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Cytopenia

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Association Analysis of Persistent Cytopenia With Efficacy and Side Effects of Anti-CD19 CAR T Therapy in Relapsed/refractory Diffuse Large B-Cell Lymphoma Patients.

Xuemei Lin, Meijing Liu, Rui Cui, Cuicui Lyu, Jia Wang, Qing Li, Nan Mou, Qi Deng,

<h4>Background: </h4> Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has been an effective salvage therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Hematological toxicity is one of the adverse events (AEs) of this therapy. But the underlying pathophysiologic mechanism of persistent cytopenia is unclear. The association of persistent ... Read more >>

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Inflammatory signals from fatty bone marrow supports the early stages of DNMT3a driven clonal hematopoiesis

Zioni, Bercovich, Chapal-Ilani, Solomon, Kopitman, Sacma, Hartmut, Scheller, Müller-Tidow, Lipka, Shlush, Minden, Kaushansky, LI Shlush,

Age related cancer is not only due to the random accumulation of mutations, but also how phenotypes are selected by the aging environment. While fatty bone marrow (FBM), is one of the hallmarks of bone marrow ageing, it is unknown whether FBM can modify the evolution of the early stages ... Read more >>

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Clonal hematopoiesis and risk of chronic liver disease

Waihay Wong, Emdin Connor, Alexander Bick, Seyedeh Zekavat, Abhishek Niroula, James Pirruccello, Laura Dichtel, Gabriel Griffin, Md Mesbah Uddin, Christopher Gibson, Veronica Kovalcik, Amy Lin, Marie McConkey, Amelie Vromman, Rob Sellar, Peter Kim, Mridul Agrawal, Joshua Weinstock, Michelle Long, Bing Yu, Rajarshi Banerjee, Rowan Nicholls, Matt Kelly, Po-Ru Loh, Steve McCarroll, Eric Boerwinkle, Ramachandran Vasan, Siddhartha Jaiswal, Andrew Johnson, Raymond Chung, Kathleen Corey, Daniel Levy, Christie Ballantyne, Benjamin Ebert, Pradeep Natarajan, ,

Chronic liver disease is a major public health burden worldwide. Despite various liver injury mechanisms, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis. We examined the association between clonal hematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 58,358 individuals from four ... Read more >>

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Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation

Anna Nam, Neville Dusaj, Franco Izzo, Rekha Murali, Robert Myers, Tarek Mouhieddine, Jesus Sotelo, Salima Benbarche, Michael Waarts, Federico Gaiti, Sabrin Tahri, Ross Levine, Omar Abdel-Wahab, Lucy Godley, Ronan Chaligne, Irene Ghobrial, Dan Landau,

<h4>ABSTRACT</h4> Somatic mutations in cancer genes have been ubiquitously detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, mutated and wildtype cells are morphologically and phenotypically similar, limiting the ability to link genotypes with cellular phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing ... Read more >>

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Mutant PPM1D- and TP53-Driven Hematopoiesis Populates the Hematopoietic Compartment in Response to Peptide Receptor Radionuclide Therapy.

Abhay Singh, Nuria Mencia-Trinchant, Elizabeth A Griffiths, Alaa Altahan, Mahesh Swaminathan, Medhavi Gupta, Matthew Gravina, Rutaba Tajammal, Mark G Faber, LunBiao Yan, Eti Sinha, Duane C Hassane, David Neil Hayes, Monica L Guzman, Renuka Iyer, Eunice S Wang, Swapna Thota,

<h4>Purpose</h4>Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied.<h4>Materials and methods</h4>We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 ... Read more >>

JCO Precis Oncol (JCO precision oncology)
[2022, 6:e2100309]

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B-CELL CYTOPENIA AND TIME TO LAST B-CELL-DEPLETING THERAPY PREDICT RESPONSE TO SARS-COV-2 VACCINES IN PATIENTS WITH LYMPHOPROLIFERATIVE DISORDERS

Mégane Tanguay, Marianne Boutin, Annemarie Laumaea, Matthew Salaciak, Alma Mendoza, Chantal Cassis, Lissa Ajjamada, Sarit Assouline, François Patenaude, Michael Webster Clark, Andrés Finzi, Nathalie A. Johnson,

Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and ... Read more >>

Vaccine (Vaccine)
[2022, :]

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A practical guide to interpreting germline variants that drive hematopoietic malignancies, bone marrow failure, and chronic cytopenias.

Simone Feurstein, Christopher N Hahn, Nikita Mehta, Lucy A Godley,

<h4>Purpose</h4>The American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines for germline variant interpretation are implemented as a broad framework by standardizing variant interpretation. These rules were designed to be specified, but this process has not been performed for most of the 200 genes associated ... Read more >>

Genet Med (Genetics in medicine : official journal of the American College of Medical Genetics)
[2022, :]

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Exome sequencing of 628,388 individuals identifies common and rare variant associations with clonal hematopoiesis phenotypes

Michael Kessler, Amy Damask, Sean O’Keeffe, Michael Van Meter, Nilanjana Banerjee, Stefan Semrau, Dadong Li, Kyoko Watanabe, Julie Horowitz, Yariv Houvras, Christopher Gillies, Joelle Mbatchou, Ryan White, Jack Kosmicki, Michelle LeBlanc, Marcus Jones, David Glass, Luca Lotta, Michael Cantor, Gurinder Atwal, Adam Locke, Manuel Ferreira, Raquel Deering, Charles Paulding, Alan Shuldiner, Gavin Thurston, Will Salerno, Jeffrey Reid, John Overton, Jonathan Marchini, Hyun Kang, Aris Baras, Gonçalo Abecasis, Eric Jorgenson, , ,

Clonal hematopoiesis (CH) refers to the expansion of certain blood cell lineages and has been associated with aging and adverse health outcomes. Here, we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal hematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify ... Read more >>

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[Research update on the association between clonal hematopoiesis with indeterminant potential and cardiovascular diseases].

Z J Tong, H T Lan, Y M Tan, J Y Xie, W Zhang, M Zhong, Z H Wang,

Zhonghua Xin Xue Guan Bing Za Zhi (Zhonghua xin xue guan bing za zhi)
[2022, 50(1):85-90]

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Genome-wide analyses of 200,453 individuals yields new insights into the causes and consequences of clonal hematopoiesis

Siddhartha Kar, Pedro Quiros, Muxin Gu, Tao Jiang, Ryan Langdon, Vivek Iyer, Clea Barcena, M.S. Vijayabaskar, Margarete Fabre, Paul Carter, Stephen Burgess, George Vassiliou,

Clonal hematopoiesis (CH) is one of the most extensively studied somatic mutational phenomena, yet its causes and consequences remain poorly understood. We identify 10,924 individuals with CH amongst 200,453 whole-exome sequenced UK Biobank participants and use their linked genome-wide DNA genotypes to map the landscape of inherited predisposition to CH. ... Read more >>

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Cytopenias After CD19 Chimeric Antigen Receptor T-Cells (CAR-T) Therapy for Diffuse Large B-Cell Lymphomas or Transformed Follicular Lymphoma: A Single Institution Experience.

Andrew Schaefer, Ying Huang, Adam Kittai, Joseph E Maakaron, Caner Saygin, Jonathan Brammer, Sam Penza, Ayman Saad, Samantha M Jaglowski, Basem M William,

<h4>Introduction</h4>Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Treatment with CD19 chimeric antigen receptor (CAR-T) cells, tisagenlecleucel and axicabtagene ciloleucel, has been associated with improved outcomes. Cytopenias were observed in clinical trials with both products; however, little is known regarding the patterns and outcomes of these cytopenias.<h4>Subjects ... Read more >>

Cancer Manag Res (Cancer management and research)
[2021, 13:8901-8906]

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Association of clonal hematopoiesis mutations with clinical outcomes: A systematic review and meta-analysis.

Malgorzata K Nowakowska, Taebeom Kim, Mikayla T Thompson, Kelly L Bolton, Anita Deswal, Steven H Lin, Paul Scheet, Mackenzie R Wehner, Kevin T Nead,

Clonal hematopoiesis (CH) mutations are common among individuals without known hematologic disease. CH mutations have been associated with numerous adverse clinical outcomes across many different studies. We systematically reviewed the available literature for clinical outcomes associated with CH mutations in patients without hematologic disease. We searched PubMed, EMBASE, and Scopus ... Read more >>

Am J Hematol (American journal of hematology)
[2022, :]

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Clonal hematopoiesis and atherosclerotic cardiovascular disease: A primer.

