Article
Multidisciplinary Sciences
Takeshi Yoroidaka, Kentaro Narita, Hiroyuki Takamatsu, Momoko Fujisawa, Shinji Nakao, Kosei Matsue
Summary: The study compared the DuraClone and EuroFlow methods for assessing MRD levels in MM patients, finding higher tCAN with EuroFlow-NGF and a significant correlation in MRD levels between the two methods. However, qualitative analysis showed discrepancies in MRD levels in 5.2% of samples, suggesting caution is needed when using DuraClone for evaluating MRD in MM.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Rose Turner, Anna Kalff, Krystal Bergin, Malgorzata Gorniak, Shaun Fleming, Andrew Spencer
Summary: This retrospective study analyzed the EuroFlow MRD results in newly diagnosed multiple myeloma patients. Patients who achieved MRD negativity had a longer progression free survival, and maintenance therapy improved PFS regardless of MRD status.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alexander Schmitz, Rasmus Froberg Brondum, Hans Erik Johnsen, Ulf-Henrik Mellqvist, Anders Waage, Peter Gimsing, Davine Hofste Op Bruinink, Vincent van der Velden, Bronno van der Holt, Markus Hansson, Niels Frost Andersen, Ulf Christian Frolund, Carsten Helleberg, Fredrik H. Schjesvold, Lucia Ahlberg, Nina Gulbrandsen, Bjorn Andreasson, Birgitta Lauri, Einar Haukas, Julie Stove Bodker, Anne Stidsholt Roug, Martin Bogsted, Marianne T. Severinsen, Henrik Gregersen, Niels Abildgaard, Pieter Sonneveld, Karen Dybkaer
Summary: This study demonstrates that longitudinal monitoring of minimal residual disease using flow cytometry can predict disease progression earlier and with higher sensitivity in multiple myeloma patients. Increasing levels of minimal residual disease in the bone marrow precede biochemically assessed changes and indicate subsequent clinical progression.
Article
Oncology
Rodrigo Fonseca, Mariano Arribas, Julia E. E. Wiedmeier-Nutor, Yael N. N. Kusne, Miguel Gonzalez Velez, Heidi E. E. Kosiorek, Richard (Duke) J. Butterfield, Ilan R. R. Kirsch, Joseph R. R. Mikhael, A. Keith Stewart, Craig Reeder, Jeremy Larsen, P. Leif Bergsagel, Rafael Fonseca
Summary: Minimal residual disease (MRD) assays allow assessment of treatment response in multiple myeloma (MM) patients, and achieving MRD negativity is associated with improved survival outcomes. The combination of highly sensitive next generation sequencing (NGS) MRD with functional imaging requires further validation. In this retrospective analysis of MM patients who underwent autologous stem cell transplant (ASCT), MRD negativity at day 100 post-ASCT was found to be the strongest prognostic indicator for longer time to next treatment (TTNT). The agreement between positron emission tomography (PET-CT) and MRD was poor, with high rates of PET-CT negativity in MRD-positive patients. Sustained MRD negativity was associated with longer TTNT regardless of baseline risk characteristics.
BLOOD CANCER JOURNAL
(2023)
Review
Genetics & Heredity
Lemei Zhu, Ran Xu, Leilei Yang, Wei Shi, Yuan Zhang, Juan Liu, Xi Li, Jun Zhou, Pingping Bing
Summary: Minimal residual disease (MRD) refers to a small number of residual tumor cells during or after treatment, which can be monitored and predicted using ctDNA detection. This review summarizes the main methods of ctDNA detection and its application in lung, breast, and colon cancer, among others.
FRONTIERS IN GENETICS
(2023)
Article
Hematology
Kota Sato, Kiyoshi Okazuka, Tadao Ishida, Jun Sakamoto, Shigeto Kaneko, Junichiro Nashimoto, Yui Uto, Mizuki Ogura, Yumiko Yoshiki, Yu Abe, Aki Maeda, Hiroyuki Hamazaki, Nobuhiro Tsukada, Yuji Hiragohri, Kenshi Suzuki
Summary: MRD-negative status in multiple myeloma is associated with favorable outcomes, and EuroFlow next-generation flow is a global standard for MRD detection. However, its high operating cost necessitates the development of a less expensive method with equivalent sensitivity. In this study, our 10-color multiparameter flow cytometry demonstrated high sensitivity to detect MRD in MM patients, offering a promising, cost-effective alternative to EuroFlow-NGF.
ANNALS OF HEMATOLOGY
(2021)
Article
Medicine, General & Internal
Stefania Oliva, Elisa Genuardi, Laura Paris, Mattia D'Agostino, Jennifer Rogers, Delia Rota-Scalabrini, Allison P. Jacob, Francesca Patriarca, Mario Luppi, Paola Bertazzoni, Cristina Velluti, Andrea Capra, Elona Saraci, Marco Rossi, Alessandro Allegra, Roberto Mina, Massimo Gentile, Ilan R. Kirsch, Angelo Belotti, Michele Cavo, Benedetto Bruno, Pellegrino Musto, Mario Boccadoro, Elena Zamagni, Francesca Gay
Summary: Limited data exist on the concordance between MFC and NGS for MRD detection in MM patients. The FORTE trial demonstrated a significant biological/prognostic agreement between MFC and NGS, suggesting their potential use as strong predictors of outcome.
Review
Oncology
Roberto Mina, Francesca Bonello, Stefania Oliva
Summary: MRD techniques are crucial for identifying small clonal fractions in multiple myeloma patients, with evidence showing a correlation between MRD negativity and survival. However, there are still unresolved issues such as optimal assessment techniques, cost-effectiveness, and the practical impact of MRD evaluation.
Review
Oncology
Charalampos Charalampous, Taxiarchis Kourelis
Summary: Multiple Myeloma (MM) is a common hematologic malignancy with significant therapeutic advances in recent years; however, a curative treatment option is still lacking. Accurate detection of Minimal Residual Disease (MRD) from a bone marrow biopsy plays a crucial role in evaluating treatment response. As patients' life expectancy increases and deep responses become more common, studying and refining the role of MRD in the disease course becomes increasingly important.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Ilias Pessach, Theodoros Spyropoulos, Eleftheria Lamprianidou, Ioannis Kotsianidis
Summary: Measurable residual disease (MRD) is an important prognostic and predictive biomarker in acute myeloid leukemia (AML), but its use is hindered by the lack of standardization in available methodologies. Multiparameter flow cytometry (MFC) offers a highly effective technology for studying both antitumor immunity and leukemic clone dynamics, leading to the development of improved MRD assessment.
Article
Hematology
Martijn W. C. Verbeek, Chiara Buracchi, Anna Laqua, Stefan Nierkens, Lukasz Sedek, Juan Flores-Montero, Mattias Hofmans, Elaine Sobral de Costa, Michaela Novakova, Ester Mejstrikova, Susana Barrena, Saskia Kohlscheen, Monika Szczepanowski, Jan Kulis, Elen Oliveira, Romana Jugooa, Anja X. de Jong, Tomasz Szczepanski, Jan Philippe, Jacques J. M. Van Dongen, Alberto Orfao, Monika Brueggemann, Giuseppe Gaipa, Vincent H. J. Van der Velden
Summary: The standardized EuroFlow protocol with CD19 as the primary B-cell marker allows for sensitive and reliable MRD assessment in BCP-ALL patients undergoing chemotherapy. An alternative gating strategy has been developed for analyzing MRD in patients treated with CD19-targeting therapies, showing high concordance with original MRD data despite variations. This indicates that overall MRD analysis remains accurate even with differences in CD19 expression.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Medical Laboratory Technology
Hyun-Young Kim, In Young Yoo, Dae Jin Lim, Hee-Jin Kim, Sun-Hee Kim, Sang Eun Yoon, Seok Jin Kim, Duck Cho, Kihyun Kim
Summary: This study evaluated the clinical utility of NGF-based MRD assessment in patients with multiple myeloma. The results showed that MRD-positive patients had shorter progression-free survival, especially in patients with high-risk cytogenetic abnormalities. Additionally, sustained MRD negativity predicted better progression-free survival in patients with stringent complete remission.
ANNALS OF LABORATORY MEDICINE
(2022)
Article
Medical Laboratory Technology
Annabel McMillan, Thien-An Tran, Daria Galas-Filipowicz, Marquita Camilleri, Catherine Lecat, Louise Ainley, Yanping Guo, Kwee Yong, Jonathan Sive
Summary: The study successfully adopted a multicolor flow cytometry (MCF) method for MM MRD detection, which can be stably delayed for up to 6 days, providing the possibility for wider use in smaller laboratories. The real-world study found that 17% of patients achieved MRD negativity after UK standard induction therapy.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2022)
Article
Medicine, General & Internal
Agnieszka Krzywdzinska, Bartosz Pula, Anna Czyz, Beata Krzymieniewska, Jolanta Kiernicka-Parulska, Anna Mierzwa, Donata Szymczak, Aneta Milanowska, Aleksandra Kiraga, Iwona Kwiecien, Joanna Zaleska, Krzysztof Jamroziak
Summary: The study demonstrates high reproducibility of using high-sensitivity flow cytometry for MM MRD assessment, with EuroFlow protocol confirmed as an effective method. Both inter-laboratory and inter-operator studies showed high concordance, but differences were noticed in immunophenotype interpretation of CD27, CD45, CD81.
Article
Oncology
Camila Guerrero, Noemi Puig, Maria-Teresa Cedena, Ibai Goicoechea, Cristina Perez, Juan-Jose Garces, Cirino Botta, Maria-Jose Calasanz, Norma C. Gutierrez, Maria-Luisa Martin-Ramos, Albert Oriol, Rafael Rios, Miguel-Teodoro Hernandez, Rafael Martinez-Martinez, Joan Bargay, Felipe de Arriba, Luis Palomera, Ana Pilar Gonzalez-Rodriguez, Adrian Mosquera-Orgueira, Marta-Sonia Gonzalez-Perez, Joaquin Martinez-Lopez, Juan-Jose Lahuerta, Laura Rosinol, Joan Blade, Maria-Victoria Mateos, Jesus F. San-Miguel, Bruno Paiva
Summary: This study established a comprehensive weighted model using machine learning algorithms to accurately predict undetectable measurable residual disease (MRD) outcomes in multiple myeloma patients, providing a new concept for personalized treatment.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Daniele Campa, Alessandro Martino, Angelica Macauda, Marek Dudzinski, Anna Suska, Agnieszka Druzd-Sitek, Marc-Steffen Raab, Victor Moreno, Stefanie Huhn, Aleksandra Butrym, Juan Sainz, Gergely Szombath, Marcin Rymko, Herlander Marques, Fabienne Lesueur, Annette Juul Vangsted, Ulla Vogel, Marcin Kruszewski, Edyta Subocz, Gabriele Buda, Elzbieta Iskierka-Jazdzewska, Rafael Rios, Maximilian Merz, Ben Schoettker, Grzegorz Mazur, Emeline Perrial, Joaquin Martinez-Lopez, Katja Butterbach, Ramon Garcia Sanz, Hartmut Goldschmidt, Hermann Brenner, Krzysztof Jamroziak, Rui Manuel Reis, Katalin Kadar, Charles Dumontet, Marzena Watek, Eva Kannik Haastrup, Grzegorz Helbig, Artur Jurczyszyn, Andres Jerez, Judit Varkonyi, Torben Barington, Norbert Grzasko, Jan Maciej Zaucha, Vibeke Andersen, Daria Zawirska, Federico Canzian
LEUKEMIA & LYMPHOMA
(2019)
Article
Oncology
Joanna Blocka, Brian G. M. Durie, Stefanie Huhn, Carsten Mueller-Tidow, Asta Foersti, Kari Hemminki, Hartmut Goldschmidt
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2019)
Letter
Oncology
Calogerina Catalano, Nagarajan Paramasivam, Joanna Blocka, Sara Giangiobbe, Stefanie Huhn, Matthias Schlesner, Niels Weinhold, Rolf Sijmons, Mirjam de Jong, Christian Langer, Klaus-Dieter Preuss, Bjorn Nilsson, Brian Durie, Hartmut Goldschmidt, Obul Reddy Bandapalli, Kari Hemminki, Asta Foersti
BLOOD CANCER JOURNAL
(2021)
Letter
Hematology
Christoph R. Kimmich, Tobias Terzer, Axel Benner, Timon Hansen, Alexander Carpinteiro, Tobias Dittrich, Kaya Veelken, Anna Jauch, Stefanie Huhn, Marco Basset, Hartmut Goldschmidt, Carsten Mueller-Tidow, Stefan O. Schoenland, Ute Hegenbart
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Hematology
Charlie N. Saunders, Subhayan Chattopadhyay, Stefanie Huhn, Niels Weinhold, Per Hoffmann, Markus M. Noethen, Karl-Heinz Joeckel, Boerge Schmidt, Stefano Landi, Hartmut Goldschmidt, Paolo Milani, Giampaolo Merlini, Dorota Rowcieno, Philip Hawkins, Ute Hegenbart, Giovanni Palladini, Ashutosh Wechalekar, Stefan O. Schoenland, Asta Foersti, Richard Houlston, Kari Hemminki
Summary: In this study, Mendelian randomization analysis identified associations between genetically predicted increased monocyte counts and the tumor necrosis factor receptor superfamily member 17 gene with AL amyloidosis risk. Additionally, potential associations with TNFRSF members 6 and 19L were also observed. The findings suggest that high circulating levels of monocytes and TNFRSF proteins may be risk factors for AL amyloidosis, providing insight into the disease's etiology.
Article
Multidisciplinary Sciences
Lynn Radamaker, Sara Karimi-Farsijani, Giada Andreotti, Julian Baur, Matthias Neumann, Sarah Schreiner, Natalie Berghaus, Raoul Motika, Christian Haupt, Paul Walther, Volker Schmidt, Stefanie Huhn, Ute Hegenbart, Stefan O. Schonland, Sebastian Wiese, Clarissa Read, Matthias Schmidt, Marcus Fandrich
Summary: The authors presented the cryo-EM structure of an AL amyloid fibril with mutational changes, disulfide bond, and glycosylation, indicating their roles in determining the protein fold and protecting the fibril core from degradation. Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs), with the influence of LCs' post-translational modifications on amyloid formation still not well understood.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Cyrus Khandanpour, Christine Eisfeld, Subbaiah Chary Nimmagadda, Marc S. Raab, Niels Weinhold, Anja Seckinger, Dirk Hose, Anna Jauch, Asta Foersti, Kari Hemminki, Thomas Hielscher, Manuela Hummel, Georg Lenz, Hartmut Goldschmidt, Stefanie Huhn
Summary: The transcription factor GFI1 plays a crucial role in regulating genes important for survival, proliferation, and differentiation of hematopoietic cells. A SNP variant of GFI1, GFI1-36N, is associated with increased risk of myelodysplastic syndrome and acute myeloid leukemia. The higher prevalence of GFI1-36N in multiple myeloma patients suggests its potential role in disease development and progression, particularly in patients with specific genetic abnormalities.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Natalie Berghaus, Sarah Schreiner, Martin Granzow, Carsten Mueller-Tidow, Ute Hegenbart, Stefan O. Schoenland, Stefanie Huhn
Summary: Light chain amyloidosis is a common type of systemic amyloidosis characterized by misfolding and aggregation of immunoglobulin light chains. In this study, the authors provide an overview of the germline utilization of IGLV-IGLJ and IGLC genes in three subgroups of patients with dominant cardiac, renal, or cardiac and renal involvement. The results reveal different patterns of IGLV family and subfamily usage in each subgroup and suggest an exclusive linkage between IGLJ1 and IGLC1 as well as between IGLJ2 and IGLC2 in fully assembled IGL mRNA.
Article
Biochemistry & Molecular Biology
Julian Baur, Natalie Berghaus, Sarah Schreiner, Ute Hegenbart, Stefan O. Schoenland, Sebastian Wiese, Stefanie Huhn, Christian Haupt
Summary: This study analyzed the exact primary structure of AL proteins and their precursor LCs in 10 lambda AL amyloidosis patients. Results showed that all AL proteins had a common C-terminal truncation region and a significant increase in the isoelectric point of V-L. Moreover, no evidence of other common post-translational modifications was found.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Letter
Hematology
Katharina Kriegsmann, Calin Manta, Ricarda Schwab, Elias K. Mai, Marc S. Raab, Hans J. Salwender, Roland Fenk, Britta Besemer, Jan Duerig, Roland Schroers, Ivana von Metzler, Mathias Haenel, Christoph Mann, Anne M. Asemissen, Bernhard Heilmeier, Uta Bertsch, Stefanie Huhn, Carsten Mueller-Tidow, Hartmut Goldschmidt, Michael Hundemer
Article
Oncology
Elias K. Mai, Stefanie Huhn, Kaya Miah, Alexandra M. Poos, Christof Scheid, Katja C. Weisel, Uta Bertsch, Markus Munder, Oscar Berlanga, Dirk Hose, Anja Seckinger, Anna Jauch, Igor W. Blau, Mathias Haenel, Hans J. Salwender, Axel Benner, Marc S. Raab, Hartmut Goldschmidt, Niels Weinhold
Summary: Mass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. Our study found that MS negativity was significantly associated with improved progression-free survival (PFS) in multiple myeloma patients, even in those patients with complete response (CR). Combining MS and baseline cytogenetics improved the prediction of outcome, and sequential MS combined with baseline disease features and minimal residual disease (MRD) can further improve its clinical value.
BLOOD CANCER JOURNAL
(2023)
Article
Cell Biology
Yasmeen Niazi, Nagarajan Paramasivam, Joanna Blocka, Abhishek Kumar, Stefanie Huhn, Matthias Schlesner, Niels Weinhold, Rolf Sijmons, Mirjam De Jong, Brian Durie, Hartmut Goldschmidt, Kari Hemminki, Asta Foersti
Summary: Multiple myeloma (MM) is a plasma cell malignancy characterized by the over-propagation of a single clone of plasma cells in the bone marrow. The genetic basis of familial MM, particularly within the non-coding genome, is still not well understood. In this study, whole-genome sequencing data was used to identify and characterize variants in the non-coding genome of MM families. The findings confirmed previously implicated biological pathways in MM development and identified 10 genes involved in mitogen-activated protein kinase (MAPK) signaling pathways, which are known to be important in MM.
Article
Hematology
Hartmut Goldschmidt, Elias K. Mai, Uta Bertsch, Roland Fenk, Eva Nievergall, Diana Tichy, Britta Besemer, Jan Durig, Roland Schroers, Ivana von Metzler, Mathias Haenel, Christoph Mann, Anne M. Asemissen, Bernhard Heilmeier, Niels Weinhold, Stefanie Huhn, Katharina Kriegsmann, Steffen P. Luntz, Tobias A. W. Holderried, Karolin Trautmann-Grill, Deniz Gezer, Maika Klaiber-Hakimi, Martin Mueller, Cyrus Khandanpour, Wolfgang Knauf, Christof Scheid, Markus Munder, Thomas Geer, Hendrik Riesenberg, Jorg Thomalla, Martin Hoffmann, Marc S. Raab, Hans J. Salwender, Katja C. Weisel
Summary: This study assessed the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone for patients with newly diagnosed transplantation-eligible multiple myeloma. The results showed that the addition of isatuximab to the induction therapy improved rates of MRD negativity without any new safety signals.
LANCET HAEMATOLOGY
(2022)