Joanne Ewing

The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study

Harinder Gill, Abdulraheem Yacoub, Aaron T. Gerds, Jake Shortt et autres

ABSTRACT: Novel therapies are needed for myelofibrosis (MF), particularly after Janus kinase (JAK) inhibitor failure. This open-label, phase 1/2 study evaluated bomedemstat, an irreversible inhibitor of lysine-specific demethylase 1, in participants with MF refractory or resistant to, inadequately controlled by, or intolerant …

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Sequential monitoring using NGS allows detection of ABL1 KD mutations in patients with chronic Phase CML: Results from the prospective calls trial

Ipek Baymul, Peter Edel, Sophie Jackson, Kate Rothwell et autres

Abstract Background BCR :ABL1 kinase domain (KD) mutations are a well-established mechanism of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML). Early detection of emerging clinically relevant mutations is crucial for timely treatment modification, yet there are currently no …

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An evaluation of a real-world, multi-disciplinary, treatment-free remission programme for patients with Chronic Myeloid Leukaemia

Joanne Ewing, Hayder Hussein, Bernard Maybury, Manoj Raghavan et autres

IntroductionThe management of chronic myeloid leukaemia (CML) has been revolutionized by the introduction of imatinib and other tyrosine kinase inhibitors (TKIs). Despite excellent efficacy, patient quality of life is often negatively affected by TKI side effects and there has recently been a …

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Genome-wide analysis defines genetic determinants of MPN subtypes and identifies a sex-specific association at CDH22 / CD40

William Tapper, Ahmed A. Z. Dawoud, Joannah Score, Andrew Chase et autres

ABSTRACT: To identify genetic variants that influence myeloproliferative neoplasm (MPN) phenotypes, we undertook a 2-stage patient-only genome-wide association study. MPN subtypes (essential thrombocythemia [ET]; polycythemia vera [PV]) were compared with each other to healthy controls and stratified analyses was performed for chromosome …

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Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial

Lise J Estcourt, Zoe McQuilten, Peter Bardy, Merrole Cole‐Sinclair et autres

The management of myelofibrosis: A British Society for Haematology Guideline

Donal P. McLornan, Bethan Psaila, Joanne Ewing, Andrew J. Innes et autres

This document represents an update of the British Society for Haematology guideline on Myelofibrosis first published in 2012 and updated in 2015. 1 These guidelines aim to provide healthcare professionals with clear guidance on stratified management for primary myelofibrosis (PMF), as well …

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Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis

Zijian Fang, Giuditta Corbizi Fattori, Thomas McKerrell, Rebecca H. Boucher et autres

Abstract Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen’s safety and activity in patients …

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Outcomes and characteristics of nonmelanoma skin cancers in patients with myeloproliferative neoplasms on ruxolitinib

Alexandros Rampotas, Luke Carter‐Brzezinski, Tim C. P. Somervaille, James Forryan et autres

ABSTRACT: Nonmelanoma skin cancers (NMSCs) in ruxolitinib-treated patients with myeloproliferative neoplasms behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis. Vigilant skin assessment, counseling on NMSC risks, and prospective ruxolitinib-NMSC studies are …

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Diagnosis and evaluation of prognosis of myelofibrosis: A British Society for Haematology Guideline

Donal P. McLornan, Anna L. Godfrey, Anna Green, Rebecca Frewin et autres

This document represents an update of the British Society for Haematology (BSH) guideline on myelofibrosis (MF) first published in 2012 and updated in 2015. 1 This guideline aims to provide healthcare professionals with clear guidance on the diagnosis and prognostic evaluation of …

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Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial

Claire Harrison, Jyoti Nangalia, Rebecca H. Boucher, Aimee Jackson et autres

PURPOSE Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy …

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Tamoxifen reduces mitochondrial respiration, oncogenic signaling and mutant allele burden in a myeloproliferative neoplasm subset

Zijian Fang, Giuditta Corbizi Fattori, Thomas McKerrell, Rebecca H. Boucher et autres

Abstract Current therapies for myeloproliferative neoplasms (MPN) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem and progenitor cells (HSPCs). TAMARIN is a Phase-II, multicenter, single-arm clinical trial assessing tamoxifen’s safety …

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A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG-7289) for the Treatment of Advanced Myelofibrosis (MF): Updated Results and Genomic Analyses

Kristen Pettit, Harinder Gill, Abdulraheem Yacoub, Terrence Bradley et autres

The need for therapies for myelofibrosis (MF) persists, especially in the setting of JAK inhibitor failure. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal potential of malignant stem cells and progenitor maturation. Bomedemstat is an oral LSD1 inhibitor clinically active …

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