Leukemia overview

 

Leukemia is a form of cancer that begins in the blood-forming cells of the bone marrow - soft, inner part of the bones. Leukemia - which literally means "white blood" in Greek - occurs when there is an excess of abnormal white blood cells in the blood. Known as leukocytes, these cells are so plentiful in some individuals that the blood actually has a whitish tinge.

Under normal circumstances, the blood-forming, or hematopoietic, cells of the bone marrow make leukocytes to defend the body against infectious organisms such as viruses and bacteria. But if some leukocytes are damaged and remain in an immature form, they become poor infection fighters that multiply excessively and do not die off as they should (see Types of Leukemia and Bone Marrow and Blood Formation). The leukemic cells accumulate and lessen the production of oxygen-carrying red blood cells (eythrocytes), blood-clotting cells (platelets), and normal leukocytes. If untreated, the surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, and eventually invade other parts of the body, such as the lymph nodes, spleen, liver, and central nervous system (brain, spinal cord). In this way, the behavior of leukemia is different than that of other cancers, which usually begin in major organs and ultimately spread to the bone marrow.

There are more than a dozen varieties of leukemia, but the following four types are the most common:

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Acute leukemias usually develop suddenly, whereas some chronic varieties may exist for years before they are diagnosed.

Leukemia Facts & Figures
Leukemia often is thought to be a childhood disease. In fact, leukemia strikes 10 times as many adults as children. The American Cancer Society (ACS) predicts that about 30,200 new leukemia cases - 27,900 adults and 2,300 children - will be diagnosed in the United States during 1999. Acute myelogenous leukemia (AML) is the most frequently reported form of leukemia in adults, and approximately 10,100 new cases are anticipated in 1999.

About 41% of the 30,200 latest cases will have chronic leukemia - an estimated 7,800 chronic lymphocytic leukemia (CLL) cases and 4,500 chronic myelogenous leukemia (CML) cases. In addition, hairy cell leukemia (HCL), a slow-growing lymphocytic cancer, will account for about 604 cases (2% of all leukemias). Sadly, it is estimated that approximately 22,100 American adults and children will die of leukemia in 1999.

Acute myelogenous leukemia (AML) is the most common adult form of leukemia, affecting nearly 5 in every 100,000 men each year.

Chronic leukemia, like many other cancers, is a "disease of old age." The average age of individuals with chronic lymphocytic leukemia (CLL) is roughly 70 years, and the average age of chronic myelogenous leukemia (CML) patients is 40 to 50 years. By contrast, acute lymphocytic leukemia (ALL) is largely a pediatric disease, usually appearing in children who are under 10 years of age.

In general, leukemia affects more men than women throughout the world, although the male: female ratio is highest in CLL patients in Western countries.

 

 

Bone Marrow
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. It fills the shafts of the long bones, the trabeculae (spaces within cancellous tissue), and even extends into the bony canals that hold the blood vessels.

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).

Stem Cells
Many of the blood cells that populate the arteries and veins are born and mature within the bone marrow. They are derived from hematopoietic cells called stem cells. Stem cells within the bone marrow continuously divide to form new cells. Some of the new cells remain unchanged as stem cells and have a lifelong capacity for self-renewal. These cells are called pluripotential cells. Other, unipotential stem cells have a limited capacity for self-renewal. Also known as progenitor cells, unipotential cells become committed to forming only one type of blood cell line - erythrocytes (red blood cells), leukocytes (white blood cells), or platelets. Colonies of progenitor cells provide offspring of increasing differentiation (maturity). They react to specific compounds known as poietins. Poietins stimulate the progenitor cells until they transform into the appropriate young blood cell known as a "blast" cell.

Although stem cells are few in number - composing no more than 3% to 5% of all cells in the marrow - they are the only cells capable of producing the progenitor cells that eventually form all of the blood elements. The number of blood cells produced every day is enormous: in the normal adult, production amounts to about 2.5 billion erythrocytes, 2.5 billion platelets, and 1.0 billion granulocytes (granular leukocytes) per kilogram of body weight.

If the stem cells stop functioning because of drugs, radiation, infection, or other toxic event, they become unable to make any of the blood cells. The circulating blood will be deficient in all types of blood cells, a condition known as pancytopenia. The inside of the bone marrow will appear empty and will lack the normal quantity of cells. This stem cell disorder, which is called aplastic anemia, may be treated by bone marrow transplant or immunosuppressive medications (see Stem Cell Transplantation). In rare circumstances, children with aplastic anemia may respond to therapy with steroids or androgens (male sex hormones); such treatments are generally discouraged in adults (see Treatment of Leukemia).

Progenitor cells also may die or lose the ability to function due to drugs, radiation, infection, or other toxic event. Depending on which progenitor cells cease to work, the person may develop pure red cell aplasia (lack of red blood cells), megakaryocytic aplasia (absence of platelets) or leukopenia (low white blood cell count).

Other types of bone marrow abnormalities, such as myeloproliferative disorder, a disease in which bone marrow cells multiply outside of the bone marrow tissue, or myelodysplastic ("preleukemia") syndromes, are the result of marrow dysfunction in either the stem cells or progenitor cell lines.

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Spleen
The spleen is a vital organ that is located on the left side of the body under the lower rib cage. It is a "ductless gland" that is closely associated with the circulatory system. The adult spleen - which holds the largest collection of blood-filtering lymphatic tissue in the body - is roughly 5 inches long and weighs about 5 to 7 ounces, but these measurements vary greatly with age, nutrition, disease status, and other factors.

The spleen contains a white pulp of lymphoid tissues and a red pulp that contains red blood cells and hollow cavities called sinuses. Both red and white pulps are abundant in phagocytes, the cells that consume foreign substances within the body. The spleen manufactures lymphocytes and other immune system cells to combat infection (see Leukocytes). It is a storehouse for healthy blood cells, and its lymphatic tissue filters out old and damaged blood cells, microorganisms, and cell waste. In case of bone marrow malfunction, the spleen may assume the role of blood cell formation.

Certain leukemia patients may develop splenomegaly - an enlarged spleen. In some forms of leukemia, such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), splenectomy (removal of the spleen) may be an effective form of treatment (see Types and Treatment of Leukemia). Splenectomy is one of many therapeutic options for HCL

Thymus Gland
The thymus gland is, to some extent, an "age-dependent" organ. It functions to create T lymphocytes (T-cells) in the developing fetus, attains its full size after a child is 2 years of age, and then shrinks to a nearly undetectable size by puberty (adolescence).

