|  |  |  | | | | Chronic Lymphocytic Leukaemia | | | | |
| | The booklets in this series are intended to provide general information about the diseases they describe.
In many cases the treatment of individual patients will differ from that described in the booklets.
At all times patients should rely on the advice of their specialist who is the only person with full information about their diagnosis and medical history.
 | What is chronic lymphocytic leukaemia? |
Chronic lymphocytic leukaemia (CLL) is a form of leukaemia in which there is an excess number of mature, but poorly functioning lymphocytes in the circulating blood. In CLL the major reason for the build-up of tumour cells is the failure of lymphocytes to die at the end of their normal life span. The rate of production of lymphocytes is not significantly increased and may even be lower than normal.
Lymphocytes are white blood cells that are vital parts of the body's immune system. Lymphocytes can be classified into sub-groups according to their function - the main groups are B cells and T cells. This is called immunophenotyping. All cases of CLL and most lymphomas (tumours of glands) affect the B cells. T cell leukaemias are extremely rare.
Many patients with CLL also have auto-immune disease, which occurs when the body produces antibodies against its own tissues. These antibodies destroy their own red blood cells causing anaemia and/or destroy the platelets. The spectrum of conditions seen includes auto-immune haemolytic anaemia (10% of patients), auto-immune platelet destruction and a combination of both.
About 15% of patients will undergo a subtle transformation of CLL - to a more rapidly progressing condition. This is called chronic lymphocytic leukaemia/prolymphocytic leukaemia (CLL/PLL), in which there are increased numbers of prolymphocytes; the other form of transformation or Richter's syndrome (rapidly progressing large cell lymphoma in a patient with CLL) is more dramatic and occurs in 5-10% of cases . These two forms tend to respond poorly to treatment and have a poorer prognosis than CLL. At present there is no test available to predict which patients are likely to undergo transformation of their disease but there is a considerable number of clinical features and laboratory tests which help to predict overall outcome.
| Who gets chronic lymphocytic leukaemia? |
Chronic lymphocytic leukaemia is overwhelmingly a disease of later life, it makes up 40% of all leukaemia in patients over 65 years old. The overall incidence is about 3/100,000 per year with a median age of onset of 65 to 70 years.
Only about 20-30% of patients are younger than 55 years of age at the time of diagnosis. There is overall male excess which is less marked with increasing age the ratio is about 2 to 1. The incidence in black and white populations is approximately equal but the disease is rare in Asians. The scarcity in Asians is seen regardless of where they are resident and of their lifestyle which suggests that this may reflect underlying differences in susceptibility.
| What are the types of chronic lymphocytic leukaemia? |
Chronic lymphocytic leukaemia shows an extremely wide variation in its clinical features. There is no formal classification system like those that exist for the acute leukaemias and lymphomas. Many studies have been carried out to develop ways of predicting which patients are likely to have a long survival and which may have more rapidly progressing disease. These include clinical staging and the results of laboratory tests as discussed below.
CLL RELATED DISEASES
There are several conditions sometimes referred to as variant CLL. These are not variants but are recognized to be distinct disease entities related to CLL. A -scoring system has been devised which considers various features of the abnormal cells mainly based on immunological typing (this looks at the presence of certain molecules or antigens in the surface of the lymphocytes and CLL cells) and is helpful to distinguish CLL reliably from these similar conditions.
B-CELL PROLYMPHOCYTIC LEUKAEMIA
This is a distinct disease entity in which almost all the leukaemia cells larger than those seen in typical CLL. The cells have a distinctive appearance and are described as prolymphocytes. This leukaemia is different from the prolymphocytic transformation of CLL in which there is a mixture of CLL cells and prolymphocytes.
The lymphocyte count is often very high at diagnosis - 100 x109/l or greater. Prolymphocytic leukaemia responds poorly to single drug treatment such as that used for typical CLL. Treatment with drug combinations of the type used for non-Hodgkin's lymphoma may be more effective. The overall prognosis is less favourable than for CLL with a median survival of about three years.
LEUKAEMIC PHASE OF NON-HODGKIN'S LYMPHOMA
Patients with non-Hodgkin's lymphoma usually have few or no lymphoma cells in their blood at the time of diagnosis. Rarely, they may present with a leukaemia resembling CLL. In later stages of the disease, they may progress into a leukaemic phase in which lymphoma cells are easily detected in the blood. Most types of non-Hodgkin's lymphoma are easily distinguished from CLL because the malignant cells look very different and the results of immunological typing are quite different.
