particularly common with certain subtypes.

Patients with acute leukemia often have several generalized symptoms. These can include weight loss, fever, and loss of appetite. Of course, these are not specific to acute leukemia and are more often caused by something other than cancer.

Most signs and symptoms of acute leukemia result from a shortage of normal blood cells due to crowding out of normal blood cell-producing bone marrow by the leukemia cells. As a result, people do not have enough properly functioning red blood cells, white blood cells, and blood platelets.

Anemia, a shortage of red blood cells, causes shortness of breath, excessive tiredness, and a "pale" color to the skin.

Not having enough normal white blood cells (called leukopenia), and, in particular, too few mature granuloctyes (called neutropenia or granulocytopenia), increases the risk of infections. Although leukemia is a cancer of white blood cells and patients with leukemia may have very high white blood cell counts, acute leukemia cells do not protect against infection. Thrombocytopenia, (not having enough of the blood platelets needed for plugging holes in damaged blood vessels), can lead to excessive bruising, bleeding, frequent or severe nosebleeds, and bleeding from the gums.

Spread of leukemia cells outside the bone marrow, called extramedullary spread, may involve the central nervous system (brain and spinal cord); CNS, the testicles, ovaries, kidneys, and other organs. Symptoms of CNS leukemia include headache, weakness, seizures, vomiting, difficulty in maintaining balance, and blurred vision. Some patients have bone pain or joint pain caused by the spread of leukemic cells to the surface of the bone or into the joint from the marrow cavity.

Leukemia often causes enlargement of the liver and spleen, two organs located on the right and left side respectively, of the abdomen. Enlargement of these organs would be noticed as a fullness, or even swelling, of the belly. These organs are usually covered by the lower ribs but when enlarged, they can be felt by the doctor examining the patient.

Leukemia may spread to lymph nodes. If the affected nodes are close to the surface of the body (lymph nodes on the sides of the neck, in the groin, underarm areas, above the collarbone, etc.), the patient, or health care provider may notice the swelling. Swelling of lymph nodes inside the chest or abdomen may also occur, but can be detected only by imaging tests such as Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans.

Acute myelogenous leukemia (AML), particularly the M5 or monocytic form, may spread to the gums, causing them to swell, be painful, and bleed. Spread to the skin can cause small pigmented (colored) spots that can look like common rashes. A tumerous collection of AML cells under the skin or other parts of the body is called a chloroma or granulocytic sarcoma.

The T-cell type of acute lymphocytic leukemia (ALL) often involves the thymus. An enlarged thymus can press on the nearby trachea (windpipe) causing coughing, shortness of breath, or even suffocation. The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. Growth of the leukemia cells may compress the SVC and cause swelling of the head and arms known as SVC syndrome. This can also affect the brain and can be life-threatening. Patients with SVC syndrome need immediate treatment.

Types of Specimens used in Diagnosis and Evaluation of Leukemia

If signs and symptoms suggest that a patient has leukemia, the doctor will need to sample cells from the patient's blood and bone marrow to make an accurate diagnosis. Other tissue and cell samples may also be taken in order to guide treatment.

Blood cell counts and blood cell examination: Changes in the numbers of different blood cell types and the appearance of these cells under the microscope help in the diagnosis of leukemia. Most patients with acute leukemia (ALL or AML) have too many white cells in their blood, not enough red blood cells, and not enough platelets. In addition, many of these white blood cells will be blasts, a type of cell normally found in the bone marrow but not in circulating blood. These immature cells do not function normally. Even though these findings suggest leukemia, usually the disease cannot be diagnosed for sure without obtaining a sample of bone marrow cells.

Bone marrow tests: In bone marrow aspiration a thin needle and a syringe are used to remove a small amount of liquid bone marrow (about 1 teaspoon). During a bone marrow biopsy procedure, a small cylindrical piece of bone and marrow (about 1/16 inch in diameter and 1/2 inch long) is removed with a slightly larger needle. Both samples usually are taken at the same time from the back of the hipbone. These tests are used to diagnosis leukemia and later, to tell if the leukemia is responding to therapy.

Blood chemistry tests: These tests measure the amount of certain chemicals in their blood but are not used to diagnose leukemia. In patients already known to have leukemia, these tests help detect liver or kidney problems due to damage caused by the spread of leukemic cells or to the side effects of certain chemotherapy drugs. These tests also help determine whether treatment is needed to correct abnormally low or high blood levels of certain minerals.

Excisional lymph node biopsy: A surgeon removes the entire lymph node (excisional biopsy). If the node is near the skin surface, this is a simple operation that can be done using a local anesthetic (numbing medication), but if the node is inside the chest or abdomen, general anesthesia (the patient is asleep) is used. This procedure is important in diagnosing lymphomas, but is only rarely needed with leukemias.

Lumbar puncture: A small needle is placed into the spinal cavity in the lower back (below the level of the spinal cord) to withdraw cerebrospinal fluid (CSF) to be examined for leukemia cells.

Laboratory Tests used to Diagnose and Classify Leukemia

All of the biopsy samples (bone marrow, lymph node tissue, blood, and cerebrospinal fluid) are examined under a microscope by a doctor with special training in blood and lymphoid tissue disease. The samples are usually examined by a pathologist (doctor specializing in diagnosis of disease by laboratory tests) and are often also reviewed by the patient's hematologist/oncologist (doctor specializing in medical treatment of cancer and blood diseases). The doctors will look at the size and shape of the cells and whether their cytoplasm contains granules, (microscopic collections of enzymes and other chemicals that help white blood cells fight infections).

