Bio sketch Prof. Vera Ulrike Bacher
Prof. Dr. med. Vera Ulrike Bacher, MD, MHBA
Department Hematology and Central Hematology Laboratory, Inselspital Bern
- 01.09.2017: Venia Legendi Hematology; Associated Professorship Bern University
- 11/2013 Außerplanmäßige Professur (“apl. Prof.“)
- 04/2008 Habilitation (Venia legendi) Internal Medicine, University of Hamburg, Germany
- 10/2013-10/2015 Master of Medical Health Administration (MHBA), University Nürnberg-Erlangen
- 02/2000 Promotion („Dr. med.“; Tübingen)
- 05/1997 Medizinisches Staatsexamen
- 1990-1997 Human Medicine Studies (Technical University Munich)
- 01.11.2017: Laboratory Expert FAMH Hematology
- 26.10.2016: Swiss approval Internal Medicine and Hematology (MEBEKO)
- 02.02.2005: Schwerpunktbezeichnung Hämatologie/Onkologie
- 23.11.2003: Facharztprüfung Innere Medizin
- Since 02/2018: “Chefärztin”
- 10/2016-01/2018: “Leitende Ärztin”, Department Hematology, Inselspital Bern
- 09/2014-09/2016: “Oberärztin”, Department Hematology/Oncology, University Medicine Göttingen
- 07/2012 – 08/2014: MLL Munich Leukemia Laboratory
- 12/2006 – 06/2012: “Oberärztin”, Department Stem Cell Transplantation, University Hamburg-Eppendorf
- 10/2005 – 11/2006: Institute Clinical Chemistry, LMU-Grosshadern
- 07/2002 – 09/2005: Hematologic Residency, LMU-Grosshadern
- 07/1997 – 06/2002: Residencies Internal Medicine
Institutional responsibilities (Selection)
- Medical leadership Clinical Cytomics Facility (flow cytometry)
- Hematologic representative Interdisciplinary Leukemia Conference
Teaching activities (Selection)
- Seminary routine hematological diagnostics; Vorlesung “Myeloproliferative neoplasms”.
- Leadership German section EU-promoted online teaching module “e-hematimage”
- Lymphoma Working Party
- Chronic Leukemia Working Committee CIBMTR
- Schweizer Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK)
- Swiss MDS Study Group
- Swiss Cytometry Society
Contribution to science
I am focusing on improving hematologic diagnostics to provide the background for more individualized and optimized therapeutic decisions in patients with malignant hematologic and hemato-oncologic disorders at diagnosis and under established and novel therapies. Thus, my research work aims to intensify the interaction between diagnostic procedures and therapeutic decisions in patients with acute and chronic myeloid and lymphoproliferative malignancies.
Starting my academic career, I have concentrated on the introduction of novel prognostic molecular markers into the diagnostic routine for patients with myeloid malignancies. These approaches aim at improving risk prediction and finding the optimal therapy intensity, e.g. regarding the indication to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). More recently, I realized the need for an integration of the next-generation sequencing (NGS) technologies into current diagnostic algorithms of myeloid malignancies. Based on these sequencing strategies, we were able to expand the spectrum of molecular MRD markers in patients with acute myeloid leukemia (AML) as compared to the previous limited marker spectrum (comprising e.g. NPM1 mutations or reciprocal transcripts suitable for quantitative PCR).
With the advent of CAR-T cell therapies for patients with aggressive B-cell malignancies in Switzerland in 2019, I began to establish diagnostic programs that may become helpful for the clinicians. We initiated an interdisciplinary diagnostic working group for establishing frame diagnostics in this context. We perform immunologic monitoring in the peripheral blood of the CAR-T cell recipients, and we introduced molecular monitoring of the CAR-T cell load by digital droplet PCR (ddPCR), recently combined with immunophenotyping.
