Hematology

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Article Hematology

One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors

Dietger Niederwieser, Helen Baldomero, Nosa Bazuaye, Caitrin Bupp, Naeem Chaudhri, Selim Corbacioglu, Alaa Elhaddad, Cristobal Frutos, Sebastian Galeano, Nada Hamad, Amir Ali Hamidieh, Shahrukh Hashmi, Aloysius Ho, Mary M. Horowitz, Minako Iida, Gregorio Jaimovich, Amado Karduss, Yoshihisa Kodera, Nicolaus Kroeger, Regis Peffault de Latour, Jong Wook Lee, Juliana Martinez-Rolon, Marcelo C. Pasquini, Jakob Passweg, Kristjan Paulson, Adriana Seber, John A. Snowden, Alok Srivastava, Jeff Szer, Daniel Weisdorf, Nina Worel, Mickey B. C. Koh, Mahmoud Aljurf, Hildegard Greinix, Yoshiko Atsuta, Wael Saber

Summary: The Worldwide Network of Blood and Marrow Transplantation promotes hematopoietic cell transplantation by evaluating activities through member societies, national registries, and individual centers. The number of HCT procedures is increasing globally, with narrowing gaps between regions.

HAEMATOLOGICA (2022)

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Article Oncology

Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia

Michael A. Pulsipher, Xia Han, Shannon L. Maude, Theodore W. Laetsch, Muna Qayed, Susana Rives, Michael W. Boyer, Hidefumi Hiramatsu, Gregory A. Yanik, Tim Driscoll, G. Doug Myers, Peter Bader, Andre Baruchel, Jochen Buechner, Heather E. Stefanski, Creton Kalfoglou, Kevin Nguyen, Edward R. Waldron, Karen Thudium Mueller, Harald J. Maier, Gabor Kari, Stephan A. Grupp

Summary: We assessed minimal residual disease (MRD) detection and B-cell aplasia after tisagenlecleucel therapy for acute lymphoblastic leukemia (ALL) to identify predictive biomarkers for relapse. The results showed that BMNGS-MRD 0 and B-cell recovery were independently associated with relapse, and detectable BMNGS-MRD reliably predicted the risk.

BLOOD CANCER DISCOVERY (2022)

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Article Hematology

TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML

Olga K. Weinberg, Alexa Siddon, Yazan F. Madanat, Jeffrey Gagan, Daniel A. Arber, Paola Dal Cin, Damodaran Narayanan, Madhu M. Ouseph, Jason H. Kurzer, Robert P. Hasserjian

Summary: This study evaluated the clinicopathologic features and outcomes of AML and MDS patients with complex karyotype (CK). The presence of TP53 mutation, especially multihit TP53 mutation, in the context of CK, identified a homogeneously aggressive disease, irrespective of blast count or therapy-relatedness.

BLOOD ADVANCES (2022)

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Article Biophysics

Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022

John A. Snowden, Isabel Sanchez-Ortega, Selim Corbacioglu, Grzegorz W. Basak, Christian Chabannon, Rafael de la Camara, Harry Dolstra, Rafael F. Duarte, Bertram Glass, Raffaella Greco, Arjan C. Lankester, Mohamad Mohty, Benedicte Neven, Regis Peffault de Latour, Paolo Pedrazzoli, Zinaida Peric, Ibrahim Yakoub-Agha, Anna Sureda, Nicolaus Kroeger

Summary: The EBMT has updated recommendations on indications for HCT and encourages harmonization of practice to aggregate experience. JACIE accreditation standards and reference to COVID-19 guidance are recommended for decision making.

BONE MARROW TRANSPLANTATION (2022)

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Article Hematology

Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience

Ava Diarra, Nicolas Duployez, Elise Fournier, Claude Preudhomme, Valerie Coiteux, Leonardo Magro, Bruno Quesnel, Mael Heiblig, Pierre Sujobert, Fiorenza Barraco, Marie Balsat, Quentin Scanvion, Eric Hachulla, David Launay, Ibrahim Yakoub-Agha, Louis Terriou

Summary: VEXAS syndrome is caused by somatic mutations in the UBA1 gene. Patients with VEXAS syndrome often display late-onset autoinflammatory symptoms and hematologic abnormalities. Allogeneic hematopoietic stem cell transplantation (ASCT) has shown promising outcomes in some patients, but further clinical trials are needed to determine its efficacy and place in the treatment arsenal for VEXAS syndrome.

BLOOD ADVANCES (2022)

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Letter Oncology

Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia

Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M. Pagel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A. Woyach, Emmanuelle Ferrant, William G. Wierda, Veerendra Munugalavadla, Ting Yu, Min Hui Wang, John C. Byrd

LEUKEMIA (2022)

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Article Cardiac & Cardiovascular Systems

Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions

Jessica Magid-Bernstein, Romuald Girard, Sean Polster, Abhinav Srinath, Sharbel Romanos, Issam A. Awad, Lauren H. Sansing

Summary: This review article provides an overview of the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of intracerebral hemorrhage (ICH). The incidence of hemorrhagic stroke has increased globally in the past 40 years, with changes in the cause over time due to improved hypertension management and increased use of anticoagulants. Preclinical and clinical trials have shed light on the underlying cause and mechanisms of injury from ICH, including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Although several trials have investigated the optimal medical and surgical management of ICH, there has been no clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management offers hope for reducing the devastating impact of this disease in the future.

