Cll treatment

cll treatment

Patients with advanced stage CLL will likely start treatment immediately. However, early-stage patients are invariably given no treatment. Instead, they are monitored closely on three to six month intervals. This is one of the most difficult things for newly diagnosed, early-stage CLL patients to accept—the watch and wait approach that is taken to the management of early-stage CLL. People tend to think that they should start treatment as soon as possible in order to maximize their chances of recovery, as is the case with most cancers. CLL is exceptional in this particular respect.

The reason for the watch and wait approach is that CLL is generally thought to be incurable. Treatments are usually aimed at controlling the disease and managing its symptoms (palliative) not at curing the disease (curative). Over time, most treatments lose their efficacy, and for this reason, it is generally agreed that treatment should not begin until it is necessary to control the symptoms of the disease. Even escalating lymphocyte counts often do not mandate treatment.

Treat the symptoms, not the counts is an expression that is often used in the management of CLL. Indeed, the start of treatment is usually determined by a patient’s symptoms. The types of symptoms that signal the start of treatment include, general lack of wellness, extreme fatigue, night sweats, low-grade fevers without any evidence of infection, significantly swollen lymph nodes, and frequent and recurrent infections. The aggressiveness of one’s CLL along with their specific prognostic indicators will also be factors in selecting the time to begin treatment. Aggressive CLL will be treated sooner rather than later.

The decision to begin treatment is an important juncture in the CLL journey. As a general rule, one doesn’t want to start treatment too early or wait too long. Selecting the right time to begin treatment and the type of treatment are very important decisions. Some patients prefer to leave these decisions entirely in the hands of their physicians, while others prefer to take an active role in determining both the timing and the selection of their treatments.

Following is a general outline of the types of treatments used in the various stages of CLL (see also: What are the stages of CLL? ): Stage 0 (elevated lymphocyte counts only) – Treatment is generally not needed.

Stage 1 (elevated lymphocyte counts and enlarged lymph nodes) – If the patient is without symptoms, treatment may still not be required. External radiation therapy to swollen lymph nodes and chemotherapy may also be considered.

Stage 2 (elevated lymphocytes, enlarged nodes, and liver or spleen enlargement) – If there are few or no symptoms, treatment may still not be required. Other possibilities at this stage include chemotherapy, external radiation to the spleen and/or lymph nodes, and clinical trials. (see also: What are clinical trials? )

Stage 3 (elevated lymphocytes and too few red blood cells; lymph nodes and liver or spleen may be enlarged) – Treatment at this stage may include any of the following: chemotherapy, external radiation to the spleen, surgery to remove the spleen (splenectomy), external radiation to the whole body (total body radiation), clinical trials of bone marrow transplantation, and clinical trials of biological therapy.

Stage 4 (elevated lymphocytes and too few platelets; lymph nodes, liver, or spleen may be enlarged, and there may be too few red blood cells) – The treatment options in stage 4 are much the same as stage 3.

Refractory CLL – Refractory means that the CLL initially or no longer responds favorably to treatment. The CLL may become refractory to a particular course of therapy in which case other therapies are used. If the CLL becomes refractory to all standard treatments, the patient’s treatment options will depend on many factors. Two options that may be available to consider include entering a clinical trial of new chemotherapy, biological response modifier, or monoclonal antibody drugs and bone marrow transplantation.

The main forms of treatment for CLL include the following:

Chemotherapy – drugs, taken either orally or intravenously, are used to kill cancer cells. Chemotherapy is called a systemic treatment because it enters the bloodstream and travels throughout the body.

Radiation therapy – x-rays or other high-energy rays are used to kill cancer cells and shrink tumors.

Biological therapy – a type of therapy that tries to get the body to fight CLL. It uses substances made by the body or made in a laboratory to boost, direct, or restore the body’s natural defences against the disease. Biological therapy is also called biological response modifier (BRM) therapy or immunotherapy.

Surgery – in some cases, if the spleen is severely swollen and causing symptoms, it may be removed in an operation called a splenectomy.

Bone Marrow Transplantation (BMT) – there are

two main types of bone marrow transplants: allogeneic and autologous. An allogeneic transplant uses healthy marrow taken from a donor whose tissue is the same as, or almost the same as, the patient’s. Donors are classified as matched related donors or matched unrelated donors (MUD). An autologous transplant uses marrow from the patient, which has been treated with drugs to destroy any cancer cells. The treated marrow is then frozen and stored until the patient is ready for transplantation.

