Lymphoma, Leukemia & HSCT

The UCT Program in "Hematologic Malignancies" is focusing on an efficient transfer of innovative findings in basic science into novel therapeutic strategies. In 2014, 141 lymphomas, 34 multiple myelomas and more than 60 leukemias were first diagnosed at the center and more than 1,600 patients were treated in the multidisciplinary outpatient and inpatient clinic. As the sole certified transplantation center in Rhineland-Palatinate, we performed 151 hemopoietic stem cell transplants (HSCT) including 87 allogeneic HSCTs of related and unrelated donors.

Clinical Research

Within our clinical research program, we performed 62 clinical trials including 10 phase I studies and enrolled 98 patients. Investigator Initiated Trial (IITs) investigated the role of Temsirolimus in mantle cell lymphoma (Hess G. Leukemia 2015) or high-dose therapy for patients with relapsed aggressive Non-Hodgkin lymphoma (NHL) (Kirschey S. Br J Haematol. 2015). Investigators of the UCT Program Hematologic Malignancies substantially contributed to pivotal national and international studies such as the BELIEF study in peripheral T-cell lymphoma (O'Connor O.A. J Clin Oncol. 2015), the GMMG-MM5 trial in multiple myeloma (Mai E.K. Leukemia 2015), the analysis of FLT3-ITD in acute myeloid leukemia (AML) (Schlenk R.F. Blood 2014).

Translational Projects

Translational research within the Program "Hematologic Malignancies" is focusing on cancer immunotherapy, leukemogenesis and genetic instability. Recent achievements include I) the analysis of CD8+ T-cells in overcoming MRD-positive leukemia (Distler E. Int J Cancer 2015); II) the role of nanoparticles in antigen-specific T-cell therapy (Zupke O. Nanomedicine 2015); III) effects of arginine depletion on cytotoxic T-cell responses (Munder M. PloS One 2013); IV) induction of synthetic vulnerability upon targeting the alt-NHEJ repair pathways in KRAS-mutant leukemia (Hähnel P.S. Blood 2014); or V) identification of SIRT1 as a novel target in AML (Sasca D. Blood 2014). Investigators are funded by all major funding agencies such as DFG, DKH or BMBF. Current efforts aim at transferring our findings in basic research into investigator initiated, hypothesis-driven clinical trials.

Most significant publications

  • Distler E., J. Albrecht, A. Brunk, S. Khan, E. Schnürer, M. Frey, A. Mottok, A.L. Jordán-Garrote, C. Brede, A. Beilhack, A. Mades, D. Tomsitz, M. Theobald, W. Herr, U.F. Hartwig 2016. Patient-individualized CD8(+) cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice. Int J Cancer. 138(5):1256-68.
  • Hess G., U. Keller, C.W. Scholz, M. Witzens-Harig, J. Atta, C. Buske, S. Kirschey, C. Ruckes, C. Medler, C. van Oordt, W. Klapper, M. Theobald, M. Dreyling. 2015. Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma. Leukemia. 29(8):1695-701.
  • Kirschey S., T. Flohr, H.H. Wolf, N. Frickhofen, M. Gramatzki, H. Link, N. Basara, N. Peter, R.G. Meyer, N. Schmitz, E. Weidmann, A. Banat, A. Schulz, K. Kolbe, G. Derigs, M. Theobald, G. Hess. 2015. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 168(6):824-34.
  • Mai E.K., U. Bertsch, J. Dürig, C. Kunz, M. Haenel, I.W. Blau, M. Munder, A. Jauch, B. Schurich, T. Hielscher, M. Merz, B. Huegle-Doerr, A. Seckinger, D. Hose, J. Hillengass, M.S. Raab, K. Neben, H.W. Lindemann, M. Zeis, C. Gerecke, I.G. Schmidt-Wolf, K. Weisel, C. Scheid, H. Salwender, H. Goldschmidt. 2015. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 29(8):1721-9.
  • O'Connor O.A., S. Horwitz, T. Masszi, A. Van Hoof, P. Brown, J. Doorduijn, G. Hess, W. Jurczak, P. Knoblauch, C. Chawla, G. Bhat, M.R. Choi, J. Walewski, K. Savage, F. Foss, L.F. Allen, A. Shustov. 2015. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 33(23):2492-9.
  • Zupke O., E. Distler, A. Jürchott, U. Paiphansiri, M. Dass, S. Thomas, U.F. Hartwig, M. Theobald, K. Landfester, V. Mailänder, W. Herr. 2015. Nanoparticles and antigen-specific T-cell therapeutics: a comprehensive study on uptake and release. Nanomedicine (Lond). 10(7):1063-76.
  • Hähnel P.S., B. Enders, D. Sasca, W.P. Roos, B. Kaina, L. Bullinger, M. Theobald, T. Kindler. 2014. Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy. Blood. 123(15):2355-66.
  • Sasca D., P.S. Hähnel, J. Szybinski, K. Khawaja, O. Kriege, S.V. Pante, L. Bullinger, S. Strand, D. Strand, M. Theobald, T. Kindler. 2014. SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia. Blood. 124(1):121-33.
  • Schlenk R.F., S. Kayser, L. Bullinger, G. Kobbe, J. Casper, M. Ringhoffer, G. Held, P. Brossart, M. Lübbert, H.R. Salih, T. Kindler, V.A. Horst, G. Wulf, D. Nachbaur, K. Götze, A. Lamparter, P. Paschka, V.I. Gaidzik, V. Teleanu, D. Späth, A. Benner, J. Krauter, A. Ganser, H. Döhner, K. Döhner; German-Austrian AML Study Group. 2014. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood. 124(23):3441-9.
  • Munder M., M. Engelhardt, D. Knies, S. Medenhoff, G. Wabnitz, C. Luckner-Minden, N. Feldmeyer, R.H. Voss, P. Kropf, I. Müller, R. Conradi, Y. Samstag, M. Theobald, A.D. Ho, H. Goldschmidt, M. Hundemer. 2013. Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion. PLoS One. 8(5):e63521.