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Chronic lymphocytic leukemia

  • Overview
  • Theory
  • Diagnosis
  • Management
  • Follow up
  • Resources
Last reviewed: 8 Jun 2025
Last updated: 21 Mar 2025

Summary

Definition

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

NY

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

NY

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

TX

Disclosures

AF declares that she has no competing interests.

Farrukh Awan, MD

Professor of Medicine

Department of Internal Medicine

UT Southwestern Medical Center

Dallas

TX

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

OH

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

UK

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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