Review
Oncology
Paola Pacelli, Donatella Raspadori, Elena Bestoso, Alessandro Gozzetti, Monica Bocchia
Summary: Next Generation Flow (NGF) is a gold standard for evaluating Minimal Residual Disease (MRD) in Multiple Myeloma (MM) patients. Although MRD assessment is not widely used in clinical practice, numerous studies have shown that MRD is a reliable long-term outcome predictor and has the potential to surpass the prognostic value of complete response (CR). NGF has a high success rate and sensitivity of 10(-6), comparable to Next Generation Sequencing molecular techniques. Some minor biases related to protocols, sample quality, and plasma cell heterogeneity can be overcome with standard protocols and MRD analysis expertise.
FRONTIERS IN ONCOLOGY
(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
Hematology
David P. Ng
Summary: Advancements in therapies for myeloma present challenges in monitoring post-therapy disease status due to limitations in flow cytometry caused by anti-CD38 monoclonal antibodies and suboptimal markers. While various techniques have been proposed to address these challenges, future targets of therapies may render present aberrancy markers ineffective in MRD testing. New markers and novel panels are needed to ensure the relevance of flow cytometric MRD testing.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2021)
Letter
Oncology
Joaquin Martinez-Lopez, Rafael Alonso, Sandy W. Wong, Rafael Rios, Nina Shah, Yanira Ruiz-Heredia, Jose Maria Sanchez-Pina, Ricardo Sanchez, Natasha Bahri, Irene Zamanillo, Maria Poza, Natalia Buenache, Cristina Encinas, Luis Juarez, Fatima Miras, Luis Collado, Santiago Barrio, Thomas Martin, Maria Teresa Cedena, Jeffrey Wolf
Summary: Making clinical decisions based on MRD results in MM patients can lead to improved outcomes, as stopping or changing treatment based on MRD status can result in prolonged PFS.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
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
Pathology
Kylee H. Maclachlan, Neil Came, Benjamin Diamond, Mikhail Roshal, Caleb Ho, Katie Thoren, Marius E. Mayerhoefer, Ola Landgren, Simon Harrison
Summary: There have been significant treatment advances in MM, with a growing number of patients achieving durable remissions. Deep response to therapy with negative MRD confers a significant survival advantage, requiring highly sensitive methods for detection.
Review
Oncology
Kritika Srinivasan Rajsri, Nainita Roy, Sohini Chakraborty
Summary: Acute myeloid leukemia (AML) is a blood cancer characterized by immature blood cells called leukemic blasts. Leukemia stem cells (LSCs) are resistant to chemotherapy and can cause disease relapse. Understanding the molecular basis of LSCs is important in identifying and targeting these cells for more effective treatment.
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
Hematology
Gaurav Chatterjee, Harshini Sriram, Sitaram Ghogale, Nilesh Deshpande, Twinkle Khanka, Karishma Girase, Shefali Verma, Gauri Arolkar, Niharika Dasgupta, Gaurav Narula, Dhanalaxmi Shetty, Chetan Dhamne, Nirmalya R. Moulik, Sweta Rajpal, Nikhil Patkar, Shripad Banavali, Sumeet Gujral, Papagudi G. Subramanian, Prashant R. Tembhare
Summary: The study identifies six consistently present low-level populations in 441 BMRD samples from 301 children, which immunophenotypically mimic abnormal B-ALL blasts. Understanding the presence and immunophenotype of these mimics is crucial for accurate interpretation in high-sensitivity MFC-BMRD analysis.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Computer Science, Interdisciplinary Applications
Eva Milara, Adolfo Gomez-Grande, Sebastian Tomas-Soler, Alexander P. Seiffert, Rafael Alonso, Enrique J. Gomez, Joaquin Martinez-Lopez, Patricia Sanchez-Gonzalez
Summary: This study proposed and implemented a method for the extraction and evaluation of bone marrow radiomics features from [F-18]FDG PET images, demonstrating the potential value of these features in image-based assessment of MRD.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2022)
Article
Oncology
Ekaterina Mikhailova, Olga Illarionova, Alexander Komkov, Elena Zerkalenkova, Ilgar Mamedov, Larisa Shelikhova, Yulia Olshanskaya, Natalia Miakova, Galina Novichkova, Alexander Karachunskiy, Michael Maschan, Alexander Popov
Summary: This study aimed to develop an antibody panel and data analysis algorithm for reliable minimal residual disease (MRD) detection in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients treated with CD19-directed therapy. The approach was adapted for possible CD19 loss and showed high qualitative concordance rates when compared to molecular techniques.
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
Medical Laboratory Technology
Jingjing Zhang, Jean Oak
Summary: Measurable/minimal residual disease (MRD) tracking is a powerful tool for assessing treatment response and predicting outcomes in acute leukemia. However, clinical and technological challenges need to be addressed to improve its utility in routine patient care.
SEMINARS IN DIAGNOSTIC PATHOLOGY
(2023)
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)
Review
Pathology
Sindhu Cherian, Lorinda A. Soma
Summary: Assessment for minimal/measurable residual disease (MRD) in B lymphoblastic leukemia/ lymphoma (B-LL/L) using flow cytometry is becoming standard practice, providing powerful prognostic information. Understanding normal immunophenotypic patterns and the impact of therapy on these patterns is crucial for accurate evaluation.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2021)
Article
Hematology
Matthew J. J. Pianko, Timothy Tiutan, Andriy Derkach, Jessica Flynn, Steven P. P. Salvatore, Insara Jaffer-Sathick, Adriana C. C. Rossi, Oscar Lahoud, Malin Hultcrantz, Urvi A. A. Shah, Kylee Maclachlan, David J. J. Chung, Gunjan L. L. Shah, Heather J. J. Landau, Neha Korde, Sham Mailankody, Alexander M. M. Lesokhin, Carlyn Tan, Michael Scordo, Edgar A. A. Jaimes, Sergio A. A. Giralt, Saad Usmani, Hani Hassoun
Summary: This retrospective analysis of patients with monoclonal immunoglobulin deposition disease (MIDD) demonstrates that renal response can be captured using both estimated glomerular filtration rate (eGFR) and proteinuria criteria. Most patients achieved a very good partial hematologic response with treatment. Isolated proteinuria may be an early manifestation of MIDD associated with reversible renal damage. Baseline eGFR predicts renal response and survival. Further prospective studies with uniform renal response criteria are needed to optimize the management of MIDD.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Benjamin Diamond, Bachisio Ziccheddu, Kylee Maclachlan, Justin Taylor, Eileen Boyle, Juan Arango Ossa, Jacob Jahn, Maurizio Affer, Tulasigeri M. Totiger, David Coffey, Namrata Chandhok, Justin Watts, Luisa Cimmino, Sydney X. Lu, Niccolo Bolli, Kelly Bolton, Heather Landau, Jae H. Park, Karuna Ganesh, Andrew McPherson, Mikkael A. Sekeres, Alexander Lesokhin, David J. Chung, Yanming Zhang, Caleb Ho, Mikhail Roshal, Jeffrey Tyner, Stephen Nimer, Elli Papaemmanuil, Saad Usmani, Gareth Morgan, Ola Landgren, Francesco Maura
Summary: Through genomic sequencing of 39 therapy-related myeloid malignancies, it was discovered that chemotherapy can accelerate the evolution of cancer cells by inducing mutations and DNA damage. Preleukemic clones (clonal hematopoiesis, CH) that exist before chemotherapy can acquire complex events and genomic drivers after chemotherapy, leading to the development of therapy-related myeloid neoplasms.
