Professor Sylvie Freeman DPhil, MBChB, MRCP, FRCPath

Institute of Immunology and Immunotherapy
Professor of ImmunoHaematology
Honorary Consultant in Haematology

Contact details

Address
Clinical Immunology Service
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Sylvie Freeman is co-director of the Clinical Immunology Service, leading Immunophenotyping for the diagnosis and monitoring of haematological malignancies. The service provides a unique 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 trials.

Research focus is in on predicting treatment resistance in acute myeloid leukemia and myelodysplasia principally by monitoring residual disease (MRD). She leads flow cytometric MRD detection for the NCRI acute myeloid leukaemia trials and is on the trial management groups of these trials. Sylvie is a member of the UK NCRI AML Working Party, European LeukemiaNet AML MRD Working Group and the International Consortium on Acute Leukemia Committee (American Society of Hematology).

Qualifications

  • Certificate of Completion of Specialist Training (Clinical Haematology), 2003
  • FRCPath (Haematology), 2002
  • DPhil, University of Oxford, 1996
  • MRCP (London), 1990
  • MBChB (Hons), University of Birmingham, 1987

Biography

Professor Sylvie Freeman’s clinical interests are in the management of acute myeloid leukaemia and myelodysplasia and diagnostics of haematological malignancies. This with her background in myeloid research led to her laboratory translation research focus on predicting treatment resistance in these myeloid malignancies.

During Professor Freeman's clinical specialist haematology training at Oxford, she completed a MRC funded DPhil followed by a MRC Clinician Scientist award. She had a clinical attachment at UCL and finished her clinical training in Bristol before being appointed in 2000 as a clinical academic at Birmingham University and honorary consultant at University Hospitals Birmingham NHS Foundation Trust. She is a member of the NCRI AML working party, the European LeukemiaNet AMLMRD Working Group and more recently the Laboratory and Diagnostic subcommittee/ International Consortium on Acute Leukemia Committee (American Society of Hematology).

NCRI AML trials are in effect a national care plan for AML therapy within the NHS. Her laboratory work in the framework of a national NCRI clinical trials collaboration addresses a key question; whether relapse prediction in AML and myelodsyplasia could be improved by sensitive detection of leukemia-specific markers. She has 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. Under her leadership the Birmingham University Clinical Immunology Service has established an international reputation for flow cytometric AML monitoring, acting as the hub reference laboratory in the UK. Sylvie has a part time role at the WHIMM in Oxford that will build on joint expertise for developing AML monitoring assays. Collaborations with the molecular expertise at KCL, Cambridge and international colleagues are critical to optimise ‘fit for purpose’ precision assays that will best inform treatment of AML including for novel therapies.

Teaching

Teaching programmes

  • MBChB - Foundations of Medical and Science Practice 3 Immunology and Haematology course
  • BMedSci  
  • MPharm 

Research

The heterogeneity of AML in terms of both disease biology and patient-specific clinical factors necessitates advances in personalised risk stratification to improve outcomes with present and future therapies. Although not a common malignancy, treatment of patients with AML is disproportionately expensive particularly if patients have treatment intensified by stem cell transplantation. There are therefore major economic as well clinical benefits to be gained by better selection of patient-appropriate targeted therapies.

Laboratory work in the framework of a national NCRI clinical trials collaboration addresses a key question; whether relapse prediction in AML and high risk myelodsyplasia could be improved by sensitive detection of leukemia-specific markers.

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 produced important data on the prognostic relevance of molecular MRD (Ivey et al NEJM 2016) as well as flow cytometric MRD (Freeman et al JCO 2018) that are now being implemented for MRD directed therapy in the younger AML patients (NCRI AML19. In addition to flow cytometric MRD monitoring by standard leukemic-aberrant-immunophenotypes 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). The group are also testing a simple assay that might 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)

Collaborations

National

  • Professor Russell (Nottingham / Guy’s Hospital), Dr Dillon (KCL), Professor Hills (Oxford / Cardiff), Professor Vyas (Oxford), Professor Huntly (Cambridge) plus other members of UK AML working group, Paul Virgo (Bristol).
  • Previously Professor Grimwade (KCL) and Professor Burnett (Cardiff).

International

  • European LeukemiaNet
  • Cloos/ Schuurhuis/ Ossenkopele (VU, HOVON group, Netherlands)
  • Plesa (Lyon), Roumier (Lille), (leads for AML flow cytometric MRD for French AML ALFA group)
  • Hourigan, (NIH National Heart, Lung and Blood Institute, Bethedsa, USA)
  • Pappaemannuil (Memorial Sloan Kettering Cancer Center, USA).

