Acute Leukemia Treatment Information

ACUTE LEUKEMIA TREATMENT INFORMATION

What is Leukemia?

Leukemia is a cancer of the blood cells. There are various types of blood cells, red blood cells to carry oxygen and white blood cells to fight infections. Also, another type of blood cell called "platelets" are fragments which assist in clotting. Amazingly, all of the various types of blood cells originate from a single type of cell, called the "pleuripotential cell", which resides in the bone marrow. Some blood cells (like the pleuripotential time) stay inside the bone marrow, while the more mature types (like red and white blood cells) are meant to circulate through the bloodstream, to go to wherever they are needed. Leukemia is usually a cancer of the white blood cells. It is divided into type general types, Acute and Chronic. This distinction is based upon their untreated behavior-- with no treatment acute leukemias will kill within months, while chronic leukemia patients may live for many years. However, there is a flipside to this--it is usually easier to cure acute leukemia than the chronic variety. Both acute and chronic leukemias are further subclassified as to the particular type of blood cell they arise from. White blood cells are larger than red blood cells and are easy to see under the microscope. Too few white blood cells ("leucopenia") leads to massive infections, with bacteria, viruses and fungi. Too few red blood cells leads to anemia, with pallor and weakness. Too few platelets lead to easy bruising and internal bleeding. Acute leukemias, unlike the chronic variety, often have normal or decreased white blood cells. A hallmark of all leukemias is insufficient production of other normal blood cells, since the resources are being diverted to the leukemic cell population (also called the "leukemic clone"). This will be seen when we look at the symptoms of leukemia.

Another crucial distinction in leukemias besides "acute" and "chronic" is between the Lymphocytic and Myelogenous types. The Lymphocytic variety comes from lymphocytes, which is a common white blood cell active in identifying and marking germs to be killed. In adults, about 1/3 of the total white blood cells are lymphocytes, and in young children up to 2/3 are lymphocytes. The Myelogenous variety comes from other blood cells besides lymphocytes, represents at least 7 different subtypes, and is often just called"non-lymphocytic" leukemia. These non-lymphocytic types may arise from the red blood cell line ("erythroleukemias") or from the platelet line ("megakaryocytic types"). Sometimes the types are found in combination, that is the disease is composed of more than one type of leukemia. Also, as the disease gets more advanced, it may start showing other "clones" instead of the "pure type" that it started as. The major divisions of acute and chronic, and lymphocytic and myelogenous, are combined into the following four labels into which all leukemias can be grouped:

ALL (Acute Lymphocytic Leukemia)
AML (Acute Myelocytic Leukemia)
CLL (Chronic Lymphocytic Leukemia)
CML (Chronic Myelogenous Leukemia)

Sometimes a previous chronic leukemia will convert into the acute variety (called "Richter's syndrome") but since the clinical behavior and treatment of the acute and chronic types are different, they are considered as two separate topics. Like all cancers, leukemia starts from a single abnormal cell, and the type of cell will determine the type of leukemia. A change occurs in the genes of this cell, that is in the information stored in the cells "DNA". Each body cell contains the information necessary to form a whole new body, but most of this is "masked" after the cell develops ("differentiates") into a particular adult cell type. The genes can be altered to command the cell to undergo uncontrolled division, and this is then cancer. Ultimately, cancer is a disease of the DNA! Different recognized genetic abnormalities are found in the various subtypes of leukemia, this is an area of active research. Anyway, the abnormal cell makes billions of copies of itself, shunting resources away from normal cells division. The "leukemic clone" takes over the bloodstream, choking off normal functioning and leading to the symptoms described below. If untreated, acute leukemia is always fatal.

How Common is Acute Leukemia?

Combining childhood and adult cases, there totals 11,000 new cases per year in the U.S.A. Acute leukemia is the most common cancer of childhood. However, only 25% of the total cases occur in children. Overall, acute leukemia strikes 5 out of 100,000 people each year.AML is 5 times more common than ALL but ALL represents 85% of cases in children. Thus, the averageALL patient is 4 years old while the averageAML patient is 60 years old. If untreated, 95% of patients will die within one year of diagnosis. The flipside of this is that most patients disease free for over four years are likely cured (as contrasted with breast cancer which commonly re-emerges years after apparently successful therapy). Overall, the risk for leukemia has been increasing over 5 decades.

What Causes or Increases the Risk for Acute Leukemia?

As for any cancer, the reason why one particular person gets acute leukemia and another does not remains unknown. However, some factors that markedly increase the chance for a person to get leukemia are well documented. "Primary" leukemia means it is the first blood cancer detected; "Secondary" leukemia arises
after treatment for some other cancer. Secondary leukemia is usuallyAML and develops an average of 5 years after treatment of another cancer. It is especially seen after treatment for Hodgkin's Disease, myeloma, lymphoma, breast or ovarian cancer. The more aggressive the the, the more likely later AML will occur.

Factors Increasing the Risk for Acute Leukemia:

1) Radiation Exposure is the best documented risk factor in adults. It causes genetic damage leading to various cancers. Fortunately, small amounts of radiation don't seem to cause leukemia, since exposure is inevitable from cosmic rays, radiation in our food (potassium-40) or emanating from metal deposits in the earth. Occasional X-rays are not associated with leukemia, but radiation therapy and atomic bomb exposure are.

