Pratt, Guy

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Biography
Guy Pratt is Professor of Haematology (Haemato-Oncology) at the University of Birmingham and Deputy Director of the Cancer Research UK Clinical Trials Unit with responsibility for Haematology trials. He is secretary for the British Society for Haematology, on the exec committee for the UK Myeloma Society and trustee for the charity Cure Leukaemia. He is an Honorary Consultant Haematologist at University Hospitals Birmingham NHS Foundation Trust. He has been a Consultant Haematologist in Birmingham since 2001 with a clinical and research interest in Multiple Myeloma, Waldenstroms Macroglobulinaemia, plasma cell disorders such as amyloidosis and CLL. He trained at Cambridge University qualifying in 1989. Following junior doctor training in London he specialized as a specialist registrar in Haematology in Liverpool and Leeds. In Leeds he completed an MD thesis in Multiple Myeloma. He was clinical lead for the 2016 NICE myeloma guidelines and had a number of previous positions nationally including BSH guideline lead for Haemato-Oncology, trustee for BSH, trustee for the charity WMUK, and chair of the BSH science and publication committee. Over the years he has developed a large number of research collaborations with over 180 peer reviewed publications and including clinical trial involvement both locally and nationally on several trials as a co-investigator and is member of UK Myeloma trials group (UKMRA).

Publication Search Results

Now showing 1 - 10 of 31
  • Publication
    Enhancement of Omicron-specific immune responses following bivalent COVID-19 booster vaccination in patients with chronic lymphocytic leukaemia.
    (Nature Publishing Group, 2024-01-25) Roberts, Thomas; Uwenedi, Grace; Bruton, Rachel; McIlroy, Graham; Damery, Sarah; Sylla, Panagiota; Logan, Nicola; Scott, Sam; Lau, May; Elzaidi, Ahmed; Plass, Siobhan; Mallick, Soumyajit; Spencer, Katie; Stephens, Christine; Bentley, Christopher; Pratt, Guy; Zuo, Jianmin; Paneesha, Shankara; Willett, Brian; Moss, Paul; Parry, Helen; General Medcine; Medical and Dental; Mcllroy, Graham; Pratt, Guy; Paneesha, Shankara; Moss, Paul
    Cancer patients who are immune suppressed remain at increased risk from COVID-19 and have recently been prioritised for additional booster bivalent vaccines. Despite this, previous studies have shown that humoral and cellular immune responses often fail to reach levels comparable to the general population following booster doses. The emergence of the omicron variant of SARS-CoV-2 has necessitated the deployment of modified bivalent mRNA vaccines that direct the synthesis of spike protein from Omicron in combination with ancestral spike. Bivalent booster vaccines have shown utility in general population studies [1,2,3] but there is little understanding of their relative immunogenicity in patients with immune suppression.
  • Publication
    Daratumumab, bortezomib and dexamethasone at first relapse for patients with multiple myeloma: A real-world multicentre UK retrospective analysis.
    (Wiley, 2023-02-23) McMillan, Annabel; Basu, Supratik; Karunanithi, Kamaraj; Parkins, Elizabeth; Lau, Edward Yan Ming; Cook, Gordon; Parrish, Christopher; Al-Kaisi, Firas; Pratt, Guy; Shafeek, Salim; Jenkins, Stephen; Memon, Danish; Bygrave, Ceri; Papanikolaou, Xenofon; Maisel, Tara; Hassan, Sandra; Moosai, Shivir; Chander, Gurvin; Rakesh, Pallav; Kishore, Bhuvan; Karim, Farheen; Talbot, Georgina; Wandroo, Farooq; Yong, Kwee; Popat, Rakesh; Haematology; Medical and Dental; Pratt, Guy; Kishore, Bhuvan
    Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12-20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15-25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments.
  • Publication
    PD-1 expression contributes to functional impairment of NK cells in patients with B-CLL
    (Nature Publishing Group, 2024-05-09) Farhat, Mustafa; Croft, Wayne; Parry, Helen M; Verma, Kriti; Kinsella, Francesca A M; Xu, Jinsong; Bone, David; McSkeane, Tina; Paneesha, Shankara; Pratt, Guy; Moss, Paul; Zuo, Jianmin; Haematology; Oncology; General Medicine; Nursing and Midwifery Registered; Medical and Dental; Parry, Helen M; Kinsella, Francesca A M; McSkeane, Tina; Paneesha, Shankara; Pratt, Guy; Moss, Paul
    No abstract available
  • Publication
    Benefits of switching from intravenous to subcutaneous daratumumab : perspectives from UK healthcare providers
    (Frontiers Media, 2023-02-23) Cook, Gordon; Ashcroft, John; Fernandez, Mariana; Henshaw, Sarah; Khalaf, Zeyad; Pratt, Guy; Tailor, Anish; Rabin, Neil; Haematology; Medical and Dental; Pratt, Guy
    Daratumumab is a CD38-directed monoclonal antibody indicated to treat multiple myeloma (MM). Daratumumab was initially administered intravenously (IV), subsequently a subcutaneous (SC) formulation was developed to increase convenience of administration. The UK was an early adopter of SC daratumumab and, as such, this report provides consensus recommendations from a group of UK MM experts, with the aim of facilitating the transition from IV to SC daratumumab for other European healthcare providers. The switch from IV to SC daratumumab has been beneficial to patients and healthcare providers, as it simplifies treatment, reduces pressure on hospitals and can improve patients' quality of life.
  • Publication
    The management of Castleman disease.
    (Wiley-Blackwell, 2021-08-02) Lomas, Oliver C; Streetly, Matthew; Pratt, Guy; Cavet, Jim; Royston, Daniel; Schey, Stephen; Ramasamy, Karthik; Haematology; Medical and Dental; Pratt, Guy
    No abstract available
  • Publication
    Diagnosis and management of Waldenström macroglobulinaemia-a British Society for Haematology guideline.
    (Wiley, 2022-01-12) Pratt, Guy; El-Sharkawi, Dima; Kothari, Jaimal; D'Sa, Shirley; Auer, Rebecca; McCarthy, Helen; Krishna, Rajesh; Miles, Oliver; Kyriakou, Charalampia; Owen, Roger; Haematology; Medical and Dental; Pratt, Guy
    Scope: The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. Methodology: This guideline was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström('s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(-related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus, bone marrow transplantation OR stem cell transplantation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.
  • Publication
    SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response
    (Nature Research, 2023-08) Bland, Philip; Saville, Harry; Wai, Patty T; Curnow, Lucinda; Muirhead, Gareth; Nieminuszczy, Jadwiga; Ravindran, Nivedita; John, Marie Beatrix; Hedayat, Somaieh; Barker, Holly E; Wright, James; Yu, Lu; Mavrommati, Ioanna; Read, Abigail; Peck, Barrie; Allen, Mark; Gazinska, Patrycja; Pemberton, Helen N; Gulati, Aditi; Nash, Sarah; Noor, Farzana; Guppy, Naomi; Roxanis, Ioannis; Pratt, Guy; Oldreive, Ceri; Stankovic, Tatjana; Barlow, Samantha; Kalirai, Helen; Coupland, Sarah E; Broderick, Ronan; Alsafadi, Samar; Houy, Alexandre; Stern, Marc-Henri; Pettit, Stephen; Choudhary, Jyoti S; Haider, Syed; Niedzwiedz, Wojciech; Lord, Christopher J; Natrajan, Rachael; Haematology; Medical and Dental; Pratt, Guy
    SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1MUT cells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction. This results in subsequent failure to resolve DNA replication intermediates and G2/M cell cycle arrest. These defects are rescued through CINP overexpression, or further targeted by a combination of ataxia-telangiectasia mutated and PARP inhibition. In vivo, PARPi produce profound antitumor effects in multiple SF3B1MUT cancer models and eliminate distant metastases. These data provide the rationale for testing the clinical efficacy of PARPi in a biomarker-driven, homologous recombination proficient, patient population.
  • Publication
    The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival.
    (Ferrata Storti Foundation, 2024-05-30) Stanulović, Vesna S; Al Omair, Shorog; Reed, Michelle A C; Roberts, Jennie; Potluri, Sandeep; Fulton-Ward, Taylor; Gudgeon, Nancy; Bishop, Emma L; Roels, Juliette; Perry, Tracey A; Sarkar, Sovan; Pratt, Guy; Taghon, Tom; Dimeloe, Sarah; Günther, Ulrich L; Ludwig, Christian; Hoogenkamp, Maarten; Honorary Consultant Haematologist; Medical and Dental; Pratt, Guy
    T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.
  • Publication
    An economic model to establish the costs associated with routes to presentation for patients with multiple myeloma in the United Kingdom.
    (Elsevier, 2023-02-24) Porteous, Alex; Gibson, Scott; Eddowes, Lucy A; Drayson, Mark; Pratt, Guy; Bowcock, Stella; Willis, Fenella; Parkin, Hannah; Renwick, Suzanne; Laketic-Ljubojevic, Ira; Howell, Debra; Smith, Alex; Stern, Simon; Haematology; Medical and Dental; Pratt, Guy
    Objectives: Patients with myeloma often face significant diagnostic delay, with up to one-third of UK patients diagnosed after an emergency presentation (EP). Compared with other routes, patients presenting as an emergency have more advanced disease, increased complications, and poorer prognosis. Methods: An economic model was developed using a decision-tree framework and lifetime time horizon to estimate costs related to different presentation routes (EP, general practitioner [GP] 2-week wait, GP urgent, GP routine, and consultant to consultant) for UK patients diagnosed as having myeloma. After diagnosis, patients received one of 3 first-line management options (observation, active treatment, or end-of-life care). Inputs were derived from UK health technology assessments and targeted literature reviews, or based on authors' clinical experience where data were unavailable. Active treatment, complication, and end-of-life care costs were included. Results: The average per-patient cost of treating myeloma (across all routes) was estimated at £146 261. The average per-patient cost associated with EP (£152 677) was the highest; differences were minimal compared with GP 2-week wait (£149 631) and consultant to consultant (£147 237). GP urgent (£140 025) and GP routine (£130 212) were associated with marginally lower costs. Complication (£42 252) and end-of-life care (£11 273) costs were numerically higher for EP than other routes (£25 021-£38 170 and £9772-£10 458, respectively). Conclusions: An economic benefit may be associated with earlier diagnosis, gained via reduced complication and end-of-life care costs. Strategies to expedite myeloma diagnosis and minimize EPs have the potential to improve patient outcomes and may result in long-term savings that could offset any upfront costs associated with their implementation.
  • Publication
    Bortezomib, melphalan, dexamethasone: a new standard of care for AL amyloidosis?
    (American Society of Clinical Oncology, 2020-08-04) Pratt, Guy; University Hospitals Birmingham NHS Foundation Trust; Haematology; Medical and Dental; Pratt, Guy
    No abstract available