Major achievements of the last 5 years
Diagnostic frame program for CAR-T cell recipients
For the recipients of CAR-T cell therapies, we designed ddPCR assays to detect and monitor different CAR-T cell products in the peripheral blood in the weeks and months following CAR-T cell infusion (collaborators: Dr. Raphael Joncourt, Dr. Gertrud Wiedemann, Dr. Naomi Porret, Hematologic Molecular Diagnostics, Inselspital Bern). We tried to correlate the manifestation of cytokine release syndrome (CRS) with the dynamics of CAR-T cell concentrations in the peripheral blood (Pabst T, Joncourt R, Shumilov E, … Bacher U. Analysis of IL-6 serum levels and CAR-T cell-specific digital PCR in the context of cytokine release syndrome. J Exp Hem, online prepublished; doi: 10.1016/j.exphem.2020.07.003). An increase of IL-6 serum levels was helpful to interpret the clinical symptoms of CRS and to take the decision for immunsuppressive intervention by tocilizumab, a monoclonal antibody targeting the IL-6 receptor.
Improving and modernizing diagnostic algorithms for AML diagnostics
Based on the increasing complexity of diagnostic methods for AML and MDS, in particular due to the introduction of NGS into hematologic laboratories, diagnostic algorithms have to be newly defined. In parallel, targeted therapies, e.g. FLT3 or IDH1/IDH2 inhibitors, are expanding. This creates the need for rapid molecular screening at diagnosis and at relapse of AML. NGS is being introduced also for minimal residual disease (MRD) assessment allowing an expansion of the molecular marker panel for follow-up diagnostics in AML patients. We were able to summarize these and other recent changes and to provide an outlook into the near future: Shumilov E, Flach J, Kohlmann A, … Bacher U. Current status and trends in the diagnostics of AML and MDS, Blood Rev., 2018; 32(6):508-519. Also we could summarize the potential of NGS for patients with relapsed AML: Flach J, Shumilov E, Wiedemann G, … Bacher U. Clinical potential of introducing next-generation sequencing in patients at relapse of acute myeloid leukemia. Hematol. Oncol. 2020; in press; doi: 10.1002/hon.2739.
Improvement of the detection of minimal residual disease (MRD) in myeloma patients
At the Central Hematology Laboratory and Clinical Cytomics Facility, we introduced the principles of Next-Generation Flow (NGF) thereby improving MRD detection in myeloma patients following autologous stem cell transplantation (ASCT). By introducing bulk lysis and an antibody composition according to EuroFlow criteria, we could improve the sensitivity level. These measurements were integrated into the BEB-2 study (Prof. Dr. Thomas Pabst, Department of Medical Oncology; clinicaltrials.gov/ct2/show/NCT03187223) that compares different conditioning regimens in myeloma patients undergoing ASCT. The same technique was used for stem cell harvests of myeloma patients within the MOCCCA study (https://clinicaltrials.gov/ct2/show/NCT03442673).
Together with Prof. Dr. Nicolas Bonadies, we established biobanking including viable bone marrow cells of bone marrow samples with MDS and other myeloid malignancies. For this purpose, we are using the modern infrastructure of the BioBank Services of the Center of Laboratory Medicine (ZLM) of the Inselspital. In cooperation with the Department of Medical Oncology and the Swiss MDS Study Group (SMSG), we started establishing the “Swiss Cohort for the Characterization of Pathogenesis and Clonal Evolution of Myeloid Neoplasms”.
- Evaluation of the applicability of NGS for molecular MRD detection in patients with multiple myeloma (collaborators: Dr. Naomi Porret, Prof. Thomas Pabst, Dr. Ekaterina Rebmann, Dr. Martin Andres). Following CD138+ plasma cell enrichment by magnet-associated cell sorting (MACS), we perform screening for 14 genes and hotspots at diagnosis of multiple myeloma and we now perform screening of the previously detected mutations in the bone marrow after myeloma therapy.
