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EASIX for prediction of survival in lower-risk myelodysplastic syndromes

Almuth Merz, Ulrich Germing, Guido Kobbe, Jennifer Kaivers, Anna Jauch, Aleksandar Radujkovic, Manuela Hummel, Axel Benner, Maximilian Merz, Peter Dreger, Thomas Luft
2019 Blood Cancer Journal  
Patients with myelodysplastic syndromes (MDS) are at risk of early death from cardiovascular complications due to the link between clonal hematopoiesis and endothelial dysfunction. EASIX (Endothelial Activation and Stress Index) has been established to predict endothelial complications after allogeneic transplantation. We investigated the impact of EASIX measured at first diagnosis on survival of patients with lower- and higher-risk MDS (no allogeneic transplantation) in two independent
more » ... independent institutions: n = 192 (training cohort) and n = 333 (validation cohort). Serum markers of endothelial cell distress were measured and correlated to EASIX. While no effects of EASIX on survival were observed in higher-risk patients, EASIX was associated with shorter survival in patients with lower-risk MDS in both cohorts (univariate: Cohort I: hazard ratio (HR): 1.46; 95% confidence interval (CI) 1.24-1.71; p-value < 0.001/Cohort II: HR 1.31 [1.17-1.48]; p-value < 0.001). Multivariate Cox regression analysis and prediction error analyses confirmed that EASIX remained a significant predictor of survival after adjustment for age, sex, cytogenetic abnormalities and bone marrow blasts in lower-risk patients. The model of the training cohort could be validated. Serum levels of Angiopioetin-2 correlated significantly with EASIX. We introduce EASIX as an easily accessible and independent predictor for survival in patients with lower-risk MDS.
doi:10.1038/s41408-019-0247-z pmid:31712595 pmcid:PMC6848148 fatcat:t3hhchygdjbefk2tziikcfb6oy

Diffusion-Weighted MRI—The Way Forward for MRI in Myeloma?

Jens Hillengass, Maximilian Merz, Ronald Alberico, Majid Chalian
2021 Hemato  
Multiple myeloma and other plasma cell disorders infiltrate the bone marrow in different patterns. While some patients show a homogeneous distribution of the clonal plasma cells others present with focal accumulations, commonly called focal lesions. Novel imaging techniques can provide information on these infiltration patterns and, due to their low invasiveness, can be performed repeatedly and therefore be used for monitoring. Conventional magnetic resonance imaging (MRI) has a high
more » ... s a high sensitivity for bone marrow assessment but cannot safely differentiate between active and inactive lesions. Therefore, positron emission tomography, especially combined with computed tomography (PET/CT), has been more widely used, at least for the monitoring of treatment response. Comparative, but mostly retrospective studies, have shown that functional MRI techniques, namely diffusion-weighted imaging (DWI), which assesses the movement of water molecules, can evaluate tissue cellularity with high sensitivity, which challenges the dominance of PET/CT in treatment response assessment. This review will discuss the benefits and challenges of DWI and compare it to other available imaging techniques used in patients with monoclonal plasma cell disorders.
doi:10.3390/hemato2040044 fatcat:deneqrjye5evhh5ya7l2jhwt4y

Fabrication and Characterization of Single-Crystal Diamond Membranes for Quantum Photonics with Tunable Microcavities

Julia Heupel, Maximilian Pallmann, Jonathan Körber, Rolf Merz, Michael Kopnarski, Rainer Stöhr, Johann Peter Reithmaier, David Hunger, Cyril Popov
2020 Micromachines  
The development of quantum technologies is one of the big challenges in modern research. A crucial component for many applications is an efficient, coherent spin–photon interface, and coupling single-color centers in thin diamond membranes to a microcavity is a promising approach. To structure such micrometer thin single-crystal diamond (SCD) membranes with a good quality, it is important to minimize defects originating from polishing or etching procedures. Here, we report on the fabrication of
more » ... the fabrication of SCD membranes, with various diameters, exhibiting a low surface roughness down to 0.4 nm on a small area scale, by etching through a diamond bulk mask with angled holes. A significant reduction in pits induced by micromasking and polishing damages was accomplished by the application of alternating Ar/Cl2 + O2 dry etching steps. By a variation of etching parameters regarding the Ar/Cl2 step, an enhanced planarization of the surface was obtained, in particular, for surfaces with a higher initial surface roughness of several nanometers. Furthermore, we present the successful bonding of an SCD membrane via van der Waals forces on a cavity mirror and perform finesse measurements which yielded values between 500 and 5000, depending on the position and hence on the membrane thickness. Our results are promising for, e.g., an efficient spin–photon interface.
doi:10.3390/mi11121080 pmid:33291795 pmcid:PMC7762039 fatcat:xcxthw222vgvdbpmiukbfy7aby

The clinical management of lenalidomide-based therapy in patients with newly diagnosed multiple myeloma

Maximilian Merz, Tobias Dechow, Mithun Scheytt, Christian Schmidt, Bjoern Hackanson, Stefan Knop
2020 Annals of Hematology  
Lenalidomide is an integral, yet evolving, part of current treatment pathways for both transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). It is approved in combination with dexamethasone as first-line therapy for transplant-ineligible patients with NDMM, and as maintenance treatment following autologous stem cell transplantation (ASCT). Although strong clinical trial evidence has supported the integration of lenalidomide into current treatment
more » ... current treatment paradigms for NDMM, applying those paradigms to individual patients and determining which patients are most likely to benefit from lenalidomide treatment are more complex. In this paper, we utilize the available clinical trial evidence to provide recommendations for patient selection and lenalidomide dosing in both the first-line setting in patients ineligible for ASCT and the maintenance setting in patients who have undergone ASCT. In addition, we provide guidance on management of those adverse events that are most commonly associated with lenalidomide treatment, and consider the optimal selection and sequencing of next-line agents following long-term frontline or maintenance treatment with lenalidomide.
doi:10.1007/s00277-020-04023-4 pmid:32296915 pmcid:PMC7340649 fatcat:c67ukhwaqvcspkxzjgbaawqpzm

Cytogenetic subclone formation and evolution in progressive smoldering multiple myeloma

Maximilian Merz, Thomas Hielscher, David Schult, Elias K. Mai, Marc S. Raab, Jens Hillengass, Anja Seckinger, Dirk Hose, Martin Granzow, Anna Jauch, Hartmut Goldschmidt
2019 Leukemia  
doi:10.1038/s41375-019-0634-2 pmid:31712777 fatcat:zbqqo5mxhrfg3dacxd3nzujcoy

Groundwater evaporation from salt pans: Examples from the eastern Arabian Peninsula

Stephan Schulz, Marcel Horovitz, Randolf Rausch, Nils Michelsen, Ulf Mallast, Maximilian Köhne, Christian Siebert, Christoph Schüth, Mohammed Al-Saud, Ralf Merz
2015 Journal of Hydrology  
doi:10.1016/j.jhydrol.2015.10.048 fatcat:ynxyzgemineyrasizgvnoqpfeu

Can 18F-NaF PET/CT before Autologous Stem Cell Transplantation Predict Survival in Multiple Myeloma?

Christos Sachpekidis, Annette Kopp-Schneider, Maximilian Merz, Anna Jauch, Marc-Steffen Raab, Hartmut Goldschmidt, Antonia Dimitrakopoulou-Strauss
2020 Cancers  
There is an unmet need for positron emission tomography (PET) radiotracers that can image bone disease in multiple myeloma (MM) in a more sensitive and specific way than the widely used 18F-fluorodeoxyglucose (18F-FDG). Sodium fluoride (18F-NaF) is a highly sensitive tracer of bone reconstruction, evolving as an important imaging agent for the assessment of malignant bone diseases. We attempted to investigate for the first time the prognostic significance of 18F-NaF PET/CT in newly diagnosed,
more » ... newly diagnosed, symptomatic MM patients planned for autologous stem cell transplantation (ASCT). Forty-seven patients underwent dynamic and static PET/CT with 18F-NaF before treatment. After correlation with the respective findings on CT and 18F-FDG PET/CT that served as reference, the 18F-NaF PET findings were compared with established factors of high-risk disease, like cytogenetic abnormalities as well as bone marrow plasma cell infiltration rate. Furthermore, the impact of 18F-NaF PET/CT on progression-free survival (PFS) was analyzed. Correlation analysis revealed a moderate, significant correlation of the 18F-NaF parameters SUVaverage and K1 in reference tissue with bone marrow plasma cell infiltration rate. However, no significant correlation was observed regarding all other 18F-NaF PET parameters. Survival analysis revealed that patients with a pathologic 18F-NaF PET/CT have a shorter PFS (median = 36.2 months) than those with a physiologic scan (median = 55.6 months) (p = 0.02). Nevertheless, no quantitative 18F-NaF parameter could be shown to adversely affect PFS. In contrast, the respective analysis for quantitative dynamic 18F-FDG PET/CT revealed that the parameters SUVmax, fractional blood volume (VB), k3 and influx from reference tissue as well as SUVaverage from MM lesions had a significant negative impact on patient survival. The herein presented findings highlight the rather limited role of 18F-NaF PET/CT as a single PET approach in MM.
doi:10.3390/cancers12051335 pmid:32456181 pmcid:PMC7281312 fatcat:zbrgzsyyp5drhkshcj3etzomoa

