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Cancer Medicine :: Leukemia - Chronic Lymphocytic - CLL Treatment

Leukemia - Chronic Lymphocytic - CLL

How is chronic lymphocytic leukemia treated?

Making treatment decisions

After the leukemia is found and staged, your cancer care team will discuss your treatment options with you. The main treatment is usually chemotherapy, but because chronic lymphocytic leukemia often grows slowly, not everyone needs to be treated right away.

It is important to take time and think about your possible choices. In choosing a treatment plan, the stage of the leukemia and other prognostic factors  are important. Other factors to consider include whether or not you are having symptoms, your age and overall health, and the likely benefits and side effects of treatment.

In considering your treatment options it is often a good idea to seek a second opinion, if possible. This may provide you with more information and help you feel more confident about the treatment plan you have chosen.

Chemotherapy for chronic lymphocytic leukemia

Chemotherapy (chemo) uses anti-cancer drugs that are taken by mouth or injected into a vein into a muscle to destroy or control cancer cells. When given this way, these drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers such as leukemia that spread throughout the body.

When treating certain types of leukemia, chemo may also be injected into the cerebrospinal fluid. Chemo given into the CSF is often the best way to treat leukemia in the area around the brain and spinal cord. This type of chemo, called intrathecal chemotherapy, is rarely needed to treat chronic lymphocytic leukemia (CLL).

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Chemotherapy cycles generally last about 3 to 4 weeks. Chemotherapy is often not recommended for patients in poor health, but advanced age by itself is not a barrier to getting chemotherapy.

The major types of chemotherapy drugs that are used to treat CLL include:

Purine analogs include fludarabine (Fludara®), pentostatin (Nipent®), and cladribine (2-CdA, Leustatin®). Fludarabine is often one of the first drugs used against CLL. These drugs can have major side effects, including an increased risk of infection.

Alkylating agents, which include chlorambucil (Leukeran®) and cyclophosphamide (Cytoxan®), have been around much longer. They are often used along with a purine analog or with other chemotherapy drugs. They may also be used by themselves (or along with a steroid drug), especially in people who can't tolerate more aggressive treatment.

A newer drug called bendamustine (Treanda®) is an alkylating agent that has some properties of a purine analog.

Corticosteroids such as prednisone, methylprednisolone, and dexamethasone.

Other drugs sometimes used for CLL include doxorubicin (Adriamycin®), methotrexate, oxaliplatin, vincristine (Oncovin®), etoposide (VP-16), and cytarabine (ara-C).

Possible side effects

Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. Common side effects include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting

Low blood counts

can affect bone marrow, leading to low blood cell counts. This can cause:

risk of infections (due to low white blood cell counts)

bruising or bleeding (due to low blood platelets)

(due to low red blood cells)

These side effects are usually short-term and go away once treatment is finished. There are often ways to lessen these side effects. For example, there are drugs to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about medicines to help reduce side effects, and let him or her know when you do have side effects so they can be managed effectively.

Drugs known as growth factors (G-CSF and GM-CSF, for example) are sometimes given to increase the white blood cell counts and thus reduce the chance of infection.

If your white blood counts are very low during treatment, you can reduce your risk of infection by carefully avoiding exposure to germs. During this time, your doctor may tell you to:

your hands often.

fresh, uncooked fruits and vegetables and other foods that might carry germs.

fresh flowers and plants because they may carry mold.

sure other people wash their hands when they come in contact with you.

large crowds and people who are sick (wearing a surgical mask offers some protection in these situations).

Antibiotics may be given before there are signs of infection or at the earliest sign that an infection may be developing. Drugs that help prevent viral and fungal infections may also be given.

Because many of the side effects of chemotherapy are caused by low white blood cell counts, some people find it helpful to keep track of their counts. If you are interested in this, ask your doctor or nurse about your blood cell counts or other blood tests and what these numbers mean.

If platelet counts are low, you may be given drugs or platelet transfusions to help protect against bleeding. Shortness of breath and extreme fatigue caused by low red blood cell counts may be treated with drugs or with red blood cell transfusions.

Tumor lysis syndrome is another possible side effect of chemotherapy. It is most common in patients who had large numbers of leukemia cells in the body before treatment and occurs most often with the first cycle of chemo. When the cells are killed, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which cannot get rid of all of these substances at once. This can lead to build up of excess amounts of certain minerals in the blood and even kidney failure. The excess minerals can lead to problems with the heart and nervous system. Doctors work to prevent these problems by giving the patient extra fluids and certain drugs, such as sodium bicarbonate, allopurinol, and rasburicase.