CIRCULATION RESEARCH (2022)

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Letter Oncology

HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk

Hengyu Li, Pinghua Yang, JingHan Wang, Jin Zhang, Qianyun Ma, Yingjie Jiang, Yani Wu, Tao Han, Daimin Xiang

Summary: Tumor-associated macrophages (TAMs) promote the activation of hepatic leukemia factor (HLF) in triple-negative breast cancer (TNBC) cells through the secretion of transforming growth factor-beta1 (TGF-beta 1) and subsequently, HLF transactivates gamma-glutamyltransferase 1 (GGT1) to enhance ferroptosis resistance. This process drives TNBC cell proliferation, metastasis, and cisplatin resistance. Additionally, TNBC cells activate the JAK2/STAT3 axis to induce TGF-beta 1 secretion by TAMs, forming a feed-forward circuit. The combination of HLF and GGT1 values can improve the accuracy of TNBC patient prognosis.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Hematology

Antibody response after 2 and 3 doses of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic cell transplant recipients

Alexis Maillard, Rabah Redjoul, Marion Klemencie, Helene Labussiere Wallet, Amandine Le Bourgeois, Maud D'Aveni, Anne Huynh, Ana Berceanu, Tony Marchand, Sylvain Chantepie, Carmen Botella Garcia, Michael Loschi, Magalie Joris, Cristina Castilla-Llorente, Anne Thiebaut-Bertrand, Sylvie Francois, Mathieu Leclerc, Patrice Chevallier, Stephanie Nguyen

BLOOD (2022)

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Article Hematology

Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial

Tait D. Shanafelt, Xin Victoria Wang, Curtis A. Hanson, Elisabeth M. Paietta, Susan O'Brien, Jacqueline Barrientos, Diane F. Jelinek, Esteban Braggio, Jose F. Leis, Cong Christine Zhang, Steven E. Coutre, Paul M. Barr, Amanda F. Cashen, Anthony R. Mato, Avina K. Singh, Michael P. Mullane, Richard F. Little, Harry Erba, Richard M. Stone, Mark Litzow, Martin Tallman, Neil E. Kay

Summary: The long-term follow-up of a randomized trial comparing ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) was presented. The study showed that IR improved progression-free survival (PFS) and overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), regardless of the immunoglobulin heavy chain variable region (IGHV) gene mutation status. Continuous ibrutinib therapy was well-tolerated in the majority of CLL patients for over 5 years.

BLOOD (2022)

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Article Oncology

LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma

Maria-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Michele Cavo, Ravi Vij, Joanne Lindsey-Hill, Dominik Dytfeld, Emanuele Angelucci, Aurore Perrot, Reuben Benjamin, Niels W. C. J. van de Donk, Enrique M. Ocio, Christof Scheid, Francesca Gay, Wilfried Roeloffzen, Paula Rodriguez-Otero, Annemiek Broijl, Anna Potamianou, Caline Sakabedoyan, Maria Semerjian, Sofia Keim, Vadim Strulev, Jordan M. Schecter, Martin Vogel, Robert Wapenaar, Tonia Nesheiwat, Jesus San-Miguel, Pieter Sonneveld, Hermann Einsele, Philippe Moreau

Summary: This is the first prospective study for relapsed/refractory multiple myeloma patients, showing a lack of clear standard of care in real-world practice for heavily pretreated patients and resulting in poor outcomes. This supports the need for new treatments with novel mechanisms of action.

LEUKEMIA (2022)

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Article Hematology

COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA

Livio Pagano, Jon Salmanton-Garc, Francesco Marchesi, Alberto Lopez-Garcia, Sylvain Lamure, Federico Itri, Maria Gomes-Silva, Giulia Dragonetti, Iker Falces-Romero, Jaap van Doesum, Uluhan Sili, Jorge Labrador, Maria Calbacho, Yavuz M. Bilgin, Barbora Weinbergerova, Laura Serrano, Jose-Maria Ribera-Santa Susana, Sandra Malak, Jose Loureiro-Amigo, Andreas Glenthoj, Raul Cordoba-Mascunano, Raquel Nunes-Rodrigues, Tomas-Jose Gonzalez-Lopez, Linda Katharina Karlsson, Maria-Josefa Jimenez-Lorenzo, Jose-Angel Hernandez-Rivas, Ozren Jaksic, Zdenek Racil, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Oliver A. Cornely

BLOOD (2022)

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Article Hematology

Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients

Nora Liebers, Claudius Speer, Louise Benning, Peter -Martin Bruch, Isabelle Kraemer, Julia Meissner, Paul Schnitzler, Hans-Georg Kra eurousslich, Peter Dreger, Carsten Mueller-Tidow, Isabel Poschke, Sascha Dietrich

BLOOD (2022)

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Review Oncology

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

Simone Cesaro, Per Ljungman, Malgorzata Mikulska, Hans H. Hirsch, Marie Von Lilienfeld-Toal, Catherine Cordonnier, Sylvain Meylan, Varun Mehra, Jan Styczynski, Francesco Marchesi, Caroline Besson, Fausto Baldanti, Raul Cordoba Masculano, Gernot Beutel, Herman Einsele, Elie Azoulay, Johan Maertens, Rafael de la Camara, Livio Pagano

Summary: SARS-CoV-2 infection can lead to severe outcomes in immunocompromised hematological patients, with high mortality rates observed. Treatment strategies focus on controlling viral replication and inflammation. However, the effectiveness and benefits of preventive and therapeutic measures in hematological patients require further investigation.

