What is Chronic Leukemia?

Leukemia is a cancer of the white blood cells . It is divided into two general types, Acute and Chronic. This is based upon their untreated behavior- with no treatment acute leukemia will kill within months, while the patient with chronic leukemia may live for many years. Both acute and chronic leukemias are further subclassified with regard to the particular white cell type they arose from.

Normally, white blood cells act as agents of the body's immune system, recognizing and destroying foreign invaders such as bacteria, viruses and fungi. White blood cells are larger than the red blood cells (which carry oxygen) and are easy to see under the microscope. Too few white blood cells will lead to massive infection, while too few red blood cells leads to the pallor and fatigue of anemia. Platelets are the third type of blood element (they are not whole cells) which allow clotting to occur. Too few platelets leads to bruising and internal bleeding. Chronic leukemia was first recognized in 1845 as a massive accumulation of white blood cells. There are normally 3,000 to 10,000 white blood cells per milliliter of whole blood, but with chronic leukemia that number may skyrocket to above 100,000. Ironically, this increased number of white blood cells will actually lead to more infections, since these abnormal cells are not effective against fighting germs, and stymie production of normal cells. Thus, chronic leukemia is also usually accompanied by a decrease in red blood cells and platelets, leading to anemia and bruising. By contrast, the acute leukemias often have normal or reduced white blood cells. Besides for acute and chronic, another major division classifying leukemias is between the lymphoctytic and the myelogenous varieties. The lymphocytic variety comes from the lymphocytes , which is a common white blood cell active in identifying and marking germs to be killed. In adults, about 1/3 of the total white blood cells are lymphocytes. The myelogenous variety comes from the other white blood cells besides lymphocytes, represents at least 7 different subtypes, and is often just called"non-lymphocytic" leukemia. The major divisions of acute and chronic, and lymphocytic and myelogenous, are combined in the following four labels into which leukemias are grouped:

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

Like all cancers, leukemia starts from a single abnormal cell, in this case a white blood cell. Normally, the division of human cells in under very tight control throughout life. The control is by the genes, which are packets of information within each cell. For any number a reasons, a cell's genes may be altered and tell the cell to start dividing out of control. For most of the cell types that form the human body, this will lead to a mass of abnormal cells called a tumor.A tumor just means a swelling. A tumor which grows only in it's local area, and doesnot spread, is called "benign"and isn't cancer.

In contrast, a tumor which can spread to any area of the body is called "malignant" and is cancer. Thus, cancer is proved by it's ability to spread, or "metastasize". Since the blood is unique in traveling all through the body to nourish it, the same definitions of "spread" cannot be used for blood cancers (i.e. leukemia) as for "solid tumors" (i.e. lung cancer). The basic way of distinguishing the many "benign" blood conditions from "malignant" ones is by their behavior. Generally, benign conditions are not fatal. However, malignant blood diseases will naturally progress to kill the patient, either quickly (acute leukemia) or slowly (chronic leukemia). Proper treatment may interfere with this natural progression to death, and possibly even cure the patient. Since the behavior and effective treatment for acute and chronic leukemias is different, they are discussed in separate transcripts. Much recent progress have been made in under- standing leukemias, and the relevant points are now summarized in sections.

How Common is Leukemia?

Each year in the United States there are 27,600 new cases of leukemia, with males getting the disease slightly more often than females. Childhood cases, which are predominantly of the acute type, are about 7000 cases, so the remaining 20,000 cases occur in adults. The adult cases are about equally split between the lymphocytic (ALL and CLL) types and the myelogenous types (AML and CML). For Chronic leukemias, CLL is overall the most common, making up 9,000 cases per year. Men are affected by this type of leukemia twice as often as women, and the average patient is 65 years old. Ninety percent of CLL patients are over 50 years old. CLL is not seen in children. On the other hand, CML makes up about 5000 cases per year, is most common in 30 to 40 year olds, and is occasionally seen in children. Overall, numbers of leukemia cases have been increasing over the past 3 decades, although survival has been increasing due to more effective treatments.

What Causes Chronic Leukemia?