Monoclonal antibodies for chronic lymphocytic leukemia

Monoclonal antibodies are man-made versions of immune system proteins (antibodies) that are designed to attach to a specific target (in this case, proteins on the surface of cancer cells). These drugs can help the patient's immune system react and destroy the cancer cells.

Rituximab

Rituximab (Rituxan) is a monoclonal antibody that targets the CD20 antigen, which is found on the surface of B lymphocytes. It is used mainly to treat certain kinds of non-Hodgkin lymphoma, but it has also become one of the main treatments for chronic lymphocytic leukemia (CLL). It is most often used along with chemotherapy, either as part of the initial treatment or as part of a second-line regimen, but it may also be used by itself.

Rituximab is given by injection into a vein (IV), usually once a week. It can also be given once a month or every few months. Common side effects are usually mild but may include chills, fever, nausea, rashes, fatigue, and headaches. Rarely, more severe side effects occur during infusions (while the drug is being given), such as trouble breathing and low blood pressure. Even if these symptoms occur during the first rituximab infusion, it is very unusual for them to recur with later doses. Rituximab can cause hepatitis B infections that were dormant (inactive) to become active again, sometimes leading to severe liver problems or even death. For that reason, your doctor may check your blood for signs of an old hepatitis infection before starting this drug. This drug may also increase a person's risk of certain infections for many months after the drug is stopped.

In rare cases of patients with very high white blood cell counts, the drug may cause a condition called tumor lysis syndrome (this was discussed in detail in the chemotherapy section). This happens when the drug kills the cancer cells so quickly that the body has trouble getting rid of the breakdown products of the dead cells. It generally only occurs during the first course of treatment.

Alemtuzumab

Alemtuzumab (Campath®) is a monoclonal antibody that targets the CD52 antigen, which is found on the surface of CLL cells and many T lymphocytes. It is used mainly in patients with CLL that is no longer responding to standard chemotherapy treatments, but it can be used earlier in the disease. It may be especially useful in cases of CLL with a chromosome 17 deletion, which are often resistant to standard treatments, but it doesn’t seem to work as well if the patient has large lymph nodes (2 inches across or larger).

Alemtuzumab is given by injection into a vein (intravenous or IV), usually several times a week. In studies, it has also been given as an injection under the skin (subcutaneously), but giving it this way is not approved by the Food and Drug Administration. The most common side effects are fever, chills, nausea, and rashes during the injection, but these effects seem to be less of a problem when it is given under the skin. It can also cause very low white blood cell counts, which increases the risk for severe bacterial and viral infections. Antibiotic and antiviral medicines are given to help protect against some of these infections, but severe and even life-threatening infections can still occur. It may also cause low red blood cell and platelet counts.

Ofatumumab

Ofatumumab (Arzerra®) is another monoclonal antibody that targets the CD20 antigen. It is used mainly in patients with CLL that is no longer responding to other treatments such as chemotherapy or alemtuzumab.

Ofatumumab is given by injection into a vein (intravenous or IV) over several hours. The standard course is once a week for 8 weeks, followed by once a month for 4 months. Infusion reactions, including fever, chills, nausea, swelling, blood pressure changes, and rashes, are common during the infusion, so medicines are given beforehand to try to lower this risk. This drug can increase a person's risk of infections. Other side effects are less common but are potentially serious, including low platelet counts (with increased risk of bleeding) and blockage (obstruction) of the intestines.

Surgery for chronic lymphocytic leukemia

Surgery has a very limited role in treating chronic lymphocytic leukemia (CLL). Because CLL cells spread so widely throughout the bone marrow and to many organs, surgery cannot cure this type of cancer. It rarely has any role even in the diagnosis of CLL, which can often be made with a blood sample. Minor surgery is sometimes needed to remove a lymph node to aid in diagnosing or staging the cancer.

Splenectomy

In rare cases, the spleen may be removed (splenectomy). This is not expected to cure the leukemia, but it can help improve some of the symptoms. Sometimes the spleen becomes so large that it presses on nearby organs and causes symptoms. If radiation or chemotherapy does not help shrink the spleen and reduce symptoms, splenectomy may be an option.

Splenectomy may also improve blood cell counts and lower the need for blood product transfusions. One of the spleen's normal functions is to remove worn-out blood cells from the bloodstream. If leukemia or other diseases cause the spleen to become too large, it may become too active in removing blood cells, leading to a shortage of red blood cells or platelets. Taking out the spleen may help prevent this. Splenectomy is used much more often for hairy cell leukemia than for regular CLL.

Most people have no problem living without a spleen. The risk for certain bacterial infections is increased, which is why doctors often recommend certain vaccines for people who have had their spleen removed.

Radiation therapy for chronic lymphocytic leukemia

Radiation therapy is treatment with high-energy rays or particles to destroy cancer cells. Radiation therapy is usually not part of the main treatment for people with chronic lymphocytic leukemia (CLL), but it is used in certain situations.

Patients may have symptoms if swollen internal organs (such as an enlarged spleen) press on other organs. For instance, pressure against the stomach may affect appetite. If these symptoms are not improved by chemotherapy, radiation therapy to help shrink the organ is often a good option.

Radiation therapy can also be useful in treating pain from bone damage caused by leukemia cells growing in the bone marrow.

Radiation therapy is sometimes given in low doses to the whole body, just before a stem cell transplant .

External beam radiation therapy, in which a machine delivers a beam of radiation to a specific part of the body, is the type of radiation used most often for CLL. Before your treatment starts, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time -- getting you into place for treatment -- usually takes longer.

The main short-term side effects of radiation therapy depend on where the radiation is aimed. Sunburn-like skin changes in the treated area are possible. Radiation to the abdomen can sometimes cause nausea, vomiting, or diarrhea. For radiation that includes large parts of the body, the effects may include fatigue and an increased risk of infection.

Leukapheresis for chronic lymphocytic leukemia

Sometimes very high numbers of leukemia cells in the blood cause problems with normal circulation. Chemotherapy may not lower the number of cells until a few days after the first dose. In the meantime, leukapheresis may be used before chemotherapy. In this procedure, the patient's blood is passed through a special machine that removes white blood cells (including leukemia cells) and returns the rest of the blood cells and plasma to the patient. This treatment lowers blood counts right away. The effect is only for a short time, but it may help until the chemotherapy has a chance to work.

A person having leukapheresis can lie in bed or sit in a reclining chair. Two IV lines are required —- the blood is removed through one IV, and then is returned to the body through the other IV. Sometimes, a single large catheter is placed in the neck or under the collar bone for the pheresis —- instead of using IV lines in the arms. This type of catheter is called a central line and has both IVs built in. Leukapheresis is not painful, but it can be hard to stay sitting or lying down in the same place for 2 or 3 hours. Also, sometimes calcium levels can drop on pheresis, causing numbness and tingling (especially in the hands and feet and around the mouth) and sometimes painful muscle spasms. These can easily be treated by giving the patient calcium.

Leukapheresis works quickly to get the leukemia cells down. However, without further treatment to kill the cancer cells (like chemotherapy), the cell count will go back up again. Leukapheresis may be given to help the patient until chemotherapy has a chance to work.

Bone marrow or peripheral blood stem cell transplant for chronic lymphocytic leukemia

The usual doses of chemotherapy drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Even though higher doses of these drugs might be more effective, they are not given because they could severely damage to bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems because of low blood cell counts.

A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy and, sometimes, radiation therapy. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Bone marrow transplant was more common in the past, but it has largely been replaced by PBSCT.

It's not yet clear how helpful stem cell transplants are in patients with chronic lymphocytic leukemia (CLL). When these treatments are used, it is most often in clinical trials looking to test their effectiveness.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. They differ in the source of the blood-forming stem cells.

Allogeneic stem cell transplant

In an allogeneic transplant, the stem cells come from someone else - usually a donor whose tissue type is almost identical to the patient's. Tissue type is based on certain substances on the surface of cells in the body. These substances can cause the immune system to react against the cells. Therefore, the closer a tissue match is between the donor and the recipient, the better the chance the transplanted cells will take and begin making new blood cells.

The donor may be a brother or sister if they are a good match. Less often, a matched unrelated donor may be found. The stem cells from an unrelated donor come from volunteers whose tissue type has been stored in a central registry and matched with that of the patient. Sometimes umbilical cord stem cells are used. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the umbilical cord is cut.

Allogeneic transplants are being studied in patients with CLL, although it's not yet clear how effective they are. Because this type of transplant can cause severe or even life-threatening complications and side effects, it may not be a good option in people who are older or have other health problems.

Non-myeloablative transplant (mini-transplant): Many people over the age of 55 can't tolerate a standard allogeneic transplant that uses high doses of chemotherapy. Some may be able to have a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant), where they receive lower doses of chemotherapy and radiation that do not completely destroy the cells in their bone marrow. They then receive the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the leukemia cells as foreign and attacks them (a graft-versus-leukemia effect).

Doctors have learned that if they use small doses of certain chemotherapy drugs and low doses of total body radiation, an allogeneic transplant can still sometimes work with much less toxicity. In fact, a patient can receive a non-myeloablative transplant as an outpatient. The major complication is graft-versus-host disease.

Many doctors still consider this procedure to be experimental for CLL and feel it is best done as part of a clinical trial.

Autologous stem cell transplant

In an autologous transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation). A process called purging may be used to try to remove any leukemia cells in the samples. The stem cells are then reinfused into the patient's blood after treatment.

Autologous transplants are generally easier for patients to tolerate than allogeneic transplants. The patient is getting his or her own cells back, so the risk of complications is smaller. This type of transplant can be done in any otherwise healthy person, but it might not be suitable for elderly patients.

Autologous stem cell transplants are being studied for use in CLL, but so far it isn't clear if they improve survival compared with standard treatment.

The transplant procedure

Blood-forming stem cells from the bone marrow or peripheral blood are collected, frozen, and stored. The patient receives high-dose chemotherapy and sometimes also radiation treatment to the entire body. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.)

The treatments are meant to destroy any cancer cells in the body. They also kill the normal cells of the bone marrow and the immune system. After these treatments, the frozen stem cells are thawed and given as a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

In allogeneic SCTs, the person getting the transplant may be given drugs to keep the new immune system in check. For the next few weeks the patient gets regular blood tests and supportive therapies as needed, which might include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition.

Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is followed by new platelet production and, several weeks later, new red blood cell production.

Patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until their white blood cell count rises above 500. They may be able to leave the hospital when their white blood cell count is near 1,000. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as outpatients.

Patients typically make regular visits to the outpatient clinic for about 6 months, after which their care is continued by their cancer doctor.

Practical points

Bone marrow or peripheral blood SCT is a complex treatment. If the doctors think a patient may benefit from a transplant, it should be done at a hospital where the staff has experience with the procedure and with managing the recovery phase. Some bone marrow transplant programs may not have experience in certain types of transplants, especially transplants from unrelated donors.

SCT is very expensive (more than $100,000) and often requires a long hospital stay. Because some insurance companies may view it as an experimental treatment, they may not pay for the procedure. It is important to find out what your insurer will cover before deciding on a transplant to get an idea of what you might have to pay.

Possible side effects

Side effects from SCT are generally divided into early and long-term effects.

The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy, and are caused by damage to the bone marrow and other quickly dividing tissues of the body. They can include low blood cell counts (with fatigue and increased risk of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

One of the most common and serious short-term effects is the increased risk of infection from bacteria, viruses, or fungi. Antibiotics are often given to try to prevent this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Some complications and side effects can persist for a long time or may not occur until months or years after the transplant. These include:

Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants. This happens when the donor immune system cells attack tissues of the patient's skin, liver, and digestive tract. Symptoms can include weakness, fatigue, dry mouth, rashes, nausea, diarrhea, yellowing of the skin and eyes (jaundice), and muscle aches. In severe cases, GVHD can be life-threatening. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. Drugs that weaken the immune system are often given to try to keep GVHD under control.

Radiation damage to the lungs, causing shortness of breath

Damage to the ovaries in women, causing infertility and loss of menstrual periods

Damage to the thyroid gland that causes problems with metabolism

Cataracts (damage to the lens of the eye that can affect vision)

Bone damage called aseptic necrosis (where the bone dies because of poor blood supply). If damage is severe, the patient will need to have part of the bone and the joint replaced.

