Leukemia

What is leukemia?
Leukemia is cancer that starts in the tissue that forms blood. To understand cancer, it helps to know how normal blood cells form.
Normal Blood Cells
Most blood cells develop from cells in the bone marrow called stem cells. Bone marrow is the soft material in the center of most bones.
Stem cells mature into different kinds of blood cells. Each kind has a special job:

White blood cells help fight infection. There are several types of white blood cells.

Red blood cells carry oxygen to tissues throughout the body.

Platelets help form blood clots that control bleeding.
White blood cells, red blood cells, and platelets are made from stem cells as the body needs them. When cells grow old or get damaged, they die, and new cells take their place.
The picture below shows how stem cells can mature into different types of white blood cells. First, a stem cell matures into either a myeloid stem cell or a lymphoid stem cell:

• A myeloid stem cell matures into a myeloid blast. The blast can form a red blood cell, platelets, or one of several types of white blood cells.
• A lymphoid stem cell matures into a lymphoid blast. The blast can form one of several types of white blood cells, such as B cells or T cells.

The white blood cells that form from myeloid blasts are different from the white blood cells that form from lymphoid blasts.

Leukemia Cells
In a person with leukemia, the bone marrow makes abnormal white blood cells. The abnormal cells are leukemia cells.
Unlike normal blood cells, leukemia cells don't die when they should. They may crowd out normal white blood cells, red blood cells, and platelets. This makes it hard for normal blood cells to do their work.

Types of Leukemia

The types of leukemia can be grouped based on how quickly the disease develops and gets worse. Leukemia is either chronic (which usually gets worse slowly) or acute (which usually gets worse quickly):

• Chronic leukemia: Early in the disease, the leukemia cells can still do some of the work of normal white blood cells. People may not have any symptoms at first. Doctors often find chronic leukemia during a routine checkup - before there are any symptoms.
  Slowly, chronic leukemia gets worse. As the number of leukemia cells in the blood increases, people get symptoms, such as swollen lymph nodes or infections. When symptoms do appear, they are usually mild at first and get worse gradually.
  
  
  
  
• Acute leukemia: The leukemia cells can't do any of the work of normal white blood cells. The number of leukemia cells increases rapidly. Acute leukemia usually worsens quickly.

The types of leukemia also can be grouped based on the type of white blood cell that is affected. Leukemia can start in lymphoid cells or myeloid cells. See the picture of these cells. Leukemia that affects lymphoid cells is called lymphoid, lymphocytic, or l
ymphoblastic leukemia. Leukemia that affects myeloid cells is called myeloid, myelogenous, or myeloblastic leukemia.
There are four common types of leukemia:

• Chronic lymphocytic leukemia (CLL): CLL affects lymphoid cells and usually grows slowly. It accounts for more than 15,000 new cases of leukemia each year. Most often, people diagnosed with the disease are over age 55. It almost never affects children.

• Chronic myeloid leukemia (CML): CML affects myeloid cells and usually grows slowly at first. It accounts for nearly 5,000 new cases of leukemia each year. It mainly affects adults.

• Acute lymphocytic (lymphoblastic) leukemia (ALL): ALL affects lymphoid cells and grows quickly. It accounts for more than 5,000 new cases of leukemia each year. ALL is the most common type of leukemia in young children. It also affects adults.

• Acute myeloid leukemia (AML): AML affects myeloid cells and grows quickly. It accounts for more than 13,000 new cases of leukemia each year. It oc curs in both adults and children.

Hairy cell leukemia is a rare type of chronic leukemia.

