Prof. Thomas Lion, MD, PhD
Modern diagnostic assays for early diagnosis and successful therapy of viral and fungal infections in immunocompromised patients.
Research, development (R&D) and diagnostics in the field of microbiology and chronic myeloid leukemia (CML) are the major areas of activity in our division. The exploitation of diagnostic assays emanating from our R&D work and the performance of specific developmental tasks were transferred to LabDia Labordiagnostik, a non-profit institution established in 2006 as a subsidiary of the St.Anna Childern´s Cancer Research Organization. A major part of our work is focused on infectious problems in oncological patients undergoing allogeneic stem cell transplantation (allo-SCT) or chemotherapy. In addition to bacteria, viral and fungal pathogens are particularly frequent causes of life-threatening infections in severely immunocompromised children. Early and reliable diagnosis is an essential prerequisite for successful therapy. We have therefore developed and, in part, patented quantitative molecular detection assays for many pathogenic viruses and clinically relevant fungal species. We were able to demonstrate that the clinical implementation of various methods developed in our division permits early assessment of impending infectious complications (Landlinger et al. Leukemia 2010; Lion et al. Leukemia 2010). The new diagnostic approaches will therefore contribute to improved treatment strategies against life-threatening infections in severely immunocompromised patients. Moreover, we have developed the basis for novel treatment strategies against invasive infections with adenoviruses which can lead to very severe diseases particularly in children undergoing allogeneic stem cell transplantation (Kneidinger et al. Antiviral Res 2012; Ibrisimovic et al. Antiviral Res 2012 und J Gene Med 2012).
An additional focus of our activities is the diagnostic monitoring of patients after allo-SCT. A European project coordinated by our center has led to the establishment of a standardized methodology for quantitative analysis of patient- and donor-derived cells (chimerism) (Lion et al. Leukemia 2012). The patented technique will soon be commercially available as a diagnostic kit. Moreover, we have recently established a diagnostic approach facilitating very early prediction of graft rejection which will permit timely therapeutic interventions (Breuer et al. Leukemia 2012).
Our recent development and clinical implementation of a molecular technique for the surveillance of mutant, therapy-resistant subclones in patients with CML provided important information on clonal development of the disease, timely detection of resistance, and clone-specific responses to treatment (Preuner et al. EJC 2012). The new insights will facilitate ensuing research which will improve our understanding of the dynamics of this type of leukemia. We will be able to pursue this task within a recently granted long-term project (Special Research Area Program funded by Austrian Science Fund).
In addition to our R&D program, we provide services as a reference laboratory for molecular diagnostics within national and international therapy trials in the fields of infectious diseases and leukemia (ALL-BFM, AML-BFM, CML-Ped, CML-11-CELSG, BFM-ALL-SCT, EWING, ENEST-1st, ENEST-Path, CARRAFLU), and we perform clinical studies addressing infectious disease-related issues.
Landlinger C, Preuner S, Bašková L, van Grotel M, Hartwig NG, Dworzak M, Mann G, Attarbaschi A, Peters C, Matthes-Martin S, Lawitschka A, van den Heuvel-Eibrink MM, Lion T. (2010) Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immuncompromised pediatric patients. Leukemia 24(12):2032-8.
Preuner S, Denk D, Frommlet F, Nesslböck M, Lion T. (2008) Quantitative monitoring of cell clones carrying point mutations in the BCR-ABL tyrosine kinase domain by ligation-dependent polymerase chain reaction (LD-PCR). Leukemia 22(10): 1956-61
Lion T, Baumgartinger, R, Watzinger F, Matthes-Martin S, Suda M, Preuner S, Futterknecht B, Lawitscka A, Peters C, Pötschger U, Gadner H. (2003) Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease. Blood 102(3): 1114-1120
Lion T, Daxberger H, Dubovsky J, Filipcik P, Fritsch G, Printz D, Peters C, Matthes S, Lawitschka A, Gadner H. (2001) Analysis of chimerism within specific leukocyte subsets for detection of residual or recurrent leukemia in pediatric patients after allogeneic stem cell transplantation. Leukemia 15(2), 307
Lion T, Henn T, Gaiger A, Kalhs P, Gadner H. (1993) Early detection of impending relapse by quantitative polymerase-chain reaction in patients with chronic myelogenous leukemia after bone marrow transplantation. Lancet 341: 275-76