2) Chemicals which increase cancer risk are called"carcinogens". They also work through the mechanism of damage to genes. The best known chemicals associated with leukemia development are benzene, toluene, mustard gas and arsenic. Drugs related to these chemicals, such as the alkylating agents (from mustard gas) used to treat cancer, or chloramphenicol (phenol) as an antibiotic, are considered "leukemogenic" (causative of leukemias). Overall, chemotherapy is considered more strongly causative of Secondary leukemia than Radiation Therapy, and both together increase the risk greater than either one alone.

3) Heredity Conditions can include gene damage increasing risk for acute leukemias. Down's syndrome (3 chromosome #21's instead of the normal 2) increases risk, and siblings of leukemia patients have a 5 times higher risk. If one identical twin gets childhood leukemia, the chance that the other twin will get it is 25%. Bloom's syn- drome patients have frequent chromosome breaks (the genes are packed along the much larger chromosomes). Fanconi's syndrome and Ataxia-Telangiectasia are other uncommon conditions with chro- mosome damage which likewise have higher leukemia development.

4) Prior Chronic Leukemia: Over 80% of patients with Chronic Myelocytic Leukemia will develop Acute Myelocytic Leukemia in the terminal stage of their disease. These patients are predominantly adults, and this type of "leukemic transformation", called"Blast Crises" , is very hard to treat.

5) Prior Blood Diseases, particularly "myelodysplastic" syndromes, also called "preleukemias" and "refractory anemias". These patients are usually over 50 years old, have abnormal blood smears, and a bone marrow which is always abnormal. These conditions may smolder for many years before becoming acute leukemia, about 30% of the time.

*** Viruses, Alcohol and Tobacco Use Haven't Been Linked to Acute Leukemia.

What are the Symptoms of Acute Leukemia?

Early Acute Leukemias will have no symptoms, as the "cancer cell burden" is insufficient to cause symptoms. As the "leukemic clone" multiplies and fills up the bone marrow, and then the circulating blood, the following symptoms may occur:

Symptoms and Signs of Acute Leukemia:

1) Infection is the most common presenting symptom (35%). This is because leukemic white blood cells don't work properly. Infections can be caused by bacteria, viruses, fungi, protozoans or parasites. Although everyone gets infections, leukemia patients get them more easily, and they tend to be harder to treat. Most patients who present with an infection have vague "flu-like" symptoms.

2) Easy Bruising or Hemorrhage (failure of the blood to clot). This is caused by a decrease in the number of circulating blood platelets, the fragments crucial to forming a clot. Low platelets ("thrombocyto- penia") can show as internal bleeding, bruising or little purple bumps on the skin surface ("petechia").

3) Fatigue and Paleness caused byanemia , which is a decrease in the number of red blood cells. About 80% of patients have some anemia, but it may be insufficient to cause symptoms.

4) Weight loss is seen in about 15% of patients. It takes lots of calories to keep the cancer cells growing.

5) Bone Pain is especially seen inALL in children. As the leukemic clone fills up the bone marrow, it pushes on nerves causing pain.

6) Abdominal Swelling may be noticed by an increase in belt size, and due to the leukemic cells filling up and stretching out the liver and spleen. This is more common with ALL than AML.

7) Glandular Swelling is caused by spread of the leukemia to lymph nodes. These are normally bean-sized kidney shaped glands which help filter blood to destroy germs. White blood cells are normally found in lymph nodes, but leukemic white cells fill them up and enlarge them. Enlarge- ment can also result from infections. Boys may have testicular swelling from leukemia growth there.

8) Nervous System problems like vision impairment, mental deterioration or leukemic infiltration of the brain lining (meningitis) are all rare but reported, especially in advanced stages of the disease.

It is important to note that all of the above symptoms are more commonly caused by other conditions besides leukemia, usually by persistent infections. The only way that leukemia can be absolutely diagnosed is via examination of blood and bone marrow, as described below.

How is Acute Leukemia Diagnosed and Evaluated?

If a patient comes to medical attention with symptoms and signs of leukemia or some other serious blood disorder, the following are standardly done:

1) Complete Physical Examination looking for paleness, infection or bruising
from lack of effective red cells, white cells and platelets respectively.
The liver and spleen are felt for enlargement, as well as the lymph gland
clusters in the neck, armpit ("axilla") and groin. In males the testicles are
examined for swelling, and a neurologic exam is done on all patients. Any new complaints such as fever, weight loss or night sweats are recorded.