Risk Factors

When you're told that you have cancer, it's natural to wonder what may have caused the disease. No one knows the exact causes of leukemia. Doctors seldom know why one person gets leukemia and another doesn't. However, research shows that certain risk factors increase the chance that a person will get this disease.
The risk factors may be different for the different types of leukemia:

• Radiation: People exposed to very high levels of radiation are much more likely than others to get acute myeloid leukemia, chronic myeloid leukemia, or acute lymphocytic leukemia.
• Atomic bomb explosions: Very high levels of radiation have been caused by atomic bomb explosions (such as those in Japan during World War II). People, especially children, who survive atomic bomb expl osions are at increased risk of leukemia.
• Radiation therapy: Another source of exposure to high levels of radiation is medical treatment for cancer and other conditions. Radiation therapy can increase the risk of leukemia.
• Diagnostic x-rays: Dental x-rays and other diagnostic x-rays (such as CT scans) expose people to much lower levels of radiation. It's not known yet whether this low level of radiation to children or adults is linked to leukemia. Researchers are studying whether having many x-rays may increase the risk of leukemia. They are also studying whether CT scans during childhood are linked with increased risk of developing leukemia.

• Smoking: Smoking cigarettes increases the risk of acute myeloid leukemia.
• Benzene: Exposure to benzene in the workplace can cause acute myeloid leukemia. It may also cause chronic myeloid leukemia or acute lymphocytic leukemia. Benzene is used widely in the chemical industry. It's also found in cigarette smoke and gasoline.
• Chemotherapy: Cancer patients treated with certain types of cancer-fighting drugs sometimes later get acute myeloid leukemia or acute lymphocytic leukemia. For example, being treated with drugs known as alkylating agents or topoisomerase inhibitors is linked with a small chance of later developing acute leukemia.
• Down syndrome and certain other inherited diseases: Down syndrome and certain other inherited diseases increase the risk of developing acute leukemia.
• My elodysplastic syndrome and certain other blood disorders: People with certain blood disorders are at increased risk of acute myeloid leukemia.
• Human T-cell leukemia virus type I (HTLV-I): People with HTLV-I infection are at increased risk of a rare type of leukemia known as adult T-cell leukemia. Although the HTLV-I virus may cause this rare disease, adult T-cell leukemia and other types of leukemia are not contagious.
• Fa mily history of leukemia: It's rare for more than one person in a family to have leukemia. When it does happen, it's most likely to involve chronic lymphocytic leukemia. However, only a few people with chronic lymphocytic leukemia have a father, mother, brother, sister, or child who also has the disease.

Having one or more risk factors does not mean that a person will get leukemia. Most people who have risk factors never develop the disease.

Symptoms

Like all blood cells, leukemia cells travel through the body. The symptoms of leukemia depend on the number of le
ukemia cells and where these cells collect in the body.
People with chronic leukemia may not have symptoms. The doctor may find the disease during a routine blood test.
People with acute leukemia usually go to their doctor because they feel sick. If the brain is affected, they may have headaches, vomiting, confusion, loss of muscle control, or seizures. Leukemia also can affect other parts of the body such as the digestive tract, kidneys, lungs, heart, or testes.
Common symptoms of chronic or acute leukemia may include:

• Swollen lymph nodes that usually don't hurt (especially lymph nodes in the neck or armpit)
• Fevers or night sweats
• Frequent infections
• Feeling weak or tired
• Bleeding and bruising easily (bleeding gums, purplish patches in the skin, or tiny red spots under the skin)
• Swelling or discomfort in the abdomen (from a swollen spleen or liver)
• Weight loss for no known reason
• Pain in the bones or joints

Most often, these symptoms are not due to cancer. An infection or other health problems may also cause these symptoms. Only a doctor can tell for sure.

Anyone with these symptoms should tell the doctor so that problems can be diagnosed and treated as early as possible.

Diagnosis

Doctors sometimes find leukemia after a routine blood test. If you have symptoms that suggest leukemia, your doctor will try to find out what's causing the problems. Your doctor may ask about your personal and family medical history.
You may have one or more of the following tests:

• Physical exam: Your doctor checks for swollen lymph nodes, spleen, or liver.
• Blood tests: The lab does a complete blood count to check the number of white blood cells, red blood cells, and platelets. Leukemia causes a very high level of white blood cells. It may also cause low levels of platelets and hemoglobin, which is found inside red blood cells.
• Biopsy: Your doctor removes tissue to look for cancer cells. A biopsy is the only sure way to know whether leukemia cells are in your bone marrow. Before the sample is taken, local anesthesia is used to numb the area. This helps reduce the pain. Your doctor removes some bone marrow from your hipbone or another large bone. A pathologist uses a microscope to check the tissue for leukemia cells.
  
