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Chronic lympocytic leukaemia (CLL)



Both Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma are the same disease. CLL is the variation that most behaves like Leukaemia and is found mostly in the blood. SLL on the other hand is the variation that is found mostly in marrow and the lymphatic system. Otherwise they behave in very similar ways and treatments are the same. Quite often the diagnosis is written as CLL/SLL when there is no clear predominance of one or the other. When researching the internet for additional information it is often best to look for CLL information since that is far more common than SLL information and they are mostly interchangeable.

CLL is the most common type of adult Leukaemia found in Western Countries. In Asian countries it is quite rare in comparison.

Diagnosis and Prognosis

CLL/SLL is considered an indolent type of NHL which means it has a long natural history. Patients generally live 8-10 years or more. As is the case with many indolent lymphomas patients often do not require any treatment when initially diagnosed, and only receive treatment when the symptoms indicate the need. This practice of watch and wait instead of treatment is very similar to other indolent types of lymphoma including follicular lymphoma.

The prognosis is also affected by the presence or absence of the mutation on the immunoglobulin heavy chain variable regions (IvGH) of the leukaemic cells. Those who have the mutation have a generally favourable prognosis, which those lacking the mutation have a higher risk of progressive disease.

Clinical significance of ZAP-70 protein expression B-cell chronic lymphocytic leukemia

Identifying this mutation requires advance testing that is not generally available for most patients. Researchers have found however that the presence of the ZAP-70 gene corresponds to this mutation. High levels of ZAP-70 gene expression are associated with unmutated cells and a worse prognosis. Here is one study that looks at the association between ZAP 70 and IvGH mutation.

ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile


There are a variety of treatment options for CLL/SLL, and they are quite similar to treatments for other types of indolent lymphoma. Treatment will usually start with the mildest treatment that is likely to be effective, reserving more aggressive treatments for later. The purine analogue types of drugs, such as Fludarabine do appear to have more positive results in CLL/SLL than in other types of NHL so many of the combination chemotherapy used to treat CLL/SLL will contain Fludarabine. Studies have shown that single agent Fludarabine alone may not be a wise treatment choice, and that Fludarabine should be combined with Cyclophosphamide. Fludarabine alone may increase the risk of autoimmune hemolytic anaemia.

Likewise the monoclonal antibody therapy Campath seems to achieve better results in CLL/SLL than Rituxan. Rituxan appears to achieve much better results in Follicular lymphoma cases. This does not mean that Rituxan is not used in CLL because it is used quite frequently.

A recent discovery is the drug Ibrutinib. Studies published at the 2012 ASH convention have shown some very impressive results for CLL. Below is just one examle.

The Bruton’s Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Promotes High Response Rate, Durable Remissions, and Is Tolerable in Treatment Naïve (TN) and Relapsed or Refractory (RR) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Patients Including Patients with High-Risk (HR) Disease: New and Updated Results of 116 Patients in a Phase Ib/II Study

Other information

There is a great deal of information devoted to CLL on the Internet so we present just an overview here. Here are some additional links with more detailed information that you may find helpful.

USA National Cancer Institute PDQ for chronic lymphocytic leukemia

Medscape: Chronic Lymphocytic Leukaemias