Hematology

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Article Hematology

Effectiveness of the BNT162b2mRNA COVID-19 vaccine in patients with hematological neoplasms in a nationwide mass vaccination setting

Moshe Mittelman, Ori Magen, Noam Barda, Noa Dagan, Howard S. Oster, Avi Leader, Ran Balicer

Summary: Limited evidence suggests that COVID-19 vaccines may be less effective in patients with impaired immunity. A study on patients with hematological neoplasms showed that vaccinated patients had a higher risk of COVID-19 infection, hospitalization, and death compared to vaccinated controls. Patients receiving treatment had an even higher risk. Ways to enhance COVID-19 immunity in this patient population should be explored.

BLOOD (2022)

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Article Hematology

Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy

Krishna R. Juluri, Qian Vicky Wu, Jenna Voutsinas, Jue Hou, Alexandre Hirayama, Erin Mullane, Nancy Miles, David G. Maloney, Cameron J. Turtle, Merav Bar, Jordan Gauthier

Summary: CD19-targeted CAR T-cell therapy has shown significant efficacy in patients with B-cell malignancies, but is associated with toxicities such as CRS and neurotoxicity. Research suggests that the severity of CRS and prelymphodepletion platelet count are independent predictors of hematologic toxicity.

BLOOD ADVANCES (2022)

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Article Hematology

Polatuzumab vedotin plus bendamustine and rituximab in relapsed/ refractory DLBCL: survival update and new extension cohort data

Laurie H. Sehn, Mark Hertzberg, Stephen Opat, Alex F. Herrera, Sarit Assouline, Christopher R. Flowers, Tae Min Kim, Andrew McMillan, Muhit Ozcan, Violaine Safar, Gilles Salles, Grace Ku, Jamie Hirata, Yi Meng Chang, Lisa Musick, Matthew J. Matasar

Summary: Polatuzumab vedotin plus bendamustine and rituximab (pola + BR) has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on the results of the GO29365 study. The study reported updated results from the randomized arms and the extension cohort, showing that pola + BR is an effective treatment option with a well-characterized safety profile.

BLOOD ADVANCES (2022)

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Review Hematology

COVID-19 in patients with hematologic malignancy

Petra Langerbeins, Michael Hallek

Summary: COVID-19 exhibits symptomatic heterogeneity and has a significant impact on the immune response of patients with hematologic malignancy. Vaccination against SARS-CoV-2 is important, but the immune response in these patients may be impaired. Antiviral drugs and monoclonal antibodies are available for prevention and treatment of COVID-19, but their efficacy may decrease against new variants.

BLOOD (2022)

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Article Hematology

Neutrophil HIF-1α stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle

Joseph A. Willson, Simone Arienti, Pranvera Sadiku, Leila Reyes, Patricia Coelho, Tyler Morrison, Giulia Rinaldi, David H. Dockrell, Moira K. B. Whyte, Sarah R. Walmsley

Summary: Neutrophils mainly rely on glycolysis for energy production, but possess a rich mitochondrial network and maintain mitochondrial membrane potential. Recent studies have shown that reactive oxygen species (ROS) released from mitochondria play a role as intracellular signaling molecules. Our study demonstrates that neutrophils can generate ROS through their mitochondria, and this release is increased in hypoxic conditions. Neutrophils regulate mitochondrial function and ROS production through the glycerol 3-phosphate pathway to maintain polarized mitochondria.

BLOOD (2022)

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Article Hematology

SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP

Eun-Ju Lee, Marina Beltrami-Moreira, Hanny Al-Samkari, Adam Cuker, Jennifer DiRaimo, Terry Gernsheimer, Alexandra Kruse, Craig Kessler, Caroline Kruse, Andrew D. Leavitt, Alfred Lee, Howard A. Liebman, Adrian C. Newland, Ashley E. Ray, Michael D. Tarantino, Jecko Thachil, David J. Kuter, Douglas B. Cines, James B. Bussel

Summary: This study investigates the impact of SARS-CoV-2 vaccination on patients with immune thrombocytopenia (ITP) and finds that vaccination can worsen preexisting ITP or lead to the development of de novo ITP. However, both situations respond well to treatment. It is recommended to proactively monitor patients with known ITP, especially those who have undergone splenectomy or have refractory disease.

BLOOD (2022)