Meeting Abstract
Hematology
Urvi A. Shah, Francesca Castro, Aishwarya Anuraj, Eliana Schach, Andriy Derkach, Nisha S. Joseph, Peter A. Adintori, Laura Guttentag, Jenna Blaslov, Justin R. Cross, Kylee H. Maclachlan, Sham Mailankody, Neha Korde, Carlyn Tan, Malin Hultcrantz, Hani Hassoun, Oscar B. Lahoud, Gunjan L. Shah, Michael Scordo, Jonathan U. Peled, David J. Chung, Heather Landau, Jun J. Mao, Neil M. Iyengar, Saad Usmani, Sergio A. Giralt, Marcel R. M. van den Brink, Alexander M. Lesokhin
Meeting Abstract
Hematology
Benjamin Diamond, Alexandra M. Poos, Bachisio Ziccheddu, Kylee H. Maclachlan, Yanming Zhang, Saad Usmani, Eileen M. Boyle, Faith E. Davies, Gareth J. Morgan, Ola Landgren, Marc S. Raab, Francesco Maura, Niels Weinhold
Meeting Abstract
Hematology
Francesco Maura, Arjun Raj Rajanna, Andriy Derkach, Bachisio Ziccheddu, Niels Weinhold, Kylee H. Maclachlan, Benjamin Diamond, Faith E. Davies, Eileen Boyle, Brian A. Walker, Alexandra M. Poos, Malin Hultcrantz, Ariosto Siqueira Silva, Oliver Hampton, Jamie Teer, Niccolo Bolli, Graham Jackson, Martin F. Kaiser, Charlotte Pawlyn, Gordon Cook, Dennis Verducci, Dickran Kazandjian, Frits van Rhee, Saad Usmani, Ken H. Shain, Marc S. Raab, Gareth J. Morgan, Ola Landgren
Meeting Abstract
Hematology
Malin Hultcrantz, Andriy Derkach, Hani Hassoun, Neha Korde, Kylee H. Maclachlan, Sham Mailankody, Dhwani Patel, Urvi A. Shah, Carlyn Tan, Theresia Akhlaghi, Issam S. Hamadeh, David J. Chung, Oscar B. Lahoud, Heather Landau, Michael Scordo, Gunjan L. Shah, Sergio A. Giralt, Alexander M. Lesokhin, Saad Usmani
Article
Hematology
Kylee H. Maclachlan, Tina Bagratuni, Efstathios Kastritis, Bachisio Ziccheddu, Sydney Lu, Venkata Yellapantula, Chris Famulare, Kimon Argyropoulos, Andriy Derkach, Elli Papaemmanuil, Ahmet Dogan, Alexander Lesokhin, Saad Z. Usmani, C. Ola Landgren, Lia M. Palomba, Francesco Maura, Meletios A. Dimopoulos
Summary: The genomic landscape of Waldenstrom macroglobulinemia (WM) is characterized by MYD88 somatic mutations which are present from precursor stages. Analysis shows sustained activity of germinal center (GC) mutational signatures, suggesting continued interaction between WM and GC. Copy number aberrations (CNA) progressively increase in symptomatic WM and relapsed disease, with MYD88 wild-type cases often demonstrating early chromosomal gains and later subclonal CNA changes. This suggests that CNA may contribute to progression risk from precursor conditions to symptomatic disease.
Article
Oncology
Carlyn Rose Tan, Andriy Derkach, David Nemirovsky, Amanda Ciardiello, Benjamin Diamond, Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Urvi Shah, Kylee Maclachlan, Dhwani Patel, Oscar B. B. Lahoud, Heather J. J. Landau, David J. J. Chung, Gunjan L. L. Shah, Michael Scordo, Sergio A. A. Giralt, Alexander Lesokhin, Saad Z. Z. Usmani, Ola Landgren, Neha Korde
Summary: This retrospective study compared the efficacy and safety of VRd and KRd as induction regimens. The results showed that KRd was associated with improved progression-free survival (PFS) and event-free survival (EFS) compared to VRd, with a more significant improvement observed in high-risk patients.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Francesco Maura, Bachisio Ziccheddu, Jenny Z. Xiang, Bhavneet Bhinder, Joel Rosiene, Federico Abascal, Kylee H. Maclachlan, Kenneth Wha Eng, Manik Uppal, Feng He, Wei Zhang, Qi Gao, Venkata D. Yellapantula, Vicenta Trujillo-Alonso, Sunita I. Park, Matthew J. Oberley, Elizabeth Ruckdeschel, Megan S. Lim, Gerald B. Wertheim, Matthew J. Barth, Terzah M. Horton, Andriy Derkach, Alexandra E. Kovach, Christopher J. Forlenza, Yanming Zhang, Ola Landgren, Craig H. Moskowitz, Ethel Cesarman, Marcin Imielinski, Olivier Elemento, Mikhail Roshal, Lisa Giulino-Roth
Summary: In this study, HRS cells were purified using fluorescence-activated cell sorting, and their whole-genome sequencing landscape was analyzed to reconstruct the chronology and likely etiology of pathogenic events in cHL. Driver gene alterations, APOBEC mutational activity, and complex structural variants were identified. The study also revealed that high ploidy in cHL is often acquired through multiple, independent chromosomal gains events, including whole-genome duplication. The findings provide important insights into the temporal reconstruction of cHL pathogenesis.
