AG Computational Hematology and Immunotherapy
- Investigation of dynamic- and machine-learning approaches for a better understanding of hematologic diseases and their complications
- Research of allogeneic stem cell transplantation (allo-SCT) and its potential complications:
- Virus reactivation (CMV,EBV)
- Graft-versus-host-disease (GvHD)
- Application of virus-specific immunotherapies
Details of research interests
Our group covers several facets of research on allogeneic hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation is one of the main therapies for intermediate- and high-risk patients with hematologic malignancies (e.g. acute myeloid leukemia (AML)). Although transplantation is an established treatment, there are several associated complications, which can reduce good clinical outcome.
Complications may arise in form of virus reactivations (human cytomegalovirus (CMV), Epstein-Barr-virus (EBV)), acute/chronic GVHD (graft-versus-host disease) and bacterial & fungal infections. Often these complications relate to demanding conditioning therapies before transplantation, which impair patient’s immunity.
Our group uses mathematical models and machine-learning approaches to identify significant parameters of complications. The development of such models can enhance the treatment of patients according to their risk profiles which will lead to a better quality in patient care and individual therapy outcomes. Ideally, patients may be prevented from or treated for complications before they occur.
Dr. med. Dr. phil. Amin Turki is a senior physician at the Department of Bone Marrow Transplantation with a long-standing experience in the diagnosis and treatment of immunosuppressed and transplanted patients. He leads the research group “Computational Hematology and Immunotherapy” and has been BMT project responsible in the on-going E-Health project “XplOit- Semantic support for predictive modelling in predictive medicine”. Dr. Turki studied Medicine and Philosophy at the Universities of Münster, Paris Descartes, Ecole Normale Supérieure and Harvard. He received his clinical training at the University Hospitals of Cologne and Essen.
Dr. Evren Bayraktar is a senior physicist and mathematician at the Department of Bone Marrow Transplantation specialized in algorithm development, computational sciences and applied mathematics. He has a dual affiliation at the Technical University Dortmund, where he is part of the Chair of applied mathematics. Dr. Bayraktar studied Physics and Mathematics at the Universities Bosporus Istanbul and TU Dortmund.
Saskia Leserer is a PhD Student at the faculty of biology working in the group "Computational Hematology and Immunotherapy". Besides her experience in the field of biology she is also familiar with chemistry. Saskia Leserer studied Chemical Biology (B.Sc. and M.Sc.) at the Technical University Dortmund and started her PhD studies in 2018.
Aleksandra Pillibeit is responsible for the documentational work in the group "Computational Hematology and Immunotherapy". She is involved in the E-health Project "XplOit" as well as the Harmony Alliance.
- One of our current projects investigates CMV reactivation after allogeneic hematopoietic stem cell transplantation. In the context of immunocompromised patients after transplantation, CMV causes important morbidity and mortality. However, there is evidence that early cytomegalovirus replication associates with reduced leukemic recurrence. The exact pathophysiology of this association is still under investigation and no predictive models are established. The aim of this study is to correlate CMV reactivation dynamics with clinical outcome parameters in order to develop a dynamic model for individualized patient outcome.
Saskias PhD project is focusing on the immune reconstitution of hematopoietic stem cell transplantation recipients. The first aim of her project is to characterize the reconstitution of immune cells for patients with acute clinically relevant reactivation of viruses, such as CMV, EBV or Herpes-Simplex virus (HSV). Her analysis should allow us to understand to what extent, virus reactivations influence the reconstitution and especially in which cell subsets (e.g. T cells, B cells and NK cells). We hypothesize that in cases of viral infections the reconstitution of the innate and adaptive immunity is delayed. It is unclear, if the analyzed viruses will show similar effects on the immune system. This first analysis is conducted with retrospectively collected virology and flow cytometry data. In a second step, prospective data from patients receiving a “virus-specific T-cell therapy”, which is established in the transplant-production facility of our clinic, will also be analyzed concerning the reconstitution of immune cells. Afterwards analyzed data should be compared to patients, without this promising therapeutic approach. Via this comparison possible differences on the cellular level should be demonstrated and characterized. Both parts of Saskia’s thesis are well integrated in the context of our group’s research. The results will be integrated in mathematical models or machine-learning approaches, with the objective to find a better care for patients.
Recent publications of group members
Turki AT, Klisanin V, Bayraktar E, Kordelas L, Trenschel R, Ottinger H; Steckel NK; Tsachakis-Mück N, Leserer S, Ditschkowski M, Koldehoff M., Fleischhauer K and Beelen DW, “Optimizing anti-T-lymphocyte globuline dosing to improve long-term outcome after unrelated hematopoietic cell transplantation for hematologic malignancies”, American Journal of Transplantation, accepted on 09-25-2019
Alashkar F, Vance C, Herich-Terhürne D, Turki AT, Schmitz C, Bommer M, Hüttmann A, Dührsen UC, Vogel U, Röth A, “Serologic Response to Meningococcal Vaccination in Patients with Cold Agglutinin Disease (CAD) in the Novel Era of Complement Inhibition”, Vaccine, 2019 Sep 24. (Epub ahead of print.) https://doi.org/10.1016/j.vaccine.2019.09.033
Turki AT, Bayraktar E, Basu O, Kehrmann J, Tzalavras A, Yi J, Liebregts T, Benkö T, Beelen DW, Steckel NK, “Ileostomy for severe, steroid-resistant graft-versus-host disease of the gastrointestinal tract”, Annals of Hematology, Jul 23. (Epub ahead of print.) https://doi.org/10.1007/s00277-019-03754-3
Turki AT et al. “Machine Learning-based acute GVHD grading” Abstract , 24th Congress of European Hematology Association (EHA) in Amsterdam, Netherlands, June 13-16, 2019 https://doi.org/10.1097/01.HS9.0000561280.44375.d2
Alashkar F, Oelmüller M, Herich-Terhürne D, Turki AT, Schmitz C, Vance C, Dührsen U, Röth A, “Immunosuppressive therapy (IST) in adult patients with acquired aplastic anemia (AA): A single-center experience at the West German Cancer Center over the past 15 years”, European Journal of Hematology, Apr 11. (Epub ahead of print.) https://doi.org/10.1111/ejh.13235
Leserer S et al. “Cytomegalovirus reactivation kinetics and peak titers as novel predictors of survival and relapse after allogeneic cell Transplantation for hematologic malignancies” Abstract, 45th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) in Frankfurt, Germany, March 24-27, 2019, to be published in Bone Marrow Transplantation
Turki AT, Lamm W, Schmidt C, Alashkar F, Beelen DW, Liebregts T, “Platelet number and sustained graft function predict intensive care survival in patients with allogeneic stem cell transplantation”, Annals of Hematology, 2019, 98(3), 811.
Turki AT, Lamm W, Liebregts T, Dührsen U “R-ICE chemotherapy with or without autologous transplantation for elderly patients with relapsed or refractory aggressive B-cell lymphomas“, Oncology Research and Treatment, 2018; 41(9):534-538.
Wohlfarth P, Turki AT, Steinmann J, Fiedler M, Steckel NK, Beelen DW, Liebregts T, “Microbiological diagnostic work-up of acute respiratory failure with pulmonary infiltrates following allogeneic hematopoietic stem cell transplantation: findings in the era of molecular and biomarker-based assays”, Biol. Blood and Marrow Transplantation (2018). https://doi.org/10.1016/j.bbmt.2018.03.007
Weiler G, Schwarz U, Rauch J, Rohm K, Lehr T, Theobald S, Kiefer S, Götz K, Och K, Pfeifer N, Handl L, Smola S, Ihle M, Turki AT, Beelen DW, Rissland J, Bittenbring J and Graft N, “XplOit: An Ontology-Based Data Integration Platform Supporting the Development of Predictive Models for Personalized Medicine”, Studies in Health Technology and Informatics; 247:21-25. 2018
Turki AT, Tsachakis-Mück N, Leserer S, Yi JH et al "Early Cytomegalovirus Reactivation and Donor Constellation Reduce Early and Late Relapse Incidence of Acute Myeloid Leukemia in a Long-Term Study", Abstract 3413 at the Annual Meeting of the American Society of Hematology, ASH 3413 , to be published in Blood
Turki AT et al. “A new Data Integration Platform for the Development of Predictive Models in Stem Cell Transplantation (XplOit)” Abstract A430, 44th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) in Lisbon, Portugal, March 18-21, 2018, to be published in Bone Marrow Transplantation