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Article Hematology

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

Behnood Bikdeli, Azita H. Talasaz, Farid Rashidi, Hooman Bakhshandeh, Farnaz Rafiee, Parisa Rezaeifar, Elahe Baghizadeh, Samira Matin, Sepehr Jamalkhani, Ouria Tahamtan, Babak Sharif-Kashani, Mohammad Taghi Beigmohammadi, Mohsen Farrokhpour, Seyed Hashem Sezavar, Pooya Payandemehr, Ali Dabbagh, Keivan Gohari Moghadam, Hossein Khalili, Mahdi Yadollahzadeh, Taghi Riahi, Atefeh Abedini, Somayeh Lookzadeh, Hamid Rahmani, Elnaz Zoghi, Keyhan Mohammadi, Pardis Sadeghipour, Homa Abri, Sanaz Tabrizi, Seyed Masoud Mousavian, Shaghayegh Shahmirzaei, Ahmad Amin, Bahram Mohebbi, Seyed Ehsan Parhizgar, Rasoul Aliannejad, Vahid Eslami, Alireza Kashefizadeh, Paul P. Dobesh, Hessam Kakavand, Seyed Hossein Hosseini, Shadi Shafaghi, Samrand Fattah Ghazi, Atabak Najafi, David Jimenez, Aakriti Gupta, Mahesh V. Madhavan, Sanjum S. Sethi, Sahil A. Parikh, Manuel Monreal, Naser Hadavand, Alireza Hajighasemi, Majid Maleki, Saeed Sadeghian, Gregory Piazza, Ajay J. Kirtane, Benjamin W. Van Tassell, Gregg W. Stone, Gregory Y. H. Lip, Harlan M. Krumholz, Samuel Z. Goldhaber, Parham Sadeghipour

Summary: A study showed that intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce the risk of death, treatment with ECMO, or venous or arterial thrombosis in critically ill patients with COVID-19 at 90-day follow-up.

THROMBOSIS AND HAEMOSTASIS (2022)

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Letter Hematology

Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study

Mael Heiblig, Marcela A. Ferrada, Matthew T. Koster, Thomas Barba, Mathieu Gerfaud-Valentin, Arsene Mekinian, Henrique Coelho, Gaelle Fossard, Fiorenza Barraco, Lionel Galicier, Boris Bienvenu, Pierre Hirsch, Guillaume Vial, Anne Blandine Boutin, Joris Galland, Guillaume Le Guenno, Adrien Bigot, Kenneth J. Warrington, Tanaz A. Kermani, Peter C. Grayson, Bhavisha A. Patel, David B. Beck, Yvan Jamilloux, Pierre Fenaux, Pierre Sujobert

BLOOD (2022)

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Article Hematology

CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome

Franziska Taube, Julia Annabell Georgi, Michael Kramer, Sebastian Stasik, Jan Moritz Middeke, Christoph Roellig, Utz Krug, Alwin Kraemer, Sebastian Scholl, Andreas Hochhaus, Tim H. Bruemmendorf, Ralph Naumann, Andreas Petzold, Roger Mulet-Lazaro, Peter J. M. Valk, Bjorn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schaefer-Eckart, Christoph Schliemann, Stefan W. Kraeuse, Mathias Haenel, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Sylvia Herold, Friedrich Stoelzel, Katja Sockel, Malte von Bonin, Carsten Mueller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Martin Bornhaeuser, Johannes Schetelig, Christian Thiede

Summary: Biallelic mutations of the CEBPA gene are associated with a favorable prognosis in acute myeloid leukemia (AML). However, the role of monoallelic mutations is poorly understood. This retrospective analysis of AML patients revealed that CEBPA(sm)(bZIP) mutations are also associated with improved overall and event-free survival. Furthermore, patients with in-frame mutations in the bZIP region had the best outcomes.

BLOOD (2022)

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Review Oncology

RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Jianwei Qu, Haimeng Yan, Yifan Hou, Wen Cao, Yang Liu, Enfan Zhang, Jingsong He, Zhen Cai

Summary: ALKBH5 is an RNA demethylase that modulates m(6)A modification and controls cell processes. It regulates gene expression by affecting multiple events in RNA metabolism and plays critical roles in various cancers.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Oncology

Liquid biopsy: current technology and clinical applications

Mina Nikanjam, Shumei Kato, Razelle Kurzrock

Summary: Liquid biopsies, including circulating extracellular nucleic acids (cfDNA and ctDNA) and circulating tumor cells (CTCs), have important clinical applications in precision oncology, such as predicting treatment response and resistance, analyzing prognosis and tumor burden, and detecting cancer at early stages. This review provides an overview of current technologies and clinical applications for liquid biopsies, highlighting the potential of this powerful tool in multiple aspects of cancer management.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Hematology

CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift?

Jason Westin, Laurie H. Sehn

Summary: The standard of care treatment for relapsed or refractory LBCL patients is high-dose chemotherapy followed by ASCT, but its feasibility and success rate are limited. CAR T-cell therapy, targeting CD19, has shown promising results in some patients and could potentially become a new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.

BLOOD (2022)

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Article Hematology

Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and re-sensitizes acute myeloid leukemia to BCL-2 inhibition

Bing Z. Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L. Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Summary: MCL-1 and BCL-2 are both overexpressed in acute myeloid leukemia (AML) and play crucial roles in the survival of AML cells and stem cells. Inhibition of MCL-1 enhances the sensitivity to BCL-2 inhibition and improves the efficacy of treatment. Additionally, MCL-1 regulates cell metabolism and leukemia-stromal interactions, providing new mechanisms for AML development.