BLOOD CANCER DISCOVERY
(2023)
Article
Oncology
Anish K. Simhal, Kylee H. Maclachlan, Rena Elkin, Jiening Zhu, Larry Norton, Joseph O. Deasy, Jung Hun Oh, Saad Z. Usmani, Allen Tannenbaum
Summary: The study investigates the global interactions in multiple myeloma (MM) using a protein interaction network and a large dataset. The analysis reveals complex immune dysregulation associated with shorter survival.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Francesco Maura, Eileen M. Boyle, David Coffey, Kylee Maclachlan, Dylan Gagler, Benjamin Diamond, Hussein Ghamlouch, Patrick Blaney, Bachisio Ziccheddu, Anthony Cirrincione, Monika Chojnacka, Yubao Wang, Ariel Siegel, James E. Hoffman, Dickran Kazandjian, Hani Hassoun, Emily Guzman, Sham Mailankody, Urvi A. Shah, Carlyn Tan, Malin Hultcrantz, Michael Scordo, Gunjan L. Shah, Heather Landau, David J. Chung, Sergio Giralt, Yanming Zhang, Arnaldo Arbini, Qi Gao, Mikhail Roshal, Ahmet Dogan, Alexander M. Lesokhin, Faith E. Davies, Saad Z. Usmani, Neha Korde, Gareth J. Morgan, Ola Landgren
Summary: This study reveals the impact of distinct genomic drivers and microenvironment changes on clinical outcome and treatment response in patients with newly diagnosed multiple myeloma treated with specific anti-CD38 antibody-containing regimens using whole-genome and single-cell RNA sequencing data.
Meeting Abstract
Oncology
Urvi Shah, Francesca Castro, Aishwarya Anuraj, Jenna Blaslov, Peter Adintori, Andriy Derkach, Michael Pollak, Kylee Maclachlan, Sham Mailankody, Neha Korde, Carlyn Tan, Malin Hultcrantz, Hani Hassoun, Gunjan Shah, Michael Scordo, Oscar Lahoud, David Chung, Heather Landau, Anita D'Souza, Ola Landgren, Sergio Giralt, Saad Usmani, Neil Iyengar, Marcel van den Brink, Alexander Lesokhin
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Oncology
Anish Simhal, Kylee Maclachlan, Rena Elkin, Jiening Zhu, Saad Usmani, Joseph O. Deasy, Jung Hun Oh, Allen Tannenbaum
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Oncology
Theresia Akhlaghi, Kylee Maclachlan, Neha Korde, Sham Mailankody, Alexander M. Lesokhin, Hani Hassoun, Sydney X. Lu, Dhwani Patel, Urvi A. Shah, Carlyn Tan, Andriy Derkach, Oscar Boutros Lahoud, Heather Jolie Landau, Gunjan L. Shah, Michael Scordo, David J. Chung, Sergio Giralt, Saad Zafar Usmani, Carl Ola Landgren, Malin Hultcrantz
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Theresia Akhlaghi, Kylee Maclachlan, Neha Korde, Sham Mailankody, Alexander M. Lesokhin, Hani Hassoun, Sydney X. Lu, Dhwani Patel, Urvi A. Shah, Carlyn Tan, Andriy Derkach, Oscar Boutros Lahoud, Heather Jolie Landau, Gunjan L. Shah, Michael Scordo, David J. Chung, Sergio Giralt, Saad Zafar Usmani, Carl Ola Landgren, Malin Hultcrantz
JOURNAL OF CLINICAL ONCOLOGY
(2022)