Treatment of chronic lymphocytic leukemia by risk group

Treatment options for people with chronic lymphocytic leukemia (CLL) vary greatly, depending on their age, the disease risk group, and the reason for treating (like the symptoms the leukemia is causing). While many people live a long time with CLL, in general it is very difficult to cure, and early treatment hasn't been shown to help people live longer. Because of this and because treatment can cause side effects, doctors often advise waiting until the disease is progressing or symptoms appear before starting treatment.

The risk group, based on the Rai staging system, is one factor when looking at treatment options. A person's age, general health, and other prognostic factors are important as well. Newer lab tests that look at chromosome changes and molecular markers may also offer important information about a patient's outlook. For example, people whose CLL cells have chromosome 17 or chromosome 11 deletions or high levels of ZAP-70 and CD38 are more likely to have faster growing forms of CLL and may need to be treated more aggressively.

Low-risk CLL

People in this group are often diagnosed based on a high lymphocyte count in the blood but otherwise have normal blood counts and do not have enlarged lymph nodes or organs. The prognosis (outlook) for people in this group is often very good, with long survival expected.

Most people can be observed with careful and frequent follow-up exams. Treatment is considered if there are signs that the leukemia is progressing or if a person develops bothersome symptoms. When needed, initial treatment is usually chemotherapy (chemo), which is described in the next section.

Intermediate- and high-risk CLL

Some patients with intermediate-risk CLL (stages I and II) may not have any symptoms and might not need treatment right away. They can often be watched for signs of disease progression and the start of new symptoms. Patients with high-risk CLL (stages III and IV) are more likely to need immediate treatment.

When treatment is needed there are many options. What treatment is used will depend upon factors like the patient's health, possible side effects, the reason that treatment is needed, and any need for a rapid response. Commonly used treatments include:

FCR: fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab (Rituxan)

PCR: pentostatin (Nipent), cyclophosphamide, and rituximab

FR: fludarabine and rituximab

CVP: cyclophosphamide, vincristine, and prednisone (sometimes with rituximab)

CHOP: cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone

Chlorambucil and prednisone

Bendamustine (sometimes with rituximab)

Alemtuzumab (Campath)

Fludarabine (sometimes with rituximab)

Other drugs or combinations of drugs may also be also used.

If the only problem is an enlarged spleen or swollen lymph nodes in one region of the body, localized treatment with low-dose radiation therapy may be used. Splenectomy (surgery to remove the spleen) is another option if the enlarged spleen is causing symptoms.

Some people who have very high-risk disease may be best treated early with some type of stem cell transplant (SCT). Because it's still not clear how effective this treatment is for CLL, most stem cell transplants are done as part of a clinical trial. Younger people may be eligible for an autologous or allogeneic SCT. Some older people who may not be able to tolerate such transplants may still be eligible for a non-myeloablative transplant (mini-transplant).

Second-line treatment of CLL

If the initial treatment is no longer working or the disease comes back, another type of treatment may help. If the initial response to the treatment lasted a long time (usually at least a few years), the same treatment can often be used again. If the initial response wasn't long-lasting, using the same treatment again isn't as likely to be helpful. The options will depend on what the first-line treatment was and how well it worked, as well as the person's health.

Many of the drugs and combinations listed above may be options as second-line treatments. For many people who have already had fludarabine, alemtuzumab seems to be helpful as second-line treatment, but it carries an increased risk of infections. Other purine analog drugs, such as pentostatin or cladribine (2-CdA), may also be tried. Ofatumumab may be another option if other second-line treatments are no longer working.

Some people may have a good response to first-line treatment (such as fludarabine) but may still have some evidence of a small number of leukemia cells in the blood, bone marrow, or lymph nodes. This is known as minimal residual disease. CLL can't be cured, so doctors aren't sure if further treatment right away will be helpful. Some small studies have shown that alemtuzumab can sometimes help get rid of these remaining cells, but it's not yet clear if this improves survival.

Treating complications of CLL

CLL can cause serious problems with the blood and some of its components. It can also (rarely) transform into another, more aggressive type of cancer. Treating CLL itself may also lead to the development of another cancer.

Sometimes very high numbers of leukemia cells in the blood cause problems with normal circulation. Chemo may not lower the number of cells until a few days after the first dose, so before the chemo is given, some of the cells may be removed from the blood with a procedure called leukapheresis. This treatment lowers blood counts right away. The effect is only for a short time, but it may help until the chemo has a chance to work. Leukapheresis was discussed in more detail in the section called “Leukapheresis for chronic lymphocytic leukemia.”