As with every cancer, the exact reason why one person gets chronic leukemia and another does not is unknown . However, several factors have been noted to increase the risk for getting this disease:

Genetic Factors run in families, or may occur spontaneously in an individual. This means some alteration of the genes occurs, which increases the chance the person will come down with chronic leukemia. Even with the change in the genes, however, this does not guarantee the person will get leukemia. There can be other factors in the environment which trigger disease in susceptible people. Getting CLL is 2 to 3 times more likely if family members have gotten it. A variety of specific defects in the genes has been seen in patients with CLL including three chromosomes ("trisomy") instead of the normal two in chromosomes number 12 or 13. Chromosomes are large packages of genetic matrial, visible in cells under the microscope, which each contain thousands of genes. The normal human has 46 chromosomes, but in leukemia this number may change to 47 or 48 within the cancerous cells. Other genetic damage may include the activation of a growth gene, called an "oncogene", which tells the cell to divide out of control. Alternatively, the cell may lose a"suppressor gene" which keeps division in check, leading to cancer. Theoretically, damage to a cell's genes from viruses, radiation or chemical irritants can activate these changes, and lead to cancer. An inborn genetic problem seen in myelogenous the"Philadelphia Chromosome", which is a when a certain piece of chromosome #9 breaks off and gets stuck onto chromosome #22. While only 2% of adults with CML have this change, they tend to do worse than those who do not have it. Interestingly, effective treatment is shown by elimination of this genetic change in those who have it.

Radiation Exposure has been associated with an increased risk for CML, but not for CLL. The reason for this discrepancy is unknown.

Virus Exposure is associated with many cancers, since viruses actually get into the genetic material of the cell and can change it. However, no previous viral exposure has been proven for CLL or CML.

Overall, we just don't know why one person gets chronic leukemia and another does not. While we can see changes in the cells for many who get it, the causes of these changes remains a mystery.

What are the Symptoms of Chronic Leukemia?

Early disease from either CLL or CML will have no symptoms. This is because the number of "leukemic clones" (that is affected cells) is too low to interfere with the normal body processes. As the number of the "clone" cells increases, symptoms will arise. There are differences between the later symptoms of CLL and CML, but the first symptoms are similar. About 25% of patients are first detected by an abnormal blood smear during a routine physical exam. When symptoms manifest, they are:

Fatigue and Pallor with reduced ability to exercise is caused by anemia, that is decreased production of the oxygen carrying red blood cells. Also, the blood becomes more "viscous" with increased white blood cells and their wastes, which leads to a general sense of tiredness.

Increased Colds and Infections, which are described in more detail below, are caused by decreased effectivewhite cells. Although the actual number of white cells may be greatly increased, they are from the leukemic clone and don't do anything to fight disease. Instead, they help prevent formation of normal white blood cells which do fight disease.

Bruising is seen when the number of platelets is decreased ("thrombocytopenia") which leads to prolonged bleeding time, or even spontaneous internal bleeding. The special white cells which produce platelets ("megakaryocytes") are inhibited by the leukemia cells, and so don't work well. Furthermore, if there is malnutrition or leukemic involvement of the liver, the clotting factors the liver produces will be decreased, and likewise lead to poor clotting and easy bruising.

Bone Pain and even spontaneous fractures are caused by leukemic infiltration of the bone. There may be general bone pain, caused by a stuffing of so many white cells into the marrow that it actually presses on nerves and hurts, or very local pain caused by the white cells actually destroying a local area of bone, which leads to greater fracture risk. This is especially true in weight-bearing areas, such as the hip and thigh, or spinal column.

Fever is caused by either infection owing to a depressed immune system, or even without infection due to by products from the leukemic cells (such as interleukins) which act on the midbrain to produce a fever.
6) Decreased Appetite is seen in most all advanced cancers, we don't know why.

Swollen Glands, or "lymph nodes" may be seen in the neck, armpit or groin. Many white blood cells normally live in these lymph glands, who's job it is to purify the blood and contain infections. When the number of white blood cells in the gland increases, either due to an infection they are fighting or leukemic involvement, the gland will swell.