In bone marrow transplantation, all of the bone marrow in the body is destroyed with high doses of chemotherapy and radiation therapy. An exception is the non-myeloablative or mini-transplant (see also: What is a mini-transplant? ). Healthy marrow, either from a donor (allogeneic) or from the patient (autologous) is then given to the patient intravenously to replace the marrow that was destroyed. Transplantation of bone marrow involves potentially serious risks, and patients require the care of skilled medical staff and state-of-the-art support services. For this reason, BMT should be performed at established transplant centers wherever possible.

Supportive treatment – includes transfusion of packed red blood cells for anemia, platelet transfusions for bleeding associated with thrombocytopenia, and antibiotics for bacterial infections.

It is important for patients to understand the goals of treatment and to participate in treatment decisions. Treatment aimed at producing complete remissions will likely be different from treatment that is intended to manage symptoms and blood counts. Before embarking on treatment, be sure to understand the goals, the track record of the drugs being used, and their side effects.

Drugs used in treating CLL are administered either as single agent therapies or as combination therapies. Most physicians agree that complete remissions are more likely with combination therapies than with single agents. The rationale to combination therapy is to use drugs that work at different parts of the cell’s metabolic processes, thereby increasing the likelihood that more cancer cells will be killed. In addition, the toxic side effects of chemotherapy may be reduced when drugs with different toxicities are combined; each at a lower dose than would be needed if one drug were used alone.

A number of drugs are used in the treatment of CLL. Following are examples of these drugs and the categories to which they belong. Where possible, the generic name is shown first followed, in parenthesis, by the trade name (capitalized) and any common names.

Alkylating agents – For many years, the standard first-line chemotherapy treatment for CLL has been the use of alkylating agents such as chlorambucil (Leukeran), cyclophosphamide (Cytoxan), and busulfan (Myleran).

Corticosteroids – Corticosteroids, such as prednisone (Deltasone), are generally used in conjunction with other drugs such as chlorambucil. They have also been evaluated as single agent therapies. When used as single agents, decreases in node, liver, and spleen enlargement commonly occur, but complete responses are rare.

Purine analogues – Perhaps best known in this category is the drug fludarabine phosphate (Fludara, FAMP). Historically, fludarabine has been used primarily as a second-line therapy, after the initially used alkylating agent (chlorambucil or cyclophosphamide) stopped showing a satisfactory response. More recently, based on impressive test results, fludarabine has gained significant ground as a first line therapy, particularly in the US. Examples of other purine analogues used in the treatment of CLL are cladribine (Leustatin, 2-chlorodeoxyadenosine, 2CdA), pentostatin (Nipent, 2-deoxycoformycin), and compound 506U78 (AraG).

Antitumor antibiotics – These drugs are antibiotic chemotherapy agents, as opposed to antibiotics that work against bacteria. Antiluekemic chemotherapy agents in this category include drugs such as doxorubicin (Adriamycin) and mitoxantrone (Novantrone).

Monoclonal antibodies (Mab or MoAb) – Monoclonal antibodies are another method of treatment that, on theoretical grounds, promises to improve our ability to control CLL. One example is alemtuzumab (Campath-1H), an anti-CD52 monoclonal antibody that is toxic to all lymphocytes and which may be effective in producing remissions in patients who have failed prior therapies, including fludarabine. Another monoclonal antibody is rituximab (Rituxan, IDEC-C2B8), which is active against cells expressing CD20. Rituximab is also in clinical studies currently in conjunction with fludarabine and cyclophosphamide. Zevalin, a 90Y labelled anti-CD20 monoclonal antibody, is the radioactive form of rituximab. Tositumomabiodine (Bexxar) is another radioactive anti-CD20 monoclonal antibody. It is combined with radioactive iodine 131, which delivers lethal radioactivity to cancer cells and also flags them for destruction by the immune system.

Growth Factors and Cytokines – Growth factors are used to stimulate the production of different types of blood cells. Filgrastim (Neupogen, G-CSF), a granulocyte stimulating factor, epoitin alfa (Epogen, Procrit), a red cell stimulating factor, and thrombopoeitin, a platelet stimulating factor are examples of growth factors.

The following table summarizes many of the drugs that are used in the treatment of CLL, some of which are still in clinical trials and not yet approved for general use:

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