There are many types of lymphomas. One is called small lymphocytic lymphoma (SLL),in which the lymphoma cells closely resemble the leukaemia cells seen in CLL. The distinction between SLL and CLL is based on the clinical behaviour of the disease; if the most prominent feature is enlarged lymph nodes with little disease in the marrow or blood then the diagnosis is SLL. If there is a marked involvement of the bone marrow and blood at the time of diagnosis it is classified as CLL.
HAIRY CELL LEUKAEMIA
Another related condition is hairy cell leukaemia which affects B-cells but has very distinct morphology and clinical features. This condition is described in a separate Leukaemia Research Fund leaflet.
T-CELL CHRONIC LYMPHOPROLIFERATIVE DISEASES
There is no such thing as T-CLL. The T-cell chronic lymphoproliferative diseases include large granular lymphocytic leukaemia, T-cell prolymphocytic leukaemia and the leukaemic phases of various T-cell lymphomas.
| What causes chronic lymphocytic leukaemia? |
There are no clearly defined risk factors for chronic lymphocytic leukaemia. No environmental exposures (radiation, chemicals, or infections) have been shown to increase the risk of developing CLL.
There is some evidence of an association between exposure to agricultural chemicals and certain viruses with an increased risk of CLL but this evidence is inconclusive. Intriguingly, there have been more cases of CLL reported in the spouses of patients than chance would predict. This suggests the possibility of shared environmental factors affecting the risk.
The only factors definitely associated with an increased risk of CLL are older age and male sex. CLL is virtually unknown in childhood, rare in young adults and becomes progressively more common from the age of about 35 years. A higher number of males are diagnosed with CLL compared to females.
There is strong evidence of genetic differences in susceptibility to CLL. In Asian populations the incidence of CLL is very low, whether they have an Asian or a Western lifestyle. Further evidence for a genetic component is the increased incidence of CLL and related conditions in close relatives of CLL patients. It has been estimated that as many as 10% of all cases may be familial. When this occurs it is common for CLL to be diagnosed at a younger age in each succeeding generation.
| What are the signs and symptoms of chronic lymphocytic leukaemia? |
About 70-80% of all new cases of CLL are chance findings on a routine blood test and between 40% and 60% of patients with CLL are free of symptoms at the time they are diagnosed. Almost all of these cases are discovered as a result of enlarged lymph nodes being noted by a doctor at a routine check-up or, more frequently, by abnormal results from routine blood tests. The number of asymptomatic cases discovered depends on the proportion of a given population having regular physical examinations or blood counts. It is common for there to be no symptoms at the time of diagnosis even when the white blood cell count is very high (greater, than 100 x109/l).
In those patients who have symptoms at the time they are diagnosed, these are most commonly weakness, fatigue, night sweats or proneness to repeated infections. On being examined, these patients have enlarged but not tender lymph nodes and enlarged liver, or spleen, or both. About 15% of patients will either be anaemic (low haemoglobin levels) or have a low platelet count. This shows that the disease has affected the normal production of blood cells in the bone marrow or that there has been auto-immune damage to the red cells or platelets.
| How is chronic lymphocytic leukaemia diagnosed? |
Unlike acute leukaemia, chronic lymphocytic leukaemia is not considered a medical emergency. Most patients have a relatively indolent form of the disease. If it is diagnosed early it is not usual to start treatment immediately. For this reason it is perfectly normal for a patient who is thought to have CLL, to be given a non-emergency appointment and be made to see a hospital specialist.
Diagnosis of CLL is usually on the basis of blood count and immunophenotyping. For a diagnosis of CLL to be made the lymphocyte count must be at least 5x109/l and the other features of CLL must be present. In all other forms of leukaemia a bone marrow sample is routinely obtained at the time of first diagnosis. Patients with early-stage CLL who are free of symptoms are not candidates for active treatment. In this group of patients, clinicians may elect not to take bone marrow samples. Bone marrow samples are least likely to be taken in older patients with slowly progressing disease. However, if there is any doubt about the differentiation between CLL and related conditions a bone marrow sample may be required. Immunophenotyping is essential to differentiate between CLL and certain closely related conditions.