The thymus is located in front of the heart. It has two lobes and contains thymocytes (immature lymphocytes), epithelial cells (cells that cover the internal and external body surfaces, including the lining of blood vessels, etc.), and macrophages (large cells that ingest microorganisms and other foreign substances; (see Leukocytes, Monocytes). T-cells primarily are responsible for cell-mediated immunity and immune system regulation. Within the thymus, immature pre-T cells develop and are able to recognize antigens (substances capable of starting a specific immune system response, e.g., bacteria, foreign proteins, etc.). The immature pre-T cells then migrate to other lymphoid tissues, such as the spleen and lymph nodes, where they mature and undergo additional differentiation. Although the thymus shrinks with age, it continues to aid immune system function throughout a person's lifetime.

Lymph Nodes
The lymph nodes are small oval or bean-shaped capsules that are strung along the a length of vessels that channel lymph and chyle on the way back to the blood. Lymph is the transparent, slightly yellow, liquid that is collected from the body's tissues, and chyle is the milky fluid taken from food in the intestine during digestion. They contain collections of lymphocytes (specialized white blood cells; nongranular leukocytes; see Leukocytes), plasma cells (antibody-releasing cells), and macrophages (large cells that ingest foreign substances and help lymphocytes to launch immune system responses).

The lymph nodes are arranged along the route of large blood vessels and are concentrated in areas such as the abdomen, underarms, groin, and neck. Small sacs called follicles within the lymph nodes contain B lymphocytes (B-cells). T-cells deep within the lymph nodes play a role in the induction of B-cell responses. B-cells eventually mature into plasma cells that produce antigen-specific antibody, which is an immune system chemical that is directed against a specific foreign substance.

During an infection, the lymph nodes increase in size, especially in infants and children. They return to normal after the infection has passed. Occasionally, a lymph node that appears permanently enlarged may reflect a cancerous condition. For example, in rare instances, leukemia that has spread outside of the bone marrow may cause enlargement of a lymph nodes(s).

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Erythrocytes (Red Blood Cells)
The erythrocytes, or red blood cells ("corpuscles"), contain hemoglobin - a substance that is able to bind with oxygen. Oxygen from the lungs is carried by the erythrocytes to all the tissues of the body. A person who has anemia, a condition caused by too few erythrocytes in the blood, will experience symptoms such as weakness, fatigue, and shortness of breath.

Leukocytes (White Blood Cells)
There are five different types of leukocytes, or white blood cells, within the body:

These cells fight viral, bacterial, and other infections and participate in the hypersensitivity responses seen in allergic reactions.

Neutrophils, basophils, and eosinophils are granulocytes - white blood cells whose main purpose is to destroy bacteria. Granulocytes are distinguished by the small particles, or granules, that reside within each cell and contain substances to fight infections. Granulocytes undergo many stages of development before becoming mature neutrophils, basophils, or eosinophils. The more immature, myeloid series of granulocytes include cells known as myeloblasts, promyelocytes, myelocytes, metamyelocytes, band forms ("stab cells"), and polymorphonuclear leukocytes (PMNs).

If there is a "block" in the development of an individual's myelogenous (granulocytic) cell line, either chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML) may result (see Types of Leukemia).

Monocytes
Monocytes are medium-to-large mobile cells that can travel along the walls of the blood vessels and adhere to tissue surfaces. They contain cellular systems that consume foreign substances by surrounding and digesting of microorganisms and foreign particles or enveloping foreign substances within the plasma membrane. Monocytes originate in the bone marrow as immature monoblasts and promonocytes. Once these early cell forms develop into monocytes, they circulate in the bloodstream for about 24 hours. If the monocytes detect an area of inflammation, they move into tissues to become macrophages - larger phagocytic cells that help lymphocytes to detect foreign microorganisms and launch immune system responses.

Lymphatic tissue contains both fixed and circulating elements. Many different types of lymphatic cells interact to combat infections and recognize abnormal cells within the body. Fixed lymphoid tissue is found in the lymph nodes, spleen, thymus, tonsils and adenoids, bone marrow, and various sites within the gastrointestinal tract, respiratory system, and liver. Circulating lymphatic cells, such as the lymphocytes (nongranular leukocytes with a single nucleus) and monocyte/macrophage cells, originate from stem cells in the blood-forming tissues. The stem cells give rise to daughter cells that ultimately develop into B-cells or T-cells. Daughter T-cells migrate to the thymus, where they mature into T-cells. It is believed that daughter B-cells complete their development within the bone marrow.

B-cells combat infections by changing into plasma cells, which secrete antibodies. Plasma cell antibodies become attached to the invading germ, which is then recognized and destroyed by the blood granulocytes. T-cells are able to detect virus-infected cells within the body. They interact with macrophages to rid the body of the virus.

If there is a "block" in the development of an individual's lymphocytes, either chronic lymphocytic leukemia (CLL) or acute lymphocytic leukemia (ALL) may result (see Types of Leukemia).

Platelets
Although platelets are classified as a type of blood cell, they are actually just pieces of megakaryocytes - bone marrow giant cells that contain a many-lobed nucleus (cell center). Platelets are the major blood-clotting elements of the body. They group together to seal off blood vessel damage caused by cuts or other traumatic injuries.

A person with a low level of platelets in the circulating blood - thrombocytopenia - may experience excessive bleeding.

 

 

Symptoms

 

The first indications of leukemia often are nonspecific or vague. They may occur with other cancerous as well as noncancerous disorders. Although signs and symptoms vary for each type of leukemia, there are some general features. Broad symptoms of leukemia may include:

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.

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

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 (see Types of Leukemia). For example, acute myelogenous leukemia (AML), particularly the M5 monocytic form, may generate telltale symptoms such as:

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:

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 (swelling of the head and arms). SVC involvement of the brain can be fatal.

 

 

Once the physician suspects that a patient's blood is abnormal, he or she will want to perform blood and bone marrow tests to rule out leukemia (see Signs and Symptoms of Leukemia). Additional tissue samples may be needed to confirm the diagnosis or to help plan treatment.

Blood Tests
In cases of questionable leukemia, a number of blood tests are performed. Such tests evaluate the type and quantity of blood cells that are present, the blood chemistry, and other factors.

