Updated consensus guidelines for the diagnosis and management of patients with HCL and HCL variant

C Clive S. Zent (1Department of Medicine and Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY) E Enrico Tiacci (University of Perugia, Perugia, Italy) R Robert J. Kreitman (3Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD) T Tamar Tadmor (Bnai Zion Medical Center, Technion, Haifa, Israel) M Martin S. Tallman (5Memorial Sloan Kettering Cancer Center, New York, NY) B Bernhard Wörmann (6Charité–Universitätsmedizin Berlin, Berlin, Germany) L Leslie A. Andritsos (7University of New Mexico Comprehensive Cancer Center, Albuquerque, NM) E Evgeny Arons (3Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD) V Versha Banerji (8Paul Albrechtsen Research Institute and Department of Medical Oncology & Hematology, CancerCare Manitoba, and Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada) J Jacqueline C. Barrientos (9Mount Sinai Comprehensive Cancer Center, Miami Beach, FL) S Seema A. Bhat (10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH) J James S. Blachly (10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH) A Alessandro Broccoli T Timothy G. Call (13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN) C Claire Dearden (14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom) J Judit Demeter (15University, Faculty of Medicine, Department of Internal Medicine and Oncology, Budapest, Hungary) S Sascha Dietrich D Dima El-Sharkawi (14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom) A Andrei Fagarasanu (18Department of Medicine, University of Alberta, Edmonton, Alberta, Canada) B Brunangelo Falini (University of Perugia, Perugia, Italy) F Francesco Forconi (19Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom) A Alina S. Gerrie (21BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, BC, Canada) D Douglas E. Gladstone A Alessandro Gozzetti (University of Siena, Siena, Italy) P Paul J. Hampel (13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN) D David J. Hermel (25Division of Hematology and Oncology, Scripps Clinic Medical Group, La Jolla, CA) S Sunil Iyengar (14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom) J James B. Johnston (8Paul Albrechtsen Research Institute and Department of Medical Oncology & Hematology, CancerCare Manitoba, and Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada) G Gunnar Juliusson T Thomas J. Kipps (University of California, San Diego School of Medicine, La Jolla, California, United States) F Francesco Lauria (28University of Siena, Siena, Italy) G Gerard Lozanski (29Department of Pathology, The Ohio State University Medical School, Columbus, OH) S Sameer A. Parikh (13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN) J Jae H. Park A Aaron Polliack (32Hadassah Hebrew University Medical Center, Jerusalem, Israel) G Graeme Quest (33Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, ON, Canada) K Kanti Rai (34Feinstein Institutes for Medical Research, Manhasset, NY) F Farhad Ravandi (Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA) T Tadeusz Robak (36Department of Hematology, Medical University of Lodz, Lodz, Poland) K Kerry A. Rogers (10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH) A Alan Saven (25Division of Hematology and Oncology, Scripps Clinic Medical Group, La Jolla, CA) J John F. Seymour (Department of Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) C Constantine S. Tam (40Department of Haematology, Alfred Hospital and Monash University, Melbourne, VIC, Australia) X Xavier Troussard (41Hématologie, CHU de Caen, Caen, France) T Thorsten Zenz P Pier Luigi Zinzani (12IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy) M Michael R. Grever (10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH)

Abstract

Abstract Hairy cell leukemia (HCL) and HCL variant (HCLv) are distinct, rare, and chronic splenic B-cell lymphomas/leukemias that partially overlap in clinicopathologic presentation but differ in genetic basis, prognosis, and management. HCL is caused by the BRAF-V600E kinase–activating mutation in >95% of the patients, usually has excellent responses to chemotherapy with purine analogues, and is also amenable to BRAF inhibitor–based targeted treatments. In contrast, HCLv lacks BRAFV600E mutation, requires combined therapy with purine analogues in addition to rituximab, and generally shows less durable responses. Here, an international team of hematologists, experts on these rare diseases, was convened by the Hairy Cell Leukemia Foundation to update the previous guidelines (published in 2017) by providing a summary of current methods to diagnose and manage patients with HCL and HCLv as well as a prospective on newer targeted therapies to further improve outcomes.

Article Details

Journal Blood
Volume / Issue Vol. 148, Issue 1
Published July 02, 2026
Pages 31-42
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (47)

C

Clive S. Zent

1Department of Medicine and Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY

E

Enrico Tiacci

University of Perugia, Perugia, Italy

R

Robert J. Kreitman

3Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

T

Tamar Tadmor

Bnai Zion Medical Center, Technion, Haifa, Israel

M

Martin S. Tallman

5Memorial Sloan Kettering Cancer Center, New York, NY

B

Bernhard Wörmann

6Charité–Universitätsmedizin Berlin, Berlin, Germany

L

Leslie A. Andritsos

7University of New Mexico Comprehensive Cancer Center, Albuquerque, NM

E

Evgeny Arons

3Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

V

Versha Banerji

8Paul Albrechtsen Research Institute and Department of Medical Oncology & Hematology, CancerCare Manitoba, and Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

J

Jacqueline C. Barrientos

9Mount Sinai Comprehensive Cancer Center, Miami Beach, FL

S

Seema A. Bhat

10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH

J

James S. Blachly

10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH

A

Alessandro Broccoli

T

Timothy G. Call

13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN

C

Claire Dearden

14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

J

Judit Demeter

15University, Faculty of Medicine, Department of Internal Medicine and Oncology, Budapest, Hungary

S

Sascha Dietrich

D

Dima El-Sharkawi

14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

A

Andrei Fagarasanu

18Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

B

Brunangelo Falini

University of Perugia, Perugia, Italy

F

Francesco Forconi

19Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

A

Alina S. Gerrie

21BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, BC, Canada

D

Douglas E. Gladstone

A

Alessandro Gozzetti

University of Siena, Siena, Italy

P

Paul J. Hampel

13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN

D

David J. Hermel

25Division of Hematology and Oncology, Scripps Clinic Medical Group, La Jolla, CA

S

Sunil Iyengar

14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

J

James B. Johnston

8Paul Albrechtsen Research Institute and Department of Medical Oncology & Hematology, CancerCare Manitoba, and Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

G

Gunnar Juliusson

T

Thomas J. Kipps

University of California, San Diego School of Medicine, La Jolla, California, United States

F

Francesco Lauria

28University of Siena, Siena, Italy

G

Gerard Lozanski

29Department of Pathology, The Ohio State University Medical School, Columbus, OH

S

Sameer A. Parikh

13Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN

J

Jae H. Park

A

Aaron Polliack

32Hadassah Hebrew University Medical Center, Jerusalem, Israel

G

Graeme Quest

33Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, ON, Canada

K

Kanti Rai

34Feinstein Institutes for Medical Research, Manhasset, NY

F

Farhad Ravandi

Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA

T

Tadeusz Robak

36Department of Hematology, Medical University of Lodz, Lodz, Poland

K

Kerry A. Rogers

10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH

A

Alan Saven

25Division of Hematology and Oncology, Scripps Clinic Medical Group, La Jolla, CA

J

John F. Seymour

Department of Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

C

Constantine S. Tam

40Department of Haematology, Alfred Hospital and Monash University, Melbourne, VIC, Australia

X

Xavier Troussard

41Hématologie, CHU de Caen, Caen, France

T

Thorsten Zenz

P

Pier Luigi Zinzani

12IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy

M

Michael R. Grever

10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH