Professor Sylvie Freeman is a Clinical academic and Honorary Consultant Haematologist in the departments of Clinical Immunology, University of Birmingham and Haematology, University Hospital Birmingham. As a co-director of the Birmingham Clinical Immunology Service, she specializes in immunophenotyping for the diagnosis and monitoring of haemotological malignancies.
Professor of ImmunoHaematology, Department of Clinical Immunology, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham.
Honorary Consultant, Department of Haematology, University of Birmingham Hospital NHS Trust
Background and Research focus
Professor Sylvie Freeman is co-director of the Clinical Immunology Service, leading Immunophenotyping for the diagnosis and monitoring of haematological malignancies. The service provides a distinct interface between the University’s substantial scientific expertise in immunohaematology and the clinical investigation and management of blood cancers and immunodeficiency in the NHS and for clinical trials. Under her direction the University of Birmingham Clinical Immunology Service has established an international reputation for flow cytometric AML monitoring, serving as the hub reference laboratory in the UK.
Sylvie’s long standing research is focussed on predicting treatment resistance in acute myeloid leukemia (AML) and myelodysplasia principally by monitoring residual disease (MRD). The heterogeneity of AML with respect to both disease biology and patient-specific clinical factors requires advances in personalised risk stratification to improve therapeutic outcomes. Although not a common malignancy, treatment of patients with AML is disproportionately expensive particularly if patients have treatment intensified by stem cell transplantation. Hence, there are major economic as well clinical benefits to be gained by better selection of patient-appropriate targeted therapies. With this in mind her group have developed and implemented immunophenotypic assays to evaluate and monitor AML during chemotherapy and allogeneic stem cell transplantation, recently extending this to novel assays tracking leukemic stem cell enriched populations with national /international collaborators.
Over the course of the last few years her laboratory have undertaken numerous studies supported by CRUK /NIHR /LLR evaluating AML residual disease monitoring by flow cytometry (MFC-MRD) within the UK MRC / NCRI acute myeloid leukaemia (AML) trials. The first study of MRD in older AML patients (NCRI AML16, CRUK funded) generated data (Freeman et al JCO 2013) that underpins MRD-directed therapy in older patients (NCRI AML18 trial). The collaborative analysis of younger patients in AML17 (NIHR funded, Prof Grimwade King’s College, London)) has generated key data on the prognostic relevance of molecular MRD (Ivey et al NEJM 2016) along with flow cytometric MRD (Freeman et al JCO in press) that are currently being implemented for MRD directed therapy in the younger AML patients (NCRI AML19). Additionally, there is a collaborative focus on developing novel assays tracking leukemic-stem-cell-enriched populations, mass cytometry deep phenotyping and combining genetic profiling with flow cytometric data. In collaboration with Prof Craddock / Prof Vyas (Oxford), the potential of LSC tracking in parallel with conventional MFC MRD pre and post allogeneic transplantation was established (Bradbury et al, Leukemia 2015) and is part of a prospective randomised RIC-transplantation programme (FIGARO trial, BloodWise funded). Her group are also testing a simple assay that could potentially identify prior to treatment AML patients unlikely to respond to standard intensive chemotherapy by blood frequency of stem-cell-like blasts (BloodWise funded, collaboration with Prof Russell/Prof Hills for NCRI AML18) and evaluate expression of cell surface molecules that are targets for established and novel antibody directed AML therapy (Khan et al Leukemia 2017). Collectively, these studies will provide independent prognostic information and develop more personalised treatment approaches in AML and high risk myelodysplasia.
Immunophenotypic diagnostics; minimal residual disease; acute myeloid leukaemia; myelodysplasia.
Professor Freeman is a Honorary Consultant Haematologist at the University of Birmingham who has an established track record for characterisation of surface markers in myeloid malignancies. She is a longstanding member of the UK National Cancer Research Institute Acute Myeloid Leukaemia Working Party and more recently the European LeukemiaNet AML MRD Working Group. Professor Freeman also serves as a Co–Investigator in several UK NCRI AML trials including AML16, AML19 and FIGARO. She also has a part time role at the WHIMM in Oxford for developing AML monitoring assays. Additionally, Professor Freeman has developed collaborations with the molecular expertise at KCL, Cambridge and international colleagues with the critical aim of optimising ‘fit for purpose’ precision assays that will best inform treatment of AML including for novel therapies. Alongside her research commitments, Professor Freeman contributes to teaching on the MBChB, BMedSci and MPharm programmes.