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

Pankaj Yadav, Maximilian Merz, Elias K. Mai, Asta Försti, Anna Jauch, Hartmut Goldschmidt, Kari Hemminki
2018 Haematologica  
Pankaj Yadav, 1 Maximilian Merz, 2 Elias K. Mai, 2 Asta Försti, 1, 3 Anna Jauch, 4 Hartmut Goldschmidt, 2,5,* Kari Hemminki 1,3* *HG and KH share co-senior authorship.  ... 
doi:10.3324/haematol.2017.184226 pmid:29419430 pmcid:PMC5865437 fatcat:vgqilmt7nrbqxkignpzufn7cre

Quantitative dynamic 18F-FDG PET/CT before autologous stem cell transplantation predicts survival in multiple myeloma

Christos Sachpekidis, Maximilian Merz, Annette Kopp-Schneider, Anna Jauch, Marc-Steffen Raab, Sandra Sauer, Jens Hillengass, Hartmut Goldschmidt, Antonia Dimitrakopoulou-Strauss
2019 Haematologica  
Author Contributions: Christos Sachpekidis performed the PET/CT studies and evaluations, analyzed the data, and drafted the manuscript; Maximilian Merz was involved in the management of the patients, analyzed  ... 
doi:10.3324/haematol.2018.213041 pmid:30765474 pmcid:PMC6717572 fatcat:ezwqud4vbzaovginzqbmxq3owe

Chemotherapy-induced peripheral neuropathy: evidence from genome-wide association studies and replication within multiple myeloma patients

Seyed Hamidreza Mahmoudpour, Obul Reddy Bandapalli, Miguel Inácio da Silva Filho, Chiara Campo, Kari Hemminki, Hartmut Goldschmidt, Maximilian Merz, Asta Försti
2018 BMC Cancer  
Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. Methods: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values< 10 − 5 were extracted; these associations were investigated within a cohort
more » ... ed within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects that developed CIPN grade 2-4 while controls developed no or sub-clinical CIPN. Logistic regression with additive model was used. Results: In total, 9 GWASs were identified from the literature on CIPN caused by different drugs (4 paclitaxel, 2 bortezomib, 1 vincristine, 1 docetaxel, and 1 oxaliplatin). Data were extracted for 526 SNPs in 109 loci. One hundred fourty-eight patients in our study population were CIPN cases (102/646 bortezomib, 17/63 thalidomide and 29/274 vincristine). In total, 13 SNPs in 9 loci were replicated in our population (p-value< 0.05). The four smallest P-values relevant to the nerve function were 0.0006 for rs8014839 (close to the FBXO33 gene), 0.004 for rs4618330 (close to the INTU gene), 0.006 for rs1903216 (close to the BCL6 gene) and 0.03 for rs4687753 (close to the IL17RB gene). Conclusions: Replicated SNPs provide clues of the molecular mechanism of CIPN and can be strong candidates for further research aiming to predict the risk of CIPN in clinical practice, particularly rs8014839, rs4618330, rs1903216, and rs4687753, which showed relevance to the function of nervous system.
doi:10.1186/s12885-018-4728-4 pmid:30111286 pmcid:PMC6094450 fatcat:h3wpy3olnrdjjgzxr2xjeed6vu

Meeting report of the 5th Heidelberg Myeloma Workshop: current status and developments in diagnosis and therapy of multiple myeloma

Maximilian Merz, Jens Hillengass, Hartmut Goldschmidt
2015 Journal of Cancer Research and Clinical Oncology  
doi:10.1007/s00432-015-1993-3 pmid:26068597 fatcat:yy2f73mquzfh7bbxq3mqow5i2q

Diagnostic and therapeutic approaches to multiple myeloma patients: 'Real-world' data from representative multicentre treatment surveys in Germany between 2008 and 2011

Thomas M. Moehler, Maximilian Merz, Lenka Kellermann, Hartmut Goldschmidt, Wolfgang Knauf
2016 Oncology Letters  
A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic
more » ... , prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists. Data were collected from chart reviews and were analysed retrospectively. Over time, an increasing number of patients were investigated for cytogenetic abnormalities (53%). Age <69 years and lack of comorbid conditions were major determinants for cytogenetic testing. Bortezomib/chemotherapy-based regimens have become the preferred first-line treatments independent of planning autologous blood stem cell transplantation (ASCT) in first-line therapy. Thalidomide-and lenalidomide-based combination therapies are typically used as second-line treatments in 31% of patients. Compared with previous reviews, the frequency of ASCT was stable, at ~30% of patients. Younger age and indicators of more severe disease, such as the presence of CRAB criteria, influenced the decision in favour of performing ASCT. Compared to previous surveys, the requirement for erythropoietin and granulocyte colony-stimulating factor, as well as transfusions of red blood cells and platelets, respectively, have decreased considerably. In summary, novel agents have led to a substantial change in the first-line and relapsed treatment approaches. Age and comorbidities remain major factors influencing treatment decisions, but cytogenetic testing to investigate myeloma-related risk profiles is increasingly integrated. The use of novel agents has affected supportive care, with reduced necessity for substitute blood products and reduced administration of bone marrow-stimulating factors.
doi:10.3892/ol.2016.5375 pmid:28105211 pmcid:PMC5228488 fatcat:zs4py6woxvehrjxrgrhtzj4tbe

