Related to this topic: Leaflets | Support | Weblinks | Equipment | Books | Your Experience | Other resources | Glossaries
Print options:
Other options:
(what's this?)
PatientPlus articles are written for doctors and so the language can be technical. However, some people find that they add depth to the articles found in the other sections of this website which are written for non-medical people.
Chronic Lymphocytic Leukaemia (CLL)
This is malignancy of B lymphocytes. Morphologically they appear normal but they are immature and so there is immunological compromise.
It is most frequent in those over 55 although it is seen at times below 35 years old. It affects white races more than black and is uncommon in those of Far Eastern origin. There is a male preponderance of 1.7:1.
There is evidence that a number of people with CLL may have a genetic predisposition1 although cases running in families are very rare. It is not related to exposure to radiation.2
Symptoms
Presentation is variable. Onset is insidious, and it is not unusual for it to be discovered incidentally after a blood count is performed for another reason.
- Susceptibility to infections including pneumonia, herpes simplex, and herpes zoster
- Enlarged lymph nodes
- Abdominal discomfort from to an enlarged spleen
- Bleeding or petechiae in skin or mucous membranes from thrombocytopenia
- Tiredness and fatigue from anaemia
Signs
- Local or generalised lymphadenopathy
- Splenomegaly in 30 to 40%
- Hepatomegaly in 20%
- Petechiae
- Pallor
Blood
- FBC shows more than 5000 lymphocytes/?L.
- Peripheral blood smear confirms lymphocytosis often with smudge cells which are artifacts from damage to lymphocytes during preparation of the slide.
- Peripheral blood flow cytometry is the most valuable test to confirm CLL. It shows circulating clonal B-lymphocytes expressing CD5, CD19, CD20(dim), CD 23, and an absence of FMC-7 staining.
- Measurement of immunoglobulin levels if there are repeated infections because monthly intravenous immunoglobulin in patients with low IgG (<500 mg/L) may help to reduce the frequency of infections.
Imaging
- Liver and spleen scan may show enlargement.
- CT of chest, abdomen or pelvis is not necessary for staging but it may show obstructive uropathy or airway obstruction from lymph node compression on organs or internal structures.
Procedures
- Bone marrow aspiration and biopsy with flow cytometry is not needed in all cases but may be necessary to establish the diagnosis and to assess other complications including anaemia and thrombocytopenia. Bone marrow examination may be necessary to distinguish between thrombocytopenia of peripheral destruction (in the spleen) and that due to marrow infiltration.
- Lymph node biopsy is required if lymph nodes enlarge rapidly to assess the possibility of transformation to a high-grade lymphoma. This transformation with fever, weight loss, and pain it is called Richter syndrome.
The Binet system is used in the Europe but in USA the Rai-Sawitsky staging predominates. The International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) has recommended integrating the two.
The Binet system is as follows:
- Stage A: Hb at least 10 g/dL, platelets at least 100 X 109, and less than 3 lymph node areas involved.
- Stage B: Hb and platelet levels as in stage A and 3 or more lymph node areas involved.
- Stage C: Hb <10 g/dL, platelets <100 X 109, or both.
The staging system is useful but it does have shortcomings in terms of predicting prognosis and who will benefit from certain interventions.3 Haemoglobin level, blood lymphocyte count, lymphocyte doubling time and bone marrow infiltration pattern are useful to identify subsets of patients in early stage with different progression and survival rates, with the 'smouldering' form of the disease being identified fairly accurately. Tumour mass, as reflected by splenomegaly, lymphadenopathy and bone marrow infiltration, affects prognosis.4
Non-Drug
Because of the risk of infection, influenza vaccination and pneumococcal vaccine should be given.
Drugs
Most patients do not need immediate chemotherapy unless they have:
- Weight loss of more than 10%
- Extreme fatigue
- Fever related to leukaemia
- Night sweats
- Progressive marrow failure
- Autoimmune anaemia or thrombocytopenia not responding to prednisolone
- Progressive splenomegaly
- Massive lymphadenopathy or progressive lymphocytosis
- Progressive lymphocytosis is defined as an increase of more than 50% in 2 months or a doubling time of less than 6 months.
Some patients develop autoimmune disease. They may benefit from prednisolone, started at a dose that may be as high as 60mg daily but reduced down as control is achieved.
Common combination regimens for chemotherapy include:
- Chlorambucil and prednisolone
- Cyclophosphamide, doxorubicin, and prednisolone (CAP)
- Cyclophosphamide, vincristine, and prednisolone (CVP)
- Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)
New drugs include fludarabine5 and monoclonal antibodies.6 NICE recommends that if there is reason to stop the first line chemotherapy as listed above, either because of adverse effects or failure to respond, that fludarabine should be the next line.7
Surgical
Splenomegaly and pancytopenia may require splenectomy. Up to 90% of patients show considerable improvement in Hb and platelets after splenectomy.
They should be immunised with Pneumococcus, Haemophilus and Neisseria meningitides vaccines at least a week before operation.
Around a quarter of patients with CLL have autoimmune phenomena. The commonest is haemolytic anaemia followed by thrombocytopenia.8 There may be immune compromise with progressive profound hypogammaglobulinaemia. A fairly common precipitant of these phenomena seems to be treatment with the purine analogues such as chlorambucil and fludarabine. Helpful treatments, if corticosteroids alone are insufficient, include cyclosporin and rituximab. The latter is one of the monoclonal antibodies.
The autoimmune complications do not not imply a poor prognosis although a major cause of death is secondary malignancy.9
Extremely high WCC (>300,000/?L) can produce a hyperviscosity syndrome affecting the CNS or respiratory system. Leukocytopheresis and urgent therapy with prednisolone and chemotherapy may be required. Virtually all patients requiring therapy also should be given allopurinol to prevent uric acid nephropathy.
Prognosis is highly variable. Some patients die within 2 or 3 years of diagnosis because of complications of CLL.
The majority live 5 to 10 years, with an initial course that is relatively benign but followed by a terminal progressive and resistant phase lasting a year or two. In the late phase there is considerable morbidity from both the disease and from complications of treatment.
Survival is generally dependent upon staging:
- Stage A: Survival >120 months
- Stage B: Survival around 61 months
- Stage C: Survival around 32 months
The management of CLL is aimed at palliation rather than cure but with improvements in care, including the potential for stem cell transplantation, cure may soon be the goal, especially in the younger patients.10
Document References
- Houlston RS, Catovsky D, Yuille MR; Genetic susceptibility to chronic lymphocytic leukemia. Leukemia. 2002 Jun;16(6):1008-14. [abstract]
- Muirhead CR, Goodill AA, Haylock RG, et al; Occupational radiation exposure and mortality: second analysis of the National Registry for Radiation Workers. J Radiol Prot. 1999 Mar;19(1):3-26. [abstract]
- Zwiebel JA, Cheson BD; Chronic lymphocytic leukemia: staging and prognostic factors. Semin Oncol. 1998 Feb;25(1):42-59. [abstract]
- Montserrat E, Rozman C; Chronic lymphocytic leukaemia: prognostic factors and natural history. Baillieres Clin Haematol. 1993 Dec;6(4):849-66. [abstract]
- Robak T; Therapy of chronic lymphocytic leukemia with purine analogs and monoclonal antibodies. Transfus Apher Sci. 2005 Feb;32(1):33-44. [abstract]
- Ferrajoli A, Faderl S, Keating MJ; Monoclonal antibodies in chronic lymphocytic leukemia. Expert Rev Anticancer Ther. 2006 Sep;6(9):1231-8. [abstract]
- NICE; Fludarabine for the treatment of lymphocytic leukaemia
- Hamblin TJ; Autoimmune complications of chronic lymphocytic leukemia. Semin Oncol. 2006 Apr;33(2):230-9. [abstract]
- Kyasa MJ, Parrish RS, Schichman SA, et al; Autoimmune cytopenia does not predict poor prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Hematol. 2003 Sep;74(1):1-8. [abstract]
- Yee KW, O'Brien SM; Chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc. 2006 Aug;81(8):1105-29. [abstract]
Internet and Further Reading
- Perry M; Chronic Lymphocytic Leukaemia. emedicine July 2005
- cancerbackup.org.uk; Chronic Lymphocytic Leukaemia Information Centre. Advice and support for patients.
- Leukaemia Research Foundation; Chronic Lymphocytic Leukaemia
DocID: 1957
Document Version: 20
DocRef: bgp1046
Last Updated: 29 Nov 2006
Review Date: 28 Nov 2008
Disclaimer: Patient UK has no control of the content of the above links. Inclusion does not imply endorsement by Patient UK.
Related pages in Patient UK
Your Experience (^ top of page)
Please add your experience about this condition / medicine
View patient experiences and discussions about this condition / medicine (4 there)Information leaflets related to this topic (^ top of page)
Leukaemia - Chronic LymphaticPatient Support related to this topic (^ top of page)
Chronic Lymphocytic Leukemia Support Association (CLLSA)
UK Chronic Lymphocytic Leukaemia ForumLinks to other selected websites related to this topic (^ top of page)
LeukaemiaOther - Useful resources (^ top of page)
Pictures, diagrams, photos, images, etc.Evidence based medicine
Online textbooks and journals
A-Z of UK Guidelines
A-Z of Online Videos
Medline
Other good health sites
Medical equipment products related to this topic (^ top of page)

Books related to this topic (^ top of page)

Want to search some more? Use the Google Search box below to search our site.

Would you like to try our advanced on-line knowledge support system designed to provide professionals with relevant up to date information about recognition and management of disease or take the Mentor Challenge?
Disclaimer: Patient UK has no control of the content of the above links. Inclusion does not imply endorsement by Patient UK.