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Bone Marrow Tests
The bone marrow is sampled by a technique known as bone marrow aspiration. During this procedure, a thin hollow needle with a syringe attachment is used to suction up, or aspirate, a teaspoon-sized sample of liquid bone marrow from the back of the hip bone. A larger needle then is employed to obtain a bone marrow biopsy ("core" biopsy), which removes roughly a 1/16 inch cylindrical piece of bone marrow from the hip site. After the bone marrow samples are obtained, they are examined by many physician specialists, including a pathologist (disease diagnosis specialist, who examines samples under a microscope), hematologist (blood specialist), and oncologist (cancer specialist).

1.       Mature cells are normal cells of the circulating blood, which are functional infection-fighters that can no longer reproduce.

2.       Immature cells are undeveloped blood cells that, although poor infection-fighters, are still able to reproduce.

3.       Blast cells are the most immature form of bone marrow cells.


The samples also are categorized according to their number of cells (cellularity), because abnormal tissue may contain inappropriate proportions of blood-forming (hematopoietic) versus fat cells. Hypercellular marrow holds too many hematopoietic cells, whereas hypocellular marrow holds too few hematopoietic cells (see Bone Marrow and Blood Formation).

Researchers have found that leukemia cells often contain genetic defects known as translocations, inversions, deletions, and additions. Translocations are genetic errors that result when parts of two chromosomes are exchanged. Inversions are produced when part of a chromosome becomes inverted (upside down) and the order of its genetic material is reversed. Deletions occur when part of a chromosome is missing, and additions are caused by duplications of all or part of a chromosome.

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Imaging Studies
It is likely that the physician will want to perform imaging studies to determine whether the leukemia has invaded other organs within the body. Such studies will include:

Causes

 

Although researchers have studied the many cellular changes associated with leukemia, no one really knows why such changes occur. It is likely that certain risk factors make individuals more prone to developing leukemia. Many factors - such as age and genetics - are probably beyond our control. Other factors, such as environmental or lifestyle-related variables, may be more correctable.

It is now known that all cancers, including leukemia, begin as a mutation in the genetic material - the DNA (deoxyribonucleic acid) - within certain cells. The external or internal causes of such change probably add up over a lifetime. Leukemia begins when one or more white blood cells experience DNA loss or damage. Those errors are copied and passed on to subsequent generations of cells. The abnormal leukemic cells remain in an immature blast form that never matures properly. They do not die off like normal cells, but tend to multiply and accumulate within the body.

DNA errors also may occur in the form of translocations - damage produced when part of one chromosome becomes displaced and attached to another chromosome. Translocations disrupt the normal sequencing of the genes. As a result, oncogenes (cancer-promoting genes) on the chromosomes may be "switched on," while tumor suppressors (cancer-preventing genes) may be switched off. Many leukemias contain translocations that affect the blood cell chromosomes. Physicians often test for these translocations to help diagnose leukemia, determine a patient's prognosis, and identify cancer recurrence (see Diagnosis of Leukemia, Cytogenetics).

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Risk Factors
Numerous risk factors may be responsible for DNA damage within the blood cells. The risk factors now believed to have the strongest associations with leukemia are:

A number of reports have suggested that strong electromagnetic fields (EMF) may be a risk factor for leukemia, although other investigations have failed to confirm these findings. Therefore, National Cancer Institute (NCI) researchers are performing several large-scale studies to try to answer the question of whether or not EMF exposure poses a cancer risk. To date, most publications indicate that leukemia is not related to EMF exposure.

 

Types

 

Leukemia is classified by how quickly it progresses. Acute leukemia is fast-growing and can overrun the body within a few weeks or months. By contrast, chronic leukemia is slow-growing and progressively worsens over years.

Acute versus Chronic Leukemia
The blood-forming (hematopoietic) cells of acute leukemia remain in an immature state, so they reproduce and accumulate very rapidly. Therefore, acute leukemia needs to be treated immediately, otherwise the disease may be fatal within a few months. Fortunately, some subtypes of acute leukemia respond very well to available therapies and they are curable (see Leukemia Treatment). Children often develop acute forms of leukemia, which are managed differently from leukemia in adults.

In chronic leukemia, the blood-forming cells eventually mature, or differentiate, but they are not "normal." They remain in the bloodstream much longer than normal white blood cells, and they are unable to combat infection well.

Myelogenous versus Lymphocytic Leukemia
Leukemia also is classified according to the type of white blood cell that is multiplying - that is, lymphocytes (immune system cells), granulocytes (bacteria-destroying cells), or monocytes (macrophage-forming cells). If the abnormal white blood cells are primarily granulocytes or monocytes, the leukemia is categorized as myelogenous, or myeloid, leukemia. On the other hand, if the abnormal blood cells arise from bone marrow lymphocytes, the cancer is called lymphocytic leukemia.

Other cancers, known as lymphomas, develop from lymphocytes within the lymph nodes, spleen, and other organs. Such cancers do not originate in the bone marrow and have a biological behavior that is different from lymphocytic leukemia (see Lymphoma).

There are over a dozen different types of leukemia, but four types occur most frequently. These classifications are based upon whether the leukemia is acute versus chronic and myelogenous versus lymphocytic, that is:

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Acute Myelogenous Leukemia (AML)
Acute myelogenous leukemia (AML) - also known as acute nonlymphocytic leukemia (ANLL) - is the most common form of adult leukemia. Most patients are of retirement age (average age at diagnosis = 65 years), and more men are affected than women. Fortunately, because of recent advances in treatment, AML can be kept in remission (lessening of the disease) in approximately 60% to 70% of adults who undergo appropriate therapy (see Treatment of Leukemia). Initial response rates are approximately 65-75% but the overall cure rates are more on the order of 40-50%.

AML begins with abnormalities in the bone marrow blast cells that develop to form granulocytes, the white blood cells that contain small particles, or granules. The AML blasts do not mature, and they become too numerous in the blood and bone marrow. As the cells build up, they hamper the body's ability to fight infection and prevent bleeding. Therefore, it is necessary to treat this disease within a short time after making a diagnosis. AML, particularly in the monocytic M5 form, may spread to the gums and cause them to swell, bleed, and become painful. AML also may metastasize (spread) to the skin, causing small colored spots that mimic a rash (see Signs and Symptoms of Leukemia).

Acute leukemia, such as AML, is categorized according to a system known as French-American-British (FAB) classification (see Leukemia Staging). FAB divides AML into eight subtypes:

In addition, patients sometimes develop isolated tumors of the myeloblasts (early granulocytes). An example of this is isolated granulocytic sarcoma, or chloroma - a malignant tumor of the connective tissue. Individuals with chloroma frequently develop AML, so they usually are treated with an aggressive, AML-specific chemotherapy program.