Based on a cell's size, shape, and granules, doctors can classify bone marrow cells into specific types. An important element of this cell classification is whether the cell appears mature (resembles normal cells of circulating blood, that can fight infections and are no longer able to reproduce) or immature (lacks features of normal circulating blood cells, not effective in fighting infections, and are able to reproduce). The most immature cells are called blasts.

The percentage of cells that are blasts is a particularly important factor. Having at least 30% blasts in the marrow is generally required for a diagnosis of acute leukemia. In order for a patient to be considered to be in remission, the blast percentage must be no higher than 5%. Sometimes this examination does not provide a definite answer, and other laboratory tests are needed.

Cytochemistry: After cells from the sample are placed on glass microscope slides, they are exposed to chemical stains (dyes) that are attracted or react with to only some types of leukemia cells. These stains cause a color change that can be seen only under a microscope. For example, one stain causes the granules of most AML cells to appear as black spots under the microscope, but it does not cause ALL cells to change colors.

Flow cytometry: This technique is sometimes used to examine the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in determining the exact type of leukemia. A sample of cells is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of leukemia cells. If the sample contains those cells, the laser will cause them to give off light which is measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.

Immunocytochemistry: As in flow cytometry, cells from the bone marrow aspiration or biopsy sample are treated with special antibodies. But instead of using a laser and computer for analysis, the sample is treated so that certain types of cells change color. The color change can be seen only under a microscope. Like flow cytometry, it is helpful in distinguishing different types of leukemia from one another and from other diseases.

Cytogenetics: Normal human cells contain 46 chromosomes, pieces of DNA and protein that control cell growth and metabolism. In certain types of leukemia, part of one chromosome may be attached to part of a different chromosome. This change, called a translocation, can usually be seen under a microscope. Recognizing these translocations helps in identifying certain types of ALL and AML and is important in determining the outlook for the patient. Some types of leukemia have an abnormal number of chromosomes. For example, ALL cells with over 50 chromosomes are more sensitive to chemotherapy. Those with less than 46 are more resistant to chemotherapy. The testing usually takes about 3 weeks, because the leukemic cells must grow in laboratory dishes for a couple of weeks before their chromosomes are ready to be viewed under the microscope. The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present.

• A translocation, written as t(1:2), for example, means a part of chromosome 1 is now located on chromosome 2.
• An inversion, written as inv 16 means that part of the chromosome 16 is upside down and is now in reverse order but is still attached to the chromosome it originated from.
• A deletion, written as -7, for example indicates part of chromosome 7 has been lost.
• An addition, +8 for example, happens when all or part of a chromosome material has been duplicated, and too many copies of it are found within the cell.

Molecular genetic studies: Certain substances, called antigen receptors, occur on the surface of lymphocytes. These receptors are important in initiating a response from the immune system. Normal lymphoid cells have many different antigen receptors, which help the body respond to many types of infection.

Lymphocytic leukemias, such as ALL, however, start from a single abnormal lymphocyte, so all cells in each patient's leukemia have the same antigen receptor. Laboratory tests of the DNA, which contain information on each cell's antigen receptors, are a very sensitive way to diagnose ALL. Because different subtypes of ALL cells have different antigen receptor features, this test is sometimes helpful in ALL classification.

Tests of leukemia cell DNA can also find most translocations that are visible under a microscope in cytogenetic tests. DNA tests can also find some translocations involving parts of chromosomes too small to be seen with usual cytogenetic testing under a microscope.

This sophisticated testing is helpful in leukemia classification because many subtypes of ALL and AML have distinctive translocations. Information about these translocations may be useful in predicting response to treatment. These tests may be used after treatment to find small numbers of leukemia cells that can be missed under a microscope. See What's New In Leukemia Research for information on recent advances in genetics.

Imaging Studies

Imaging studies are ways of producing pictures of the inside of the body. There are several imaging studies that might be done in people with leukemia.

X-rays: During the course of diagnosis and evaluation of a person with leukemia, a chest x-ray and a bone scan are often obtained. These may show a mass in the chest, or evidence of leukemia in the bones or rarely in the joints.

Computed tomography (CT scan): This is a special kind of x-ray, in which the beam moves around the body, taking pictures from different angles. These images are then combined by a computer to produce a detailed cross-sectional picture of the inside of the body. CT scans are not often used in leukemia, but they can show enlargement of lymph nodes around the heart and trachea (windpipe) or in the back of the abdomen due to spread of leukemia cells. Involvement of these areas is more common in ALL than in AML.

Magnetic resonance imaging (MRI): This procedure uses powerful magnets and radio waves to produce computer-generated pictures of internal organs. The pictures look very similar to a CT scan, but are more detailed. This scan may be used when there is concern about leukemia involving the brain.

Gallium scan and bone scan: For this procedure, the radiologist injects a radioactive chemical that collects in areas of cancer or infection. This accumulation of radioactivity can then be viewed by a special camera. These tests are useful when a patient has bone pain that might be due to bone infection or cancer involving bones. This test is not used when the patient has already been diagnosed with leukemia.

Ultrasound: This test uses sound waves to produce images of internal organs. The test can distinguish solid from fluid-filled masses. It can help to show whether the kidneys, liver, or spleen have been affected by leukemia.