Summary
Definition
History and exam
Key diagnostic factors
- abdominal fullness or discomfort
- splenomegaly
Other diagnostic factors
- weakness and fatigue
- unexplained weight loss
- bruising and bleeding
- pallor
- recurrent infections
- hepatomegaly
- lymphadenopathy
- neurologic findings
- associated systemic immunologic disorders
Risk factors
- middle age
- male sex
- white ancestry
- western hemisphere location
- environmental exposures
- genetic predisposition
- Epstein-Barr virus
- infectious mononucleosis
Diagnostic tests
1st tests to order
- CBC with differential
- peripheral blood smear
- bone marrow trephine biopsy and aspiration (morphology assessment)
- immunophenotyping (immunohistochemistry or flow cytometry)
- comprehensive metabolic panel
- serum lactate dehydrogenase (LDH)
- viral serology for hepatitis B and C
Tests to consider
- molecular analysis (for BRAF V600E mutation or IGHV4-34 rearrangement)
- CT chest, abdomen, and pelvis
Treatment algorithm
no indication(s) for treatment
indication(s) for treatment present: without splenic rupture or massive splenomegaly or marked thrombocytopenia precluding chemotherapy
indication(s) for treatment present: with massive symptomatic splenomegaly or splenic rupture or marked thrombocytopenia precluding chemotherapy
early relapse (<2 years) or refractory disease
late relapse (≥2 years)
Contributors
Authors
Ambuj Kumar, MD, MPH
Professor
USF Health Office of Research
Department of Internal Medicine, College of Medicine
Moffitt Cancer Center & Research Institute, Department of Health Outcomes & Behavior
University of South Florida
Tampa, FL
Disclosures
AK declares that he has no competing interests.
Mohamed A. Kharfan-Dabaja, MD, MBA, FACP
Professor
Division of Hematology-Oncology
Blood and Marrow Transplantation Program
Mayo Clinic
Jacksonville, FL
Disclosures
MKD declares that he has attended an advisory board for Incyte Corporation.
Acknowledgements
Dr Ambuj Kumar and Dr Mohamed Kharfan-Dabaja would like to gratefully acknowledge Dr Benjamin Djulbegovic, a previous contributor to this topic.
Disclosures
BD declares that he has no competing interests.
Peer reviewers
Roger Lyons, MD
Clinical Professor of Medicine
University of Texas Health Science Center San Antonio
San Antonio, TX
Disclosures
RL declares that he has no competing interests.
Christopher D'Angelo, MD
Assistant Professor
Division of Oncology & Hematology
University of Nebraska Medical Center
Omaha, NE
Disclosures
CDA declares that he has received consulting fees from Abbvie, Beigene, Genmab, Curis Inc, Bristol Myers Squibb.
Claire Dearden, BSc, MD, FRCP, FRCPath
Consultant Haematologist
The Royal Marsden Hospital
Sutton
Surrey
UK
Disclosures
CD declares that she has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
References
Key articles
Parry-Jones N, Joshi A, Forconi F, et al. Guideline for diagnosis and management of hairy cell leukaemia (HCL) and hairy cell variant (HCL-V). Br J Haematol. 2020 Dec;191(5):730-7.Full text Abstract
Troussard X, Maître E, Paillassa J. Hairy cell leukemia 2024: update on diagnosis, risk-stratification, and treatment - annual updates in hematological malignancies. Am J Hematol. 2024 Apr;99(4):679-96.Full text Abstract
Zent CS, Tiacci E, Kreitman RJ, et al. Updated consensus guidelines for the diagnosis and management of patients with HCL and HCL variant. Blood. 2026 Jul 2;148(1):31-42.Full text Abstract
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: hairy cell leukemia [internet publication].Full text
Robak T, Matutes E, Catovsky D, et al. Hairy cell leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26(suppl 5):v100-7.Full text Abstract
Troussard X, Maître E, Cornet E. Hairy cell leukemia 2022: update on diagnosis, risk-stratification, and treatment. Am J Hematol. 2022 Feb 1;97(2):226-36.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
- Chronic lymphocytic leukemia (CLL)
- Mantle cell lymphoma
- Prolymphocytic leukemia
More DifferentialsGuidelines
- Updated consensus guidelines for the diagnosis and management of patients with hairy cell leukemia (HCL) and HCL-variant
- NCCN clinical practice guidelines in oncology: hairy cell leukemia
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