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What is Leukemia:

From the Greek meaning "white blood". Leukemia is a cancer of a marrow cell. The term refers to a group of closely related malignant conditions affecting the immature blood-forming cells in the bone marrow. so is that certain cells in the body become abnormal. Another is that the body keeps producing large numbers of white cells.


Under normal circumstances, cells are formed, mature, carry out their function, and die. New cells are constantly being formed to take their places. Normal blood contains 3 major groups of cells: white blood cells, red blood cells, and platelets. All 3 types develop from one immature cell type called stem cells in a process called hematopoiesis.
 


In humans, the bones are not solid, but are made up of two distinct regions. The outer, weight-bearing area is hard, compact, and calcium-based. It surrounds a lattice-work of fibrous bone known as cancellous tissue. The inner region, or marrow - which is one of the largest organs of the body - is located within the bones.

 

The marrow may contain fat cells, fluid, fibrous tissue, blood vessels, and hematopoietic, or blood-forming, cells. Marrow looks yellow when it holds many fat cells; it appears red when it has more blood-forming material. The marrow is the principal site for hematopoiesis (blood formation), which, after birth, occurs primarily within the bones of the legs, arms, ribs, sternum (breastbone), and vertebrae (backbones).

 


 

 

Leukemia occurs when immature or mature cells multiply in an uncontrolled manner in the bone marrow. It is classified as lymphocytic or myeloid, according to the type of cell that is multiplying abnormally, and either acute, signifying rapidly progressing disease with a predominance of highly immature (blastic) cells, or chronic, which denotes slowly progressing disease with greater numbers of more mature cells

 

 

What Causes Leukemia:

 

The exact cause of most cases of leukemia is not known. But doctors have found that this cancer is linked to a number of risk factors.

  • Smoking is considered a risk factor for leukemia, as for other cancers, but many people who have leukemia never smoked, and many people who smoke never get leukemia. Potential leukemia-causing chemicals in tobacco smoke include benzene, polonium-210, and polycyclic aromatic hydrocarbons (PAHs). These carcinogens (cancer-causing substances) are absorbed by the lungs and are spread via the bloodstream. It is estimated that one in four cases of acute myelogenous leukemia (AML) is the result of cigarette smoking.

  • Long-term exposure to chemicals such as benzene or formaldehyde, typically in the workplace, is considered a risk factor for leukemia, but this accounts for relatively few cases of the disease.

  • Exposure to extraordinarily high doses of radiation is a risk factor, although this accounts for relatively few cases of leukemia. It is important to note, however, that standard diagnostic X-rays pose little or no increase in leukemia risk.

Other risk factors for leukemia include the following:

  • Previous chemotherapy: Drugs called alkylating agents used to treatment certain types of cancers are linked to development of leukemia later.  Acute myelogenous leukemia (AML) has been reported after chemotherapy and/or radiotherapy for various solid tumors (breast cancer, ovarian cancer), blood malignancies, and nonmalignant conditions. The chemotherapeutic agents most often associated with secondary leukemias are procarbazine, chlorambucil, etoposide, mechlorethamine, teniposide, and cyclophosphamide. The risk is increased when these drugs are combined with radiation therapy.

  • Human T-cell leukemia virus 1 (HTLV-1): Infection with this virus is linked to human T-cell leukemia. Excess leukemias also have been reported in workers who are exposed to animal viruses - for example, butchers, slaughterhouse workers, and veterinary practitioners.

  • Myelodysplastic syndrome: This blood disorder increases the risk of acute myelogenous leukemia.

  • Down syndrome and other genetic diseases: Leukemia risk is increased 15-fold among children with Down's syndrome, which is a genetically linked chromosomal abnormality (usually an extra copy of chromosome 21). Three rare inherited disorders - Fanconi's anemia, Bloom's syndrome, and ataxia telangiectasia - also have a greatly increased risk of leukemia. In addition, leukemia varies among racial and ethnic groups with different genetic make-ups.

  • Family history: Having a first-degree relative who has chronic lymphocytic leukemia increases your risk of having the disease by as much as 4 times that of someone who does not have an affected relative.

  • Age - Roughly 60% to 70% of leukemias occur in people who are older than 50.

    Translocations are another type of DNA problem that can lead to leukemia. Human DNA is packaged in 23 pairs of chromosomes. If DNA from one chromosome gets attached to the wrong chromosome, cancer can result.

     

Types of Leukemia:

 

Bone marrow, the material filling the body's bones, is the adult source of the body's blood cells and produces two blood cell lines, the myeloid and the lymphoid.

Myeloid Cell Line. The myeloid cell line includes early cells that mature into red blood cells, blood clotting agents (platelets), and some white blood cells. These white blood cells include macrophages, eosinophils, and neutrophils.

Lymphoid Cell Line. The lymphoid cell line includes two of the body's primary infection fighters known as T-cell and B-cell lymphocytes . Part of their role is to produce antibodies, factors that can target and attack specific foreign agents (antigens) in the body.

Depending on the types of cell the disease appears in one of four major forms:

  • Acute lymphocytic leukemia- Acute lymphocytic leukemia, also called acute lymphoblastic leukemia and acute lymphoid leukemia, is a common leukemia. About 4,000 new cases are diagnosed each year in the United States. Most cases of acute lymphocytic leukemia (ALL) occur in children under age 10, but it can appear in all age groups. ALL is an acute leukemia, which means it is a disease that gets worse quickly.

  • Acute myelogenous leukemia characterized by the uncontrolled proliferation and accumulation of abnormal immature cells, referred to as leukemic blasts. These cells fill the marrow spaces and enter the blood.

  • Chronic myelogenous leukemia - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate, and

  • Chronic lymphocytic leukemia are less rapidly progressive.

The former, however, requires treatment in nearly all cases at the time of diagnosis, whereas the later may, in some cases, be non-progressive for long periods

 

 

Symptoms of Leukemia:

 

Broad symptoms of leukemia may include:

  • Fatigue

  • Malaise (vague feeling of bodily discomfort)

  • Abnormal bleeding

  • Excessive bruising

  • Weakness

  • Reduced exercise tolerance

  • Weight loss

  • Bone or joint pain

  • Infection and fever

  • Abdominal pain or "fullness"

  • Enlarged spleen, lymph nodes, and liver

  • Chronic leukemia often goes undetected for many years until it is identified in a routine blood test. In fact, nearly one in five chronic leukemia patients have no symptoms at the time of their diagnosis. Most symptoms of acute leukemia are caused by a lack of normal blood cells. This is due to overcrowding of the blood-forming bone marrow by leukemia cells.

Signs of Blood Abnormalities
Once the patient's blood is tested, signs of specific blood abnormalities may be noted, such as:

  • Anemia - a low number of erythrocytes (red blood cells) within the blood. Anemia can cause fatigue, "pale" skin coloration, and respiratory difficulties such as shortness of breath.

  • Leukopenia - a low number of normal leukocytes (white blood cells) that may increase the risk of infection. A reduction in WBC count is also encountered with toxemia and septicemia.

  • Neutropenia (granulocytopenia) - too few mature neutrophils, the mature bacteria-destroying white blood cells that contain small particles, or granules.

  • Thrombocytopenia - a low number of blood-clotting platelets that can result in excessive bruising, abnormal bleeding, or frequent bleeding of the nose or gums.

  • Thrombocytosis - a high number of platelets. Some patients, especially those with chronic myelogenous leukemia (CML), may exhibit thrombocytosis, although their platelets may not clot properly, causing bruising and bleeding difficulties.

  • Because leukemia may cause enlarged spleen (splenomegaly) and enlarged liver hepatomegaly (enlarged liver), the overgrowth of these organs may appear as belly "fullness" or swelling. Such fullness may be palpated (felt) by the physician during physical examination. Lymph node enlargement may or may not be apparent, although imaging studies should be able to confirm any lymphatic disease.

  • Leukemia that has spread to the brain may produce central nervous system effects, such as headaches, seizures, weakness, blurred vision, balance difficulties, or vomiting.

Certain forms of leukemia produce more distinct symptoms. For example, acute myelogenous leukemia (AML), particularly the M5 monocytic form, may generate tell-tale symptoms such as:

  • swollen, painful, and bleeding gums - if AML has spread to the oral tissue;

  • pigmented (colored) rash-like spots - if AML has spread to the skin; or

  • chloromas - if AML has spread to the skin or other organs.

The T-cell variety of acute lymphocytic leukemia (ALL) may cause the thymus to enlarge and press on the trachea (windpipe). Such pressure may lead to:

  • shortness of breath,

  • coughing, or

  • suffocation.

If the overgrown thymus presses upon the superior vena cava (SVC), the large vein that carries blood from the head and arms back to the heart, this may produce SVC syndrome. SVC involvement of the brain can be fatal.

 

 

Diagnosis of Leukemia:

 

The following methods may be used to diagnose leukemia:

 

  • The signs and symptoms may suggest a diagnosis of leukaemia. On examination there may be enlarged lymph glands, hepatomegaly and/or splenomegaly.

  • A urine sample is checked for blood.

  • Blood tests such as a full blood count will check the number of each type of white blood cell in the sample. It will indicate the presence of anaemia or a reduction in the number of platelets.

  • A blood film is done to check the appearance of the blood cells. This involves taking a very small amount of blood from the sample and smearing it on a slide, which is then viewed under a microscope. Immature or abnormal blood cells can be seen on the slide.

  • Bone marrow biopsy involves the removal of some bone and marrow from the sternum or the hipbone. This is usually done under local anaesthetic, although in small children general anaesthetic may be required. The sample of bone marrow is spread on a slide and examined under a microscope.

 

 

  • Special tests such as flow cytometry are used to detect markers on blood cells that help identify the type of leukemia.

A beam of light (usually laser light) of a single frequency (colour) is directed onto a hydrodynamically focused stream of fluid. A pair of detectors are aimed at the point where the stream passes through the light beam; one in line with the light beam and one perpendicular to it. Each suspended particle passing through the beam scatters the light in some way, and chemicals in the particle may be excited into emitting light at a lower frequency than the light source. This combination of scattered and fluorescent light is picked up by the two detectors, and by analyzing fluctuations in brightness and frequency at each detector it is possible to deduce various facts about the physical and chemical structure of each individual particle.

  • X-rays, ultrasound, computed tomography (CT) scans or magnetic resonance imaging (MRI) may be required to check if leukaemic cells have been deposited around the body

 

 

Treatment of Leukemia:

 

Chemotherapy, radiotherapy and bone marrow transplant (BMT) are used to treat leukaemia. There are different types of chemotherapy (called protocols) each involving a number of anticancer drugs given at the same time.

The effectiveness of treatment for leukaemia depends on the type and stage of the disease. Acute leukaemia often goes into remission. However, many people with acute leukaemia have a relapse (the disease returns).

Chronic leukaemias develop more slowly than the acute types, but respond less well to chemotherapy and are rarely cured.

 

Acute leukaemia

Acute leukaemia is treated with chemotherapy to destroy the abnormal cancer cells. Mixtures of drugs are given into a vein in a series of treatment courses.

 

Medicines are available which reduce the side-effects of chemotherapy such as nausea. Hair may fall out during treatment but it re-grows once the chemotherapy has stopped. Some people may be able to use "cold caps" which cool the scalp and help prevent hair loss.

If the leukaemia returns (relapses), intensive treatment may be given. This involves a bone marrow or a stem cell transplant. Bone marrow or stem cell transplants allow much higher doses of chemotherapy to be given.