College/UHB

  • Professor Craddock

Other activities

  • Member of the UK NCRI Acute Myeloid Leukaemia Working Party
  • Member of Trial Management Group of NCRI AML Trials (AML18, AML19, FIGARO)
  • Member of the European LeukemiaNet Acute Myeloid Leukemia MRD Working Group
  • Member of the Laboratory and Diagnostic subcommittee /International Consortium on Acute Leukemia Committee (American Society of Hematology).
  • Honorary Consultant University Hospitals Birmingham NHS Foundation Trust
  • Honorary contract WHIMM, Oxford University

Publications

Highlight publications

Freeman, S, Hills, R, Virgo, P, Khan, N, Couzens, S, Dillon, R, Gilkes, A, Upton, L, Nielsen, OJ, Cavenagh, JD, Jones, G, Khwaja, A, Cahalin, P, Thomas, I, Grimwade, D, Burnett, AK & Russell, NH 2018, 'Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in standard- risk patients without NPM1 mutations', Journal of Clinical Oncology . https://doi.org/10.1200/JCO.2017.76.3425

UK NCRI AML Trial Group, Freeman, SD, Hills, RK, Russell, NH, HOVON AML Trial Group, Cloos, J, Kelder, A, Ossenkoppele, GJ & Schuurhuis, GJ 2018, 'Induction response criteria in acute myeloid leukaemia: implications of a flow cytometric measurable residual disease negative test in refractory adults', British Journal of Haematology. https://doi.org/10.1111/bjh.15698

Schuurhuis, GJ, Heuser, M, Freeman, S, Béné, M-C, Buccisano, F, Cloos, J, Grimwade, D, Haferlach, T, Hills, RK, Hourigan, CS, Jorgensen, JL, Kern, W, Lacombe, F, Maurillo, L, Preudhomme, C, van der Reijden, BA, Thiede, C, Venditti, A, Vyas, P, Wood, BL, Walter, RB, Döhner, K, Roboz, GJ & Ossenkoppele, GJ 2018, 'Minimal/measurable residual disease in AML: consensus document from ELN MRD Working Party', Blood. https://doi.org/10.1182/blood-2017-09-801498

Ivey, A, Hills, RK, Simpson, MA, Jovanovic, JV, Gilkes, A, Grech, A, Patel, Y, Bhudia, N, Farah, H, Mason, J, Wall, K, Akiki, S, Griffiths, M, Solomon, E, McCaughan, F, Linch, DC, Gale, RE, Vyas, P, Freeman, SD, Russell, N, Burnett, AK & Grimwade, D 2016, 'Assessment of Minimal Residual Disease in Standard-Risk AML', The New England Journal of Medicine, vol. 374, pp. 422-433. https://doi.org/10.1056/NEJMoa1507471

Bradbury, C, Houlton, AE, Akiki, S, Gregg, R, Rindl, M, Khan, J, Ward, J, Khan, N, Griffiths, M, Nagra, S, Hills, R, Burnett, A, Russell, N, Vyas, P, Grimwade, D, Craddock, C & Freeman, S 2015, 'Prognostic value of monitoring a candidate immunophenotypic leukaemic stem/progenitor cell population in patients allografted for acute myeloid leukaemia', Leukemia, vol. 29, pp. 988-991. https://doi.org/10.1038/leu.2014.327

Recent publications

Article

Craddock, C, Jackson, A, Siddique, S, Hodgkinson, A, Mason, J, Andrew, G, Nagra, S, Malladi, R, Peniket, A, Gilleece, M, Salim, R, Tholouli, E, Potter, V, Crawley, C, Wheatley, K, Protheroe, R, Vyas, P, Hunter, A, Parker, A, Wilson, K, Pavlu, J, Byrne, J, Dillon, R, Khan, N, McCarthy, N & Freeman, S 2020, 'An Augmented Reduced Intensity Regimen does not Improve Post-Allogeneic Transplant Outcomes in Acute Myeloid Leukemia', Journal of Clinical Oncology .

Snel, AN, Kelder, A, Scholten, WJ, Khan, N, Metzner, M, Irno-Consalvo, M, Sugita, M, de Jong, A, Oude Alink, S, Eidhof, H, Wilhelm, M, Feuring-Buske, M, Slomp, J, van der Velden, VHJ, Sonneveld, E, Guzman, M, Roboz, GJ, Buccisano, F, Vyas, P, Freeman, S, Bachas, C, Ossenkoppele, GJ, Schuurhuis, GJ & Cloos, J 2020, 'Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting', British Journal of Haematology. https://doi.org/10.1111/bjh.16594

Short, NJ, Zhou, S, Fu, C, Berry, DA, Walter, RB, Freeman, SD, Hourigan, CS, Huang, X, Nogueras, GG, Hwang, H, Qi, X, Kantarjian, H & Ravandi, F 2020, 'Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-analysis.', JAMA Oncology. https://doi.org/10.1001/jamaoncol.2020.4600