Abdominal Fullness, often seen as an increase in belt size, is due to the same process which swells the lymph glands above swelling the spleen and liver. These organs normally contain great numbers of white blood cells, and with leukemia this number increases further, swelling them up.

For patients with CLL, the above symptoms, when untreated, are progressive and often accompanied by breathing problems as the "leukemic infiltrate" of cancer cells collects around the lungs, and kidney problems from clearing the leukemic waste products. There will be progressive infections as the immune system deteriorate, much like AIDS patients get. The most common infections in these patients (who are said to be "immunocompromised") are:

a) Viral Infections, especially herpes zoster which is a continuation of the chicken pox almost all children get. The virus continues to live in nerves of the spine, and comes out when the immune system weakens. It causes blisters and burning pain in the area which is supplied by the nerve it was hiding in. In practice, there there will often be a strip of affected area on the chest or abdomen. The pain may be very severe and chronic, and require narcotics for relief. Anti-virus medications like zovirax can help shorten the duration and severity of each outbreak. Other viral infections like "cytomegalovirus" (CMV), "Epstein-Barr" virus (EBV) or Hepatitis often respond to specific therapies, once the diagnosis is made.
b) Bacterial Infections from low levels of affective antibody in the bloodstream. The most common are strepstaphcausing pneumonia, and hemophilus which causes influenza type problems. Severe infections of the heart (carditis), kidneys (nephritis) and brain linings (meningitis) can be caused by bacteria. The bacteria can spread in the bloodstream (bacteremia) causing high fever, extreme illness, and death. Fortunately, if caught early bacterial infections will usually be cured by powerful antibiotics, given through the veins.
c) Fungal Infections, most commonly thrush (candida) may cause painful sores in the mouth and throat, looking like white patches or inflamed blisters. These can be treated with anti-fungal medicines like nystatin mouthwashes or mycelex troches. Without treatment, eating is often just too painful. If a fungus invades the bloodstream ("fungemia") or vital organs, then powerful anti-fungal drugs like amphotericin-B must be given through the veins during hospitalization.
d) Protozoal Infections are those related to ameaba-like creatures. Most common is "pneumocytis carnii pneumonia" (PCP) which can be treated with sulfa drugs. Rarer ones include "toxoplasmosis" (from cats) causing brain lesions, and cryptococcus causing severe diarrhea.
e) Parasitic Infections such as liver flukes, tapeworm and muscle worms are also seen in patients who are "immunocompromised", and may be treated using various de-worming agents.

The above list was not meant to be comprehensive, but to give some idea of the extreme variety of infections a person with chronic leukemia can get. Thus, symptoms are often not due to the leukemia itself, but as a consequence of the immune-system damage it causes.

In CLL, the above conditions with usually be progressive until the patient dies by infection, anemia, malnutrition and debility (collectively called "inanition"). However, even the untreated patient may go many years with the disease, and longer if they get treatment for symptoms. Patients with CLL tend to live longer than those with CML. About 10% of patients experience conversion to a quickly lethal variety of leukemia, "Richter's syndrome", which is refractory to most any therapy. When this deadly transformation occurs, it is usually late in the disease.

In CML, the disease commonly goes through "phases". The first is the "Chronic Phase", which lasts about 4 years, where the symptoms are easily controlled. The second the"Acute Phase", which is development of a acute leukemia which is very resistant to treatment. This acute phase is also called "Blast Crises" (named for an immature type of white cells called a "blast") and eventually develops in over 85% of patients with CML. The risk of developing blast crises is about 20% per year in a CML patient. About 15% of patients get a phase in between the chronic and acute phase, called the "Accelerated Phase", which is basically a pronounced worsening of symptoms of fatigue, poor appetite, organ swelling and infections. Unfortunately, this phase has also been resistant to therapy. Anyway, the progression is toward acute phase with it's rapid weight loss, high fevers, infections, internal bleeding, and rapid demise of the CML patient.

How is Chronic Leukemia Diagnosed and Evaluated?

