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
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
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
Roberia Mendonca de Pontes, Juan Flores-Montero, Luzalba Sanoja-Flores, Noemi Puig, Roberto J. Pessoa de Magalhaes, Alba Corral-Mateos, Anna Beatriz Salgado, Omar Garcia-Sanchez, Jose Perez-Moran, Maria-Victoria Mateos, Leire Burgos, Bruno Paiva, Jeroen te Marvelde, Vincent H. J. van der Velden, Carlos Aguilar, Abelardo Barez, Aranzazu Garcia-Mateo, Jorge Labrador, Pilar Leoz, Carmen Aguilera-Sanz, Brian Durie, Jacques J. M. van Dongen, Angelo Maiolino, Elaine Sobral da Costa, Alberto Orfao
Summary: The study found that B-cell regeneration during therapy in multiple myeloma patients is not significantly associated with patient outcomes, and therapy and hemodilution impact bone marrow B-cell recovery to some extent.
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)
Review
Oncology
Hong Ding, Juan Xu, Zhimei Lin, Jingcao Huang, Fangfang Wang, Yan Yang, Yushan Cui, Hongmei Luo, Yuhan Gao, Xinyu Zhai, Weicui Pang, Li Zhang, Yuhuan Zheng
Summary: MRD in MM plays a critical role in disease pathogenesis, demonstrating unique cytogenetic aberrations and gene expression profiles. Different risk MM exhibit diverse MRD features, with clonal evaluation potentially occurring at the MRD stage. MM MRD before and after treatment shows distinct differences.
BIOMARKER RESEARCH
(2021)
Article
Immunology
Jana Neirinck, Annelies Emmaneel, Malicorne Buysse, Jan Philippe, Sofie Van Gassen, Yvan Saeys, Xavier Bossuyt, Stefanie De Buyser, Mirjam van der Burg, Martin Perez-Andres, Alberto Orfao, Jacques J. M. van Dongen, Bart N. Lambrecht, Tessa Kerre, Mattias Hofmans, Filomeen Haerynck, Carolien Bonroy
Summary: The study tested PIDOT in 887 consecutive patients suspicious of PID and found that it has high sensitivity and specificity for diagnosing lymphoid-PID, particularly for discriminating patients with SCID, ID, and CVID. The combination of PIDOT and serum immunoglobulin levels can guide further immunophenotypic FCM analyses for accurate PID diagnostics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Duanfeng Jiang, Yanan Zhang, Shiming Tan, Jing Liu, Xin Li, Congming Zhang
Summary: This study validated the superiority of the BMPL enrichment assay in MRD analysis in patients with multiple myeloma. The hemodilution of bone marrow aspirates is the main factor affecting the reliability of MRD determination.
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
Pathology
Henry Hui, Kathy A. Fuller, Luna Eresta Jaya, Yusuke Konishi, Teng Fong Ng, Richard Frodsham, Graham Speight, Kazuhiro Yamada, Sarah E. Clarke, Wendy N. Erber
Summary: This study evaluated an automated imaging flow cytometric method for identifying IGH abnormalities in multiple myeloma patients without the need for cell isolation. The method successfully detected chromosomal abnormalities involving IGH in plasma cells, with a detection limit as low as 0.05% of all cells. This high-throughput immuno-flowFISH method offers increased precision in detecting critical genetic lesions in multiple myeloma.
JOURNAL OF CLINICAL PATHOLOGY
(2022)
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
Carlos Bravo-Perez, Maria Sola, Raul Teruel-Montoya, Maria Dolores Garcia-Malo, Francisco Jose Ortuno, Vicente Vicente, Felipe de Arriba, Andres Jerez
Summary: The response rates in multiple myeloma have increased significantly, leading to a focus on measuring minimal residual disease (MRD) in order to assess and treat patients. The use of novel agents has created a paradigm shift in MM treatment, raising questions about standard measures, high sensitivity methods, and the relevance of current response criteria. Lessons learned from other neoplasms and efforts to harmonize methods for measuring MRD in MM are discussed in this review.