  There are two ways your doctor can obtain bone marrow. Some people will have both procedures during the same visit:
• Bone marrow aspiration: The doctor uses a thick, hollow needle to remove samples of bone marrow.
• Bone marrow biopsy: The doctor uses a very thick, hollow needle to remove a small piece of bone and bone marrow.

Hemophilia

What is hemophilia?

Hemophilia is not one disease but rather one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting. The term is most commonly used to refer to two specific conditions known as hemophilia A and hemophilia B, which will be the main subjects of this article. Hemophilia A and B are distinguished by the specific gene that is mutated (altered to become defective) and codes for a defective clotting factor (protein) in each disease. Rarely, hemophilia C is encountered, but its effect on clotting is far less pronounced than A or B.

Hemophilia A and B are inherited in an X-linked recessive genetic pattern and are therefore much more common in males. This pattern of inheritance means that a given gene on the X chromosome expresses itself only when there is no normal gene present. For example, a boy has only one X chromosome, so a boy with hemophilia has the defective gene on his sole X chromosome (and so is said to be hemizygous for hemophilia). Hemophilia is the most common X-linked genetic disease.Although it is much rarer, a girl can have hemophilia, but she would have to have the defective gene on both of her X chromosomes or have one hemophilia gene plus a lost or defective copy of the second X chromosome that should be carrying the normal genes. If a girl has one copy of the defective gene on one of her X chromosomes and a normal second X chromosome, she does not have hemophilia but is said to be heterozygous for hemophilia (a carrier). Her male children have a 50% chance of inheriting the one mutated X gene and thus has a 50% chance of inheriting hemophilia from their carrier mother.

Hemophilia A occurs in about 1 out of every 5000 live male births. Hemophilia A and B occurs in all racial groups. Hemophilia A is about four times more common than B; B occurs in about 1 out of 20- 34,000 live male births.Hemophilia has been called the Royal Disease because Queen Victoria, Queen of England from 1837 to 1901, was a carrier। Her daughters passed the mutated gene on to members of the royal families of Germany, Spain, and Russia. Alexandra, Queen Victoria's granddaughter, who became Tsarina of Russia in the early 20th century when she married Tsar Nicholas II, was a carrier. Their son, the Tsarevich Alexei, suffered from hemophilia.

What causes hemophilia?

As mentioned above, hemophilia is caused by a genetic mutation. The mutations involve genes that code for proteins that are essential in the blood clotting process. The bleeding symptoms arise because blood clotting is impaired.The process of blood clotting involves a series of complex mechanisms, usually involving 13 different proteins classically termed I through XIII and written with Roman numerals। If the lining of the blood vessels becomes damaged, platelets are recruited to the injured area to form an initial plug. These activated platelets release chemicals that start the clotting cascade, activating a series of 13 proteins known as clotting factors. Ultimately, fibrin is formed, the protein that crosslinks with itself to form a mesh that makes up the final blood clot. The protein involved with hemophilia A is factor VIII (factor 8) and with hemophilia B is factor IX (factor 9).

What are the signs and symptoms of hemophilia?

Hemophilia can vary in its severity, depending upon the particular type of mutation (genetic defect). The degree of symptoms depends upon the levels of the affected clotting factor. Severe disease is defined as <1%>With severe hemophilia (A or B), bleeding begins at an early age and may occur spontaneously. Those with mild hemophilia may only bleed excessively in response to injury or trauma. Female carriers of hemophilia have variable degrees of factor activity; some may have near normal levels and do not show any bleeding tendencies, while some may have less than the predicted 50% reduction and may bleed more often than non-carrier females.

In severe hemophilia, bleeding episodes usually begin within the first 2 years of life. Heavy bleeding after circumcision in males is sometimes the first sign of the condition. Symptoms may develop later in those with moderate or mild disease. The bleeding of hemophilia can occur anywhere in the body. Common sites for bleeding are the joints, muscles, and gastrointestinal tract. Specific sites and types of bleeding are discussed below.