Before transplantation, very high doses of chemotherapy and sometimes radiotherapy are given to destroy all the bone marrow, both abnormal and normal. This improves the chance of completely curing the leukaemia.

Then normal bone marrow cells, donated from a close relative or carefully removed from the person's own bone marrow, are infused into the bloodstream with a drip.

Stem cell transplant involves transplanting stem cells, rather than bone marrow cells. Stem cells can be harvested (collected) from a leukaemia patient's own blood or from a donor. New alternatives, which are currently experimental, include harvesting stem cells from umbilical cord blood or placentas of new born babies.

 


 

SKIN-TUNNELED CATHETER

A skin-tunneled catheter is a flexible plastic tube passed through the skin of the chest and inserted into the subclavian vein, which leads to the heart.  It is often used in people who have leukaemia or other cancers and need to have regular chemotherapy and blood tests.  Using the catheter, drugs can be injected directly into the bloodstream and blood samples can be obtained easily.

 

The catheter is inserted under local anaesthesia and can remain in position for months.  The external end is plugged when not in use.  Because the catheter is inserted through the skin some distance away from the site of entry into the vein, the risk of infection is reduced.

 

Using the catheter

The catheter is tunneled under the skin and enters the subclavian vein to lie with its tip in the heart.  A syringe can be attached to inject drugs.

 

 

Chronic leukaemia

Treatment for chronic leukaemia depends on its type and stage. Often treatment is not started unless there are symptoms. In the early stage, treatment aims to control symptoms by reducing the number of abnormal cells in the blood.
 

Biological therapy may be an option for certain types of leukaemia, such as chronic myeloid leukaemia (CML). This involves treatment with natural substances.
 

As the condition becomes more advanced, treatment may consist of mild chemotherapy, blood transfusion and antibiotics for infections. Some evidence indicates that in chronic myeloid leukaemia, bone marrow transplantation can prolong life if performed during its chronic phase.
 

Another available treatment is monoclonal antibodies. Antibodies are proteins that are produced by certain cells in response to infection. They usually attach themselves to bacteria or viruses and help to destroy them. A type of specifically manufactured monoclonal antibody that recognizes and selectively destroys leukaemia cells can be infused into the body. An example is alemtuzumab (MabCampath), which is used to treat chronic lymphocytic leukaemia (CLL).
 


 

Bone Marrow Transplant

The choice of treatment and timing of BMT depends on a number of factors including the patient's age and general health, and the type and stage of the leukaemia. In a bone marrow transplant, cancerous or abnormal bone marrow is replaced with healthy marrow.  Before the transplant, the recipient's abnormal bone marrow is eliminated by chemotherapy or radiotherapy.  Healthy marrow may have been supplied by a donor or by the patient when the underlying disease was inactive.  Up to 1 litre (2 pints) of bone marrow may be extracted from the hipbone with a syringe through a hollow needle.

BMT may be allogenic or autologous. Allogenic BMT requires a donor, often a relative, whose tissue type is a match for that of the patient. With autologous BMT some of the patient's own bone marrow is removed, treated with chemotherapeutic drugs to kill all the abnormal cells and frozen to be used later.

With both types of BMT the patient receives high doses of chemotherapy and radiation to destroy their bone marrow and any leukaemic cells in the body. The donor, or autologous bone marrow, is then injected into the patient. BMT requires specialized care and support to prevent infection or rejection of the bone marrow.

Transplantation procedures are difficult, and side effects are common. They include nausea, vomiting, fatigue, mouth sores, and loss of appetite. The procedures can also be dangerous and carry a small risk for death. One of the most serious side effects of both bone marrow and stem cell transplants is the risk of infection, which can persist for several months after the transplant. Pneumonia, cytomegalovirus, aspergillus, and Pneumocystis carini I (a protozoan) are among the most important life-threatening infections.

 

Dated 19 January 2013

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