- Evaluation of the dynamics of different interleukines in the serum of CAR-T cell recipients to improve the predictability of cytokine release syndrome (CRS) (collaborators: Dr. Michael Horn, PD Dr. Michael Nagler, University Institute of Clinical Chemistry; Prof. Thomas Pabst, Department of Medical Oncology; Myriam Legros, Center of Laboratory Medicine, Inselspital Bern).
- Evaluation of the molecular and flow cytometric detectability of CAR-T cells in the cerebrospinal fluid (CFS) of the recipients of CAR-T cell therapies (collaborators: Dr. Corinne Widmer, University Hospital Zürich; Dr. Naomi Porret, Dr. Gertrud Wiedemann, Prof. Sacha Zeerleder, Department of Hematology; Prof. Thomas Pabst, PD Dr. Urban Novak, Department of Medical Oncology, Inselspital Bern).
- Development / design of common primers for the molecular detection of different CAR-T cell products within a national cooperation (collaborators: Dr. Françoise Solly and PD Dr. Caroline Arber, CHUV; Dr. Corinne Widmer, USZ; Dr. Naomi Porret, Dr. Gertrud Wiedemann, Department of Hematology; Prof. Dr. Thomas Pabst, Department of Medical Oncology, Inselspital Bern).
List of collaborators
- Prof. Dr. Thomas Pabst, PD Dr. Urban Novak, Dept. of Medical Oncology, Inselspital Bern
- Prof. Dr. Sacha Zeerleder, Dr. Katarzyna Jalowiez, PD Dr. Nicolas Bonadies, PD Dr. Alicia Rovo, Dept. of Hematology, Inselspital Bern
- Prof. Dr. Carlo Largiadèr, Yolanda Aebi, Michael Hayoz, PD Dr. Michael Nagler, PD Dr. Michaela Fux, University Institute of Clinical Chemistry, Inselspital Bern
- Myriam Legros, Denise Stalder-Zeerleder, Clinical Cytomics Facility, Center of Laboratory Medicine, Inselspital Bern
- PD Dr. Caroline Arber, Department of Hematology, Lausanne University Hospital (CHUV
- Dr. Françoise Solly, Hematologic Laboratory, Lausanne University Hospital (CHUV)
- Dr. Corinne Widmer, Prof. Dr. Stefan Balabanov, Department of Medical Oncology and Hematology, University Hospital Zürich
- Prof. Dr. Sara Meyer, Department of Biomedicine, University Hospital Basel
- PD Dr. Georg Stüssi, Department of Hematology, Ente Ospedaliero Cantonale di Bellinzona
- Prof. Dr. Thomas Matthes, Dr. Bijan Moshaver, Department of Hematology, University Hospital Geneva (HUG)
- Prof. Dr. Nicolaus Kröger, Dr. Evgenii Klyushnikov, PD Dr. Max Christopeit, Anita Badbaran, Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Germany
- Dr. Evgenyi Shumilov, Inna Shakhanova, Department of Hematology and Medical Oncology, University Medicine Göttingen, Germany
- Dr. Johanna Flach, Medical Department III, Faculty Mannheim of Heidelberg University, Germany
- Dr. Thomas Stübig, Department Internal Medicine II / Hematology, Oncology, Campus Kiel, University Hospital Schleswig-Holstein
- Prof. Dr. Katharina Götze, Medical Department III, Klinikum Rechts der Isar, Technical University Munich, Germany
- Prof. Yschai Ofran, Hematology and Bone Marrow Transplantation Department, Ramban Health Care Campus, Haifa, Israel
- Prof. Pia Ranaani, Beilinson Medical Center, Petach-Tikva, Israel
- Prof. Mehdi Hamadani, Scientific Director, CIBMTR Lymphoma Working Committee, Medical College of Wisconsin, USA
- Prof. Daniel Weisdorf, Division of Hematology, Oncology and Transplantation, University of Minnesota Clinical and Translational Science Institute, Minneapolis, USA
- Dr. Pedro Martin-Cabrera, Department of Hematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK