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Cancer Treatment
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Chronic Lymphocytic Leukemia (CLL)
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 Chronic Lymphocytic Leukemia is white blood cells (called lymphocytes) disease. This is the most common type of leukemia.
What is Chronic Lymphocytic Leukemia (CLL)?
Chronic Lymphocytic Leukemia is white blood cells (called lymphocytes) disease. This is the most common type of leukemia. Under normal circumstances, blood cells are reproduced in controlled and organized way. On the other hand, in leukemia this process goes out of control and lymphocytes are reproduced without any control and live too long, that’s why there are extra lymphocytes in blood flow. These leukemia lymphocytes look like regular ones, but they immature and work improperly by replacing normal blood cells (white, red and blood plates) in the bone marrow with time.
Generally, Chronic Lymphocytic Leukemia is slow-developing one, and many of patients suffering from it do not require any treatment for months or years. Even so, there are patients who require the treatment from the moment of diagnosis.
Usually, older people get sick with Chronic Lymphocytic Leukemia; it rarely appears in people under 40 years old.
What causes CLL?
The factor, which causes CLL, is unknown, but researches for possible reasons of this disease are taking place permanently. Like any other types of leukemia, this disease is noncontagious and uncommunicable. Among most of people, who were suffering from leukemia there was found no evidence that CLL is an inheritable illness or that the offspring of suffering from it people has higher risk to become ill.
What are the disease symptoms?
It’s hard to diagnose this illness in its early stages because of slow development process. Some of people do not have any symptoms at all and disease is diagnosed by blood test, which was done for completely different analysis.
Symptoms are likely to include:
Frequent infections – because of lack of healthy white blood cells that fight with microbes and viruses;
Weariness – lack of red blood cells (anemia) causes to weariness, sometimes to shortness of breath because of affected lymphocytes that take too much place in the bone marrow;
Bleedings and ecchymosis – lack of blood plates may cause unexplained ecchymosis or bleedings, for instance nose bleeding. Blood plates count may be low due to affected lymphocytes that take too much place in the bone marrow;
Tumorous lymph nodes – anomalous lymphocytes may accumulate in lymph nodes and may cause neck, arm-pits or crotch tumescence, and this tumescence is not accompanied with pain;
Sometimes the lien is extended and becomes sensitive to contacting lump in left upper part of the belly;
Inflated belly;
Fever or night perspiration;
Weight loss.
Anyway, if above-mentioned symptoms are appeared, it is necessary to visit a doctor as soon as possible. However, you need to remember that similar symptoms may appear also in other diseases that are not cancerous.
How a diagnosis is made?
A family doctor will examine you and give an appointment card to blood examination. In the case of abnormal blood count, a family doctor will refer you to the hospital in order to get an advice and treatment by specialist.
After checking your full medical history a hospital physician will carry out a physical examination. He will examine whether lymph nodes, lever and lien are extended. You will do additional blood tests in order to recognize the disease type more precisely. If blood tests show leukemia cells presence, perhaps, the doctor would find it necessary to make a bone marrow test in order to confirm the diagnosis and to plan the proper and best treatment for you.
Bone marrow sampling
For the test purposes, a small sample of bone marrow is taken from the back part of hip bone or breast bone and it is examined with the microscope in order to see an abnormal presence of white blood cells. After this abnormal cells type recognition it would be possible to define a type of leukemia we deal with.
The bone marrow sampling is being carried out under local anesthesia. After performing local anesthesia, a needle is gently inserted to the bone through the skin, and a bone marrow sample is taken with help of injector. Sometimes a small bit of bone marrow should be taken, in other words, biopsy and in this case the test will protract additional few minutes. It is possible to make this test during regular hospitalization or day hospitalization and it will last only 15 minutes. During the test you may feel some discomfort or pain; medications may help to minimize this effect.
Additional tests
Additional tests give physicians more information about the specific type of chronic lymphocytic leukemia and its reaction to treatment. Blood and bone marrow tests include:
• Immunophenotyping – during this test the samples are being tested in order to see which white blood cells are abnormal. White blood cells types are recognized by specific proteins testing, which are located on cells surfaces.
• Cytogenetic analysis – during this test leukemia cells chromosomes are being tested. Complicated protective chromosomes control cell activity. In CLL disease, changes in disease cells chromosomes may occur. An exact detection of changes characteristics helps the doctor to choose the best way of treatment planning. Also, this is helpful for indication of leukemia reaction to treatment. These changes are acquired and nonheritable. These are only changes of leukemia cells and are not found in any other cells of body.
• Antibody levels tests (antibody immunoglobulin) in blood and specific proteins presence detection, which may cause damage to red blood cells and blood plates.
Likewise, low levels of antibody immunoglobulin might be connected with repeated infections and sometimes it is necessary to give a permanent transfusion of antibody immunoglobulin for body infections prevention.
Usually, chest x-ray examination is being carried out in order to confirm that your lungs are in normal condition. Sometimes, if there is a small doubt concerning the diagnosis, a sample of extended lymph nodes should be taken in order to examine cells with microscope. This is the biopsy test of lymph nodes and it can be performed with either local or full anesthesia. It is referred to a small surgery, during this operation a whole node is removed and sent to the laboratory testing. Most people return home in the same day. After the surgery you will have got a small injury with a few sutures. The last ones are usually removed within 7-10 days.
Perhaps, it would be necessary to do CT test in order to see how many nodes are affected by CLL, and if the lien is extended. CT test is a type of x-ray examination where 3D picture of face and body is built by computer. The test takes approx. 10-15 minutes. Most people return home immediately.
Disease development
Chronic Lymphocytic Leukemia stages
One of the goals during CLL initial investigation is disease stage definition. This definition makes possible to suppose leukemia extant and helps to understand when and what treatment is required and most suitable for each person.
There are two stage methods usually used for CLL: Rai method and Binet method.
Binet stage method
Stage A patient’s white blood cells count is high, and there are less then three areas of extended lymph nodes.
Stage B patient’s white blood cells count is high, and there are three or more areas of extended lymph nodes.
Stage C patient’s white blood cells count is high; likewise, patient’s red blood cells count or blood plates count or both of them are low.
Countable areas of lymph nodes are neck, arm-pits, crotch, lever or lien. If lymph nodes of both arm-pits are inflated, they are countered as single area only.
Research also showed that stage A of CLL usually doesn’t require treatment. In B and C stages, if you are given treatment, it’s possible that you might have remission periods.
Rai stage method
Many of Israel physicians use Rai method. By this method CLL is classified according to the following stages:
Stage 0: High count of lymphocytes only
Stage 1: High lymphocytes and extended lymph nodes
Stage 2: High lymphocytes with or without extended lymph nodes with lien or lever extension
Stage 3: Accompanied anemia
Stage 4: Low blood plates
CLL is a chronic disease with slow development, usually during a number of years; all symptoms possibly are not going to appear in early stages and doctor will be satisfied with follow-up management.
If you will be given treatment in later stages, it’s possible that you will have remission periods with a very few symptoms of active leukemia in blood, bone marrow or your lymph nodes, if at all. When disease returns, you will be able to obtain an additional treatment. Perhaps in time, CLL will become resistant to treatment and it might be harder to achieve remission. In this stage, it will be hard for your bone marrow to continue production of required blood cells and, perhaps, you might suffer from infections or more bleedings.
Transformation (type changing)
The disease may suddenly develop faster in a very few of patients with CLL. This phenomenon is called transformation; disease changes its type and acts in more aggressive way, similar to lymphoma with high cancerous level. It is possible to diagnose transformation with the help of blood tests or according to acerbation. Symptoms may include fever, weight loss and sudden inflation of affected lymph nodes.
Such symptoms as fever and weight loss are frequent.
It is important to point out that transformation phenomenon is rare and does not occur in majority of patients.
Chronic Lymphocytic Leukemia treatment
Treatment Goals
Today CLL is not considered as a curable disease. The goal of treatment is to make it possible for people to live their normal life without symptoms. Modern treatment succeeded in achieving remission for a number of years among the majority of patients. There are additional ongoing researches all the time and new treatments are being developed according to their results. It takes a few years for a new treatment testing and the patients under this treatment need to be on follow-up for a long period of time so that doctors will be able to estimate treatment results. Specialists believe that they will succeed to develop such treatment in future that leads to the disease abolition.
Early stages of CLL
Many people with CLL in stage A do not require treatment, unless their leukemia disease is developing. Often CLL in stage A does not cause any symptoms and develops very slowly. Early treatment in this stage will not prolong patient’s life, but it may lead to side effects.
Even if you are not given treatment, it is important to make tests and blood counts periodically, because this is only the way for a doctor to manage follow-up of disease development.
Actually, process of giving treatment begins only if disease starts to develop or if symptoms begin to embarrass a patient. Your doctor will discuss with you both advantages and disadvantages of treatment.
Advanced stages of CLL
Chemotherapy is a widespread treatment of CLL. It may be given orally in tablets or intravenously (intravenous chemotherapy). Sometimes, combination of tablets for swallowing and injections may be given. Your doctor will choose the best and most suitable treatment for you according to your testing results.
Chemotherapy
Chemotherapy is anticancer medications usage (cytotoxicity) for cancerous cells dispersion and their reproduction stoppage. Medications are transferred from the blood circulation and reach cancerous cells in every area and body organ.
Tablets
Some of CLL patients receive an initial chemotherapy treatment in tablets, usually the Chlorambucil medication. Tablets are given in different treatment regimes, according to patient needs and generally for the period of seven days monthly. Dosage is changing according to the blood tests results before every treatment cycle. Frequently, this treatment is combined with steroids.
Injections
Some patients require a different treatment that is given intravenously by single medications or combination of several medicines. Generally, intravenous chemotherapy is given once per month during a number of days. This treatment is usually given under day hospitalization and depends on medicine type you are taken. Commonly used medicine for CLL therapy is Fludarabine, which is taken either orally or intravenously.
Side effects
High sensitivity to infections
Treatment that you receive is going to destroy white leukemia blood cells, as well as a part of normal white blood cells will be damaged. Your blood counts will be checked routinely during the treatment in order to confirm that they are within normal limits. If white blood count is too low, the treatment will be delayed for some period of time in order to help white blood cells recover themselves.
Sometimes, white blood cells levels could be very low and that’s why you might be more vulnerable to infections. If fever or any other sign of infection appears, you should go to the hospital immediately and, perhaps, it would be necessary for you to take an antibiotic injection.
CLL patients intent to develop a herpes zoster. It’s viral infection that causes red and painful skin rash of small blisters. If you think that herpes zoster is being developed, you must make an emergency call to your physician or hospital, because there is an effective therapy for prevention of its eruption or reduction of its influence.
If you are in contact with a toddler that is given immunization at family health center or another medical clinic, it is important for him to take his polio immunization by injection and not by swallowing it.
Increased anemia risk, traumatism and bleedings
Chemotherapy is liable to affect also your red blood cells and blood plates.
• Low red blood cells count is called anemia and it may cause weariness and shortness of breath;
• Low blood plates count causes blood clotting defect and ecchymosis, nose bleedings and some other abnormal bleeding may occur. Attention must be paid to blood blisters in oral cavity or small red dot skin rash on the legs.
Red cells and plates blood count takes much more time to recover; therefore, from time to time perhaps, you will need blood or plates transfusion in order to support normal cells. These transfusions are given under day hospitalization. Increasing of transfusions will also increase a risk for “reaction” appearance to blood or plates, which causes high fever and trembling. In order to avoid this phenomenon, you will be given an injection of steroids and antihistamines before every transfusion.
Additional side effects
Chemotherapy in the form of tablets is usually accompanied by a very few side effects. For example, Chlorambucil may cause a slight sickliness. If you suffer from sickliness, you need to discuss it with your doctor because there are very effective medications that suppress or prevent it. Chlorambucil may also cause skin rash, but it is a less common phenomenon.
Chemotherapy in the form of endovenous injections usually causes more side effects and they are changing according to the medication type. Fludarabine usually causes small immediate side effects. Perhaps, during treatment you will suffer from fever, trembling and joints pain, but these side effects are usually short. Fludarabine may increase predisposition to pneumonia, and your doctor might give you an antibiotic with medications for viral and fungal infections in order to prevent these problems during the Fludarabine treatment.
There are probable additional side effects such as sickliness, allergy, pain and ulcer in oral cavity, loss of hair and weariness.
Many patients are able to live their almost completely normal life during the treatment. However, if you are given chemotherapy for a long period of time, you may have noticed increased weariness and necessity to do everything slowly. Some patients feel weariness even during the off treatment periods. It is important to slow down the rate and not to overstrain. If you have activities that you can’t give up, try to find other hours to rest during the day.
Steroid treatment
Steroids (prednisone, dexamethasone or dexamethazone) are often given together with chemotherapy treatment. In CLL disease, prednisone is used as a chemo treatment.
Steroids are given also in the cases of quick involution of red blood cells count. The problem lies in red blood cells destruction in blood circulation and spleen, this phenomenon is called hemolysis. If you develop hemolysis, you will also develop anemia as well in a short time after. Symptoms include shortness of breath, weariness, white of the eye yellowing and dark urine. If you suddenly feel especially tired or shortness of breath, you should make an emergency call to your doctor or hospital in order to get treatment or blood tests that may be necessary for you.
Side effects
During the steroid treatment period, you may feel increased appetite and energy, falling asleep problems. If you are taking steroids for months, it would be possible for you to experience the following additional side effects:
• Swollen ankles because of liquid accumulation;
• Blood pressure increase;
• Increased risk for infections;
• High level of blood sugar;
• Sugar in urine;
• Weight increase.
CLL patients are not given steroid treatment for a long period of time; therefore they are not developing these side effects. You should stop taking steroids step by step. Sudden interruption may cause bad feeling and weariness, that’s why a dosage need to be lessen gradually during a specific period of time. If you require treatment stopping, your doctor will explain you how to do this in the best way.
All these side affects are temporary and they will disappear gradually after finishing the steroid treatment.
Treatment of monoclonal antibodies
Treatment of monoclonal antibodies is a relatively new one. Antibodies are proteins that constitute a part of natural body immune system against infections; they identify non self cells and organisms and destroy them. Monoclonal antibodies are programmed to recognize specific types of proteins on specific cancerous cells surfaces.
Monoclonal antibody that is called Alemtuzumab (MAb Campath) may be used for chronic lymphocytic leukemia treatment. It’s possible to give this antibody in the only form of endovenous or subdermic injection or in combination with chemotherapy for patients that did not receive chemotherapy in the past. This antibody is especially active against leukemia cells in blood and bone marrow and less against expanded nodes.
Additional type of monoclonal antibody that is possible for usage is Rituximab (Mabtera); it’s given in the form of endovenous infusion. It is possible for you to obtain this treatment at outpatient clinic or you will be invited for the one night hospitalization. Usually, the combination of Mabtera and chemo treatment is used and can not be provided as a single manipulation.
Some patients may suffer from high fever, trembling and low blood pressure while taking these medications, but these side effects are usually short-lasting ones. Additional side effects may include sickliness and bad resistance to infections. Most of patients may have little side effects during these treatments.
Monoclonal antibody treatment may diminish a quality of antibody producing cells and vaccine cells, and decrease the body resistance to infections in this way. Usually, patients who are taking monoclonal antibody during more then six months need to take also an antibiotic and medications against infections. CMV antibody infection is particularly common among patients that receive MAb Campath treatment.
Radiation Therapy
Radiation therapy is being carried out by high energy beams that destroy cancerous cells and causing the lowest damage to healthy cells. This therapy is rarely used for CLL treatment, but it can be useful when lymph or spleen is expanded too much.
Radiation therapy is given at the hospital Radiation Oncology Department. Treatment cycle usually include five visits in working days. Generally, CLL treatment lasts about a week or two.
Treatment side effects are changing according to treated area. Radiation therapy of spleen may cause sickliness or diarrhea.
Stem cells transplantation
Bone marrow is situated in the bones and produces all the red, white cells and plates in blood. Stem cells are immature blood cells situated in the bone marrow and these blood cells are developing from them. It’s possible to separate them from the bone marrow or collect from the blood flow.
Stem cells transplantation makes it possible chemotherapy giving in a very high dosage. Chemotherapy destroys cells in the bone marrow. After that you will get stem cells intravenous infusion in order to replace the bone marrow destroyed and in this way your body will be able to produce blood cells that you are need of. It’s possible to obtain somebody’s donation of stem cells (homogeneous transplantation) or from your own stem cells (autogenous transplantation) that were previously collected and frost till appearance of necessity. There is a possibility to do homogeneous transplantations only to patients who have brother or sister and found suitable by the tissue matching test. One more possibility of getting bone marrow is from non-family member donor, if he was found matching by tissue matching test.
Is this therapy will influence my fertility?
Some of CLL therapy medications may cause temporary or constant damage to fertility. If you require intensive chemo or radiation treatment before bone marrow or stem cells transplantation, it is possible that you will suffer from permanent damage to fertility. Men may freeze their seed before the therapy.
If you are worrying about your fertility, discuss it with your doctor before starting the therapy. If you have a partner, perhaps both of you should discuss your fears with the physician.
If a therapy is not liable to damage fertility, it is recommended to use contraceptives during the treatment and six months after in order to prevent pregnancy. It is because chemotherapy may cause damage to embryo during this period.
Your doctor knows exactly what therapy you are going to get and that’s why he is the one that can answer all your questions. Prepare a list of questions you may want to ask him in order to be sure that you understand everything about your therapy and its influence on you before starting it.
Complementary therapy
Complementary treatments help to control every phenomenon caused as a result of disease:
Patients suffering from infections may need to take an antibiotic in order to take care of.
Patients with very low red blood cells levels (anemia) may require intravenous blood infusion for their red blood cells number increasing.
Sometimes, patients with very low antibodies levels and predisposition to infection may require getting antibodies (immunoglobulin) by intravenous infusion.
Follow-up
CLL is a long time disease. Today, treatments are useful and can control the disease for many years. You will have to make periodical visits to your physician and perform routine blood tests. If you experience new symptoms or suffer from any problem between tests date, you should inform your doctor as soon as possible.
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