Sylvie D. Freeman
A5028452852- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Retinoids in leukemia and cellular processes
- Glycosylation and Glycoproteins Research
- Hematological disorders and diagnostics
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Neutropenia and Cancer Infections
- Proteoglycans and glycosaminoglycans research
- Galectins and Cancer Biology
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Blood disorders and treatments
- Monoclonal and Polyclonal Antibodies Research
- Protein Tyrosine Phosphatases
- Immune cells in cancer
- Cell Adhesion Molecules Research
University of Birmingham
2016-2025
Guy's and St Thomas' NHS Foundation Trust
2013-2025
Cardiff University
2018-2025
Queen Elizabeth Hospital Birmingham
2012-2024
University College Birmingham
2024
Institute of Immunology
2022-2023
Cancer Research UK Clinical Trials Unit
2021
Santa Casa de Misericórdia de Marília
2021
North Bristol NHS Trust
2013-2018
University College London
2018
Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number genetic markers and morphology-based assessment remission. Sensitive detection leukemia-specific marker (e.g., mutation in gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during
Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardization harmonization of ongoing manner has updated the 2018 ELN recommendations based on significant developments field. New revised were established during in-person online meetings, a 2-stage Delphi poll was conducted to optimize consensus. All are...
There has been little survival improvement in older patients with acute myeloid leukemia (AML) the last two decades. Improving induction treatment may improve rate and quality of remission consequently survival. In our previous trial, younger patients, we showed improved for majority when adding gemtuzumab ozogamicin (GO) to chemotherapy.Untreated AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 84 years) were randomly assigned receive chemotherapy either...
Older patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. We investigated whether measuring chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease (MFC-MRD) detection has prognostic value in older than age 60 years or is simply surrogate for known age-related risk factors.Eight hundred ninety-two unselected treated intensively the United Kingdom National Cancer Research Institute AML16 Trial were assessed prospectively...
Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate extent its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other response criteria. Methods As part NCRI AML17 trial, 2,450 younger adult patients AML high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After 1 (C1),...
Abstract Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize validate 16 classes describing 100% AML Each class represents diverse biological subgroups, is associated with distinct clinical presentation, likelihood response to induction chemotherapy, risk relapse...
To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics.
Immunity against phosphopeptide antigens lacking in leukemia patients can be restored with stem cell transplantation.
Background The current World Health Organization classification of myelodysplastic syndromes is based morphological evaluation bone marrow dysplasia. In clinical practice, the reproducibility recognition dysplasia usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities.Design Methods We aimed to develop validate a flow cytometric score for diagnosis syndrome. Four reproducible parameters were analyzed: CD34+...
Our understanding of the perturbation normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic (LSC) arrested at a progenitor-like stage expressing surface CD34. We show that in ∼25% AML, with distinct genetic mutation pattern where >98% cells are CD34(-), there multiple, nonhierarchically arranged CD34(+) and CD34(-) LSC populations. Within...
Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated a high risk disease relapse. Strategies reduce recurrence urgently required. Registry data demonstrated improved outcomes using sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), impact this intensified regimen has not been studied...
Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations common myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during evolution acute leukemia (AML), where we observed stage-specific diametrically opposite functions at early late stages disease. During disease maintenance, WT exerts an oncogenic function that may be therapeutically targeted. In contrast, acts a tumor suppressor AML induction....
Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of assay. Experts from MRD Working Party European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on agreement, obtained via combination cross-sectional questionnaire, live discussions, Delphi poll. The recommendations...
Abstract Patients with FLT3 -mutated AML have a high relapse rate and suboptimal outcomes. Many co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR those destined to can be identified or rising levels of MRD, called molecular failure. This provides window pre-emptive intervention, but there is little evidence guide treatment. The use inhibitors (FLT3i) appears attractive their has not yet been evaluated. We 56 patients treated FLT3i at mutation was an ITD in 52,...