• Hemarthrosis (bleeding into the joints) is characteristic of hemophilia. The knees and ankles are most often affected. The bleeding causes distension of the joint spaces, significant pain, and over time, can be disfiguring. Over time, joint destruction occurs, and joint replacement surgeries can be required.
  
  
• Bleeding into the muscles may occur with hematoma formation (compartment syndrome).
  
  
• Bleeding from the mouth or nosebleeds may occur. Bleeding after dental procedures is common, and oozing of blood from the gums may occur in young children when new teeth are erupting.
  
  
• Bleeding from the gastrointestinal tract can lead to blood in the stool.
  
  
• Bleeding from the urinary tract can lead to blood in the urine (hematuria).
  
  
• Intracranial hemorrhage (bleeding into the brain or skull) can lead to symptoms such as nausea, vomiting, and/or lethargy.
  
  
• Increased bleeding after surgery or trauma is characteristic of hemophilia

How is hemophilia diagnosed?

The majority of patients with hemophilia have a known family history of the condition. However, about one-third of cases occur in the absence of a known family history. Most of these cases without a family history arise due to a spontaneous mutation in the affected gene. Other cases may be due to the affected gene being passed through a long line of female carriers.

If there is no known family history of hemophilia, a series of blood tests can identify which part or protein factor of the blood clotting mechanism is defective if an individual has abnormal bleeding episodes.

The platelet (a blood particle essential for the clotting process) count should be measured as well as two indices of blood clotting, the prothrombin time (PT) and activated partial thromboplastin time (aPTT). A normal platelet count, normal PT, and a prolonged aPTT are characteristic of hemophilia A and hemophilia B. Specific tests for the blood clotting factors can then be performed to measure factor VII or factor IX levels and confirm the diagnosis.

Genetic testing to identify and characterize the specific mutations responsible for hemophilia is also available in specialized laboratories.

Is it possible to know if you are a carrier of hemophilia?

Since men with the genetic mutation will have hemophilia, a man who does not have the condition cannot be a carrier of the disease. A woman who has a son with known hemophilia is termed an obligate carrier, and no testing is needed to establish that she is a carrier of hemophilia.

Women whose carrier status is unknown can be evaluated either by testing for the clotting factors or by methods to characterize the mutation in the DNA. The DNA screening methods are generally the most reliable.

Prenatal diagnosis is also possible with DNA-based tests performed on a sample obtained through amniocentesis or chorionic villus sampling. Most individuals are seen and tested by consultants who specialize in genetically linked diseases।

What are treatments for hemophilia?

The mainstay of treatment is replacement of the blood clotting factors. Clotting factor concentrates can be purified from human donor blood or made in the laboratory using methods that do not use donor blood. This type of therapy is known as replacement therapy. Clotting factor replacement therapy is carried out by infusing the clotting factor concentrates into a vein, much like a blood transfusion. This type of therapy can be administered at home with proper instruction and training.

Depending upon the severity of the condition, replacement therapy may be carried out on an as-needed basis (called demand therapy) or on a regular basis to prevent bleeding episodes (known as prophylactic therapy).

People who have mild cases of hemophilia A are sometimes treated with the drug desmopressin, also known as DDAVP. This drug stimulates release of more clotting factor by the body. It is administered either slowly through the intravenous route (IV) oroccasionally, in nasal spray form.

Pain relievers may be prescribed for symptom relief, but pain relievers other than aspirin or non-steroidal anti-inflammatory medications (such as naproxen, ibuprofen) must be used, since these types of drugs further inhibit the blood's ability to clot. Acetaminophen (Tylenol and others) is often given for pain relief.

What are complications of treatment?

Inhibitors

A major complication of treatment is the development of so-called inhibitors to the clotting factors. Inhibitors (antibodies) are produced because the body sees the factor concentrates used to treat patients to reduce or prevent bleeding, as foreign and activates an immune response in the patient to destroy the foreign substances (factor VIII or factor IX).