LEUKEMIA (2022)

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Article Hematology

CD38 knocKout natural killer cells expressing an affinity optimized CD38 chimeric antigen receptor successfully target acute myeloid leukemia with reduced effector cell fratricide

Mark Gurney, Arwen Stikvoort, Emma Nolan, Lucy Kirkham-McCarthy, Stanislav Khoruzhenko, Rama Shivakumar, Sonja Zweegman, Niels W. C. J. Van de Donk, Tuna Mutis, Eva Szegezdi, Subhashis Sarkar, Michael O'Dwyer

Summary: There is strong biological rationale for combining alloeneic natural killer (NK) cell therapies with a chimeric antigen receptor (CAR) to improve the targeting of acute myeloid leukemia (AML). However, CD38 expression on NK cells and its induction during ex vivo NK cell expansion pose challenges to the development of a CD38 CAR-NK cell therapy. This study successfully used gene editing technology to reduce CD38 expression in expanded NK cells, resulting in reduced fratricide and enhanced targeting of primary AML cells. Additionally, pretreatment of AML cells with all-trans retinoic acid further augmented the cytotoxic potential of CD38 CAR-NK cells. These findings support the investigation of CD38 knockdown - CD38 CAR-NK cells as a promising immunotherapeutic approach for AML treatment.

HAEMATOLOGICA (2022)

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Article Hematology

World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management

William Shomali, Jason Gotlib

Summary: The eosinophilias are a group of diseases that can cause organ damage. Diagnosis relies on various tests, including blood and marrow examination. Prognosis depends on identifying the subtype of eosinophilia. Treatment aims to reduce organ damage and requires individualized therapy.

AMERICAN JOURNAL OF HEMATOLOGY (2022)

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Review Hematology

Updates on targeted therapies for acute myeloid leukaemia

Sabine Kayser, Mark J. Levis

Summary: Research on the pathogenic mechanisms of AML has made remarkable advances in recent years, especially in the importance of cytogenetic and molecular aberrations. The development of new compounds targeting AML at a molecular level, based on increased understanding of AML pathogenesis facilitated by next-generation sequencing, has turned many hopeful predictions into therapeutic realities.

BRITISH JOURNAL OF HAEMATOLOGY (2022)

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Article Hematology

Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy

Elise A. Chong, Cecile Alanio, Jakub Svoboda, Sunita D. Nasta, Daniel J. Landsburg, Simon F. Lacey, Marco Ruella, Siddharth Bhattacharyya, E. John Wherry, Stephen J. Schuster

Summary: The use of PD1 inhibitor pembrolizumab after CD19-directed CAR T-cell therapy may be safe and achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy.

BLOOD (2022)

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Article Cardiac & Cardiovascular Systems

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women

Anna C. O'Kelly, Erin D. Michos, Chrisandra L. Shufelt, Jane V. Vermunt, Margo B. Minissian, Odayme Quesada, Graeme N. Smith, Janet W. Rich-Edwards, Vesna D. Garovic, Samar R. El Khoudary, Michael C. Honigberg

Summary: In addition to conventional risk factors, women also face sex-specific risk factors for cardiovascular disease. Key stages of a woman's reproductive history, such as early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes, and absence of breastfeeding, are associated with increased future cardiovascular disease risk. The menopause transition period also represents an accelerated cardiovascular disease risk, with timing, mechanism, and symptoms of menopause playing a role. Differences in conventional risk factors explain some, but not all, of the observed associations between reproductive history and cardiovascular disease; further research is needed to understand hormonal effects and unique sex-specific mechanisms. A history of reproductive risk factors provides an opportunity for comprehensive screening, refinement of risk assessment, and implementation of prevention strategies to optimize women's long-term cardiometabolic health.

CIRCULATION RESEARCH (2022)

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Review Oncology

Catch me if you can: how AML and its niche escape immunotherapy

Sarah Tettamanti, Alice Pievani, Andrea Biondi, Gianpietro Dotti, Marta Serafini

Summary: Despite progress in AML research, the survival rate for patients remains low, highlighting the need for innovative therapies. Recent focus has been on immunotherapeutic strategies targeting leukemic cells, but studies emphasize the role of the leukemic microenvironment in facilitating tumor escape mechanisms. A rational combination of complementary immunotherapy strategies may be beneficial in preventing escape mechanisms without increasing toxicity in the complex AML landscape.

LEUKEMIA (2022)

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