The prognostic significance of [18F]FDG PET/CT in multiple myeloma according to novel interpretation criteria (IMPeTUs)

Christos Sachpekidis, Maximilian Merz, Marc-Steffen Raab, Uta Bertsch, Vivienn Weru, Annette Kopp-Schneider, Anna Jauch, Hartmut Goldschmidt, Antonia Dimitrakopoulou-Strauss
2021 EJNMMI Research  
Purpose [18F]FDG PET/CT is the elective imaging modality for treatment monitoring in multiple myeloma (MM). However, MM is a heterogeneous disease from an imaging point of view, raising challenges in interpretation of PET/CT. We herein investigated the prognostic role of the novel Italian Myeloma criteria for PET Use (IMPeTUs) in MM patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT). Methods Forty-seven patients with newly diagnosed MM
more » ... diagnosed MM underwent [18F]FDG PET/CT before commencement of treatment (baseline PET/CT). Thirty-four of them (72.3%) were also examined after completion of ASCT (follow-up PET/CT). PET/CT analysis was based on the IMPeTUs criteria, which take into consideration—among others—the metabolic state of the bone marrow based on the 5-point Deauville score (DS), the number and metabolic state of focal [18F]FDG-avid lesions, as well as the presence of paramedullary disease (PMD) and extramedullary disease (EMD). We analyzed whether parameters from IMPeTUs correlate with clinically relevant parameters and patients' outcome, as assessed by progression-free survival (PFS). Results Median follow-up from baseline and follow-up PET/CT were 85.1 months and 76.7 months, respectively. The number of focal, [18F]FDG-avid lesions significantly correlated with the bone marrow infiltration rate and the R-ISS stage, while the presence of PMD was associated with LDH. After univariate survival analysis, the number of focal, [18F]FDG-avid lesions both before and after therapy as well as the presence of PMD and EMD before therapy adversely affected PFS. Multivariate survival analysis for baseline parameters confirmed that the number of focal, [18F]FDG-avid lesions and the presence of EMD are associated with adverse prognosis, irrespective of the ISS stage and/or the presence of high-risk cytogenetic abnormalities. The 5-point DS of [18F]FDG uptake in reference bone marrow and focal lesions showed a significant decrease as response to treatment, but it did not affect PFS. Conclusion Several parameters utilized in IMPeTUs predict PFS in MM patients, suggesting the potentially significant role of the new criteria in patient stratification and response assessment. Additional studies are warranted for the further evaluation of IMPeTUs in the direction of establishment of robust cut-off values with a prognostic significance in the disease.
doi:10.1186/s13550-021-00846-y pmid:34628525 fatcat:ajvqsctlxjahzlozdo6kqsm7xe

Synthesis, Photophysical and Electronic Properties of New Red to NIR Emitting Donor‐Acceptor Pyrene Derivatives

Julia Merz, Maximilian Dietz, Yvonne Vonhausen, Frederik Wöber, Alexandra Friedrich, Daniel Sieh, Ivo Krummenacher, Holger Braunschweig, Michael Moos, Marco Holzapfel, Christoph Lambert, Todd B. Marder
2019 Chemistry - A European Journal  
for generous financial support by the Bavarian State Ministry of Science, Research, and the Arts for the Collaborative Research Network "Solar Technologies go Hybrid", the DFG (GRK 2112) and the Julius-Maximilians  ... 
doi:10.1002/chem.201904219 pmid:31593316 fatcat:jyt4k4lshbd4jf27lw65h66poe

Survival of patients with lymphoplasmacytic lymphoma and solitary plasmacytoma in Germany and the United States of America in the early 21 st century

Janick Weberpals, Dianne Pulte, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Maximilian Merz, Hermann Brenner
2017 Haematologica  
doi:10.3324/haematol.2016.157768 pmid:28280077 pmcid:PMC5451350 fatcat:xnvhm6qsvfaltmpvqlgfobttli
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