If a patient present to the doctor with symptoms suggestive of chronic leukemia, or a routine blood test is suspicious, the following "workup" will be done:

Physical Examination: Should be complete, including a pelvic exam in women. Some particular items noted are skin paleness and texture, signs of jaundice (yellowing of eyes) showing liver problems, enlarged glands in the neck, groin or armpit region, and swelling of the liver or spleen on abdominal exam. Any swelling of a limb may be the result of blockage of draining lymph channels by enlarged lymph nodes. The patient is checked for fatigue, fever, bruising and signs of recent weight loss.

Routine Blood and Urine Tests include the standard Complete Blood Count (CBC) which documents anemia (shown as a hemoglobin under 12 grams) and the size and shape of the red blood cells. The CBC also gives the number of platelets (normally 150,000 - 400,000) with under 100,000 indicating too few and under 50,000 being at high risk for spontaneous internal bleeding. Very importantly, the CBC tells the number of white blood cells per milliliter of blood (normally 3,000 to 10,000). In chronic leukemia, the number of white cells is high, generally 15,000 to 200,000. In some cases it may even exceed 500,000. The cells are examined in a blood smear, called a"differential", describing the type of white cells present, along with abnormal sizes and shapes. In CLL the predominant white cells will be lymphocytes, while in CML they are are any other type of white cell, or even red blood cells ("erythrocytes") or platelets. The point is that the CBC is a basic and simple test which may help diagnose the type of leukemia, and also follow response to treatment. Note: just having a high white blood count on a CBC does not automatically mean leukemia!

Other conditions such as infection or a "leukemoid reaction" from drugs or bugs may dramatically (but temporarily) increase the white blood cell count, so other tests are mandatory.

The next standard blood test is a Blood Chemistry Panel (SMA) which tells sodium, potassium, chloride and bicarbonate (together called "electrolytes") and blood sugar and cholesterol. It also measures liver and kidney function with enzyme tests, and suggests whether someone has had a recent heart attack. Uric acid is an important test included in the SMA, it is a by-product of numerous white cells being broken down; uric acid is excreted through the kidneys. Too high uric acid in the blood can crystallize in the tissues to cause gout, or in the kidneys to make painful kidney stones.

A standard Urinalysis (UA) tells about blood, protein and sugar in urine, as well as urinary tract infection or crystals of uric acid or calcium. If infection is suspected, the sample can be "plated out" onto a growth media dish to let the germs grow, identify their specific type, and prescribe the right antibiotic. Overall kidney function ("creatinine clearance") and amounts of excreted uric acid and calcium can be calculated from a 24 hour collected urine sample.

Another blood test which helps distinguish actual leukemia from the leukemoid reaction is theLAP score (CLL) andNAP score (CML). These tests, which called "alkaline phosphatase" in the white cells, are low in leukemia but normal or high in benign conditions.

Bone Marrow Biopsy is a crucial part of the evaluation of leukemia. Commonly it is done under local anesthesia from the hip bone above each buttock. Boring needles are used to penetrate the hard outer "cortex" of the bone and remove a core of the soft marrow inside. The importance of bone marrow biopsy is that the white blood cells are actually being produced within the bone marrow prior to their delivery into the bloodstream. Only in the bone marrow can the actual types and numbers of cells produced be accurately tallied. Occasionally, bone marrow biopsy is skipped in patients with CLL who's diagnosis can be clearly confirmed by blood evaluation, but it's always done if the diagnosis is in doubt. Bone marrow biopsy may be repeated during treatment to monitor response to therapy, and confirm "remission" (clearing of all leukemic cells from the body).

Radiology Tests include standard Chest X-Ray looking for tumors and signs of pneumonia or lymphocytic infiltration of the pleural lining of the lungs. For a suspicious Chest X-Ray, a confirmatory Chest CT scan is ordered, it will provide much greater detail than plain X-Ray. To confirm the presence of an enlarged liver or spleen, or look for lymph gland swelling within the abdomen, an Abdominal CT scan is helpful. If an area of bone becomes painful, PlainX-Rays of the bone can help tell if there is a destructive tumor present, and a "Bone Scan" (where radioactive dye is injected into a vein and preferentially taken up by cancer spread to bone) may show abnormalities even if a plain X-ray is normal. A scan is taken of the whole body after the dye is injected, so any suspicious area of bone may be examined. In general, more than 1/2 of the cortex of a bone area must be destroyed to show up on an plain X-ray, so bone scan is more sensitive. Other exotic tests like Magnetic Resonance Imaging (MRI), liver-spleen scan, Brain CT scan, IVP and Barium enema should only be ordered if specific symptoms will justify their discomfort and high cost.

