Article
Oncology
Nitin Jain, Philip Thompson, Jan Burger, Alessandra Ferrajoli, Koichi Takahashi, Zeev Estrov, Gautam Borthakur, Prithviraj Bose, Tapan Kadia, Naveen Pemmaraju, Koji Sasaki, Marina Konopleva, Elias Jabbour, Naveen Garg, Xuemei Wang, Rashmi Kanagal-Shamanna, Keyur Patel, Wei Wang, Jeffrey Jorgensen, Sa Wang, Wanda Lopez, Ana Ayala, William Plunkett, Varsha Gandhi, Hagop Kantarjian, Susan O'Brien, Michael Keating, William G. Wierda
Summary: The iFCG regimen with only 3 cycles of chemotherapy is an effective, time-limited regimen for patients with CLL with mutated IGHV and without del(17p)/TP53 mutation. The treatment resulted in high rates of complete remission and undetectable measurable residual disease in the marrow, with excellent 3-year progression-free and overall survival rates.
Article
Oncology
Robert Szasz, Bela Telek, Arpad Illes
Summary: This study compared the impact of fitness on prolonged cytopenias and reported real-life data on FCR treatment. The findings show a decrease in the number of patients treated with FCR in recent years, likely due to the availability of targeted therapies.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
Review
Chemistry, Multidisciplinary
Makhloufi Zoulikha, Wei He
Summary: Chronic lymphocytic leukemia (CLL) is an incurable disorder that requires innovative therapeutic strategies and improved drug delivery process for better treatment effectiveness. This review discusses the use of different types of nanocarriers in fighting against CLL and their features.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kristan V. Piroeva, Charlotte Mcdonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe, Vladimir B. Teif
Summary: This study compared the nucleosome positions in chronic lymphocytic leukemia (CLL) patients and healthy individuals, and found significant changes in nucleosome positioning in CLL. The spacing between nucleosomes was shortened, and changes in nucleosome occupancy were linked to chromatin remodeling and reduced DNA methylation. Nucleosome positioning can be used to classify CLL subtypes and monitor disease progression.
Article
Oncology
Drew R. R. Nannini, Rene Cortese, Peter Egwom, Senthilnathan Palaniyandi, Gerhard C. Hildebrandt
Summary: This study found that age-related DNA methylation changes are associated with chronic lymphocytic leukemia (CLL) relapse. Analysis of DNA methylation in 35 CLL patients revealed that extrinsic and PhenoAge acceleration were negatively correlated with time to CLL relapse, while GrimAge acceleration was positively correlated. Simultaneous assessment of extrinsic and GrimAge acceleration in male patients could distinguish those with early and later relapses. These results provide insight into the association between age-related DNA methylation changes and CLL relapse.
CLINICAL EPIGENETICS
(2023)
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
Billy Michael Chelliah Jebaraj, Stephan Stilgenbauer
Summary: Telomeres play a crucial role in chronic lymphocytic leukemia (CLL), with their dysfunction shaping the disease progression. Members of the shelterin complex and TERT activation are closely associated with CLL cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Hematology
Fabienne Meier-Abt, Junyan Lu, Ester Cannizzaro, Marcel F. Pohly, Sandra Kummer, Sibylle Pfammatter, Laura Kunz, Ben C. Collins, Ferran Nadeu, Kwang Seok Lee, Peng Xue, Myriam Gwerder, Michael Roiss, Jennifer Huellein, Sebastian Scheinost, Sascha Dietrich, Elias Campo, Wolfgang Huber, Ruedi Aebersold, Thorsten Zenz
Summary: This study uncovered mutations affecting protein expression in CLL and identified signaling pathways associated with trisomy 12. STAT2 protein expression was linked to specific drug responses, providing a protein expression reference map for CLL.
Article
Oncology
David Allard, Pavel Chrobak, Yacine Bareche, Bertrand Allard, Priscilla Tessier, Marjorie A. Bergeron, Nathalie A. Johnson, John Stagg
Summary: Our study identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway. The therapeutic potential of targeting CD73 in CLL was investigated using genetically engineered mice, revealing a pro-leukemic role for CD73 in an autochthonous mouse model of CLL. Our findings suggest that targeting CD73 in CLL in combination with anti-PD-1/PD-L1 immunotherapies may be beneficial, with sex potentially contributing to responses to adenosine-targeting agents.