2) Laboratory Tests include standard Complete Blood Count ("CBC") that checks red blood cell count, white blood cells count, and platelets. Blood "smear" is made and the shape of the blood cells are viewed under the microscope. This is the way that particular types of white blood cells are identified. The basic types are lymphocytes (30%), neutrophils (60%), Eosinophils (5%), Monocytes (3%) and Basophils (1%). Signs of infection include multi-segmented areas in the neutrophils, increased percentage of lymphocytes, or "toxic granulation" particles in these cells. Also, the actual number or white cells per cubic milliliter of blood is often above or below the normal value (4,000 - 10,000) with infections or leukemia. It is important to remember that the blood smear from the circulating blood only gives an idea of what is going on in the bone marrow, which must be examined in to diagnose leukemia (see below). Also obtained is a Chemistry Panel ("SMA") which tells blood sodium, potassium, bicarbonate, glucose, cholesterol, and liver and kidney function. Also, it tests for calcium, phosphorus and uric acid which may be abnormal. Tests of blood clotting ability arePT , PTT and bleeding time. A urinalysis ("UA") tells about infection, blood, sugar or protein in the urine.

3) Radiology Tests include standard Chest X-ray which shows pneumonia tumors in the chest. If the Chest X-ray is abnormal, a CT scan of the chest is commonly obtained. CT scans of the abdomen and pelvis, bone scans and brain scans are only obtained if there are symptoms in those areas.

4) Specialized Tests for Leukemia include Bone Marrow Biopsy. The biopsy means a special needle is stuck into the hip bone, just above the buttock, and some marrow sucked out for examination. This is usually done on each side, since two samples are more accurate than one. It is done under local anesthesia and takes about 15 minutes. The bone marrow is placed in solution and a smear made upon a microscope slide. By examining this slide, a pathologist can diagnose leukemia or other blood disorders, but not necessarily the specific subtype. We can see how many of the white blood cells are "blasts", that is new and presumably leukemic cells. We can also see how many cells the bone marrow is producing, if it is overly full of cells (which causes them to get deformed) or depleted of blood cells ("hypocellular"). Repeat tests of the bone marrow will be needed to gauge the effectiveness of therapy.

The first step is to distinguish between a lymphocytic or non-lymphocytic subtype, by looking at the cells to see if they are lymphocytes or not. The next step is to help rule-out the chance that an increased number of white blood cells is due to an infection -- that is a "leukemoid reaction". For this, a test called Lymphocyte (or Neutrophil) acid Phosphatase,("LAP") is done on the cells and the LAP score calculated. High LAP scores are more likely to mean infection. If "Auer Rods" are seen in the circulating cells, the disease will almost certainly beAML. Acute leukemia is likely if the "Philadelphia Chromosome" is seen, as it is in 10% of children and 30% of adults with AML or ALL.

There are particular staining techniques to identify the 7 subtypes of AML, the classifications of which are discussed below . A newer and more accurate way of classifying bothAML and ALL is "immunophenotyping". This means testing for surface cell markers produced by each specific type of leukemia. Immunophenotyping will tell at which stage of development the cell became leukemic, that is how "differentiated" it is. This has important treatment implications, since more differentiated leukemias tend to need more treatment to eradicate them.For lympho- cytic leukemias, immunophenotyping distinguishes between the "B" and"T" cell subtypes. This is important since the less common "T" cell subtype (20%) may require more aggressive treatment.

Spinal Tap is an important test to tell whether the fluid bathing the brain and spinal cord ("cerebral spinal fluid or CSF ") is invaded by leukemic cells. If so, then aggressive treatment will be mandatory to clear this area of disease. The spinal fluid, the brain linings it bathes ("meninges") and the testicles in males are considered "sanctuary sites" meaning that leukemic cells can hide there to escape regular treatment. Thus, it must be ascertained if these areas are involved, with spinal tap and testicular biopsy , to see if they will need extra therapy to eradicate disease there. Since these areas are often the first site of relapse after treatment, continued monitoring of them after treatment is essential to detect any relapse early.

All leukemia comes from blood cells, which normally function to provide the body's cells with oxygen (red blood cells), protect them from invading germs (white blood cells), and promote blood clotting after an injury (platelets). This system usually functions beautifully, and it's proper workings are crucial to human life. The division of these blood cells is normally under tight control. When a cell starts dividing out of control, it becomes "cancerous."

Cancer starts in just one cell! Acute leukemias are cancers of blood cells, and are one of two basic types. The first is "Acute Lymphocytic Leukemia" (ALL) which starts in a popular type of white blood cell ("lymphocyte"), and the second is "Acute Non-Lymphocytic Leukemia" (ANLL) which includes cancers arising from every other type of blood cell besides the lymphocyte.

"Acute Myelocytic Leukemia" (AML) is the most common type in this second category. It is critical to get prompt diagnosis and proper treatment for acute leukemia; this can literally make the difference between life and death. Understanding your options will give you the peace-of-mind of knowing you have done everything possible to ensure a successful outcome for yourself or a loved one.

CancerAnswers's material explains, in plain English, the definition, types, risk factors, frequency, symptoms, evaluations, historical and latest effective treatments for acute leukemia. We describe chemotherapy, radiation, immune therapy and bone marrow transplantation, along with their side-effects and results. While we don't promise cure, we tell you everything you must know to help you make the right choices today for dealing with an acute leukemia problem.

This is just an excerpt of CancerAnswers's report on Acute Leukemia. Much more, including latest treatment, can be sent to you by mail when you order the complete Acute Leukemia transcript at a nominal cost. Thank you for using CancerAnswers as your information resource.