Lymphangiography is where dye is put into leg veins and plain X-rays are taken to image the lymph glands in the pelvis, it isn't justifiable for leukemia but is used in other cancers where the lymph nodes may be involved, such as Hodgkin's Disease.

Specialized Pathology Tests include looking for the particular type of cell that has become cancerous by the process of "immunophenotyping" . Basically, all blood cells start out from a common precursor"stem cell", and cells put out special protein markers on their surfaces as they mature, called antigens. By identifying these antigens, we can tell exactly the cell type we are dealing with. Also, the antibodies that the white cells excrete can be identified. Another type of test, especially for AML, is looking for changes in the genes, shown by chromosomal abnormalities. This chromosome analysis includes looking for the Philadelphia chromosome, an extra chromosome #8, and changes which can be found in up to 75% of patients with CML during their disease. The chromosome analysis is usually done on the bone-marrow biopsy cells, but can be done on a regular blood smear if the cancerous cells are present in sufficient numbers. The science jargon word for chromosome analysis is "karyotype" . Finer tests for gene rearrangements which can lead to cancer are done by specialized laboratories, and include tests such as "Southern Blotting" and "Polymerase Chain Reaction" to identify actual genes.

What are the Types of Chronic Leukemia?

We previously identified the main types of chronic leukemia as CLL and CML. As many types of these leukemias are possible as types of blood cells. These cells, when normal, function as white cells, red cells, and platelets:

"Lymphocytic" leukemia means originating from lymphocytes, as with CLL . It is closely related to Chronic Lymphocytic Lymphoma and arised from from the long-lived B lymphocytes which are major components of the immune system.

"Myelocytic" or "myeloid" leukemia comes from other white cells, such as Neutrophils, Basophils, or Eosinophils . The leukemia may be"promyelocytic" meaning that it arises from cells which are in the process of, but have not yet become, these mature white cells. All of these are grouped under"CML".

"Erythrocytic" means the leukemia has features of red blood cells, which are called erythrocytes . Depending upon where in stem cell maturation the cancer causing mutation occurred, the erythrocytic and myelocytic types can be mixed.

"Megakarocytic" means arising from the megakaryocytes, giant white cells that live in the bone marrow and put out platelets.

"Myelomonocytic" means a smoldering leukemia with unexplained increase monocytes, yet another white blood cell. it starts as a slowly progressing chronic leukemia in the elderly, but then converts to an aggressive acute form.

"Hairy Cell Leukemia" is 2% of leukemia, with men affected 5 times as often as women. It is a variant of B-lymphocytic leukemia and has different therapy.

How is the Extent of Chronic Leukemia Evaluated?

The extent of most cancers is given by their "stage", which tells how large they grown and how far they have spread. Unlike solid cancers where the diameter of a tumor can be measured, and the extent of it's spread noted, blood-borne cancers are disseminated through the body at their onset. Thus, the "staging" used for solid tumors is not applicable to leukemia. Instead, some physicians stage the disease by the extent of blood abnormalities and symptoms. Some research centers stage CML based upon chromosomal analysis only . Certain factors for chronic leukemia are known to be "poor prognostic signs", meaning the disease appears more advanced. Some of these signs are:

a) Involvement of the tissue of the lung, kidney or liver, with failure of these critical organs to function properly.
b) Bone lesions caused by infiltration of the cancer into local bone areas.
c) Filling of the bone with coarse fiber ("myelofibrosis") i.e. failing marrow.
d) Multiple chromosome abnormalities in cells examined in the laboratory. However, lack of the Philadelphia chromosome is bad!
e) Rapidly deteriorating normal blood cell numbers, such as uncontrolled anemia, lack of platelets, or skyrocketing numbers of white blood cells. These can be indications of transformation to an acute phase of leukemia. Survival withCML averages 1 year without the Philadelphia chromosome, and 4 years with it. One-quarter of patients live over 5 years, and some live over 10 years. This may be improved with latest, effective treatment. For Hairy Cell leukemia, survival averages 8 years, but has been dramatically improved with new therapies.

For CLL, an accepted staging system is theModified Rai ("Rye") Classification:

It is important to remember that the above survival numbers are just textbook averages, it says nothing about how any individual will do. Predicting lifespan is both poor science and poor medical practice; we are M.D.'s, not M. Dieties. Individual often live long and satisfying lives with their disease.

What is the Conventional Treatment for Chronic Leukemia?

The treatment has differed depending upon the particular type of leukemia. For CLL, historically no treatment has been recommended for patients who do not have symptoms from the disease! This is because CLL is usually very indolent (slowly progressing) and most patients are elderly and would not tolerate aggressive therapy well anyway. This dictum in medicine is "primum no nocere"-- first do no harm. Also, since CLL cells tend to be slowly growing, they do not respond well to the typical type of chemotherapy, which kills rapidly dividing cells (as cancer cells usually are). Thus, giving strong chemotherapy for asymptomatic CLL would tend to kill many normal cells, with little effect on the cancer. Giving conventional radiation treatments would also have no positive effect, since this is a local treatment (to one small body area) for a systemic disease. Similarly, there is commonly nothing to remove surgically.

While no treatment is recommended in the absence of symptoms, there are times to start treatment for CLL. These are:

a) Severe disease where the bone marrow gets so stuffed with lymphocytes that it can't produce enough red cells and platelets to sustain the patient.
b) Massive enlargement of the spleen (which is stuffed with lymphocytes); this also traps red blood cells and leads to anemia.
c) Enlargement of lymph nodes causing lymph flow blockage and limb swelling.
d) Worsening symptoms of fever, weight loss and night sweats (usually caused by extensive bone marrow involvement and by-products of the leukemia cells).
e) "Leukemic Infiltration" of a particular area, like bone or brain lining, causing symptoms such as fractures or meningitis.

When a decision is made to start treating CLL, the usual way is to give chemotherapy to reduce the number of lymphocytes. The most common drugs are "alkylators" like like chlorambucil andcyclophosphamide . These are chemically related to mustard gas used in World War I, but now available as convenient pills. These drugs are taken for "cycles" lasting 10 days through several weeks, with varying schedules depending upon the practitioner and results anticipated. Blood counts are monitored by standard CBC to adjust the dosage of the chemotherapy.

Total disease remission is not the goal; instead it's alleviation of symptoms. Prednisone (a cortisone derivative) is toxic to white blood cells and may be used alone for symptoms of anemia or low platelets.

If treatment with these agents fails, the "second line" drugs are "nucleosides" like Fludarabine and Cladribine , these are given intravenously in cycles for 4-7 days every 4 weeks. They similarly lower the white blood cell count and improve anemia and low platelets. If the leukemia is refractory even to these, then "third line" drug regimens using combination chemotherapy like CHOP (which has 4 agents) will be needed.

Chemotherapy has various side effects depending upon the drugs used, but basically it wipes out quickly dividing cells. Thus nausea, diarrhea, mouth sores, anemia, infections, hair thinning and fatigue are common to many drugs.Prednisone over time will cause bone thinning, fat redistribution to the abdomen and face, and more chance for gastrointestinal bleeding. The more aggressive the chemotherapy, the more possible side effects. Fortunately, the side-effects are often manageable with newer drugs that reduce nausea (i.e. Zofran) or drugs that stimulate red-blood cells production (erythro-poetin). One side-effect from the effectiveness of the drugs is a rapid killing of the leukemic white blood cells, with their death products clogging up the bloodstream with uric acid leading to gout. Special medications (i.e. allopurinol) help uric acid to be safely excreted in the urine. It is important to drink lots of fluids to help flush out the kidneys also. Overall, current chemotherapy is not curative for CLL but does improve symptoms and probably slightly prolongues lifespan.

Surgery has a very limited place in CLL management , since the disease is systemic. Removal of the spleen may help correct anemia unresponsive to prednisone.

Radiation Treatment for CLL is similarly limited by leukemia being a body-wide process. Local radiation, which is painless, may be given to enlarged lymph node areas in an attempt to reduce limb swelling, of for leukemic infiltration of bone making for pain and fracture risk. Another use of radiation is shrinking the spleen in (instead of removing it surgically) in patients who's large spleens trap red cells and platelets.

Radiation is administered by a"radiation oncologist", a physician specializing in it. Prior to local radiation treatment, a "simulation" is done on a replica machine to mark out the area to get treated. Watercolor marks, and eventually permanent tattoos, will show where to aim the radiation beam. The actual treatment is painless and takes only a couple of minutes per day, usually given 3 or 5 days per week. The doses for killing leukemia cells are low (about 30 Gray) so no significant side-effects are seen from radiating small areas. When radiating the spleen, frequent blood counts are obtained to control the dose given and assess results. Radiation is excellent for helping relieve pain from the disease without narcotic drugs; it's effectiveness for reducing limb swelling is less but still worth a try.

For CML, chemotherapy is started at diagnosis. Although chemotherapy has not been proven to increase survival in CML, it definitely helps improve the quality of the patient's life. It is crucial to manage the white blood cell count. For the "chronic phase" of CML, the most common drugs are hydroxyurea and busulfan. Hydroxyurea, also called "hydrea" for short, is the best drug since it is given orally, has rapid action, and less side effects than busulfan. The treatment in the chronic phase is started when the white count goes over 50,000 and is commonly 2 to 4 grams daily of hydroxyurea. This is typically halved as the white count comes down, and symptoms of anemia and swollen spleen abate. Allopurinol (300 mg/day) orally is given to prevent the uric acid by products of dying white cells from causing gout. The chronic phase may last years.

During the accelerated and acute phases of CML, the above chemotherapy is discontinued. Other drugs are then tried, but have frankly not proven very successful. The idea is to give supportive therapy to treat particular symptoms, such as transfusions and radiation treatments for local painful areas of disease. The spleen may also be radiated to try to spleen size and anemia, as with CLL. This is safer than the surgical removal of the spleen ("splenectomy") in these patients. Patients may get such high white blood cell counts that the blood stream gets clogged up with them (leukostasis) causing mental clouding, trouble breathing, and sustained painful erection (priapism) in men. A way of quickly but temporarily decreasing the white count is "leukophoresis" which literally means filtering them out of the blood with a special machine. This is used in combination with hydroxyurea for emergency white cell reduction. Sometime the white blood cells actually increase the apparent (but not real) platelet count on automatic counting machines used in today's laboratories, it's important for human eyes to review blood smears. As you can see, conventional treatment for both CLL and CML is not curative, but meant to prologue life and improve it's quality.

What is the Latest Effective Treatment?

While supportive therapies have become better, they are not a cure. For CLL, the disease waxes and wanes and the patient usually succumbs to anemia, infection, debility, or other medical condition ("co-morbid factors"). As mentioned, these patients tend to be elderly and will not tolerate aggressive chemotherapy, which has not been shown to be curative anyway for this condition! Also, with the long course of the illness it isn't always possible to know if someone has been really "cured" or not. For the patient in otherwise good health who wishes to be aggressive, there is some indication that CLL may be put into prolonged remission, and occasionally cured, by a series of "total lymphoid"radiation therapy. This is similar to the treatment given for low grade B-cell lymphoma, and these diseases may be indistinguishable. It has been known for many years that whole-body radiation quickly reduces the white blood cell count, and it has been used at low doses (less than 1 Gray) several times per week for a couple weeks to induce remission.

