Chronic lymphocytic leukemia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 2 Jun 2025

Last updated: 21 Mar 2025

Chronic lymphocytic leukemia (CLL) is an indolent hematologic cancer that occurs with increasing age.

Usually presents with absolute lymphocytosis as an incidental finding on routine complete blood count (CBC) or with asymptomatic lymphadenopathy.

Diagnosed by CBC with differential, peripheral blood smear, and flow cytometry.

Variable clinical course with most patients experiencing very slow progressive disease.

Clinical and laboratory criteria are used to determine treatment approach and prognosis.

Management includes active surveillance (observation) or targeted therapies if treatment is indicated. Chemoimmunotherapy or immunotherapy may be considered for selected patients.

Definition

CLL is an indolent lymphoproliferative disorder in which monoclonal B lymphocytes (≥5000 cells/microliter [≥5 × 10⁹/L]) are predominantly found in peripheral blood.[1] Lymphocytosis is sustained for at least 3 months.[2] If these cancer cells are predominantly found in lymph nodes, the disorder is called small lymphocytic lymphoma.

History and exam

Key diagnostic factors

shortness of breath and fatigue
lymphadenopathy
splenomegaly
hepatomegaly

Full details

Other diagnostic factors

B symptoms
recurrent infections
epistaxis
pallor
petechiae

Full details

Risk factors

age over 60 years
male sex
white ethnicity
family history of CLL

Full details

Diagnostic tests

1st tests to order

CBC count with differential
flow cytometry
peripheral blood smear

Full details

Tests to consider

serum beta-2 microglobulin
fluorescent in situ hybridization (FISH)
molecular genetic tests
direct antiglobulin test (DAT)
serum quantitative immunoglobulin
lymph node biopsy
bone marrow aspirate and trephine biopsy
CT scan/fluorodeoxyglucose (FDG)-PET/CT

Full details

Treatment algorithm

ACUTE

asymptomatic early stage (Binet A and B; Rai 0-II)

advanced stage (Binet C; Rai III-IV) or with indications for treatment (e.g., symptoms)

ONGOING

relapsed or refractory disease

Contributors

Authors

Jacqueline C. Barrientos, MD, MS

Associate Professor

Department of Medicine

Zucker School of Medicine at Hofstra/Northwell

CLL Research & Treatment Program

Northwell Health Cancer Institute

Lake Success

Disclosures

JCB has been a consultant for Beigene, Abbvie, and AstraZeneca; received honoraria from Janssen; and received research funding from Oncternal, VelosBio, and Pharmacyclics.

Joanna M. Rhodes, MD, MSCE

Assistant Professor

Department of Medicine

Zucker School of Medicine at Hofstra/Northwell

CLL Research and Treatment Program

Northwell Health Cancer Institute

Lake Success

Disclosures

JMR has received fees for consulting for Abbvie, Genentech, Pharmacyclics, Beigene, AstraZeneca, Morphosys, Epizyme, ADC Therapeutic, TG Therapeutics, Versatem, SeaGen, and Jannsen. JMR’s institution has received research support from Oncternal Pharmaceutics, Pharmacyclics, Acerta, Loxo Oncology, Velosbios, Abbvie, and AstraZeneca.

Acknowledgements

Dr Jacqueline C. Barrientos and Dr Joanna M. Rhodes would like to gratefully acknowledge Dr Vidhya Murthy, Dr Shankaranarayana Paneesha, and Dr Robert Chen, previous contributors to this topic.

Disclosures

VM has received a consultancy fee from Janssen, and a grant from Takeda for the ASH Annual Meeting 2014. SP has received consultancy and speaker fees from Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Takeda. RC declares that he has no competing interests.

Peer reviewers

Alessandra Ferrajoli, MD

Associate Medical Director, Professor

Department of Leukemia Center

The University of Texas MD Anderson Cancer Center

Houston

Disclosures

AF declares that she has no competing interests.

Farrukh Awan, MD

Professor of Medicine

Department of Internal Medicine

UT Southwestern Medical Center

Dallas

Disclosures

FA declares that he has no competing interests.

Paolo F. Caimi, MD

Associate Professor

Department of Medicine

Case Western Reserve University

Case Comprehensive Cancer Center

Cleveland

Disclosures

PFC has received honoraria from Celgene for participation in a speaker bureau, and from Kite Pharma for participation in an advisory board.

Daniel Catovsky, MD, FRCP, FRCPath, DSc, FMedSc

Consultant Haemato-oncologist

Section of Haemato-Oncology

The Institute of Cancer Research

Sutton

Disclosures

Unfortunately, we have since been made aware that DC is deceased

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21;131(25):2745-60.Full text Abstract

Walewska R, Parry-Jones N, Eyre TA, et al. Guideline for the treatment of chronic lymphocytic leukaemia. Br J Haematol. 2022 Jun;197(5):544-57.Full text Abstract

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: chronic lymphocytic leukemia/small lymphocytic lymphoma [internet publication].Full text

Eichhorst B, Robak T, Montserrat E, et al; ESMO Guidelines Committee. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021 Jan;32(1):23-33.Full text Abstract

Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021 Dec 1;96(12):1679-705.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Leukemic phase of lymphoma
More Differentials
Guidelines
- Chronic lymphocytic leukemia/small lymphocytic lymphoma
- Hematopoietic cell transplantation (HCT)
More Guidelines
Patient information
Leukemia (chronic lymphocytic)
More Patient information
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Chronic lymphocytic leukemia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

asymptomatic early stage (Binet A and B; Rai 0-II)

advanced stage (Binet C; Rai III-IV) or with indications for treatment (e.g., symptoms)

relapsed or refractory disease

Contributors

Authors

Jacqueline C. Barrientos, MD, MS

Disclosures

Joanna M. Rhodes, MD, MSCE

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Alessandra Ferrajoli, MD

Disclosures

Farrukh Awan, MD

Disclosures

Paolo F. Caimi, MD

Disclosures

Daniel Catovsky, MD, FRCP, FRCPath, DSc, FMedSc

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice