A translational research initiative related to the professorship in malignant lymphoproliferative diseases at the Dept. og Hematology, Aarhus University Hospital.

The objective of the iLymph research programme is to stimulate the development and validation of biomarkers for: (1) Early detection, disease progression, and recurrence of lymphoma/lymphatic leukemia (LL), especially in high‐risk individuals; and: (2). Risk assessment of primary and secondary LL.

The team

The researchers attached to iLymph through their individual projects and areas of expertise are (i) Post doctoral scientists , (ii) PhD students, (iii) those close to start of PhD programme with an already formulated PhD protocol and (iv) pre‐graduate projects.  The lead coordinator of the iLymph project is professor Francesco  d’Amore, Dept. of Hematology, AUH, who holds  a clinical professorship in malignant lymphoproliferative diseases initially  (2010‐2015) funded  by the Karen Elise Foundation and subsequently by the Regional Research Fund of Region Midt (2015 - onwards).  The research network also counts several senior scientists from different disciplines, who interact on one or  multiple topics as co‐supervisors  within the individual research projects.

The project matrix

All scientific activities within the iLymph project develop and interact within the framework of a ’project matrix’ consisting of two major domains, one represented by disease‐defined fields of research (vertical bars) and the other by cross‐sectional topics applicable within the different disease‐specific fields (horizontal bars). Each field or topic is related to an individual scientist or research team and may contain one or more individual projects, which, at the present stage of iLymph development, are either ongoing or in the pipeline. There are currently five disease‐defined LL fields within iLymph: (i) Hodgkin lymphoma (HL), (ii) Peripheral T‐cell lymphoma (PTCL), (iii) Diffuse large B‐cell lymphoma (DLBCL), (iv) Follicular lymphoma (FL) with focus on transformed follicula lymphoma(tFL) and (v) Immunodeficiency‐associated lymphoma (IDL) with focus on Post-Transplant Lymphoproliferative Disease (PTLD) and HIV‐associated lymphoma (HIV‐L). Along with these five disease‐specific fields, there are eight cross‐sectional research topics: (i) Epidemiology, (ii) genomics, (iii) proteomics, (iv) microenvironment, primarily focusing on tumour microenvironment, (v) angiogenesis, (vi) diagnostic imaging, primarily focusing on PET/CT‐related issues within different types of lymphomas, (vii) cell therapies, currently primarily focusing on allogeneic stem cell transplantation, a treatment methodology, which in Dennmark is only available in Aarhus and Copenhagen, and (viii) early phase clinical trials, with focus on phase I and II clinical trials to test novel drugs individually or in synergistic combination in the context of investigator‐ and company‐initiated studies.

Clinical trials: In 2012, we published the largest clinical study on PTCL conducted so far, the NLG‐T‐01 trial in the Journal of Clinical Oncology. The results of the NLG‐T‐01 trial are mentioned in both European and  North‐American guidelines for the treatment of PTCL and represent a major reference for the recommendation of upfront high‐dose therapy with autologous stem cell support in transplant eligible PTCL patients. Moreover, we coordinated, from the Department of Hematology at AUH/AU and in collaboration with the German high‐grade lymphoma group, the first international phase III study in PTCL (the ACT trial). The ACT study completed its recruitment phase in December 2013 (N=252) and the final analysis of trial data will be performed in Q2 2015.

Publications 20102014/2015: The number of iLymph‐related publications has been markedly increasing over the last four years (2010‐2014). Since the beginning of the professorship granted by Karen Elise Jensen Foundation in February 2010, a total of 33 publications have been produced. So far, seven iLymph‐related manuscripts have already been published by mid-March 2015,

PhD projects: In the period 2010‐2016, a total of 10 PhD projects were either successfully concluded (4, i.e. 3

as main and 1 as co‐supervisor), initiated (4, i.e. 3 as main and 1 as co‐supervisor), prepared in order to start in 2016 (2, as main supervisor).

Annual research seminar: An annual 2‐day research seminar has been held at Schur Conference Center, Glud, Denmark in May since 2010. At the seminar, young researchers pre‐graduate, pre‐PhD and PhD students together with postdocs have presented and discussed their work in the iLymph plenum. Keynote speakers are invited to give expert overviews on topics relevant to the ongoing projects. All seminars have been extremely valuable for the exchange of ideas and practical solutions to challenges in the different projects. We aim to continue this unifying multidisciplinary tradition.

Perspectives                          

The primary goal of iLymph is to improve the cure rate and the quality of life of patients suffering from LL  through innovative therapeutic strategies based on effective translation of discoveries in disease biology, immunology, and molecular genetics and on risk‐adapted treatment strategies. More specifically, iLymph research activities are expected to consolidate an already existing national and international network for the study of LL. Discoveries on the biological mechanisms and determinants of clinical behaviour of LL originating within the iLymph network will provide the platform for collaborative trials testing novel biomarker‐driven, risk‐adapted therapeutic approaches on a national and international scale. The network is designed to ensure patient access to new investigational drugs and to allow easy access to phase I and early phase II programmes. A prominent toll for this will be the accomplishment of an already ongoing effort to offer our clinical trial office in Aarhus as a common clinical trial office for Nordic lymphoma trials initiated within the Nordic Lymphoma Group. The planned projects are expected to strengthen and expand existing international collaborations, attract foreign researchers, and further heighten the educational level in the research and management of lymphoma and LL at our university hospital/university as well as at national level. In line with this strategy, the iLymph research project pursues as a mid‐term goal to establish a center of excellence in translational research and experimental therapy of lymphoma and lymphatic leukemia based in Aarhus.