People with CLL often have weakened immune systems and are at high risk for certain kinds of infections. Doctors may suggest vaccines to prevent some of these infections. Sometimes the drugs used to treat CLL may increase the risk of certain infections. Patients on these drugs are placed on antibiotics and anti-viral drugs to help lower the risk of these infections. Even if they aren’t on a drug linked to a high risk of infection, patients with CLL are watched closely for infection. Finding and treating infections early is an important part of follow-up for people with CLL, even in those who aren't getting treatment with chemotherapy.

People with CLL sometimes have low levels of the antibodies needed to fight infections. As a result, they may get frequent or severe infections with bacteria, such as pneumonia or sinus infections. This condition, called hypogammoglobulinemia, can be found by a blood test. It is treated by giving antibodies (called immunoglobulin) as an infusion into a vein (IV).

Sometimes CLL alters a patient's immune system in a way that causes it to attack his or her own red blood cells (called auto-immune hemolytic anemia) or blood platelets (immune-mediated thrombocytopenia). These conditions are treated with drugs that weaken the immune response. Steroids such as prednisone are often helpful, as are other drugs such as cyclosporine. Monoclonal antibodies like rituximab can also help in some cases.

One of the most serious complications of CLL is a change (transformation) of the leukemia to a high-grade or aggressive type of non-Hodgkin lymphoma called diffuse large cell lymphoma. This happens in about 5% of CLL cases, and is known as Richter syndrome. Treatment is often the same as it would be for lymphoma, but these cases are often hard to treat.

Less often, CLL may transform to prolymphocytic leukemia. As with Richter syndrome, these cases can be hard to treat. Some studies have suggested that certain drugs such as cladribine (2-CdA) and alemtuzumab may be helpful.

In rare cases, patients with CLL may have their leukemia transform into acute lymphocytic leukemia (ALL). 

Acute myeloid leukemia (AML) is another rare complication in patients who have been treated for CLL. Drugs such as chlorambucil and cyclophosphamide can damage the DNA of blood-forming cells. These damaged cells may go on to become cancerous, leading to AML, which is very aggressive and often hard to treat .

What happens after treatment for chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) is rarely able to be cured. Still, most patients live for many years with the disease. Some CLL patients can live for years without treatment, but most eventually need to be treated. Most patients with CLL are treated on and off for years. Treatment may stop for a while, but it never really ends. 

Follow-up care

Before, during, and after treatment, your doctors will want to watch you closely. It is very important to go to all of your follow-up appointments. During these visits, your doctors will ask questions about any problems you may have and may do exams and lab tests or x-rays and scans to look for signs of cancer or treatment side effects. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have. It is important that you report any new symptoms to the doctor right away so that the cause can be found and treated, if needed.

Checkups may include careful physical exams, blood tests, and other tests as needed. A benefit of follow-up care is that it gives you a chance to discuss questions and concerns that can arise.

Lifestyle changes during and after treatment for chronic lymphocytic leukemia

You can't change the fact that you have had cancer. What you can change is how you live the rest of your life – making choices to help you stay healthy and feel as well as you can. This can be a time to look at your life in new ways. Maybe you are thinking about how to improve your health over the long term. Some people even start during cancer treatment.

Making healthier choices

For many people, a diagnosis of cancer helps them focus on their health in ways they may not have thought much about in the past. Are there things you could do that might make you healthier? Maybe you could try to eat better or get more exercise. Maybe you could cut down on the alcohol, or give up tobacco. Even things like keeping your stress level under control may help. Now is a good time to think about making changes that can have positive effects for the rest of your life. You will feel better and you will also be healthier.

You can start by working on those things that worry you most. Get help with those that are harder for you. For instance, if you are thinking about quitting smoking and need help, call the American Cancer Society for information and support. This tobacco cessation and coaching service can help increase your chances of quitting for good.

Eating better

Eating right can be hard for anyone, but it can get even tougher during and after cancer treatment. Treatment may change your sense of taste. Nausea can be a problem. You may not feel like eating and lose weight when you don't want to. Or you may have gained weight that you can't seem to lose. All of these things can be very frustrating.

