TY - JOUR A1 - Rasche, Leo A1 - Kumar, Manoj A1 - Gershner, Grant A1 - Samant, Rohan A1 - Van Hemert, Rudy A1 - Heidemeier, Anke A1 - Lapa, Constantin A1 - Bley, Thorsten A1 - Buck, Andreas A1 - McDonald, James A1 - Hillengass, Jens A1 - Epstein, Joshua A1 - Thanendrarajan, Sharmilan A1 - Schinke, Carolina A1 - van Rhee, Frits A1 - Zangari, Maurizio A1 - Barlogie, Bart A1 - Davies, Faith E. A1 - Morgan, Gareth J. A1 - Weinhold, Niels T1 - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis? JF - Theranostics N2 - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM. KW - multiple myeloma KW - diffusion weighted mri KW - spleen KW - tumor burden KW - high risk KW - extramedullary hematopoiesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982 VL - 9 IS - 16 ER - TY - JOUR A1 - Steinhardt, Maximilian Johannes A1 - Zhou, Xiang A1 - Krummenast, Franziska A1 - Meckel, Katharina A1 - Nickel, Katharina A1 - Böckle, David A1 - Messerschmidt, Janin A1 - Knorz, Sebastian A1 - Dierks, Alexander A1 - Heidemeier, Anke A1 - Lapa, Constantin A1 - Einsele, Hermann A1 - Rasche, Leo A1 - Kortüm, Klaus Martin T1 - Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma JF - International Journal of Immunopathology and Pharmacology N2 - We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab (“Pom-PAD-Dara”), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM. KW - CD38 KW - MOR202 KW - daratumumab KW - multiple myeloma KW - refractory KW - relapse Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236235 VL - 34 ER - TY - JOUR A1 - Steinhardt, Maximilian J. A1 - Krummenast, Franziska C. A1 - Rosenwald, Andreas A1 - Gerhard-Hartmann, Elena A1 - Heidemeier, Anke A1 - Einsele, Hermann A1 - Topp, Max S. A1 - Duell, Johannes T1 - R-CHOP intensification with mid-cycle methotrexate and consolidating AraC/TT with BCNU/aHSCT in primary aggressive lymphoma with CNS involvement JF - Journal of Cancer Research and Clinical Oncology N2 - Purpose Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival. Methods We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status. Results Overall response rate to Ping-Pong was 100% measured by CT/MRI, including 93.75% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75% after a 4.8-year follow-up currently. Conclusion Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population. KW - lymphoma KW - HD KW - MTX KW - R-CHOP Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267731 SN - 1432-1335 VL - 148 IS - 1 ER -