Tests to detect chromosome abnormalities in the leukaemia cells are not part of the routine diagnostic work-up for CLL. They may be done routinely in larger centres or as part of scientific studies of the disease. Although they are not considered essential for diagnosis are important to predict prognosis. Staging in CLL (see below) can be done on the basis of blood samples and of physical examination.
| How is chronic lymphocytic leukaemia staged? |
Staging of CLL is of particular importance in helping to decide when to begin treatment and estimate prognosis and survival. There are two main staging systems used for CLL - these are called the Rai and the Binet system and are summarised in the table below.
| Raised number of lymphocytes (in blood or marrow) | >10 years | | As 0 + enlarged nodes | 7 years | | As 0 + enlarged spleen/liver, =/- enlarged nodes | 7 years | | As 0 + anaemia, +/- enlarged nodes, liver or spleen | 3-5 years | | As 0 + low platelets, +/- anaemia, enlarged nodes, liver or spleen | 3-5 years | | Less than 3 areas of enlarged lymph nodes | >10 years | | 3 or more areas of enlarged lymph node | -5 years | | Anaemia +/- low platelets | 3-5 years |
[Median Survival a note
Median survival is often misunderstood by patients and family to mean the maximum expected lifespan. In fact, it is the time at which one would expect half of a group of patients diagnosed at the same time to still be alive many of those still alive will live for many more years, decades even. It is also important to realize that not all patients who die after being diagnosed with CLL die from CLL. Particularly in the case of elderly patients, many will die from other diseases. Finally, one should always remember that survival data is historical and may not reflect improvements based on newer drugs or treatments.]
There is a modified Rai three-stage system that classes stage 0 as low-risk, stages 1 and 2 as intermediate-risk and stages 3 and 4 as high-risk. The modified system is sometimes used in the context of clinical trials.
The Binet system is used more commonly in Europe whereas the Rai system tends to be used in the United States. Although the Binet system does not include a category for a high lymphocyte count in isolation, it is normally possible to compare results of clinical trials even when they do not use the same system.
A condition called smouldering CLL is recognized,-. These are patients who would be classed as Binet stage A but who have the following features:
 | Haemoglobin >13g/dl |
| Lymphocyte count <30x109/l |
| Minimal or no lymph node enlargement |
| Non-diffuse pattern of bone marrow disease |
| Lymphocyte doubling time (period in which the number of lymphocytes double in the peripheral blood) >12 months |
In one study of patients with smouldering CLL only 15% of patients had shown any progression of the condition after 5 years and 80% were alive at 10 years.
NEW PROGNOSTIC MARKERS
Although their exact importance is not yet established, several new tests in addition to cytogenetics are being studied for their potential value in predicting which patients may have more aggressive CLL.
The first of these findings was a rearrangement (mutation) of certain genes (immunoglobulin genes) . This mutation occurs in normal antibody producing B lymphocytes when they encounter an antigen (this test is called IgVH gene status). Re-arranged IgVH genes are thought to indicate relatively mature B-cells and are associated with slower disease progression and longer survival. Unmutated IgVH genes (sometimes referred to as germline configuration) are thought to show immaturity of the B-cell which seems to be more associated with aggressive disease. Unfortunately, the test for IgVH status is beyond the capacity of most hospital routine laboratories so this test is not of great value in day-to-day practice.
A marker on the surface of CLL cells called CD38 seems to also have prognostic significance; In this case high levels of CD38 are associated with a poorer outcome; although CD38 results usually correlate with the IgVH gene status results, it is an independent variable. This test is relatively simple but levels of CD38 may vary over the course of the disease requiring repeated sampling. The newest test, for a protein called ZAP-70, is much easier to perform in a routine hospital laboratory. Early results suggest that the ZAP-70 status may be more stable over time than CD38 values. Preliminary results suggest that this may be an important tool in advising patients and in planning treatment; much work remains to be done to confirm the value of ZAP-70.
| How is chronic lymphocytic leukaemia treated? |
PRINCIPLES OF TREATMENT
It is generally agreed that, with the possible exception of stem cell transplants for younger patients, there is no curative treatment currently available for CLL. Despite this most patients will, happily, have a long survival and this means that they may well receive a number of different types of treatment during the course of their disease. A significant minority of patients will never require treatment at any time.
For those patients who do require treatment there are three basic aspects of treatment-:
| treatment (if required) of the newly diagnosed patient, |
| treatment of patients with progressive disease or disease resistant to standard treatments, and |
| treatment of complications such as infections or autoimmune disease. |
This section on treatment will be organized according to these aspects. Firstly, we will discuss decisions on when a patient need be referred to a specialist, how it is decided when, and if, treatment should start and the actual details of treatment. Secondly, we will consider what is called second-line treatment, used for progressive or resistant disease. Finally, we shall discuss treatment of complications; it is important to realize that such complications may occur at any time, indeed some patients will receive treatment for complications even though their leukaemia is stable and requires no therapy.