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Chronic Myelogenous Leukemia (CML)
Chronic myelogenous leukemia (CML) is known as a myeloproliferative disorder - that is, it is a disease in which bone marrow cells proliferate (multiply) outside of the bone marrow tissue.

CML is easy to diagnose, since it has a genetic peculiarity, or marker, that is readily identifiable under a microscope. About 95% of CML patients have a genetic translocation between chromosomes 9 and 22 in their leukemic cells. This abnormality, which is known as the Philadelphia chromosome (Ph1), is named after the city in which it was discovered. The Philadelphia chromosome causes uncontrolled reproduction and proliferation of all types of white blood cells and platelets (blood clotting factors). Sadly, CML is not yet curable by standard methods of chemotherapy or immunotherapy.

CML tends to occur in middle- and retirement-aged people (the median age is 67 years). It occasionally affects people in their 20s, but it is rare in the very young; only 2% to 3% of childhood leukemias are CML. Early disease often is without symptoms (asymptomatic) and is discovered accidentally. Individuals with more advanced cases of CML may appear sickly and experience fevers, easy bruising, and bone pain. Laboratory and physical findings include enlarged spleen (splenomegaly), a high white blood cell count, and absent or low amounts of the white blood cell enzyme alkaline phosphatase (see Symptoms of Leukemia).

Like other forms of leukemia, CML is not "staged" (see Leukemia Staging). Rather, this unstable disease is categorized according to the three phases of its development: chronic, accelerated, and blast.

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Acute Lymphocytic Leukemia (ALL)
Acute lymphocytic leukemia (ALL) - also known as acute lymphoblastic leukemia - is a malignant disease caused by the abnormal growth and development of early nongranular white blood cells, or lymphocytes. The leukemia originates in the blast cells of the bone marrow (B-cells), thymus (T-cells), and lymph nodes (see Bone Marrow and Blood Formation). ALL occurs predominantly in children, peaking at 4 years of age. ALL is seen more frequently in industrialized nations, and it is slightly more common among white children and boys.

ALL often is diagnosed after a patient experiences a 4- to 6-week period of illness. Initial symptoms may include a nonspecific infection (e.g., respiratory infection) that persists or recurs despite antibiotic therapy. During this period, the person may start to experience aching bone pain in the back, limbs, and/or joints. Walking difficulties may be seen in some children who have extreme swelling of the large joints. But the symptoms that most often suggest referral for a blood count (measure of the number of blood cells within the blood) are a purplish-brown rash or the onset of excessive bruising (see Signs and Symptoms of Leukemia).

If ALL is T-cell in type, the thymus is involved. Leukemia-related enlargement of the thymus may lead to coughing, shortness of breath, or compression of the superior vena cava (SVC), the large vein that carries blood from the head and arms back to the heart). Such venous blockage may induce head and arm swelling and may cause a life-threatening condition known as SVC syndrome.

Both children and adults with ALL are at risk of developing complications due to central nervous system (CNS) involvement. CNS invasion is especially likely among patients with the L3 subtype of ALL. When leukemic cells infiltrate the CNS, they can cause increased pressure within the skull and paralysis of cranial nerves that connect the brain with other organs, muscles, etc.

Age is an important prognostic factor in ALL. Studies have suggested that patients who are younger than 35 years of age fare better than older patients; however, this observation may be related to the higher incidence of the Philadelphia chromosome (Ph1) among older ALL patients - a subgroup that has a poorer chance of survival (see Chronic Myelogenous Leukemia). Fortunately, though, 60% to 80% of children and adults with ALL will achieve complete remission of the disease after completing appropriate therapy.

There is no standard staging system for ALL (see Leukemia Staging). Rather, ALL is categorized according to a system known as the French-American-British (FAB) Morphological Classification Scheme for ALL:

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Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia is the most common leukemia in North America and in Europe. It is a disease of older adults and is very rare among people who are younger than 50 years of age. Men with CLL outnumber women by a 2-to-1 average. The disease usually is detected accidentally during a doctor's examination for an unrelated complaint.

CLL is thought to result from the gradual accumulation of mature, long-lived lymphocytes. Therefore, this cancer is caused not so much by overgrowth as it is by the extreme longevity and build-up of malignant cells. Although the rate of accumulation varies among individuals, the extensive tumor burden eventually causes complications in all CLL patients.

CLL is classified by one of two staging systems, although these systems are based on cytology (the study of cell characteristics) and are different from the staging used to evaluate other, nonleukemic cancers. The first system - known as Rai Classification - is used more often in the United States; the other system - known as Binet Staging - is more popular in Europe. Both methods are correlated with prognosis.

Rai Classification
Rai Classificationseparates chronic lymphocytic leukemia into low-, intermediate-, and high-risk categories, which correspond with stages 0, I & II, and III & IV, respectively:

Binet Staging
Binet Staging classifies CLL according to the number of lymphoid tissues that are involved (i.e., the spleen and the lymph nodes of the neck, groin, and underarms), as well as the presence of low red blood cell count (anemia) or low number of blood platelets (thrombocytopenia):

One major advantage of the Binet system is its ability to highlight the splenic form of CLL, which may have a better prognosis than when classified by the Rai system.

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Table 3: Clinical Features in Rai & Binet Staging

STAGE

LYMPHO-
CYTOSIS

LYMPHA-
DENOPATHY

HEPATOMEGALY or SPLENOMEGALY

HEMO-
GLOBIN (g/dL)

PLATE-
LETS
(x 103/µL)

RAI

 

 

 

 

 

0

YES

NO

NO

greater than 11

greater than 100

I

YES

YES

NO

greater than 11

greater than 100

II

YES

YES/NO

YES

greater than 11

greater than 100

III

YES

YES/NO

YES/NO

less than 11

greater than 100

IV

YES

YES/NO

YES/NO

ANY

less than 100 

BINET

 

 

 

 

 

A

YES

YES / NO(less than 3 nodal groups positive)

YES / NO

greater than 10

greater than 100

B

YES

YES / NO(<3 nodal groups positive)

YES / NO

less than 10

greater than 100

C

YES

YES / NO

YES / NO

less than 10

less than 100

Lymphocytosis = high numbers of lymphocytes
Lymphadenopathy = lymphatic disease
Hepatomegaly = enlarged liver
Splenomegaly = enlarged spleen

There are a few more types and subtypes of chronic leukemia, the most notable of which are hairy cell leukemia, prolymphocytic leukemia, T-cell chronic lymphocytic leukemia, and chronic myelomonocytic leukemia.

Hairy cell leukemia (HCL), like CLL, is a slow-growing lymphocytic cancer. It is distinguished by its appearance under the microscope, because the lymphocytes have many fine, "hairy" projections from their surfaces. HCL is typically a disease of middle-aged males. Most individuals report nonspecific symptoms that are partially caused by anemia. Yet HCL differs from CLL with respect management (see Treatment of Leukemia).

Both prolymphocytic leukemia (PLL) and T-cell chronic lymphocytic leukemia (T-CLL; also known as large granular lymphocyte leukemia, or LGL) are unusual forms of CLL. They are very rare, and account for only about 1% of all CLL cases. PLL, like CLL, is mostly seen in men. More than half of the cells in PLL are prolymphocytes, which are larger than CLL cells and have less condensed genetic material. T-CLL results from the reproduction of cells that resemble normal large granular lymphocytes. PLL and T-CLL are more aggressive in nature than other forms of CLL, and they are less likely to respond to treatment.

There is some dispute about the categorization of chronic myelomonocytic leukemia (CMML). Some groups consider CMML to be a "pre-leukemia," or "myelodysplastic syndrome," rather than a malignant disorder. It is a disease that is found in older individuals. Patients may be asymptomatic (without symptoms) and be diagnosed accidentally, or they may have symptoms of tiredness, bruising and/or abdominal discomfort from an enlarged spleen. CMML may be inactive, or it may progress slowly over months and years. CMML eventually transforms into an acute, usually fatal form of leukemia.

 

Stages

Most cancer patients are assigned a clinical "stage" after undergoing a diagnostic work-up. American physicians often use the four-stage TNM system - a classification system developed and recently revised by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC; International Union Against Cancer). According to this system, staging is based on the size of the tumor and how far it has spread from its original location in the body.

Because leukemia starts in the bone marrow and often has spread to other organs by the time it is detected, there is no need for traditional staging. Instead, physicians rely upon cytologic (cellular) classification systems to identify the type and subtype of leukemia. Cell classification systems, in turn, help to predict the prognosis, or outcome, of specific forms of leukemia and the likely response to treatment.

The most popular classification method for acute leukemia is the French-American-British (FAB) system. According to FAB classification, acute leukemia is divided into eight subtypes of acute myelogenous leukemia (AML) and three subtypes of acute lymphocytic leukemia (ALL) (see Types of Leukemia). FAB originally was based upon the microscopic appearance of leukemia cells; however, in recent years, researchers have discovered that cellular characteristics such as genetic make-up and numbers of specific cell types help to classify leukemia and predict its outcome.

Chronic lymphocytic leukemia (CLL) is classified by one of two cytologic staging systems, which known as Rai Classification and Binet Staging, respectively.

Leukemia is not a single disease (see Types of Leukemia). Instead, the term leukemia refers to a number of related cancers that start in the blood-forming cells of the bone marrow. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. In addition, children with leukemia have special needs that are best met by care in pediatric cancer centers. Such centers have trained medical professionals whose sole purpose is to address the unique concerns of children.

In general, there are five major approaches to the treatment of leukemia:

1.       chemotherapy to kill leukemia cells using strong anti-cancer drugs (see Chemotherapy);

2.       interferon therapy to slow the reproduction of leukemia cells and promote the immune system's anti-leukemia activity;

3.       radiation therapy to kill cancer cells by exposure to high-energy radiation (see Radiotherapy);

4.       stem cell transplantation (SCT) to enable treatment with high doses of chemotherapy and radiation therapy; and

5.       surgery to remove an enlarged spleen or to install a venous access device (large plastic tube) to give medications and withdraw blood samples.

Oncologists administer these treatments in a variety of combinations (see Chemotherapy and Radiotherapy). Each method has its advantages and drawbacks. It usually is worthwhile to get a second opinion about treatment before entering into a specific program; in some instances, a second opinion may be required by the patient's insurance company. For example, stem cell transplantation (SCT) is very costly (more than $100,000) and entails a long stay in the hospital. Some insurance companies still consider this to be an "experimental" procedure and will not pay for SCT-related expenses.

The treatment of leukemia depends on a number of factors. The most important of these are the histopathologic (diseased tissue) type of leukemia, its stage, and certain prognostic features, such as the patient's age and overall health (see Leukemia Staging).

Interferon Therapy
Interferons are a class of proteins that are released by virus-infected cells. They help normal cells to make antiviral proteins. Interferons also help the body to reduce leukemia cell proliferation (growth and reproduction), while strengthening the body's immune response.

Interferon-alpha (INFa) is a type of interferon that frequently is used to treat leukemia. In addition, based on an patient's response to INFa, a physician can better predict the anticipated length of survival.

Interferon-alpha can be given by a number of methods - that is, by injection into a vein, into a muscle, or under the skin - although subcutaneous (under the skin) injection is the customary route. INF-a usually is offered to all newly diagnosed patients who are not candidates for stem cell transplantation (see Stem Cell Transplantation). Often IFN-a is started at a low dose (e.g., 3 MIU daily), with gradual increases over time. Unfortunately, though, this drug is not without side effects. Possible IFN-related complaints include fevers, chills, muscle aches, bone pain, headaches, concentration difficulties, fatigue, nausea, vomiting, and general flu-like symptoms when starting the drug. Such symptoms usually last for 1 to 2 weeks, but may be lessened by drugs such as acetaminophen. Side effects recur if the INF-a dosage is increased, but they are temporary and usually improve after INF-a therapy is completed.

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Stem Cell Transplantation
Cancer therapy (chemotherapy, radiation therapy, etc.) can damage or destroy normal cells, as well as cancer cells. Many chemotherapeutic drugs, in particular, can harm rapidly dividing cells such as the blood-forming stem cells of the bone marrow (see Bone Marrow and Blood Formation). Yet high drug doses are needed to treat leukemia effectively. So what can be done?

Physicians have begun to solve this problem by performing stem cell transplantation (SCT). Stem cells are blood-forming (hematopoietic) cells of the bone marrow; they continuously divide to form the new blood cells that populate the arteries and veins. The SCT procedure enables physicians to give chemotherapy and radiotherapy in doses that are strong enough to eliminate leukemia cells. The injured bone marrow then is replenished by a transplant of stem cells, which can manufacture the necessary new blood cells.

Stem cells for SCT can be gathered from different sources:

The cells are carefully frozen and stored until the patient has completed high-dose treatments for leukemia. Such treatments usually consist of a 3-day course of chemotherapy (for example, with cyclophosphamide, cytarabine, etoposide, melphalan, or busulfan) with/without a 3-day course of total body irradiation (TBI) (see Chemotherapy and Radiotherapy). After therapy, the stem cells are thawed and given to the patient by means of a blood transfusion.