For CML, newer drugs include alpha-interferon, an agent normally found as part of the immune system, which can be given as 3 to 5 million units under the skin each day. This drug may control the chronic phase for years, and even convert those with a Philadelphia chromosome to normal chromosome status! In these select patients, a prolongation of survival, or possibly even cure, may occur (but the chances are small). The very best treatment for CML today isbone-marrow transplant, started in patients under 55 years old, in the chronic phase, who have a suitably matched donor (often a sibling). Bone-marrow transplant involves puncturing the hips bones many times from the donor to remove marrow. This is done under general anesthesia, is not at all dangerous, but can leave puncture scars at the top surface of both buttocks. The marrow is specially prepared and stored, while the CML patient is prepared for transplant. The patients original marrow, which contains the leukemic cells, must be totally destroyed. This is done with using high doses of chemotherapy just prior to the transplant. Also, whole-body radiation therapy (usually 6 sessions of 15 minutes each over 3 days) may be used to be sure all the leukemic cells are killed before the transplant. The donor bone marrow is then "reinfused" (that is transplanted) into a regular vein in the patient, and finds it's own way into the bone while circulating in the bloodstream. The new marrow will hopefully "take" and start producing new blood cells, but until it does the patient is at very high risk for infection and must be hospitalized in a sterilized environment. It usually takes 2-4 weeks before the new marrow is functional. Once it is, the patient can be discharged with medications to prevent infection and rejection.

Side-effects of getting bone marrow from another individual ("allogeneic") are more than when a person donates their own marrow for later use ("autologous") . It may become possible to effectively clean a person's own marrow (purging) but this is difficult for leukemias, since they arise from the marrow itself! Thus, while for breast cancer transplants are autologous, for leukemia they are usually allogeneic. Expected side-effects arise from the preparation ("ablation") for the transplant, and then after the donor marrow is administered. Most common are nausea, diarrhea and fatigue.

Also, temporary hair loss ("alopecia") and permanent loss of fertility ("sterility") are expected. If radiation is used as a part of the preparation, nausea is worse, glands temporarily swell, skin redness, mouth sores and sore throat is common. These are all temporary. After the new marrow is infused, the patient is at very high risk for any infection, so preventative ("prophylactic") antibiotics are given. Also, the patient will be anemic weak from lack of red blood cells (which live about 4 months), and have easy bruising from platelets (which last about 10 days). These problems will abate as the new marrow takes over and produces blood cells. A serious side-effect is "graft versus host disease " or"GVH" for short. This happens if the new marrow actually rejects the body it's put into. It is more likely if the previous marrow was not completely destroyed, or if the donor marrow is not a close enough match. Some degree of GVH is expected, is shown by skin splotches and blood tests, and is controlled with immune-suppressing anti-rejection drugs like prednisone and cyclosporine. This is a double-edged sword, however, since these drugs also lower the immune system's ability to fight infection. In severe cases GVH can be fatal, but today it is usually well controlled with medication (sometime for the rest of the patient's life). Other possible side effects are lung damage ("pneumonitis"), kidney damage ("nephritis") and liver damage ("hepatitis" and "veno-occlusive disease"). These may show up weeks to months after the transplant, and cataracts or second cancers may occur in long-term survivors. Overall, the death rate ("mortality") from transplant is down to about 10%, which is a major improvement over the past 10 years. There is even talk of doing the transplants at smaller community hospitals, instead of just big universities. Newer drugs which stimulate the newly infused marrow (erythropoeitin and neupogen) to produce red cells and white cells respectively have much improved success rates. The results of bone-marrow transplant for CML now show over 50% survival at 5 years, so it the best available treatment (albeit drastic) for this disease. Fortunately, it is becoming less drastic and more routine all the time. It can now be recommended for the patient with CML who wishes to be aggressive.

The newest treatment for Hairy-Cell leukemia is Cladribine (2-CdA). It is given by vein for seven days, just one time. over 95% of people respond with 80% being fine at 5 years and apparently cured. This happy outcome shows the great progress that is being made in treating chronic leukemias.

If you're interested in learning more about cancer and leukemia treatment, a nursing education might be a good career choice. You may be able to get education grants from hospitals to continue your medical education, as many hospitals would love nurses to continue their college education.

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Chronic Leukemia. Much more, including latest additional treatments for Chronic Leukemia can be found on our order page. Thank you for using CancerAnswers as your information resource.