Inhibitors to factor VIII are the mostcommon and occur inabout one-third of those with severe hemophilia A and about 1 out of every 50 people with mild or moderate hemophilia A. They typically develop in childhood in those with severe hemophilia A and later in life in milder cases. Inhibitors destroy both the replacement factor VIII concentrates as well as any factor VIII that is present in the body. This is a serious complication of treatment because the factor concentrates are no longer effective in treating the condition. The action of inhibitors to destroy factor VIII concentrates shows different degrees of severity among individuals and can even vary over time in the same individual.

In about two-thirds of cases, the inhibitors disappear on their own or with treatment known as immune tolerance therapy (ITT) or immune tolerance induction (ITI). In cases of severe hemophilia A with persistence of inhibitors, other factor concentrates, such as activated prothrombin complex concentrate or recombinant factor VIIa, are administered to attempt to help control bleeding.The development of inhibitors to factor IX is much less common and occurs in about 1% of those with hemophilia B। However, these can cause a very serious allergic reaction when factor IX concentrates are given. Immune tolerance therapy to eliminate inhibitors is less successful than with hemophilia A.

Infections

Blood-borne infections, such as the HIV virus and hepatitis B and C, were a major complication of treatment for hemophilia during the 1980s. These infections were transmitted through the factor concentrates and other blood products that were used to treat hemophilia. The use of large blood donor pools to prepare factor concentrates and the lack of specific tests for infectious agents both contributed to the contamination of blood products used to treat hemophilia. By 1985, about 90% of people with severe hemophilia were infected with the HIV virus, and about half of all people with hemophilia were HIV-positive. Today, improved screening and manufacturing practicesincluding virus removing techniques as well as the development of recombinant factors have essentially eliminated this tragic complication of treatment.

Can hemophilia be prevented?

Hemophilia is a genetic (inherited) disease and cannot be prevented. Genetic counseling, identification of carriers through molecular genetic testing, and prenatal diagnosis are available to help individuals understand their risk of having a child with hemophilia.

What is the outlook (prognosis) for hemophilia?

Before factor concentrates were developed, those with hemophilia had a significantly decreased life expectancy. Life expectancy before the 1960s for those with severe hemophilia was limited to 11 years. Currently, the mortality (death) rate for males with hemophilia is twice that of healthy males. As me

ntioned before, the increase in HIV and hepatitis infections associated with therapy during the 1980s led to a corresponding increase in death rates.

Currently, prompt and adequate treatment can greatly reduce the risks of life-threatening bleeding episodes and the severity of long-term damage to joints, but joint deterioration remains a chronic complication of hemophilia।

What are possible future treatments for hemophilia?

Multiple trials and studies are underway to examine the possibility to use gene therapy to replace the defective genes in hemophilia. To date, stable and sustained production of the deficient clotting factors

has not been achieved in humans, but this is an area of active investigation that holds great promise for the future.

Hemophilia At A Glance

• Hemophilia is one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting.
  
  
• Hemophilia A and B are inherited in an X-linked recessive genetic pattern, so males are commonly affected while females are usually carriers of the disease.
  
  
• Hemophilia A is caused by a deficiency of clotting Factor VIII, while hemophilia B (also called Christmas disease) results from a deficiency of Factor IX.
  
  
• Hemophilia varies in its severity among affected individuals.
  
  
• Symptoms include excessive bleeding from any site in the body; long-term damage to joints from repeated bleeding episodes is characteristic.
  
  
• Treatment involves coagulation factor replacement therapy.
  
  
• The formation of inhibitors to the treatment factor concentrates is a significant complication of treatment.
  
  
• Gene therapy treatments are a source of active research and hold promise for the future.

Blood Transfusion

Introduction

A blood transfusion is the transfer of blood or blood products from one person (donor) into another person's bloodstream (recipient). This is usually done as a life saving maneuver to replace blood cells or blood products lost through severe bleeding, during surgery when blood loss occurs or to increase the blood count in an anemic patient. The following material is provided to all patients and/or their family members regarding blood transfusions and the use of blood products. Although in most situations the likelihood of a blood transfusion associated with surgery is uncommon, at times patients may require blood products. You are encouraged to discuss your particular risk of transfusion with your doctor.