SCT are classified as autologous or allogeneic, based on characteristics of the cell donor. Autologous SCT, also known as autologous bone marrow transplant (autoBMT), is a procedure in which a patient's own stem cells (immature cells from which all blood cells develop) are removed from the bone marrow. This type of transplant is not frequently used, because it is very difficult to guarantee that normal stem cells have been separated from leukemic cells, even after purging, that is treatment of stem cells with drugs, immunologic agents, heat, or other substances/methods to kill or remove leukemic cells.

Another form of autologous SCT is peripheral blood stem cell transplantation, or leukapheresis. The patient's blood is passed through a machine that removes the stem cells, then returns the blood to the patient. This procedure usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any remaining leukemia cells. The stem cells are stored until they are transplanted back into the patient. Leukapheresis may be performed alone or with autoBMT, although most physicians prefer to use leukapheresis by itself.

Allogeneic SCT, also known as allogeneic bone marrow transplant (alloBMT), is a form of transplant in which the stem cells are gathered from a donor whose tissue type closely matches the patient's tissue type. Such donors usually are relatives (brother, sister, child) or, occasionally, a matched unrelated donor (MUD). AlloBMT usually is reserved for individuals who are younger than 55 and who have a compatible family donor - that is, a donor with compatible human leukocyte antigen (HLA), a protein found on the surface of some cells, such as leukocytes). Allogeneic donor cells actually may help to fight leukemia cells because they initiate a response known as the "graft versus leukemia" reaction.

If the person receives an allogeneic transplant, he or she must be treated with drugs that suppress rejection reactions (e.g., cyclosporine, methotrexate, prednisone, and antilymphocyte globulin [ALG] or antithymocyte globulin [ATG]). For example, "graft-versus-host disease" (GVHD) is a result of rejection reactions that occur in 25 to 50% of cases (see Chronic GVHD). The leukemia patient should ensure that SCT is performed at a qualified medical facility. The treatment staff should be experienced in all types of transplants, including MUD transplants, as well as patient care during the recovery period.

Transplant patients typically are kept in protective isolation in the hospital until their total white blood cell (WBC) count is above 500. During this time, the individual receives supportive care, such as intravenous nutrition, treatment with antibacterial and antifungal medications, and transfusions with red blood cells and platelets. Within 2 to 3 weeks, the stem cells usually begin to make white blood cells. Next, platelets are produced, followed several weeks later by the manufacture of red blood cells. Once the WBC count approaches 1,000, the patient generally can be discharged from the hospital. Daily outpatient check-ups may be scheduled for several weeks, followed by regular appointments over a 6-month period. The individual's oncologist usually will schedule an exam at the SCT clinic 1 year after treatment; thereafter, clinic appointments are made only if symptoms return.

Side effects due to SCT may occur shortly after treatment, or they may develop much later. Early complications usually are related to the cellular injury caused by high-dose chemotherapy and radiotherapy (for example, temporary hair loss, anemia, leukopenia, thrombocytopenia, and gastrointestinal symptoms like nausea, vomiting, and diarrhea (see Chemotherapy and Radiotherapy). Long-term or chronic complications may include:

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Surgery
Surgery does not play a major role in the management of leukemia. The reasons for this are two-fold: (1) leukemia cells usually are widespread throughout the body at the time of diagnosis, so they cannot be "cut out" like other forms of cancer; and (2) surgery is not needed for diagnosis, since bone marrow aspiration usually is adequate to confirm the disease (see Diagnosis of Leukemia).

Aside from the insertion of a venous access device (a plastic tube that is surgically implanted into a large vein in the chest or upper arm) to reduce the need for repeated needle sticks during drug injections or removal of blood samples, splenectomy (removal of the spleen) may be the only surgical procedure performed during the treatment of leukemia.

The spleen normally helps to filter out old and damaged blood cells from the circulation (see Bone Marrow and Blood Formation). If leukemia causes substantial spleen enlargement of more than 4 centimeters (> 4 cm), it may press upon other organs and cause abdominal symptoms. In addition, an overgrown spleen may become too effective in removing blood cells and cause a shortage of red blood cells or platelets. Therefore, surgical removal of the spleen is a form of therapy that may improve symptoms and blood profiles in some leukemia patients, such as individuals with chronic lymphocytic leukemia (CLL) or hairy cell leukemia. The primary danger of splenectomy, especially in people with compromised immune systems, is infection in the blood or tissues (sepsis). Microorganisms commonly involved in such sepsis include pneumococci, meningococci, E. coli, Haemophilus influenzae, and staphylococci.

 

 

Chemotherapy is a general term that is used to describe cancer-killing drugs. Such drugs can be given intravenously, through a vein; orally, by mouth; subcutaneously, injected under the skin; intramuscularly, injected into a muscle; or intrathecally, injected into the cerebrospinal fluid (CSF).

Chemotherapy for leukemia is varied, because there are many different forms of this disease. In general, though, leukemia treatment relies on combination chemotherapy with a number of different anticancer drugs. Such drugs destroy cancer cells by preventing them from growing and dividing rapidly. Unfortunately, a number of the body's normal, noncancerous cells also divide rapidly and therefore are harmed by chemotherapy. Specifically, the hair follicles, red and white blood cells, blood-clotting platelets, and cells that line the gastrointestinal system may be damaged or destroyed, causing side effects. Such side effects depend upon the type and dose of drugs taken, as well as the length of time that they are used.

Chemotherapeutic side effects may include temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea.

Tumor lysis syndrome is a specific side effect of leukemia therapy that occurs when there is a rapid breakdown of leukemia cells due to chemotherapeutic drugs. The cells split apart and release cell fragments, metabolic byproducts, and minerals into the bloodstream. These substances can damage the kidneys, heart, and nervous system. Therefore, physicians often monitor acute leukemia patients for this syndrome. They may prescribe fluids, sodium bicarbonate, and allopurinol (a drug used to reduce uric acid in the blood) to rid the body of unwanted chemicals and cell remains.

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Acute Myelogenous Leukemia (AML)
Perhaps the most common drug treatment plan AML is the combination of 3 days of an anthracycline (e.g., daunorubicin, doxorubicin) and 7 days of ara-C. This plan is known as the three plus seven method. Some oncologists also add the drug 6-thioguanine to the mix (see option 2), although most studies indicate that this agent does not improve the rates or length of remission.

