Matthew Cross1, Claire Dearden2. 1. The Royal Marsden Hospital and the Institute of Cancer Research, Sutton, UK. 2. The Royal Marsden Hospital and the Institute of Cancer Research, Sutton, UK. claire.dearden@rmh.nhs.uk.
Abstract
PURPOSE OF REVIEW: To summarise diagnostic clinical/laboratory findings and highlight differences between classical hairy cell leukaemia (HCLc) and hairy cell leukaemia variant (HCLv). Discussion of prognosis and current treatment indications including novel therapies, linked to understanding of the underlying molecular pathogenesis. RECENT FINDINGS: Improved understanding of the underlying pathogenesis of HCLc, particularly the causative mutation BRAF V600E, leading to constitutive activation of the MEK/ERK signalling pathway and increased cell proliferation. HCLc is caused by BRAF V600E mutation in most cases. Purine nucleoside analogue (PNA) therapy is the mainstay of treatment, with the addition of rituximab, improving response and minimal residual disease (MRD) clearance. Despite excellent responses to PNAs, many patients will eventually relapse, requiring further therapy. Rarely, patients are refractory to PNA therapy. In relapsed/refractory patients, novel targeted therapies include BRAF inhibitors (BRAFi), anti-CD22 immunoconjugate moxetumomab and Bruton tyrosine kinase inhibitors (BTKi). HCLv has a worse prognosis with median overall survival (OS), only 7-9 years, despite the combination of PNA/rituximab improving front-line response. Moxetumomab or ibrutinib may be a viable treatment but lacks substantial evidence.
PURPOSE OF REVIEW: To summarise diagnostic clinical/laboratory findings and highlight differences between classical hairy cell leukaemia (HCLc) and hairy cell leukaemia variant (HCLv). Discussion of prognosis and current treatment indications including novel therapies, linked to understanding of the underlying molecular pathogenesis. RECENT FINDINGS: Improved understanding of the underlying pathogenesis of HCLc, particularly the causative mutation BRAFV600E, leading to constitutive activation of the MEK/ERK signalling pathway and increased cell proliferation. HCLc is caused by BRAFV600E mutation in most cases. Purine nucleoside analogue (PNA) therapy is the mainstay of treatment, with the addition of rituximab, improving response and minimal residual disease (MRD) clearance. Despite excellent responses to PNAs, many patients will eventually relapse, requiring further therapy. Rarely, patients are refractory to PNA therapy. In relapsed/refractory patients, novel targeted therapies include BRAF inhibitors (BRAFi), anti-CD22 immunoconjugate moxetumomab and Bruton tyrosine kinase inhibitors (BTKi). HCLv has a worse prognosis with median overall survival (OS), only 7-9 years, despite the combination of PNA/rituximab improving front-line response. Moxetumomab or ibrutinib may be a viable treatment but lacks substantial evidence.
Authors: Yazan F Madanat; Lisa Rybicki; Tomas Radivoyevitch; Deepa Jagadeesh; Robert Dean; Brad Pohlman; Matt Kalaycio; Mikkael A Sekeres; Mitchell R Smith; Brian T Hill Journal: Clin Lymphoma Myeloma Leuk Date: 2017-07-14
Authors: Michael Grever; Leslie Andritsos; Versha Banerji; Jacqueline C Barrientos; Seema Bhat; James S Blachly; Timothy Call; Matthew Cross; Claire Dearden; Judit Demeter; Sasha Dietrich; Brunangelo Falini; Francesco Forconi; Douglas E Gladstone; Alessandro Gozzetti; Sunil Iyengar; James B Johnston; Gunnar Juliusson; Eric Kraut; Robert J Kreitman; Francesco Lauria; Gerard Lozanski; Sameer A Parikh; Jae Park; Aaron Polliack; Farhad Ravandi; Tadeusz Robak; Kerry A Rogers; Alan Saven; John F Seymour; Tamar Tadmor; Martin S Tallman; Constantine S Tam; Enrico Tiacci; Xavier Troussard; Clive Zent; Thorsten Zenz; Pier Luigi Zinzani; Bernhard Wörmann Journal: Leukemia Date: 2021-05-04 Impact factor: 11.528
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