María A Zuriaga, José J Fuster,

Despite current standards of care, a considerable risk of atherosclerotic cardiovascular disease remains in both primary and secondary prevention. In this setting, clonal hematopoiesis driven by somatic mutations has recently emerged as a relatively common, potent and independent risk factor for atherosclerotic cardiovascular disease and other cardiovascular conditions. Experimental studies ... Read more >>

Clin Investig Arterioscler (Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis)
[2021, :]

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Unexplained Anemia in the Elderly.

Jose C Alvarez-Payares, Sebastián Rivera-Arismendy, Pablo Ruiz-Bravo, Sara M Sánchez-Salazar, Rene A Manzur, Sara I Ramirez-Urrea, Andres Puello,

Anemia is frequently diagnosed in elderly patients, and it is a key indicator of many reactive and clonal conditions. Furthermore, the older age is the most common presenting age for myelodysplastic syndromes (MDS). Anemia in older age may be attributed to an inflammatory state due to senescence, comorbidities, nutritional deficiencies, ... Read more >>

Cureus (Cureus)
[2021, 13(11):e19971]

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Complete blood count and cell population data parameters from the Abbott Alinity hq analyzer are useful in differentiating myelodysplastic syndromes from other forms of cytopenia.

Sang Mee Hwang, Youngwon Nam,

<h4>Introduction</h4>Myelodysplastic syndromes (MDS) are characterized by morphologic dysplasia and cytopenia and have a propensity for acute leukemic transformation. However, dysplasia is diagnosed by morphology, thus having cell population data (CPD) that can differentiate cytopenic patients with MDS from other conditions may facilitate accurate diagnosis. We assessed the utility of complete ... Read more >>

Int J Lab Hematol (International journal of laboratory hematology)
[2021, :]

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Diagnostic error regarding the cause of cytopenia when increasing psychotropic drugs: Two case reports.

Yoshihiro Matsumoto, Nobutaka Ayani, Chie Omichi, Nozomu Oya, Teruyuki Matsuoka, Tsutomu Kobayashi, Junya Kuroda, Jin Narumoto,

Several psychotropic drugs can cause cytopenia, especially after increasing dosages or initiating treatment. However, cytopenia in patients with psychiatric disorders can also be due to other conditions such as leukemia. In this report, we discuss two cases of cytopenia that occurred during the adjustment of psychotropic medications in patients with ... Read more >>

Asian J Psychiatr (Asian journal of psychiatry)
[2022, 67:102952]

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When are idiopathic and clonal cytopenias of unknown significance (ICUS or CCUS)?

Afaf E W G Osman,

Rapid advances in sequencing technology have led to the identification of somatic mutations that predispose a significant subset of the aging population to myeloid malignancies. Recently recognized myeloid precursor conditions include clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS). These conditions can present diagnostic challenges ... Read more >>

Hematology Am Soc Hematol Educ Program (Hematology. American Society of Hematology. Education Program)
[2021, 2021(1):399-404]

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Case Report: Sirolimus Alleviates Persistent Cytopenia After CD19 CAR-T-Cell Therapy.

Limin Xing, Yihao Wang, Hui Liu, Shan Gao, Qing Shao, Lanzhu Yue, Zhaoyun Liu, Huaquan Wang, Zonghong Shao, Rong Fu,

Chimeric antigen receptor T (CAR-T) cells show good efficacy in the treatment of relapsed and refractory B-cell tumors, such as acute B-cell leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The main toxicities of CAR-T include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and severe infection. It is ... Read more >>

Front Oncol (Frontiers in oncology)
[2021, 11:798352]

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Untangling the Relationship between Clonal Hematopoiesis and Ovarian Cancer Therapies.

Koichi Takahashi,

J Natl Cancer Inst (Journal of the National Cancer Institute)
[2021, :]

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Somatic Mutations in Cardiovascular Disease.

