journal
https://read.qxmd.com/read/38523019/prognostication-in-chronic-lymphocytic-leukemia
#1
JOURNAL ARTICLE
Riccardo Moia, Gianluca Gaidano
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. CLL is a highly heterogeneous disease: some patients may never require therapy and others relapse several times after different therapeutic strategies. Therefore, in CLL, prognostic markers are essential to capture high-risk patients for different clinical endpoints including early treatment requirement, early progression after BTK or BCL2 inhibitors and Richter transformation. In early stage CLL, different biological and clinical biomarkers have been identified to predict time to treatment requirement that could be used to identify the most appropriate population for early intervention clinical trial...
March 1, 2024: Seminars in Hematology
https://read.qxmd.com/read/38493076/metabolic-reprogramming-in-the-cll-tme-potential-for-new-therapeutic-targets
#2
JOURNAL ARTICLE
Helga Simon-Molas, Chiara Montironi, Anna Kabanova, Eric Eldering
Chronic lymphocytic leukemia (CLL) cells circulate between peripheral (PB) blood and lymph node (LN) compartments, and strictly depend on microenvironmental factors for proliferation, survival and drug resistance. All cancer cells display metabolic reprogramming and CLL is no exception - though the inert status of the PB CLL cells has hampered detailed insight into these processes. We summarize previous work on reactive oxygen species (ROS), oxidative stress, and hypoxia, as well as the important roles of Myc, and PI3K/Akt/mTor pathways...
February 15, 2024: Seminars in Hematology
https://read.qxmd.com/read/38443280/clonal-hematopoiesis
#3
EDITORIAL
Jaroslaw P Maciejewski
No abstract text is available yet for this article.
February 2, 2024: Seminars in Hematology
https://read.qxmd.com/read/38431463/tet2-mutation-as-prototypic-clonal-hematopoiesis-lesion
#4
JOURNAL ARTICLE
Luca Guarnera, Babal K Jha
Loss of function TET2 mutation (TET2MT ) is one of the most frequently observed lesions in clonal hematopoiesis (CH). TET2 a member TET-dioxygenase family of enzymes that along with TET1 and TET3, progressively oxidize 5-methyl cytosine (mC) resulting in regulated demethylation of promoter, enhancer and silencer elements of the genome. This process is critical for efficient transcription that determine cell lineage fate, proliferation and survival and the maintenance of the genomic fidelity with aging of the organism...
February 2, 2024: Seminars in Hematology
https://read.qxmd.com/read/38423847/clonal-hematopoiesis-and-autoimmunity
#5
JOURNAL ARTICLE
Ashwin Kishtagari, Robert W Corty, Valeria Visconte
Clonal hematopoiesis (CH) has been associated with aging, occurring in about 10% of individuals aged >70 years, and immune dysfunction. Aged hematopoietic stem and progenitor cells exhibit pathological changes in immune function and activation of inflammatory pathways. CH clones commonly harbor a loss of function mutation in DNMT3A or TET2, which causes increased expression of inflammatory signaling genes, a proposed mechanism connected to CH and the development of age-related diseases. Additionally, inflammation may stress the hematopoietic compartment, driving the expansion of mutant clones...
February 2, 2024: Seminars in Hematology
https://read.qxmd.com/read/38429201/clonal-hematopoiesis-in-the-setting-of-hematopoietic-cell-transplantation
#6
JOURNAL ARTICLE
Christopher J Gibson, R Coleman Lindsley, Lukasz P Gondek
Clonal hematopoiesis (CH) in autologous transplant recipients and allogeneic transplant donors has genetic features and clinical associations that are distinct from each other and from non-cancer populations. CH in the setting of autologous transplant is enriched for mutations in DNA damage response pathway genes and is associated with adverse outcomes, including an increased risk of therapy-related myeloid neoplasm and inferior overall survival. Studies of CH in allogeneic transplant donors have yielded conflicting results but have generally shown evidence of potentiated alloimmunity in recipients, with some studies showing an association with favorable recipient outcomes...
February 1, 2024: Seminars in Hematology
https://read.qxmd.com/read/38368146/the-molecular-map-of-cll-and-richter-s-syndrome
#7
JOURNAL ARTICLE
Amit Sud, Erin M Parry, Catherine J Wu
Clonal expansion of B-cells, from the early stages of monoclonal B-cell lymphocytosis through to chronic lymphocytic leukemia (CLL), and then in some cases to Richter's syndrome (RS) provides a comprehensive model of cancer evolution, notable for the marked morphological transformation and distinct clinical phenotypes. High-throughput sequencing of large cohorts of patients and single-cell studies have generated a molecular map of CLL and more recently, of RS, yielding fundamental insights into these diseases and of clonal evolution...
January 23, 2024: Seminars in Hematology
https://read.qxmd.com/read/38368147/looking-to-achieve-cure-the-first-time-around-for-dlbcl-patients-who-are-older-and-or-with-co-morbidities
#8
JOURNAL ARTICLE
Elizabeth A Brem, Laurie H Sehn
Diffuse large B-cell lymphoma (DLBCL) is an aggressive but often curable malignancy. Older patients, especially those 80 years and older, have poor outcomes compared to those < 60, likely due to a number of reasons including disease biology, comorbidities, and treatment intolerance. Prospective data informing the treatment of older patients and those with multiple co-morbidities is limited. Here, we intend to review available data for regimens other than standard R-CHOP (rituximab, cyclophosphamide, adriamycin, prednisone) or R-pola-CHP (rituximab, polatuzumab vedotin [pola], cyclophosphamide, adriamycin, prednisone), tools available that may aid in treatment selection, and future directions, including the incorporation of newer treatment modalities into therapy for more vulnerable patients...
January 22, 2024: Seminars in Hematology
https://read.qxmd.com/read/38350765/a-tower-of-babel-of-acronyms-the-shadowlands-of-mgus-mbl-chip-tcus
#9
JOURNAL ARTICLE
Carlos Bravo-Perez, Carmelo Gurnari
With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in otherwise healthy individuals. These conditions do not fulfill the criteria of their presumed cancer counterparts, and thus have been recognized as their precursor states. This is the case of monoclonal gammopathy of unknown significance (MGUS), the first blood premalignancy state described, preceding multiple myeloma (MM) or Waldenström macroglobulinemia (WM)...
January 19, 2024: Seminars in Hematology
https://read.qxmd.com/read/38403501/the-crossroads-of-cancer-therapies-and-clonal-hematopoiesis
#10
JOURNAL ARTICLE
Abhay Singh, Suresh Balasubramanian
The intricate interplay between Clonal Hematopoiesis (CH) and the repercussions of cancer therapies has garnered significant research focus in recent years. Previously perceived as an age-related phenomenon, CH is now closely linked to inflammation ("Inflammaging") and cancer, impacting leukemogenesis, cancer progression, and treatment responses. This review explores the complex interplay between CH and diverse cancer therapies, including chemotherapy, targeted treatments, radiation, stem cell transplants, CAR-T cell therapy, and immunotherapy, like immune checkpoint inhibitors...
January 18, 2024: Seminars in Hematology
https://read.qxmd.com/read/38341340/immune-driven-clonal-cell-selection-at-the-intersection-among-cancer-infections-autoimmunity-and-senescence
#11
JOURNAL ARTICLE
Simona Pagliuca, Francesca Ferraro
Immune surveillance mechanisms play a crucial role in maintaining lifelong immune homeostasis in response to pathologic stimuli and aberrant cell states. However, their persistence, especially in the context of chronic antigenic exposure, can create a fertile ground for immune evasion. These escaping cell phenotypes, harboring a variety of genomic and transcriptomic aberrances, chiefly in human leukocyte antigen (HLA) and antigen presentation machinery genes, may survive and proliferate, featuring a scenario of clonal cell expansion with immune failure characteristics...
January 17, 2024: Seminars in Hematology
https://read.qxmd.com/read/38311515/clonal-hematopoiesis-in-children-with-predisposing-conditions
#12
JOURNAL ARTICLE
Enrico Attardi, Seth J Corey, Marcin W Wlodarski
Clonal hematopoiesis in children and young adults differs from that occuring in the older adult population. A variety of stressors drive this phenomenon, sometimes independent of age-related processes. For the purposes of this review, we adopt the term clonal hematopoiesis in predisposed individuals (CHIPI) to differentiate it from classical, age-related clonal hematopoiesis of indeterminate potential (CHIP). Stress-induced CHIPI selection can be extrinsic, such as following immunologic, infectious, pharmacologic, or genotoxic exposures, or intrinsic, involving germline predisposition from inherited bone marrow failure syndromes...
January 14, 2024: Seminars in Hematology
https://read.qxmd.com/read/38311514/germline-predisposition-for-clonal-hematopoiesis
#13
JOURNAL ARTICLE
Yasuo Kubota, Aaron D Viny
Clonal hematopoiesis (CH) is an entity hallmarked by skewed hematopoiesis with persistent overrepresentation of cells from a common stem/progenitor lineage harboring single-nucleotide variants and/or insertions/deletions. CH is a common and age-related phenomenon that is associated with an increased risk of hematological malignancies, cardiovascular disease, and all-cause mortality. While CH is a term of the hematological aspect, there exists a complex interaction with other organ systems, especially the cardiovascular system...
January 14, 2024: Seminars in Hematology
https://read.qxmd.com/read/38302313/vaccinations-in-patients-with-chronic-lymphocytic-leukemia
#14
JOURNAL ARTICLE
Elizabeth R Francis, Jennifer Vu, Catherine Ostos Perez, Clare Sun
Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction resulting in heightened susceptibility to infections and elevated rates of morbidity and mortality. A key strategy to mitigate infection-related complications has been immunization against common pathogens. However, the immunocompromised status of CLL patients poses challenges in eliciting an adequate humoral and cellular immune response to vaccination. Most CLL-directed therapy disproportionately impairs humoral immunity. Vaccine responsiveness also depends on the phase and type of immune response triggered by immunization...
January 6, 2024: Seminars in Hematology
https://read.qxmd.com/read/38290860/transforming-cll-management-with-immunotherapy-investigating-the-potential-of-car-t-cells-and-bispecific-antibodies
#15
JOURNAL ARTICLE
Azra Borogovac, Tanya Siddiqi
Immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies or T-cell engagers, have revolutionized the treatment landscape for various B-cell malignancies, including B-acute lymphoblastic leukemia and many non-Hodgkin lymphomas. Despite their significant impact on these malignancies, their application in chronic lymphocytic leukemia (CLL) management is still largely under investigation. Although the initial success of CD19-directed CAR T-cell therapy was observed in 3 multiply relapsed CLL patients, with 2 of them surviving over 10 years without relapse, recent CAR T-cell therapy trials in CLL have shown reduced response rates compared to their efficacy in other B-cell malignancies...
January 5, 2024: Seminars in Hematology
https://read.qxmd.com/read/38242773/b-cell-receptor-immunoglobulin-stereotypy-in-chronic-lymphocytic-leukemia-key-to-understanding-disease-biology-and-stratifying-patients
#16
JOURNAL ARTICLE
Andreas Agathangelidis, Thomas Chatzikonstantinou, Kostas Stamatopoulos
Sequence convergence, otherwise stereotypy, of B cell receptor immunoglobulin (BcR IG) from unrelated patients is a distinctive feature of the IG gene repertoire in chronic lymphocytic leukemia (CLL) whereby patients expressing a particular BcR IG archetype are classified into groups termed stereotyped subsets. From a biological perspective, the fact that a considerable fraction (∼41%) of patients with CLL express (quasi)identical or stereotyped BcR IG underscores the key role of antigen selection in the natural history of CLL...
December 26, 2023: Seminars in Hematology
https://read.qxmd.com/read/38220499/role-of-the-tumor-microenvironment-in-cll-pathogenesis
#17
JOURNAL ARTICLE
Alexander F Vom Stein, Michael Hallek, Phuong-Hien Nguyen
Chronic lymphocytic leukemia (CLL) cells extensively interact with and depend on their surrounding tumor microenvironment (TME). The TME encompasses a heterogeneous array of cell types, soluble signals, and extracellular vesicles, which contribute significantly to CLL pathogenesis. CLL cells and the TME cooperatively generate a chronic inflammatory milieu, which reciprocally reprograms the TME and activates a signaling network within CLL cells, promoting their survival and proliferation. Additionally, the inflammatory milieu exerts chemotactic effects, attracting CLL cells and other immune cells to the lymphoid tissues...
December 26, 2023: Seminars in Hematology
https://read.qxmd.com/read/38326144/integration-of-pet-in-dlbcl
#18
JOURNAL ARTICLE
Katharine L Lewis, Judith Trotman
F-fluorodeoxyglucose positron emission tomography-computerized tomography (18 FDG-PET/CT) is the gold-standard imaging modality for staging and response assessment for most lymphomas. This review focuses on the utility of 18 FDG-PET/CT, and its role in staging, prognostication and response assessment in diffuse large B-cell lymphoma (DLBCL), including emerging possibilities for future use.
December 24, 2023: Seminars in Hematology
https://read.qxmd.com/read/38342663/second-line-treatment-of-diffuse-large-b-cell-lymphoma-evolution-of-options
#19
JOURNAL ARTICLE
N Fabbri, A Mussetti, A Sureda
In the era of immunochemotherapy, approximately 60%-70% of diffuse large B-cell lymphoma (DLBCL) patients achieve remission with first-line rituximab-based chemoimmunotherapy. However, 30%-40% relapse after initial response to first-line therapy and, out of them, 20%-50% are refractory or experience early relapse. The second-line therapy algorithm for DLBCL has recently evolved, thanks to the recent approval of new therapeutic agents or their combinations. The new guidelines suggest a stratification of relapsed/refractory (R/R) DLBCL based on the time to relapse...
December 14, 2023: Seminars in Hematology
https://read.qxmd.com/read/38199906/effective-sequencing-of-chimeric-antigen-receptor-t-cell-therapy-in-the-treatment-of-lbcl-in-2023
#20
JOURNAL ARTICLE
Christine E Ryan, Caron A Jacobson
Over the last decade, CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has profoundly changed the management of relapsed/refractory large-B-cell lymphoma (LBCL). At present, there are three FDA-approved anti-CD19 CAR T-cell products for LBCL: axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). Two of these (axi-cel & liso-cel) are approved for use in the second-line setting under certain conditions. As CAR T-cell therapy continues to define a new role in the treatment armamentarium for LBCL, questions remain regarding which product to use and how to sequence CAR T-cell therapy with other therapeutic options...
December 12, 2023: Seminars in Hematology
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