Article
Oncology
Veronika Riebl, Sandra Maria Dold, Dagmar Wider, Marie Follo, Gabriele Ihorst, Johannes M. Waldschmidt, Johannes Jung, Michael Rassner, Christine Greil, Ralph Waesch, Monika Engelhardt
Summary: This study established a highly sensitive single-tube 10-color MFC panel for MRD detection in multiple myeloma samples, evaluated additional rare markers, and compared MRD levels in apheresis and bone marrow samples. The results highlight the importance of evaluating both sample types with this novel MFC panel.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Alejandro Medina-Herrera, Maria Eugenia Sarasquete, Cristina Jimenez, Noemi Puig, Ramon Garcia-Sanz
Summary: The assessment of responses in multiple myeloma patients is crucial, and minimal residual disease (MRD) has become one of the most informative parameters to differentiate treatment responses and prognosis. Various strategies can be used to detect and quantify MRD, but not all of them have undergone extensive validation. This article provides an overview of the current state of MRD detection in multiple myeloma and discusses future directions in this field.
Review
Medicine, General & Internal
Niels W. C. J. van de Donk, Charlotte Pawlyn, Kwee L. Yong
Summary: Multiple myeloma is the second most common haematological malignancy in high-income countries. Current treatment strategies have extended patient survival, but the majority will ultimately die from the disease. Diagnostics and risk stratification are crucial for prognosis and treatment strategies.
Article
Hematology
Cirino Botta, Catarina Maia, Juan-Jose Garces, Rosalinda Termini, Cristina Perez, Irene Manrique, Leire Burgos, Aintzane Zabaleta, Diego Alignani, Sarai Sarvide, Juana Merino, Noemi Puig, Maria-Teresa Cedena, Marco Rossi, Pierfrancesco Tassone, Massimo Gentile, Pierpaolo Correale, Ivan Borrello, Evangelos Terpos, Tomas Jelinek, Artur Paiva, Aldo Roccaro, Hartmut Goldschmidt, Herve Avet-Loiseau, Laura Rosinol, Maria-Victoria Mateos, Joaquin Martinez-Lopez, Juan-Jose Lahuerta, Joan Blade, Jesus F. San-Miguel, Bruno Paiva
Summary: Large-scale immune monitoring is increasingly used in clinical trials, but manual interpretation of multidimensional data poses challenges. FlowCT is a semi-automated workspace that can analyze large datasets, including preprocessing, normalization, dimensionality reduction, clustering, and predictive modeling tools.
Article
Hematology
Bruno Paiva, Jesus San-Miguel, Herve Avet-Loiseau
Summary: Multiple myeloma survival is longer with deeper response, but there are conflicting results regarding complete remission and minimal residual disease negativity. Some patients with persistent M protein have undetectable MRD. We reviewed the frequency of this discrepancy and suggest MRD assessment for patients achieving very good partial response or better.
Article
Oncology
Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Ana Jimenez-Ubieto, Laura Rosinol, Albert Oriol, Rafael Rios, Anna Sureda, Maria Jesus Blanchard, Miguel Teodoro Hernandez, Valentin Cabanas Perianes, Isidro Jarque, Juan Bargay, Mercedes Gironella, Felipe De Arriba, Luis Palomera, Yolanda Gonzalez-Montes, Josep M. Marti, Isabel Krsnik, Jose Maria Arguinano, Maria Esther Gonzalez, Luis Felipe Casado, Ana Pilar Gonzalez-Rodriguez, Lucia Lopez-Anglada, Noemi Puig, Maria Teresa Cedena, Bruno Paiva, Maria-Victoria Mateos, Jesus San-Miguel, Juan-Jose Lahuerta, Joan Blade, Inaki F. Troconiz
Summary: Response kinetics in multiple myeloma have been studied using a mathematical model to assess the prognostic value of serum monoclonal component (MC) response kinetics. The study identified two patient subgroups with significantly different progression-free survival based on the resistance parameter calculated by the model.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Article
Oncology
Alice Nevone, Maria Girelli, Silvia Mangiacavalli, Bruno Paiva, Paolo Milani, Pasquale Cascino, Maggie Piscitelli, Valentina Speranzini, Claudio Salvatore Cartia, Pietro Benvenuti, Ibai Goicoechea, Francesca Fazio, Marco Basset, Andrea Foli, Martina Nanci, Giulia Mazzini, Serena Caminito, Melania Antonietta Sesta, Simona Casarini, Paola Rognoni, Francesca Lavatelli, Maria Teresa Petrucci, Pier Paolo Olimpieri, Stefano Ricagno, Luca Arcaini, Giampaolo Merlini, Giovanni Palladini, Mario Nuvolone
Summary: A study has found that the N-glycosylation of amyloidogenic kappa LCs exhibits a distinctive sequence and spatial pattern, primarily located in the framework region 3 of the E strand, which may be associated with their pathogenic behavior.
Article
Hematology
Adam D. Cohen, Maria-Victoria Mateos, Yael C. Cohen, Paula Rodriguez-Otero, Bruno Paiva, Niels W. C. J. van de Donk, Thomas Martin, Attaya Suvannasankha, Kevin C. De Braganca, Christina Corsale, Jordan M. Schecter, Helen Varsos, William Deraedt, Liwei Wang, Martin Vogel, Tito Roccia, Xiaoying Xu, Pankaj Mistry, Enrique Zudaire, Muhammad Akram, Tonia Nesheiwat, Lida Pacaud, Irit Avivi, Jesus San-Miguel
Summary: The CARTITUDE-2 study evaluated the safety and efficacy of cilta-cel in patients with multiple myeloma who had previously received anti-BCMA treatment. The results showed that cilta-cel induced favorable responses in patients who had exhausted other therapies.
Article
Oncology
Fredrik Schjesvold, Bruno Paiva, Vincent Ribrag, Paula Rodriguez-Otero, Jesus F. San-Miguel, Pawel Robak, Markus Hansson, Maika Onishi, Habib Hamidi, Vikram Malhi, Monique Dail, Apurva Javery, Grace Ku, Marc S. Raab
Summary: This phase Ib/II trial evaluated the safety and efficacy of cobimetinib alone and in combination with venetoclax, with or without atezolizumab in patients with relapsed/refractory multiple myeloma. The results showed that cobimetinib alone and in combination with venetoclax, with or without atezolizumab, was safe and tolerable, with moderate anti-tumor activity overall, and higher activity in patients with translocation t(11;14).
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Letter
Oncology
Juan-Jose Garces, Jesus F. San-Miguel, Bruno Paiva
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Catia Simoes, Maria-Carmen Chillon, David Martinez-Cuadron, Maria-Jose Calasanz, Maria-Belen Vridiales, Iria Vazquez, Montserrat Hernandez-Ruano, Benat Ariceta, Paula Aguirre-Ruiz, Leire Burgos, Diego Alignani, Sarai Sarvide, Sara Villar, Ana Alfonso Pierola, Felipe Prosper, Rosa Ayala, Joaquin Martinez-Lopez, Juan Miguel Bergua Burgues, Susana Vives, Jose A. Perez-Simon, Maria Garcia-Fortes, Teresa Bernal del Castillo, Mercedes Colorado, Mayte Olave, Juan I. Rodriguez-Gutierrez, Jorge Labrador, Marcos Gonzalez, Jesus F. San-Miguel, Miguel angel Sanz, Pau Montesinos, Bruno Paiva
Summary: Clonal evolution in acute myeloid leukemia (AML) can be reconstructed using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS). Mutational analysis of dysplastic cells and leukemic blasts at the onset of AML identified stable, branching, and clonal evolution patterns. Techniques other than single-cell multiomics can be used to detect measurable residual disease (MRD) and genetic traits associated with treatment resistance in patients achieving complete response (CR). Whole-exome sequencing revealed different clonal involvement in dysplastic myeloerythropoiesis, leukemic transformation, and chemoresistance.
Editorial Material
Hematology
Bruno Paiva, Maria-Jose Calasanz
Article
Biochemistry & Molecular Biology
Marta Larrayoz, Maria J. Garcia-Barchino, Jon Celay, Amaia Etxebeste, Maddalen Jimenez, Cristina Perez, Raquel Ordonez, Cesar Cobaleda, Cirino Botta, Vicente Fresquet, Sergio Roa, Ibai Goicoechea, Catarina Maia, Miren Lasaga, Marta Chesi, P. Leif Bergsagel, Maria J. Larrayoz, Maria J. Calasanz, Elena Campos-Sanchez, Jorge Martinez-Cano, Carlos Panizo, Paula Rodriguez-Otero, Silvestre Vicent, Giovanna Roncador, Patricia Gonzalez, Satoru Takahashi, Samuel G. Katz, Loren D. Walensky, Shannon M. Ruppert, Elisabeth A. Lasater, Maria Amann, Teresa Lozano, Diana Llopiz, Pablo Sarobe, Juan J. Lasarte, Nuria Planell, David Gomez-Cabrero, Olga Kudryashova, Anna Kurilovich, Maria V. Revuelta, Leandro Cerchietti, Xabier Agirre, Jesus San Miguel, Bruno Paiva, Felipe Prosper, Jose A. Martinez-Climent
Summary: The lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) has hindered therapeutic discoveries. To overcome this limitation, researchers used genetically engineered mice to develop bone marrow tumors that mimic MM pathogenesis. Integrative analyses of mice and patients revealed a common genetic pathway that accelerates disease progression and immune evasion mechanisms that remodel the bone marrow microenvironment differently.
Article
Oncology
Anna Beatriz dos Santos Salgado, Roberto Jose Pessoa Magalhaes, Roberia M. Pontes, Eduarda da Silva Barbosa, Juan Flores-Montero, Luzalba Sanoja-Flores, Marcelo Gerardin Poirot Land, Glicinia Pimenta, Helio dos Santos Dutra, Elaine S. Costa, Alberto Orfao, Angelo Maiolino
Summary: Lenalidomide maintenance and measurable residual disease (MRD) detected by next-generation flow cytometry were independent prognostic factors for relapse risk in multiple myeloma patients in Brazil. The use of lenalidomide maintenance and MRD monitoring remains a challenge in low-income countries. This study demonstrates the benefits of lenalidomide maintenance and MRD monitoring in improving survival outcomes and identifying early relapse risk in multiple myeloma patients.
Article
Oncology
Bruno Paiva, Irene Manrique, Julie Rytlewski, Timothy Campbell, Christian C. Kazanecki, Nathan Martin, Larry D. Anderson Jr, Jesus G. Berdeja, Sagar Lonial, Noopur S. Raje, Yi Lin, Philippe Moreau, Jesus F. San-Miguel, Nikhil C. Munshi, Shari M. Kaiser
Summary: This study analyzed the MRD kinetics in multiple myeloma patients treated with CAR T cells and found that MRD status is a key predictor of progression-free survival. Patients with undetectable MRD at 3 months and beyond had longer PFS if they achieved complete response, while reappearance of normal plasma cells in MRD-negative patients was associated with inferior PFS.
BLOOD CANCER DISCOVERY
(2023)
Article
Medicine, Research & Experimental
Annieck M. Diks, Hans de Graaf, Cristina Teodosio, Rick J. Groenland, Bas de Mooij, Muktar Ibrahim, Alison R. Hill, Robert C. Read, Jacques J. M. van Dongen, Magdalena A. Berkowska
Summary: This study used high-dimensional flow cytometry to monitor the cellular responses to Bordetella pertussis challenge in the blood of 15 healthy donors. The results showed that individuals protected against colonization exhibited different early cellular responses compared to colonized individuals. These early cellular immune responses can be further characterized and potentially linked to an efficient mucosal immune response, ultimately evaluating the protective efficacy of new B. pertussis vaccine candidates.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Hematology
Bruno Paiva, Irene Manrique, Meletios A. Dimopoulos, Francesca Gay, Chang-Ki Min, Sonja Zweegman, Raphael Teipel, Maria -Victoria Mateos, Nicola Giuliani, Michele Cavo, Christine Rojas Hopkins, Weijun Fu, Kaveri Suryanarayan, Alexander Vorog, Cong Li, Bingxia Wang, Jose Estevam, Richard Labotka, Ajeeta B. Dash, Ivan Spicka
Summary: Measurable residual disease (MRD) evaluation is helpful in determining treatment duration in multiple myeloma (MM). However, limited longitudinal data exists on MRD during maintenance. This study investigated the prognostic value of MRD dynamics and found that MRD status at randomization and MRD dynamics during maintenance impact progression-free survival (PFS) risk. These findings support the significance of MRD assessment during maintenance in MM.
Article
Genetics & Heredity
Julian Dekker, Jacques J. M. van Dongen, Marcel J. T. Reinders, Indu Khatri
Summary: The IMGT database provides an overview of the germline alleles for the TR loci, but lacks information on population specificity and allelic frequencies. In this study, the researchers meticulously identified complete germline alleles and their frequencies across 26 different human populations. They found a diverse profile of TR germline alleles in different populations, with the highest diversity in Africans and specific alleles in Asian populations. Interestingly, the alleles in the IMGT database are common across all super-populations. The newly created population-matched TR database represents a valuable resource for further research.
GENES AND IMMUNITY
(2022)