In each section we will describe the recommendations contained in the BCSH guidelines and then explain these, heading by heading. First, we will offer a brief description of the main drugs used in treatment of patients with CLL.
ALKYLATING AGENTS
The most commonly used of these is a drug called chlorambucil; for many years this was the main drug used in treatment of CLL. Another drug of this type called cyclophosphamide may be used with similar effectiveness.
ANTHRACYCLINES
Anthracyclines are drugs commonly used in treatment of leukaemias and lymphomas. They are often used in combination with other drugs.
PURINE ANALOGUES
DNA in our cells includes components called purines and pyrimidines. Purine analogues are drugs which are very similar in shape and chemically to natural purines but when cells try to use them to make DNA they do not fit properly and they stop the process and thus stop the cell from dividing. Lymphocytes, which are the affected cells in CLL, are particularly vulnerable to the effects of purine analogues; the main forms used in treatment of CLL are called fludarabine and cladribine.
N.B. Any patient who has been treated with a purine analogue should receive irradiated blood products for any future transfusions. This is to prevent a condition called transfusion associated GvHD.
MONOCLONAL ANTIBODIES
A monoclonal antibody is an antibody that has been created in a laboratory and binds specifically to a component (antigen) present in the membrane of lymphocytes and/or other cells. It is a new kind of treatment that is very different from chemotherapy. Most chemotherapies are chemicals that kill all rapidly dividing cells in your body. A monoclonal antibody is designed to bind to the specific antigen and with the help of the patient's immune system, this cell is destroyed. The monoclonal antibodies currently being used in treatment of CLL are Alemtuzumab (MabCampath), and Rituxan (Rituximab).
STEROIDS
There is no evidence that treatment with steroids combined with the above agents have benefit in CLL. However, they are important in two situations:
| Patients with Stage C disease should receive a short course of prednisolone before starting chlorambucil. This steroid will improve the blood counts and they will tolerate better chlorambucil |
| To control autoimmune complications |
MISCELLANEOUS
For patients whose illness does not respond to any of the specific treatments described above, various combinations of the drugs described may be used.
| Management of CLL |
INDICATIONS FOR REFERRAL
The Department of Health has issued guidelines for family doctors indicating when patients should be referred for specialist investigation for suspected cancer. The typical indications for referral to a haematologist include a high white count with excessive numbers of lymphocytes (especially in the presence of anaemia or a low platelet count); presence of enlarged lymph nodes or liver/spleen; and symptomatic disease (weight loss over 10% in last 6 months, fever over 38C for two or more weeks, extreme fatigue or night sweats).
INDICATIONS FOR TREATMENT
For many patients with CLL there will be few, if any, periods when they require in-patient treatment for their illness; patients may require inpatient treatment if they develop a severe infection. Patients who have no significant symptoms at the time of diagnosis and whose laboratory results indicate early stage disease are likely to be offered check-ups but no treatment this is often called a watch and wait approach.
The criteria suggested in the guidelines for commencing therapy are:
Progressive marrow failure: development or worsening of anaemia or low platelets
Massive (>10cm) or progressive lymph node enlargement
Massive (>6cm) or progressive enlargement of the spleen
Progressive lymphocytosis
| 5% increase over 2 months |
| doubling - the lymphocyte count in the blood <6 months |
Systemic symptoms
| Weight loss > 10% in last 6 months |
| Fever >38C for 2 or more weeks |
| Extreme fatigue |
| Night sweats |
Autoimmune haemolytic anaemia or ITP (see below)
| It is important to rule out other possible causes for these symptoms, such as infection. |
| Treatment Strategy |
INITIAL TREATMENT
Treatment of early stage disease is not indicated
| There is clear evidence that patients do not benefit from, and therefore do not require, treatment for early stage CLL. For these patients the recommendation is routine check-ups but no active treatment this is often called watch and wait. |
For patients who are not candidates for a transplant entry into the CLL4 clinical trial should be considered.
| This trial randomly allocates patients to receive either chlorambucil, fludarabine alone or fludarabine with cyclophosphamide and is considering the value of different prognostic tests and quality of life issues, as well as the outcome of treatment |
For patients for whom fludarabine is not advised (those with severe renal impairment or autoimmune disease) and a transplant would not be considered, chlorambucil is recommended. (There is no evidence that adding an anthracycline improves survival in this group.)
