TY - JOUR A1 - Saussele, Susanne A1 - Hehlmann, Ruediger A1 - Fabarius, Alice A1 - Jeromin, Sabine A1 - Proetel, Ulrike A1 - Rinaldetti, Sebastien A1 - Kohlbrenner, Katharina A1 - Einsele, Hermann A1 - Falge, Christine A1 - Kanz, Lothar A1 - Neubauer, Andreas A1 - Kneba, Michael A1 - Stegelmann, Frank A1 - Pfreundschuh, Michael A1 - Waller, Cornelius F. A1 - Oppliger Leibundgut, Elisabeth A1 - Heim, Dominik A1 - Krause, Stefan W. A1 - Hofmann, Wolf-Karsten A1 - Hasford, Joerg A1 - Pfirrmann, Markus A1 - Müller, Martin C. A1 - Hochhaus, Andreas A1 - Lauseker, Michael T1 - Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV JF - Leukemia N2 - Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later. KW - Chronic myeloid leukaemia KW - Molecularly targeted therapy KW - Risk factors KW - Risk factors KW - Translational research Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227528 VL - 32 IS - 5 ER - TY - JOUR A1 - Marischen, Lothar A1 - Englert, Anne A1 - Schmitt, Anna-Lena A1 - Einsele, Hermann A1 - Loeffler, Juergen T1 - Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus JF - BMC Immunology N2 - Background: The saprophytic fungus Aspergillus fumigatus reproduces by generation of conidia, which are spread by airflow throughout nature. Since humans are inhaling certain amounts of spores every day, the (innate) immune system is constantly challenged. Even though macrophages and neutrophils carry the main burden, also NK cells are regarded to contribute to the antifungal immune response. While NK cells reveal a low frequency, expression and release of immunomodulatory molecules seem to be a natural way of their involvement. Results: In this study we show, that NK cells secrete chemokines such as CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES early on after stimulation with Aspergillus fumigatus and, in addition, adjust the concentration of chemokines released to the multiplicity of infection of Aspergillus fumigatus. Conclusions: These results further corroborate the relevance of NK cells within the antifungal immune response, which is regarded to be more and more important in the development and outcome of invasive aspergillosis in immunocompromised patients after hematopoietic stem cell transplantation. Additionally, the correlation between the multiplicity of infection and the expression and release of chemokines shown here may be useful in further studies for the quantification and/or surveillance of the NK cell involvement in antifungal immune responses. KW - Aspergillus fumigatus KW - aspergillosis KW - NK cells KW - chemokines KW - CCL4 KW - multiplicity of infection KW - MIP-1β Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176331 VL - 19 IS - 39 ER -