If treatment caused weight changes or eating or taste problems, do the best you can and keep in mind that these problems usually get better over time. You may find it helps to eat small portions every 2 to 3 hours until you feel better. You may also want to ask your cancer team about seeing a dietitian, an expert in nutrition who can give you ideas on how to deal with these treatment side effects.

One of the best things you can do after cancer treatment is put healthy eating habits into place. You may be surprised at the long-term benefits of some simple changes, like increasing the variety of healthy foods you eat. Getting to and staying at a healthy weight, eating a healthy diet, and limiting your alcohol intake may lower your risk for a number of types of cancer, as well as having many other health benefits.

Rest, fatigue, and exercise

Extreme tiredness, called fatigue, is very common in people treated for cancer. This is not a normal tiredness, but a "bone-weary" exhaustion that doesn't get better with rest. For some people, fatigue lasts a long time after treatment, and can make it hard for them to exercise and do other things they want to do. But exercise can help reduce fatigue. Studies have shown that patients who follow an exercise program tailored to their personal needs feel better physically and emotionally and can cope better, too.

If you were sick and not very active during treatment, it is normal for your fitness, endurance, and muscle strength to decline. Any plan for physical activity should fit your own situation. An older person who has never exercised will not be able to take on the same amount of exercise as a 20-year-old who plays tennis twice a week. If you haven't exercised in a few years, you will have to start slowly – maybe just by taking short walks.

Talk with your health care team before starting anything. Get their opinion about your exercise plans. Then, try to find an exercise buddy so you're not doing it alone. Having family or friends involved when starting a new exercise program can give you that extra boost of support to keep you going when the push just isn't there.

If you are very tired, you will need to balance activity with rest. It is OK to rest when you need to. Sometimes it's really hard for people to allow themselves to rest when they are used to working all day or taking care of a household, but this is not the time to push yourself too hard. Listen to your body and rest when you need to. 

Keep in mind that exercise can improve your physical and emotional health.

It improves your cardiovascular (heart and circulation) fitness.

Along with a good diet, it will help you get to and stay at a healthy weight.

It makes your muscles stronger.

It reduces fatigue and helps you have more energy.

It can help lower anxiety and depression.

It can make you feel happier.

It helps you feel better about yourself.

And long term, we know that getting regular physical activity plays a role in helping to lower the risk of some cancers, as well as having other health benefits.

What`s new in chronic lymphocytic leukemia research and treatment?

There are many studies of chronic lymphocytic leukemia (CLL) being done in labs and in clinical trials around the world.

Genetics of chronic lymphocytic leukemia

Scientists are making great progress in understanding how changes in a person's DNA can cause normal bone marrow cells to develop into leukemia cells. Learning about changes in the genes (regions of the DNA) that often occur in CLL is providing insight into why these cells grow too quickly, live too long, and fail to develop into normal blood cells. Doctors are also learning how to use these changes to help them determine a person's outlook and whether they will need treatment.

New treatment combinations

Many different drugs are now used to treat CLL. Doctors are looking into which combinations of these drugs are most effective, offering the best chance for long-term survival with the fewest side effects.

The role of stem cell transplants in CLL is still not well-defined. Doctors aren't sure which type of transplant (autologous, allogeneic, or mini-transplant) might be most effective, or which drugs should be used along with the transplant. Studies are now being done to try to answer these questions.

New drugs for chronic lymphocytic leukemia

Dozens of new drugs are being tested for use against CLL. Many of these drugs are targeted at specific parts of cancer cells, while others are more like standard chemotherapy drugs. Flavopiridol and lenalidomide are 2 drugs that have shown promise in early studies against some hard-to-treat cases of CLL.

Oblimersen (Genasense®) is a drug that has been studied for use in CLL. In studies, giving this drug along with chemo was more likely than chemo alone to cause the CLL to go into remission and stay there.

A number of new monoclonal antibodies (man-made versions of immune system proteins) are now being studied for use in CLL treatment. Some of these antibodies, such as lumiliximab and ofatumumab, are used to try to prompt the immune system to attack leukemia cells. They are being tested either alone or in combination with chemotherapy.

Other antibodies are attached to substances that can poison cancer cells, and are known as immunotoxins. They act as homing devices to deliver the toxins directly to the cancer cells. An immunotoxin known as BL22 has shown a great deal of promise in treating hairy cell leukemia (HCL) in clinical trials. A newer version of this drug, known as HA22 (CAT-8015) is now being tested for use against CLL.

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