J Brett Heimlich, Alexander G Bick,

Advances in population-scale genomic sequencing have greatly expanded the understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of these genomic datasets identified an unexpected risk factor for CVD, somatically acquired DNA mutations. In this review, we provide an overview of somatic mutations and their contributions to CVD. We ... Read more >>

Circ Res (Circulation research)
[2022, 130(1):149-161]

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The Application of NextGen Sequencing in the Diagnosis of Myeloid Neoplasms in Myeloma Patients With Cytopenia.

Jinming Song, Hailing Zhang, Ning Dong, Xiaohui Zhang, Mohammad Hussaini, Akriti Jain, Lynn Moscinski, Ken Shain, Rachid Baz, Melissa Alsina, Taiga Nishihori, Ling Zhang,

<h4>Background</h4>Multiple myeloma (MM) is an incurable clonal neoplasm that usually requires long-term treatment, which may result in secondary cytopenia(s) and myeloid neoplasms. We investigated the landscape of mutations detected by NextGen sequencing (NGS) in myeloma patients with cytopenia.<h4>Methods and materials</h4>MM patients (n = 196) with cytopenia(s) and NGS results were identified and ... Read more >>

Clin Lymphoma Myeloma Leuk (Clinical lymphoma, myeloma & leukemia)
[2021, :]

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Do Not Forget About the Ticks: An Unusual Cause of Fever, GI Distress, and Cytopenias in a Child With ALL.

Stephanie P Ungar, Joyce Varkey, Joanna Pierro, Elizabeth Raetz, Adam J Ratner,

We report the case of a 5-year-old male with B-cell acute lymphoblastic leukemia in remission, receiving maintenance chemotherapy, who presented with fever, emesis, diarrhea, headache, and lethargy. He developed rapidly progressive cytopenias and was found to have acute human granulocytic anaplasmosis as well as evidence of past infection with Babesia ... Read more >>

J Pediatr Hematol Oncol (Journal of pediatric hematology/oncology)
[2021, :]

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Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia.

Sabrin Tahri, Tarek H Mouhieddine, Robert A Redd, Luisa M Lampe, Katarina I Nilsson, Habib El-Khoury, Nang Kham Su, Amin H Nassar, Elio Adib, Govind Bindra, Sarah Abou Alaiwi, Lorenzo Trippa, David P Steensma, Jorge Castillo, Steven P Treon, Irene M Ghobrial, Adam S Sperling,

Clonal hematopoiesis (CH) is associated with adverse outcomes in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma undergoing autologous stem cell transplantation. Still, its implications for patients with indolent NHL have not been well studied. Here, we report the prevalence of CH in patients with Waldenström macroglobulinemia (WM) and its ... Read more >>

Blood Adv (Blood advances)
[2021, :]

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Clonal hematopoiesis driven by DNMT3A and TET2 mutations: role in monocyte and macrophage biology and atherosclerotic cardiovascular disease.

Isidoro Cobo, Tiffany Tanaka, Christopher K Glass, Calvin Yeang,

<h4>Purpose of review</h4>Clonal hematopoiesis of indeterminate potential (CHIP), defined by the presence of somatic mutations in hematopoietic cells, is associated with advanced age and increased mortality due to cardiovascular disease. Gene mutations in DNMT3A and TET2 are the most frequently identified variants among patients with CHIP and provide selective advantage ... Read more >>

Curr Opin Hematol (Current opinion in hematology)
[2022, 29(1):1-7]

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Suspected clonal hematopoiesis as a natural functional assay of TP53 germline variant pathogenicity.

Cristina Fortuno, Kelly McGoldrick, Tina Pesaran, Jill Dolinsky, Lily Hoang, Jeffrey N Weitzel, Victoria Beshay, Huei San Leong, Paul A James, Amanda B Spurdle,

PURPOSE:Some variants identified by multigene panel testing of DNA from blood present with low variant allele fraction (VAF), often a manifestation of clonal hematopoiesis. Research has shown that the proportion of variants with low VAF is especially high in TP53, the Li-Fraumeni syndrome gene. Based on the hypothesis that variants ... Read more >>

Genet Med (Genetics in medicine : official journal of the American College of Medical Genetics)
[2021, :]

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