| Adding an anthracycline causes more toxicity with no clear benefit. |
There is insufficient evidence to routinely recommend high dose chlorambucil as an initial treatment for CLL.
| Some studies have suggested that the outcome may be better with high-dose chlorambucil but these were difficult to compare with standard practice so more evidence is needed before this could be routinely recommended. |
If a patient may be a candidate for a transplant then an initial treatment, such as fludarabine, which is likely to achieve a complete, or near complete remission should be chosen. Because there is no definitive proof of the benefit of an autologous stem cell transplant, there is a European study (CLL-5) that investigates this issue and is offered to the patients. In this study patients are randomly allocated to have a transplant immediately after therapy or the procedure is delayed until the disease comes back
| It is important to keep to a minimum the time after fludarabine therapy - before collection of stem cells from the blood. |
Alemtuzumab is not recommended for untreated CLL.
Rituximab used alone is not recommended for untreated CLL.
Rituximab combined with fludarabine (with or without cyclophosphamide) requires further evaluation before it can be routinely recommended.
| At present the use of monoclonal antibody-based treatments is reserved for patients who have either relapsed after standard therapy or who did not respond to standard therapy. |
SECOND LINE AND SUBSEQUENT THERAPY
| Patients who relapse after having an initial response to low-dose chlorambucil may be treated with a further course of chlorambucil |
| Patients who do not respond to low-dose chlorambucil may be treated with fludarabine. If patients have severe renal disease or an autoimmune condition they are not recommended to receive fludarabine; these patients should receive CHOP therapy. CHOP is a combination of drugs widely used in treatment of lymphoma and is used in patients with CLL in transformation- Richter's- alone or combined with Rituximab |
| Patients who initially responded to fludarabine, and who experience progression over a year after receiving fludarabine, may be treated again with fludarabine alone. |
| Patients who develop progressive disease within one year of receiving fludarabine may be treated with a combination of fludarabine and cyclophosphamide. |
| There is no single agreed treatment approach for patients who do not respond to fludarabine or who respond initially but whose disease becomes unresponsive. Options include: |
| High-dose methyl prednisolone (a steroid), especially for patients with markedly enlarged lymph nodes or with abnormalities of a gene called p53 (or both); |
| Alemtuzumab is licensed for and recommended in patients who do not have very enlarged lymph nodes and who have previously been treated with alkylating agents and who are not responding to fludarabine; |
| Rituximab alone is not recommended for previously treated CLL. Rituximab with fludarabine (with or without cyclophosphamide) -seem very effective further studies are needed; |
| Autologous transplantation should be considered for patients with a good response to treatment who are fit enough to withstand high-dose chemotherapy and total body irradiation. Autologous transplantation should be done in the context of a clinical trial such as the MRC CLL 5 trial.(as outlined above) |
| A donor transplant may be considered for younger, fitter patients who have been previously treated and who have poor risk disease. Suitable patients should be referred at an early stage (to minimize the risk of drug-resistance developing). Although this is considered potentially curative, it is important to stress that the side-effects (short and long term) of this treatment are much greater than for conventional treatments. |
| Splenectomy may be of benefit in selected patients who have symptoms caused by a very enlarged spleen or to improve the blood count in patients with auto-immune disease. |
| Management of complications |
PREVENTION AND TREATMENT OF INFECTIONS
Infection is a common complication of CLL; this is partly a result of the disease itself and partly a complication of treatment. It results from a number of factors including low levels of antibody (hypogammaglobulinaemia), low numbers of normal white cells (neutropaenia), impaired function of lymphocytes (especially T and NK cell), and defective function of the complement system (a part of the immune response). Infection is a particularly significant danger in the elderly, those with advanced disease and those receiving treatment. There is some evidence that purine analogue treatment may carry a higher risk of infection.
Most infections are bacterial the respiratory tract (nose, throat and lungs) being especially vulnerable. Blood poisoning (septicaemia), kidney infections, and infections of soft-tissues and the urogenital system are also common. Fungus infections, viral illnesses and infections with normally harmless organisms (opportunistic infections) used to considered rare but they are being seen more often in patients treated with purine analogues, high-dose steroids and Alemtuzumab.
| Prevention |
Antibiotics
| Patients who have had repeated chest or urinary infections may be given cycling antibiotic cover (prevention by a sequence of different antibiotics taken one after another). There are no large studies to prove whether this works or not at present it will depend on the judgement of individual doctors whether they use this approach. |
Prophylaxis against pneumocystis carinii
| All patients who are receiving purine analogues or Alemtuzumab should receive septrin or inhaled pentamidine as a precaution against a respiratory infection called pneumocystis carinii pneumonia. The preventive antibiotics should continue for six months after stopping purine analogues or alemtuzumab. |
Intravenous immunoglobulin
| Patients with hypogammaglobulinaemia and recurrent bacterial infections should be given intravenous immunoglobulin, especially if antibiotics have proved ineffective. |
Immunisation
| Immunisation is often less effective in patients with CLL than in unaffected people. In particular, there is a poor response to vaccination against diphtheria, typhoid, mumps, influenza, pneumococcus and haemophilus. A special type of vaccine called a conjugated vaccine often proves more effective for CLL patients and, where such a vaccine is available, it should be used in preference. |
Although it is standard practice to recommend annual influenza vaccination for CLL patients, the effectiveness is uncertain; patients should not assume they are protected.
| Treatment of infections |
Patients and carers need to be aware of the special risks of infection and of the need to seek immediate medical attention as soon as the patient suspects they may have an infection. Minor infections can be treated on an outpatient basis but major infections will require treatment in hospital. As infections in CLL patients can be very serious, it is normal to start on broad-spectrum antibiotics as soon as all the essential laboratory samples have been collected.
AUTOIMMUNE CYTOPAENIAS
As mentioned, many patients with CLL develop autoimmune conditions; often these affect the blood cells with the result that patients may become anaemic or have low platelet counts (ITP). Although these conditions may be present at diagnosis, they more usually develop during the illness. There is some evidence that autoimmune haemolytic anaemia (AIHA), which is destruction of red cells by antibodies, is more common after treatment with purine analogues.
It is recommended that patients who do develop AIHA or ITP should be treated in the same way as patients with these conditions who do not have CLL.
Re-treatment with a purine analogue is NOT recommended in a patient who has previously developed AIHA or ITP while receiving a purine analogue.
The risk of AIHA in patients with a positive DAT but no evidence of red cell destruction is not known. Purine analogues should be used with care in this situation with regular checks of the Hb and the DAT.
TRANSFORMATION (RICHTER'S SYNDROME)
Development of lymphoma occurs in 5 10% of patients with CLL; the lymphoma may be present at diagnosis of CLL but most develop during the course of the disease. Special tests have shown that some of the lymphomas have arisen from by transformation of CLL cells while others originate from a distinct cell population. Most cases are of the type known as diffuse large B-cell lymphoma (DLBCL).
No standard treatment recommendation is made in the guidelines for Richters transformation of CLL; sufficient evidence is not yet available but usually these patients are treated as those with high risk B-cell lymphomas. Any patient developing Richters transformation will have their treatment decided on an individual basis after discussion with his or her doctor.
| Summary |
Chronic lymphocytic leukaemia is a form of cancer which affects blood producing cells in the bone marrow. The disease is unknown in childhood, very uncommon in young people and becomes progressively more common with increasing age. Men are more likely to be affected than women. The majority of patients with CLL have a slowly progressing form with a survival of ten years or more. Chronic lymphocytic leukaemia is not considered curable with the possible exception of younger patients who receive stem cell transplants. A minority of patients have a more rapidly progressing form of the disease with a much shorter median survival. Standard practice is not to treat patients who have early-stage disease or have no clinical symptoms. There is no evidence that early treatment prolongs survival for these patients. Treatment is started either when patients become symptomatic or when laboratory results indicate that the disease is progressing.
The mainstay of treatment is chemotherapy. In most cases this involves low doses of drugs taken by mouth. The drugs most commonly used are chlorambucil, prednisolone and fludarabine. Radiotherapy has a very limited role in treatment of chronic lymphocytic leukaemia. Most people with CLL would not be considered for a stem cell transplant because of their age and the indolent nature of their disease. For younger patients with rapidly progressing disease a transplant may be curative. There is not yet sufficient evidence to be sure that transplanted patients have achieved cures.
Most patients are able to enjoy a good quality of life for many years, with little or no treatment. For the minority of patients with more rapidly progressing or late-stage disease more intensive therapy may be required. In between 10% to 15% of patients the disease will transform into either prolymphocytic leukaemia or into a high-grade non-Hodgkin's lymphoma (Richter's syndrome). |
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