Your options may be limited by time and health factors, so it is important to begin carrying out your decision as soon as possible. For example, if friends or family members are donating blood for a patient (directed donors), their blood should be drawn at least two working days prior to the anticipated need to allow adequate time for testing and labeling. You are also encouraged to check with your insurance company for their reimbursement policy.

The safest blood product is your own, so if a transfusion is likely, this is your lowest risk choice. Unfortunately this option is usually only practical when preparing for elective surgery. In most other instances the patient can not donate their own blood due to the acute nature of the need for blood. Although you have the right to refuse a blood transfusion, this decision may hold life-threatening consequences. If you are a parent deciding for your child, you as the parent or guardian must understand that in a life-threatening situation your doctors will act in your child's best interest to insure your child's health and well being in accordance with standards of medical care regardless of religious beliefs. Please carefully review this material and decide with your doctor which option(s) you prefer.

To assure a safe transfusion make sure your healthcare provider who starts the transfusion verifies your name and matches it to the blood that is going to be transfused.

If during the transfusion you have symptoms of shortness of breath, itching, fever or chills or just not feeling well, alert the person transfusing the blood immediately.

Blood can be provided from two sources: autologous blood (using your own blood) or donor blood (using someone else's blood).

Autologous Blood (using your own blood)

Pre-operative donation - donating your own blood before surgery. The blood bank draws your blood and stores it until you need it during or after surgery. This option is only for non-emergency (elective) surgery. It has the advantage of eliminating or minimizing the need for someone else's blood during and after surgery. The disadvantage is that it requires advanced planning which may delay surgery. Some medical conditions may prevent the pre-operative donation of blood products.

Intra-operative autologous transfusion - recycling your blood during surgery. Blood lost during surgery is filtered, and put back into your body during surgery. This can be done in emergency and elective surgeries. It has the advantage of eliminating or minimizing the need for someone else's blood during surgery. Large amounts of blood can be recycled. This process cannot be used if cancer or infection is present.

Post-operative autologous transfusion - recycling your blood after surgery. Blood lost after surgery is collected, filtered and returned to your body. This can be done in emergency and elective surgeries. It has the advantage of eliminating or minimizing the need for someone else's blood during surgery. This process can't be used in patients where cancer or infection is present.

Hemodilution - donating your own blood during surgery. Immediately before surgery, some of your blood is taken and replaced with IV fluids. After surgery, your blood is filtered and returned to you. This is done only for elective surgeries. This process dilutes your own blood so you lose less concentrated blood during surgery. It has the advantage of eliminating or minimizing the need for someone else's blood during surgery. The disadvantage of this process is that only a limited amount of blood can be removed, and certain medical conditions may prevent hemodilution.

Apheresis - donating you own platelets and plasma. Before surgery, your platelets and plasma, which help stop bleeding, are withdrawn, filtered and returned to you when you need it later. This can be done only for elective surgeries. This process may eliminate the need for donor platelets and plasma, especially in high blood-loss procedures. The disadvantage of this process is that some medical conditions may prevent apheresis, and in actual practice it has limited applications.

Donor Blood (Using someone else's blood)

All donor blood is tested for safety making its risks very small, but no screening program is perfect and risks, such as contraction of the hepatitis virus or other infectious disease still exist.

Volunteer blood - blood collected from the community blood supply (blood banks). This has the advantage of being readily available, and can be life-saving when your own blood is not available. The disadvantage is that there is a risk of disease transmission, such as hepatitis or AIDS, and allergic reactions.

Designated donor blood - blood is collected from the donors you select. You can select people with your own blood type who you feel are safe donors. Like volunteer blood, there is still a risk of disease transmission, such as hepatitis and AIDS, and allergic reactions. This process usually requires several days for advanced donation. It may not necessarily be safer than volunteer donor blood.

Blood Transfusion At A Glance

• Transfusion of your own blood (autologous) is the safest method but requires planning ahead and not all patients are eligible.
  
  
• Directed donor blood allows the patient to receive blood from known donors.
  
  
• Volunteer donor blood is usually readily available and when properly tested has a low incidence of adverse events.
  
  
• Blood conserving techniques are an important aspect of limiting transfusion requirements.