Sylvie Freeman, Robert K Hills, Paul Virgo, Naeem Khan, Steve Couzens, Richard Dillon, Amanda Gilkes, Laura Upton, Ove Juul Nielsen, James D Cavenagh, Gail Jones, Asim Khwaja, Paul Cahalin, Ian Thomas, David Grimwade, Alan K Burnett, Nigel H Russell. Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Standard- Risk Patients without NPM1 Mutations. J Clin Oncol Mar 30 2018 36(15): 1486–1497
Gerrit J Schuurhuis, Michael Heuser, Sylvie Freeman, Marie-Christine Béné , Francesco Buccisano, Jacqueline Cloos David Grimwade, Torsten Haferlach, Robert K Hills, Christopher S Hourigan, Jeffrey L Jorgensen, Wolfgang Kern, Francis Lacombe, Luca Maurillo, Claude Preudhomme, Bert A van der Reijden, Christian Thiede, Adriano Venditti, Paresh Vyas, Brent L Wood, Roland B Walter, Konstanze Döhner1, Gail J Roboz and Gert J Ossenkoppele. Minimal/Measurable Residual Disease in AML: Consensus Document from ELN MRD Working Party. Blood Jan 2018, DOI: 10.1182/blood-2017-09-801498
Rosemary E. Gale, Teodora Popa, Melissa Wright, Naeem Khan, Sylvie D. Freeman, Alan K Burnett, Nigel H. Russell, Robert K. Hills, David C. Linch. No evidence that CD33 splicing SNP impacts the response to GO in younger adults with AML treated on UK MRC/NCRI trials. Blood Jan 2017 DOI: 10.1182/blood-2017-08-802157
Khan N, Hills RK, Virgo P, Couzens S, Clark N, Gilkes A, Richardson P, Knapper S, Grimwade D, Russell NH, Burnett AK and Freeman SD. Expression of CD33 is a predictive factor for effect of Gemtuzumab Ozogamicin at different doses in adult acute myeloid leukemia. Leukemia 2017 May; 31(5): 1059–1068
Khan N, Hills RK, Knapper S, Steadman L, Qureshi U, Rector JL, Bradbury C, Russell NH, Vyas P, Burnett AK, Grimwade D, Hole PS and Freeman SD. Normal Hematopoietic Progenitor Subsets Have Distinct Reactive Oxygen Species, BCL2 and Cell-Cycle Profiles That Are Decoupled from Maturation in Acute Myeloid Leukemia. PloS one. 2016 Sep 26;11(9):e0163291
Lynn Quek, Georg Otto, Catherine Garnett, Ludovic Lhermitte, Dimitris Karamitros, Bilyana Stoilova, I-Jun Lau, Jessica Doondeea, Batchimeg Usukhbayar, Alison Kennedy, Marlen Metzner, Nicolas Goardon, Adam Ivey, Christopher Allen, Rosemary Gale, Benjamin Davies, Alexander Sternberg, Sally Killick, Hannah Hunter, Paul Cahalin, Andrew Price, Andrew Carr, Michael Griffiths, Paul Virgo, Stephen Mackinnon, David Grimwade, Sylvie Freeman, Nigel Russell, Charles Craddock, Adam Mead, Andy Peniket, Catherine Porcher, Paresh Vyas. Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. Journal of Experimental Medicine. 2016 Jun 28
Adam Ivey, Robert K Hills, Michael A Simpson, Jelena V Jovanovic, Amanda Gilkes, Angela Grech, Yashma Patel, Neesa Bhudia, Hassan Farah, Joanne Mason, Kerry Wall, Susanna Akiki,Michael Griffiths, Ellen Solomon, Frank McCaughan David C Linch, Rosemary E Gale, Paresh Vyas, Sylvie D Freeman, Nigel Russell, Alan K Burnett, David Grimwade. Assessment of minimal residual disease in standard risk AML. New England Journal of Medicine. 2016 Jan 20.
Grimwade D, Freeman SD. Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “Prime Time”? Blood 2014 Jul 21.
Charlotte Bradbury, Aimee E Houlton, Susanna Akiki, Richard Gregg, Max Rindl, Josephine Khan, Janice Ward, Naeem Khan, Mike Griffiths, Sandeep Nagra, Robert Hills, Alan Burnett, Nigel, Russell, Paresh Vyas, David Grimwade, Charles Craddock, Sylvie D. Freeman. Prognostic value of monitoring a candidate immunophenotypic leukemic stem/progenitor cell population in patients allografted for acute myeloid leukemia. Leukemia, 2015 April; 29(4): 988-991
Sylvie D. Freeman, Paul Virgo, Steve Couzens, David Grimwade, Nigel Russell, Robert K. Hills and Alan K. Burnett. Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol. 2013 Nov 10;31(32):4123-31