Please Note: The option number does not imply that one regimen is superior over another.

Option 1: Chemotherapy with daunorubicin (Cerubidine®) or doxorubicin (Adriamycin®), plus cytarabine (ara-C;Cytosar-U®); also called "DA"

Option 2: Chemotherapy with daunorubicin (Cerubidine®) or doxorubicin (Adriamycin®), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®); also called "DAT"

Option 3: Chemotherapy with cytarabine (ara-C; Cytosar-U®) and idarubicin (Idamycin®)

Option 4: Chemotherapy with mitoxantrone (Novantrone®) and etoposide (VePesid®)
**not FDA-approved for the treatment of leukemia

Option 5: Chemotherapy with amsacrine (AMSA), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®). Individuals with the M3 subtype of AML - otherwise known as promyelocytic leukemia (PML) - benefit most from a special form of induction therapy using the drug all-trans retinoic acid (ATRA). In particular, patients who have genetic translocations of chromosomes 15 and 17 exhibit marked changes in their leukemic cells after ATRA therapy. ATRA induces terminal differentiation (maturation) of the leukemic cells and restored blood formation.

Option 6: Chemotherapy with all-trans retinoic acid (ATRA)

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Chronic Myelogenous Leukemia (CML)
The chemotherapeutic options for CML are as follows:

Option 1: Chemotherapy with hydroxyurea (Hydrea®)

Option 2: Chemotherapy with busulfan (Myleran®)

Acute Lymphocytic Leukemia (ALL)
Chemotherapy for ALL usually begins with a three-drug schedule such as:

Option 1: Chemotherapy with prednisone, vincristine sulfate (Oncovin®), and an anthracycline drug (e.g., daunorubicin)

Option 2: Chemotherapy with prednisone. vincristine (Oncovin ®), and L-asparaginase (Elspar®) or cyclophosphamide (Cytoxan®)

Consolidation therapy for ALL (1-3 months in adults; 4-8 months in children) may involve treatment with combination chemotherapy or antimetabolites such as methotrexate and 6-mercaptopurine (6-MP):

Option 1: Chemotherapy with prednisone, vincristine (Oncovin®), L-asparaginase (Elspar®) and daunorubicin, followed by Cyclophosphamide (Cytoxan®), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®)

Option 2: Chemotherapy with methotrexate sodium plus 6-mercaptopurine (6-MP; Purinethol®)

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Chronic Lymphocytic Leukemia (CLL)
Chemotherapy for CLL may be postponed if the patient has early-stage disease and shows no related symptoms (see Treatment of Leukemia). Yet, if necessary, induction chemotherapy may be started with an alkylating agent such as chlorambucil or cyclophosphamide. If the physician suspects the existence of autoimmune (against the person's own body) blood problems, a corticosteroid like prednisone may be added to the mix.

Option 1: Chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) plus prednisone, if needed

Research suggests that combination chemotherapy with cyclophosphamide, vincristine, and prednisone (COP) is no better than chlorambucil alone in achieving remission or prolonging survival. Perhaps more importantly, the neurotoxicity (nerve-damaging effects) of vincristine may make it an unacceptable choice for elderly patients. Clinical trials in later-stage CLL patients have reported some responses from combination chemotherapies that include an anthracycline drug like doxorubicin (Adriamycin®, Rubex®) (e.g., chlorambucil, doxorubin, and prednisone, or CAP; cyclophosphamide, vincristine, doxorubicin, and prednisone, or CHOP).

In recent years, a class of compounds known as purine analogs have been developed for the treatment of CLL. Three such drugs - fludarabine (arabinofuranosyl-2-fluoroadenine-5'-monophosphate), pentostatin (2-deoxycoformycin), and cladribine (2-chlorodeoxyadenisine; 2-CDA) - have been tested as single-agent treatments against CLL. Yet these drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.

Option 2: Chemotherapy with fludarabine phosphate (Fludara®), pentostatin (2-deoxycoformycin; "DCF"; Nipent®)*, or cladribine (2-chlorodeoxyadenosine; "2-CDA"; Leustatin®) **Not FDA-approved for the treatment of CLL

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Hairy Cell Leukemia (HCL)
Most newly diagnosed patients with HCL will receive chemotherapy with a purine analog.

Option 1: Chemotherapy with cladribine (2-chlorodeoxyadenosine; 2-CDA; Leustatin®)

Option 2: Chemotherapy with pentostatin (2-deoxycoformycin; "DCF"; Nipent®)

Leukemia is not a single disease (see Types of Leukemia). Instead, the term leukemia refers to a number of related cancers that start in the blood-forming cells of the bone marrow. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. In addition, children with leukemia have special needs that are best met by care in pediatric cancer centers. Such centers have trained medical professionals whose sole purpose is to address the unique concerns of children.

In general, there are five major approaches to the treatment of leukemia:

1.       chemotherapy to kill leukemia cells using strong anti-cancer drugs (see Chemotherapy);

2.       interferon therapy to slow the reproduction of leukemia cells and promote the immune system's anti-leukemia activity;

3.       radiation therapy to kill cancer cells by exposure to high-energy radiation (see Radiotherapy);

4.       stem cell transplantation (SCT) to enable treatment with high doses of chemotherapy and radiation therapy; and

5.       surgery to remove an enlarged spleen or to install a venous access device (large plastic tube) to give medications and withdraw blood samples.

Oncologists administer these treatments in a variety of combinations (see Chemotherapy and Radiotherapy). Each method has its advantages and drawbacks. It usually is worthwhile to get a second opinion about treatment before entering into a specific program; in some instances, a second opinion may be required by the patient's insurance company. For example, stem cell transplantation (SCT) is very costly (more than $100,000) and entails a long stay in the hospital. Some insurance companies still consider this to be an "experimental" procedure and will not pay for SCT-related expenses.

The treatment of leukemia depends on a number of factors. The most important of these are the histopathologic (diseased tissue) type of leukemia, its stage, and certain prognostic features, such as the patient's age and overall health (see Leukemia Staging).

Interferon Therapy
Interferons are a class of proteins that are released by virus-infected cells. They help normal cells to make antiviral proteins. Interferons also help the body to reduce leukemia cell proliferation (growth and reproduction), while strengthening the body's immune response.

Interferon-alpha (INFa) is a type of interferon that frequently is used to treat leukemia. In addition, based on an patient's response to INFa, a physician can better predict the anticipated length of survival.

