CLL overview

CLL overview

CLL is an indolent B-cell malignancy that is characterized by a progressive accumulation of leukemic cells in peripheral blood, bone marrow, and lymphoid tissue. It can present in the lymph nodes, spleen, bone marrow, and other lymphoid tissue.1,2


CLL is the most common adult leukemia in Western countries, representing 7% of newly diagnosed cases of NHL.1–3

The median age at CLL diagnosis between 2006 and 2010 was 71 years. The median age at death from CLL, however, was 79 years, illustrating the indolent course this disease often follows.3 For patients presenting with early stage CLL, the median OS is close to 15 years.4
*Year range: 2006-2010. Data collected from


The diagnosis of CLL

The diagnosis of CLL requires at ≥5,000 clonal B lymphocytes/μL in peripheral blood.1

  • <5,000 B lymphocytes/μL in the absence of lymphadenopathy, organomegaly, or other clinical features of CLL is defined as monoclonal B lymphocytosis (MBL)1
  • The rate of progression from MBL to CLL requiring treatment is 1.1%1



Small lymphocytic lymphoma (SLL) is a related disease with the same characteristics as CLL, except that it typically presents in the lymph nodes only. If the disease progresses to the blood and other lymphoid tissue, it is considered CLL.1


Evolution of treatment

Although the majority of patients with CLL require treatment at some point, CLL is generally an indolent disease and many patients do not require treatment at time of diagnosis. Most patients undergo a period of 'watchful waiting,' until the disease progresses or the patient becomes symptomatic.4

Treatment options are determined by patient 'fitness' and disease course. Three categories of patients with CLL have been proposed, based on medical fitness:5

  • 'Go-go'

    medically fit patients that are functionally independent with no or mild comorbidities and a normal life expectancy

  • 'Slow-go' 

    medically less fit patients with mild comorbidities and an unknown life expectancy

  • 'No-go' 

    medically frail patients with severe or numerous comorbidities, dependence in one or more daily activities, and a shorter life expectancy


Chemoimmunotherapy is the commonly used induction or first-line treatment for patients with CLL, but is only for ‘fit’ patients who can tolerate it.1,4,5

Chemoimmunotherapy combines chemotherapy agents with immunotherapy treatments, usually monoclonal antibodies (mAb).1,5

Patients with "high-risk" cytogenetic markers (e.g. a 17p chromosomal deletion or mutations at certain genetic loci such as TP53) are more likely to develop resistance to chemotherapy-based treatment and have poor outcomes.1,5

The ESMO recommends that these patients should be offered an effective initial chemoimmunotherapy regimen, followed by an allogeneic stem cell transplantation within clinical trials.5

Targeted therapy

The emergence of novel, targeted therapy options is evolving the treatment landscape of B-cell malignancies. These small-molecule agents target key mechanisms involved in the molecular pathogenesis of CLL.


Targeted therapies act through inhibition of intracellular signaling pathways, disruption of the tumor microenvironment or modulation of immune responses.5,6

B-cell malignancies

B-cell malignancies include most non-Hodgkin lymphomas (NHL), some leukaemias, and myelomas.7


Click here to access our resources section, which contains a range of useful documents and links with more information about B-cell malignancies.

B-cell signalling

Click below to download the B-cell malignancies brochure.

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  1. National Comprehensive Cancer Network. Non-Hodgkin’s Lymphomas, version 1. 2014.

  2. Shaffer AL III, Young RM, Staudt LM. Pathogenesis of human B cell lymphomas. Annu Rev Immunol. 2012;30:565-610.

  3. SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. Accessed August 16, 2013.

  4. Del Giudice I, Mauro FR, Foà R. Chronic lymphocytic leukemia in less fit patients: “slow-go”. Leuk Lymphoma. 2011;52:2207-2216.

  5. Eichhorst B et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22(Supplement 6):vi50-vi54.

  6. Burger JA. Nurture versus nature: the microenvironment in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2011;2011:96-103.

  7. Mitchell M et al. A multisource approach to improving epidemiologic estimates: application to global B cell malignancies. ISRN Oncol. 2012; 2012:129713.

  8. Kil LP et al. Burton’s tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia. Am J Blood Res. 2013;3:71-83.

  9. Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012;31:119-132.

  10. Dreyling M et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24(4):857-877.

  11. The non-Hodgkin’s Lymphoma Classification Project. A Clinical Evaluation of the international Lymphoma Study Group Classification of Non-Hodgkin’s Lymphoma. Blood. 1997;89(11):3909-3918.

  12. ten Hacken E, Burger J. Molecular Pathways: Targeting the microenvironment in chronic lymphocytic leukemia focus on the B cell receptor. Clin Cancer Res. 2014;20:548-556.

  13. Burger JA et al. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood 2009;114:3367-3375