HAEMATOLOGICA (2022)

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Article Hematology

Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL

Tanya Siddiqi, Jacob D. Soumerai, Kathleen A. Dorritie, Deborah M. Stephens, Peter A. Riedell, Jon Arnason, Thomas J. Kipps, Heidi H. Gillenwater, Lucy Gong, Lin Yang, Ken Ogasawara, Jerill Thorpe, William G. Wierda

Summary: Lisocabtagene maraleucel, an autologous CD19-directed CAR T-cell therapy, shows promising safety and efficacy in patients with relapsed/refractory CLL/SLL, providing a potential new treatment option for these patients who develop resistance to current therapies.

BLOOD (2022)

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Review Hematology

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis

Nico Gagelmann, Francesco Passamonti, Christine Wolschke, Radwan Massoud, Christian Niederwieser, Raissa Adjalle, Barbara Mora, Francis Ayuk, Nicolaus Kroeger

Summary: Vaccination against SARS-CoV-2 has shown lower antibody response in patients with hematological malignancies compared to solid cancer and healthy controls. Different types of hematological malignancies also exhibit varying outcomes. Further studies on timing, value of boosters, and long-term efficacy are warranted.

HAEMATOLOGICA (2022)

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Article Hematology

Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study

Bhavisha A. Patel, Emma M. Groarke, Jennifer Lotter, Ruba Shalhoub, Fernanda Gutierrez-Rodrigues, Olga Rios, Diego Quinones Raffo, Colin O. Wu, Neal S. Young

Summary: Patients with severe aplastic anemia (SAA) are treated with bone marrow transplant (BMT) or immunosuppression (IST) depending on individual factors. The addition of eltrombopag (EPAG) to standard IST for SAA improves hematologic responses. However, the rates and characteristics of long-term complications, relapse, and clonal evolution with this new regimen are not yet known. This study reports a cumulative relapse rate of 39% in responding patients and a clonal evolution rate of 15% in all treated patients at 4 years. Relapse occurred at distinct timepoints and most relapsed patients responded to retreatment. Clonal evolution to high-risk abnormalities was noted in 5.7% of patients and was associated with poorer overall survival.

BLOOD (2022)

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Article Hematology

PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity

Christopher Ronald Funk, Shuhua Wang, Kevin Z. Chen, Alexandra Waller, Aditi Sharma, Claudia L. Edgar, Vikas A. Gupta, Shanmuganathan Chandrakasan, Jaquelyn T. Zoine, Andrew Fedanov, Sunil S. Raikar, Jean L. Koff, Christopher R. Flowers, Silvia Coma, Jonathan A. Pachter, Sruthi Ravindranathan, H. Trent Spencer, Mala Shanmugam, Edmund K. Waller

Summary: Manufacturing CART cells with PI3K delta/gamma inhibitor enriches CD8(+) CART cells with stem-like qualities and enhances the efficacy in eliminating CLL in vivo.

BLOOD (2022)

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Review Oncology

Exploring immunotherapy in colorectal cancer

Junyong Weng, Shanbao Li, Zhonglin Zhu, Qi Liu, Ruoxin Zhang, Yufei Yang, Xinxiang Li

Summary: Immunotherapy with immune checkpoint blockade has shown progress in the treatment of metastatic colorectal cancer (mCRC), although its effectiveness is limited. This review summarizes treatment strategies, discusses the mechanism and application of immune checkpoint blockade in mCRC treatment, and provides the latest research and clinical trial results.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Hematology

Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort

Constantine S. Tam, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Ryan Jacobs, Stephen Opat, Paul M. Barr, Alessandra Tedeschi, Livio Trentin, Rajat Bannerji, Sharon Jackson, Bryone J. Kuss, Carol Moreno, Edith Szafer-Glusman, Kristin Russell, Cathy Zhou, Joi Ninomoto, James P. Dean, William G. Wierda, Paolo Ghia

Summary: The CAPTIVATE study is an international phase 2 study that investigated the efficacy of fixed-duration treatment with ibrutinib plus venetoclax in patients with chronic lymphocytic leukemia. The study showed promising results, with high complete response rates and durable responses, even in high-risk patients.

BLOOD (2022)

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Article Hematology

Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE

Jesus San-Miguel, Herve Avet-Loiseau, Bruno Paiva, Shaji Kumar, Meletios A. Dimopoulos, Thierry Facon, Maria-Victoria Mateos, Cyrille Touzeau, Andrzej Jakubowiak, Saad Z. Usmani, Gordon Cook, Michele Cavo, Hang Quach, Jon Ukropec, Priya Ramaswami, Huiling Pei, Mia Qi, Steven Sun, Jianping Wang, Maria Krevvata, Nikki DeAngelis, Christoph Heuck, Rian Van Rampelbergh, Anupa Kudva, Rachel Kobos, Ming Qi, Nizar J. Bahlis

Summary: In patients with transplant-ineligible newly diagnosed multiple myeloma, daratumumab-based therapy reduces the risk of disease progression or death. MRD-negative status and sustained MRD negativity are associated with improved progression-free survival, and daratumumab-based therapy improves rates of MRD negativity lasting 6 or 12 months.

BLOOD (2022)

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