Dillon, R, Potter, N, Freeman, S & Russell, N 2020, 'How we use molecular minimal residual disease (MRD) testing in acute myeloid leukaemia (AML).', British Journal of Haematology. https://doi.org/10.1111/bjh.17185

Dillon, R, Hills, RK, Freeman, SD, Potter, N, Jovanovic, J, Ivey, A, Kanda, AS, Runglall, M, Foot, N, Valganon, M, Khwaja, A, Cavenagh, J, Smith, ML, Ommen, HB, Overgaard, U, Dennis, M, Knapper, S, Kaur, H, Taussig, DC, Mehta, P, Raj, K, Novitzky-Basso, I, Nikolousis, E, Danby, RD, Krishnamurthy, P, Hill, K, Finnegan, D, Alimam, S, Hurst, E, Johnson, P, Khan, AB, Salim, R, Craddock, CF, Ruth Lilian Spearing, D, Gilkes, AF, Gale, RE, Alan Kenneth Burnett, Russell, NH & Grimwade, D 2020, 'Molecular MRD status and outcome after transplantation in NPM1-mutated AML', Blood, vol. 135, no. 9, pp. 680-688. https://doi.org/10.1182/blood.2019002959

Basheer, F, Giotopoulos, G, Meduri, E, Yun, H, Mazan, M, Sasca, D, Gallipoli, P, Marando, L, Gozdecka, M, Asby, R, Sheppard, O, Dudek, M, Bullinger, L, Döhner, H, Dillon, R, Freeman, S, Ottmann, O, Burnett, A, Russell, N, Papaemmanuil, E, Hills, R, Campbell, P, Vassiliou, GS & Huntly, BJP 2019, 'Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML', The Journal of Experimental Medicine, vol. 216, no. 4, pp. 966-981. https://doi.org/10.1084/jem.20181276

Freeman, SD & Hourigan, CS 2019, 'MRD evaluation of AML in clinical practice: are we there yet?', Hematology, vol. 2019, no. 1, pp. 557-569. https://doi.org/10.1182/hematology.2019000060

Milne, P, Wilhelm-Benartzi, C, Grunwald, MR, Bigley, V, Dillon, R, Freeman, SD, Gallagher, K, Publicover, A, Pagan, S, Marr, H, Jones, GL, Dickinson, AM, Grech, A, Burnett, AK, Russell, NH, Levis, M, Knapper, S & Collin, M 2019, 'Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia', Blood Advances, vol. 3, no. 20, pp. 3052-3061. https://doi.org/10.1182/bloodadvances.2019000197

Burnett, AK, Hills, RK, Nielsen, OJ, Freeman, S, Ali, A, Cahalin, P, Hunter, A, Thomas, IF & Russell, NH 2018, 'A comparison of FLAG-Ida and daunorubicin combined with clofarabine in high-risk acute myeloid leukaemia: data from the UK NCRI AML17 Trial', Leukemia. https://doi.org/10.1038/s41375-018-0148-3

Khan, N, Hills, R, Virgo, P, Knapper, S, Grimwade, D, Russell, NH, Burnett, AK & Freeman, S 2017, 'Expression of CD33 is a predictive factor for effect of Gemtuzumab Ozogamicin at different doses in adult acute myeloid leukemia', Leukemia, vol. 31, no. 5, pp. 1059-1068. https://doi.org/10.1038/leu.2016.309

Gale, RE, Popa, T, Wright, M, Khan, N, Freeman, SD, Burnett, AK, Russell, NH, Hills, RK & Linch, DC 2017, 'No evidence that CD33 splicing SNP impacts the response to GO in younger adults with AML treated on UK MRC/NCRI trials', Blood. https://doi.org/10.1182/blood-2017-08-802157

Russell, NH, Freeman, SD & Craddock, C 2017, 'Obituary: Professor David Grimwade (1962-2016)', Bone Marrow Transplantation, vol. 52, no. 2, pp. 171-172. https://doi.org/10.1038/bmt.2016.350

Editorial

Freeman, S & Craddock, C 2020, 'Less is not necessarily more: toward a rational selection of the conditioning regimen in acute myeloid leukemia', Journal of Clinical Oncology , vol. 38, no. 12, pp. 1249-1251. https://doi.org/10.1200/JCO.19.03161

Review article

Ravandi, F, Walter, RB & Freeman, SD 2018, 'Evaluating measurable residual disease in acute myeloid leukemia', Blood Advances, vol. 2, no. 11, pp. 1356-1366. https://doi.org/10.1182/bloodadvances.2018016378

Buccisano, F, Dillon, R, Freeman, SD & Venditti, A 2018, 'Role of minimal (measurable) residual disease assessment in older patients with acute myeloid leukemia', Cancers, vol. 10, no. 7, 215. https://doi.org/10.3390/cancers10070215

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