Jérôme Paillassa 1, Elsa Maitre 2,3, Nadia Belarbi Boudjerra 4, Abdallah Madani 5, Raihane Benlakhal 6,
Thomas Matthes 7, Eric Van Den Neste 8, Laura Cailly 9, Luca Inchiappa 10, Mohammed Amine Bekadja 11,
Cécile Tomowiak 9 and Xavier Troussard 2,12,*
1 Service des Maladies du Sang, CHU d’Angers, 49000 Angers, France; jerome.paillassa@chu-angers.fr
2 Hématologie Biologique, Structure Fédérative D’oncogénétique Cyto-Moléculaire du CHU de Caen
(SF-MOCAE), CHU de Caen, 14000 Caen, France; maitre-e@chu-caen.fr
3 Unité MICAH, INSERM1245, Université Caen-Normandie, 14000 Caen, France
4 Service d’Hématologie, CHU Béni Messous, Alger 16308, Algeria; nboudjerra@hotmail.fr
5 Service d’Hématologie, CHU de Casablanca, Casablanca 20000, Morocco; madani.hemato@gmail.com
6 Service d’Hématologie, CHU Aziza Othmena, Tunis 1002, Tunisia; raihane.benlakhal@gmail.com
7 Service d’Hématologie, Département d’Oncologie et Service de Pathologie Clinique, Département de
Diagnostic, Hôpital Universitaire de Genève, 1205 Genève, Switzerland; thomas.matthes@hcuge.ch
8 Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1000 Brussels, Belgium;
eric.vandenneste@saintluc.uclouvain.be
9 Service d’Onco-Hématologie et de Thérapie Cellulaire, CHU de Poitiers, 86000 Poitiers, France;
laura.cailly20@gmail.com
10 Service d’Hématologie, Institut Paoli-Calmette, 13397 Marseille, France
11 Service d’Hématologie et de Thérapie Cellulaire, EHU Oran, Oran 31000, Algeria; mabekadja@yahoo.fr
12 Hematologie CHU Caen Normandie, 14000 Caen, France
* Correspondence: troussard-x@chu-caen.fr; Tel: +33-2-31-06-50-14
Simple Summary: The diagnosis of hairy-cell leukemia (HCL) and HCL-like disorders including
the variant form of HCL (HCL-V), splenic diffuse red pulp lymphoma (SDRPL) and splenic
marginal zone lymphoma (SMZL) is a challenge in clinical practice. We discuss the major points for
the diagnosis of HCL and HCL-like disorders and we propose recommendations for the diagnosis
of HCL, treatment in first line and in relapsed/refractory patients.
Abstract:
Introduction:
Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative
disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside
analogs (PNAs), such as cladribine (CDA) or pentostatin (P). However, some patients eventually
relapse and over time HCL becomes resistant to chemotherapy. Many discoveries have been made
in the pathophysiology of HCL during the last decade, especially in genomics, with the
identification of the BRAFV600E mutation and cellular biology, including the importance of signaling
pathways as well as tumor microenvironment. All of these new developments led to targeted
treatments, especially BRAF inhibitors (BRAFis), MEK inhibitors (MEKis), Bruton’s tyrosine kinase
(BTK) inhibitors (BTKis) and recombinant anti-CD22 immunoconjugates.
Results:
The following major changes or additions were introduced in these updated guidelines: the clinical relevance of
the changes in the classification of splenic B-cell lymphomas and leukemias; the increasingly important diagnostic role of BRAFV600E mutation; and the prognostic role of the immunoglobulin (IG) variable (V) heavy chain (H) (IGHV) mutational status and repertory. We also wish to insist on the specific involvement of bones, skin, brain and/or cerebrospinal fluid (CSF) of the disease at diagnosis or during the follow-up, the novel targeted drugs (BRAFi and MEKi) used for HCL treatment, and the increasing role of minimal residual disease (MRD) assessment.
Conclusion:
Here we present recommendations for the diagnosis of HCL, treatment in first line and in
relapsed/refractory patients as well as for HCL-like disorders including HCL variant (HCL-V)/splenic B-cell lymphomas/leukemias with prominent nucleoli (SBLPN) and splenic diffuse red pulp lymphoma (SDRPL).
Keywords:
hairy-cell leukemia; HCL; hairy-cell leukemia variant; HCL-V; splenic diffuse red pulp
lymphoma; SDRPL; diagnosis; treatment; recommendations; flow cytometry; BRAFV600E mutation;
BRAF inhibitors