Review
Oncology
Yu Nie, Xiaoya Yun, Ya Zhang, Xin Wang
Summary: Metabolic reprogramming plays a vital role in the initiation and progression of chronic lymphocytic leukemia (CLL). This review summarizes the critical metabolic processes in CLL and discusses the regulation of metabolism by cells in the microenvironment and oncogenes/tumor suppressor regulators. Targeting metabolic enzymes or signal pathways may impede the progression of CLL.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Medicine, General & Internal
Shenmiao Yang, Xiaojun Huang, Robert Peter Gale
Summary: Transplantation has been used to treat chronic lymphocytic leukemia for over 35 years, but is only considered for less than 1% of highly selected patients. While some patients may achieve long-term leukemia-free survival with transplants, they also come with significant morbidity and mortality. The anti-leukemia effects of transplants are influenced by various factors, including drugs, radiation, and immune mechanisms.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Mazyar Shadman
Summary: Chronic lymphocytic leukemia is an immunocompromised blood cancer that can be treated with targeted agents like BTK inhibitors or BCL2 inhibitors, but currently there is no cure for the disease.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Medicine, General & Internal
Martin Simkovic, Pavel Vodarek, Monika Motyckova, Dominika ecsiova, Petra Rozsivalova, Heidi Mocikova, Pavla Stepankova, Alice Sykorova, Katerina Hrochova, Filip Vrbacky, David Belada, Pavel Zak, Lukas Smolej
Summary: The RCD regimen is an effective treatment option for elderly patients with relapsed CLL, with significant predictors of shorter PFS being TP53 deletion/mutation, advanced Rai stage, and >= 2 previous lines of treatment. The addition of cyclophosphamide to the R-Dex regimen maintains similar efficacy, even with a 50% reduction in the dexamethasone dose.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Peter Hillmen, Alexandra Pitchford, Adrian Bloor, Angus Broom, Moya Young, Ben Kennedy, Renata Walewska, Michelle Furtado, Gavin Preston, Jeffrey R. Neilson, Nicholas Pemberton, Gamal Sidra, Nicholas Morley, Kate Cwynarski, Anna Schuh, Francesco Forconi, Nagah Elmusharaf, Shankara Paneesha, Christopher P. Fox, Dena R. Howard, Anna Hockaday, Julia M. Brown, David A. Cairns, Sharon Jackson, Natasha Greatorex, Nichola Webster, Jane Shingles, Surita Dalal, Piers E. M. Patten, David Allsup, Andrew Rawstron, Talha Munir
Summary: This study compares the efficacy of ibrutinib and rituximab with fludarabine, cyclophosphamide, and rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients. The results show that ibrutinib and rituximab significantly improve progression-free survival compared to the standard chemoimmunotherapy.
Article
Biochemical Research Methods
Phillip Loehr, Stefan Schiele, Tim Tobias Arndt, Stefanie Gruetzner, Rainer Claus, Christoph Roemmele, Gernot Mueller, Christoph Schmid, Kevin M. Dennehy, Andreas Rank
Summary: This study analyzed the changes in lymphocyte subsets in COVID-19 patients and found that cell counts of lymphocytes and their subsets are reduced in severe cases. Age and gender also play a role in the altered cell counts.
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Oncology
Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie Jose Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, Patrick M. Reagan
Summary: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown durable long-term responses with manageable safety in patients with relapsed/refractory mantle cell lymphoma (MCL) and may benefit those with high-risk characteristics.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Misha C. Tran, Yasmin Hasan, Amy Wang, Kamil Yenice, Julien Partouche, Wendy Stock, Richard A. Larson, Satyajit Kosuri, James L. LaBelle, Justin Kline, Peter A. Riedell, Andrew S. Artz, Ralph Weichselbaum, Michael R. Bishop, Bulent Aydogan, Hongtao Liu
Summary: Relapse after allo-SCT is a common issue, and a second SCT can be considered for treatment. The study explored the feasibility of combining IM-TMI with fludarabine and melphalan for conditioning in patients undergoing a second or greater allo-SCT. The results showed that the combination therapy was feasible and achieved favorable outcomes.
Article
Hematology
Andrew J. Shih, Tomi Jun, Andrew D. Skol, Riyue Bao, Lei Huang, Sapana Vora, Megan E. McNerney, Eric A. Hungate, Michelle M. Le Beau, Richard A. Larson, Aaron Elliott, Hsiao-Mei Lu, Robert Huether, Felicia Hernandez, Friedrich Stolzel, James M. Allan, Kenan Onel
Summary: Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). A set of clinical criteria has been proposed to identify t-MN patients with high risk of CPS (HR-CPS). Among the identified HR-CPS patients, 37% had pathogenic or likely pathogenic variants, compared to 0% in the low-risk CPS patients. These simple clinical criteria help identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Oncology
John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Christopher Abbazio, William G. Wierda
Summary: The CAPTIVATE study demonstrates that fixed-duration ibrutinib plus venetoclax is effective in controlling chronic lymphocytic leukemia, including patients with high-risk genomic features. This treatment provides durable progression-free survival and similar overall survival rates.
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Johanna S. S. Enke, Nic G. G. Reitsam, Tina Schaller, Rainer Claus, Constantin Lapa, Alexander Dierks
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Oncology
David A. Sallman, Monzr M. Al Malki, Adam S. Asch, Eunice S. Wang, Joseph G. Jurcic, Terrence J. Bradley, Ian W. Flinn, Daniel A. Pollyea, Suman Kambhampati, Tiffany N. Tanaka, Joshua F. Zeidner, Guillermo Garcia-Manero, Deepa Jeyakumar, Rami Komrokji, Jeffrey Lancet, Hagop M. Kantarjian, Lin Gu, Yajia Zhang, Anderson Tan, Mark Chao, Carol O'Hear, Giridharan Ramsingh, Indu Lal, Paresh Vyas, Naval G. Daver
Summary: This study reported the final phase Ib data of magrolimab and azacitidine in patients with untreated higher-risk MDS. The results showed that the combination therapy of magrolimab and azacitidine promotes macrophage-mediated phagocytosis of tumor cells and has synergistic effects. The study demonstrates the good safety and efficacy of this combination therapy in treating higher-risk MDS patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Michael L. Wang, Wojciech Jurczak, Pier Luigi Zinzani, Toby A. Eyre, Chan Y. Cheah, Chaitra S. Ujjani, Youngil Koh, Koji Izutsu, James N. Gerson, Ian Flinn, Benoit Tessoulin, Alvaro J. Alencar, Shuo Ma, David Lewis, Ewa Lech-Maranda, Joanna Rhodes, Krish Patel, Kami Maddocks, Nicole Lamanna, Yucai Wang, Constantine S. Tam, Talha Munir, Hirokazu Nagai, Francisco Hernandez-Ilizaliturri, Anita Kumar, Timothy S. Fenske, John F. Seymour, Andrew D. Zelenetz, Binoj Nair, Donald E. Tsai, Minna Balbas, Richard A. Walgren, Paolo Abada, Chunxiao Wang, Junjie Zhao, Anthony R. Mato, Nirav N. Shah
Summary: This study evaluated the safety and efficacy of Pirtobrutinib, a noncovalent BTK inhibitor, in patients with mantle-cell lymphoma who had previously received covalent BTK inhibitors. The results showed that Pirtobrutinib demonstrated durable efficacy and was well tolerated in this heavily pretreated patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Luise Victoria Claass, Patrick Mayr, Lisa Paschold, Thomas Weber, Denis Terziev, Bertram Jehs, Richard Brill, Johannes Dober, Bruno Maerkl, Claudia Wickenhauser, Piotr Czapiewski, Martin Trepel, Rainer Claus, Mascha Binder
Summary: SARS-CoV-2 vaccines do not seem to be associated with the development of lymphomas in the lymph nodes of the deltoid region used for vaccination. The study found that cases of unilateral axillary lymphomas occurred both before and after the introduction of SARS-CoV-2 vaccines, and there was no evidence of a correlation between the vaccines and the malignant clonotypes.
Article
Medicine, Research & Experimental
Lisa Schweizer, Tina Schaller, Maximilian Zwiebel, Oezge Karayel, Johannes Bruno Mueller-Reif, Wen-Feng Zeng, Sebastian Dintner, Thierry M. Nordmann, Klaus Hirschbuehl, Bruno Maerkl, Rainer Claus, Matthias Mann
Summary: SARS-CoV-2 can cause damage to lung tissue and other organs in the human body, and this study aimed to analyze these effects comprehensively. Using a mass spectrometry proteomics workflow, the researchers identified inflammatory responses as the initial reaction in all tissues. They also found specific patterns of damage in different organs, such as diffuse alveolar damage in the lungs and organ-specific changes in the kidneys, liver, and lymphatic and vascular systems. In the brain, secondary inflammatory effects were linked to neurotransmitter receptors and myelin degradation. These findings contribute to our understanding of the mechanisms of COVID-19 and provide insights for organ-specific therapeutic interventions.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Alexander E. Perl, Richard A. Larson, Nikolai A. Podoltsev, Stephen Strickland, Eunice S. Wang, Ehab Atallah, GaryJ. Schiller, Giovanni Martinelli, Andreas Neubauer, Jorge Sierra, Pau Montesinos, Christian Recher, Sung-Soo Yoon, Yoshinobu Maeda, Naoko Hosono, Masahiro Onozawa, Takayasu Kato, Hee-Je Kim, Nahla Hasabou, Rishita Nuthethi, Ramon Tiu, Mark J. Levis
Summary: The ADMIRAL trial investigated the efficacy of using the FLT3 inhibitor gilteritinib as maintenance therapy after hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory FLT3-mutated AML. The results showed that gilteritinib maintenance therapy improved survival rates and was well-tolerated in patients post-HSCT.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