Interferon-alpha can be given by a number of methods - that is, by injection into a vein, into a muscle, or under the skin - although subcutaneous (under the skin) injection is the customary route. INF-a usually is offered to all newly diagnosed patients who are not candidates for stem cell transplantation (see Stem Cell Transplantation). Often IFN-a is started at a low dose (e.g., 3 MIU daily), with gradual increases over time. Unfortunately, though, this drug is not without side effects. Possible IFN-related complaints include fevers, chills, muscle aches, bone pain, headaches, concentration difficulties, fatigue, nausea, vomiting, and general flu-like symptoms when starting the drug. Such symptoms usually last for 1 to 2 weeks, but may be lessened by drugs such as acetaminophen. Side effects recur if the INF-a dosage is increased, but they are temporary and usually improve after INF-a therapy is completed.

Back to Top

Stem Cell Transplantation
Cancer therapy (chemotherapy, radiation therapy, etc.) can damage or destroy normal cells, as well as cancer cells. Many chemotherapeutic drugs, in particular, can harm rapidly dividing cells such as the blood-forming stem cells of the bone marrow (see Bone Marrow and Blood Formation). Yet high drug doses are needed to treat leukemia effectively. So what can be done?

Physicians have begun to solve this problem by performing stem cell transplantation (SCT). Stem cells are blood-forming (hematopoietic) cells of the bone marrow; they continuously divide to form the new blood cells that populate the arteries and veins. The SCT procedure enables physicians to give chemotherapy and radiotherapy in doses that are strong enough to eliminate leukemia cells. The injured bone marrow then is replenished by a transplant of stem cells, which can manufacture the necessary new blood cells.

Stem cells for SCT can be gathered from different sources:

The cells are carefully frozen and stored until the patient has completed high-dose treatments for leukemia. Such treatments usually consist of a 3-day course of chemotherapy (for example, with cyclophosphamide, cytarabine, etoposide, melphalan, or busulfan) with/without a 3-day course of total body irradiation (TBI) (see Chemotherapy and Radiotherapy). After therapy, the stem cells are thawed and given to the patient by means of a blood transfusion.

SCT are classified as autologous or allogeneic, based on characteristics of the cell donor. Autologous SCT, also known as autologous bone marrow transplant (autoBMT), is a procedure in which a patient's own stem cells (immature cells from which all blood cells develop) are removed from the bone marrow. This type of transplant is not frequently used, because it is very difficult to guarantee that normal stem cells have been separated from leukemic cells, even after purging, that is treatment of stem cells with drugs, immunologic agents, heat, or other substances/methods to kill or remove leukemic cells.

Another form of autologous SCT is peripheral blood stem cell transplantation, or leukapheresis. The patient's blood is passed through a machine that removes the stem cells, then returns the blood to the patient. This procedure usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any remaining leukemia cells. The stem cells are stored until they are transplanted back into the patient. Leukapheresis may be performed alone or with autoBMT, although most physicians prefer to use leukapheresis by itself.

Allogeneic SCT, also known as allogeneic bone marrow transplant (alloBMT), is a form of transplant in which the stem cells are gathered from a donor whose tissue type closely matches the patient's tissue type. Such donors usually are relatives (brother, sister, child) or, occasionally, a matched unrelated donor (MUD). AlloBMT usually is reserved for individuals who are younger than 55 and who have a compatible family donor - that is, a donor with compatible human leukocyte antigen (HLA), a protein found on the surface of some cells, such as leukocytes). Allogeneic donor cells actually may help to fight leukemia cells because they initiate a response known as the "graft versus leukemia" reaction.

If the person receives an allogeneic transplant, he or she must be treated with drugs that suppress rejection reactions (e.g., cyclosporine, methotrexate, prednisone, and antilymphocyte globulin [ALG] or antithymocyte globulin [ATG]). For example, "graft-versus-host disease" (GVHD) is a result of rejection reactions that occur in 25 to 50% of cases (see Chronic GVHD). The leukemia patient should ensure that SCT is performed at a qualified medical facility. The treatment staff should be experienced in all types of transplants, including MUD transplants, as well as patient care during the recovery period.

Transplant patients typically are kept in protective isolation in the hospital until their total white blood cell (WBC) count is above 500. During this time, the individual receives supportive care, such as intravenous nutrition, treatment with antibacterial and antifungal medications, and transfusions with red blood cells and platelets. Within 2 to 3 weeks, the stem cells usually begin to make white blood cells. Next, platelets are produced, followed several weeks later by the manufacture of red blood cells. Once the WBC count approaches 1,000, the patient generally can be discharged from the hospital. Daily outpatient check-ups may be scheduled for several weeks, followed by regular appointments over a 6-month period. The individual's oncologist usually will schedule an exam at the SCT clinic 1 year after treatment; thereafter, clinic appointments are made only if symptoms return.

Side effects due to SCT may occur shortly after treatment, or they may develop much later. Early complications usually are related to the cellular injury caused by high-dose chemotherapy and radiotherapy (for example, temporary hair loss, anemia, leukopenia, thrombocytopenia, and gastrointestinal symptoms like nausea, vomiting, and diarrhea (see Chemotherapy and Radiotherapy). Long-term or chronic complications may include:

Back to Top

Surgery
Surgery does not play a major role in the management of leukemia. The reasons for this are two-fold: (1) leukemia cells usually are widespread throughout the body at the time of diagnosis, so they cannot be "cut out" like other forms of cancer; and (2) surgery is not needed for diagnosis, since bone marrow aspiration usually is adequate to confirm the disease (see Diagnosis of Leukemia).

Aside from the insertion of a venous access device (a plastic tube that is surgically implanted into a large vein in the chest or upper arm) to reduce the need for repeated needle sticks during drug injections or removal of blood samples, splenectomy (removal of the spleen) may be the only surgical procedure performed during the treatment of leukemia.

The spleen normally helps to filter out old and damaged blood cells from the circulation (see Bone Marrow and Blood Formation). If leukemia causes substantial spleen enlargement of more than 4 centimeters (> 4 cm), it may press upon other organs and cause abdominal symptoms. In addition, an overgrown spleen may become too effective in removing blood cells and cause a shortage of red blood cells or platelets. Therefore, surgical removal of the spleen is a form of therapy that may improve symptoms and blood profiles in some leukemia patients, such as individuals with chronic lymphocytic leukemia (CLL) or hairy cell leukemia. The primary danger of splenectomy, especially in people with compromised immune systems, is infection in the blood or tissues (sepsis). Microorganisms commonly involved in such sepsis include pneumococci, meningococci, E. coli, Haemophilus influenzae, and staphylococci.