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BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies.
Blood Rev
January 2025
Clinic of Hematology, University Clinical Centre of Serbia, Serbia; Faculty of Medicine, University of Belgrade, Serbia. Electronic address:
Targeted therapies, consisting of Bruton tyrosine kinase inhibitors (BTKis) or BCL-2 inhibitors, are the mainstay of contemporary treatments for chronic lymphocytic leukemia (CLL). The most common adverse effects (AEs) of BTKis are fatigue, bruising, infection, hematological and cardiovascular AEs. While AEs during treatment are usually mild (grades 1 and 2), grade 3 and 4 AEs have been detected in some patients, necessitating additional medical care and temporary or permanent drug discontinuation.
View Article and Find Full Text PDFCentral nervous system posttransplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation successfully treated with combination therapy of acalabrutinib and immunochemotherapy: A case report and literature review.
EJHaem
February 2025
Department of Lymphoma and Myeloma Research Center Beijing Gobroad Boren Hospital Beijing China.
Here, we report a case of Epstein-Barr virus-positive central nervous system-post-transplant lymphoproliferative disorder (CNS-PTLD) patient who failed to achieve complete metabolic remission (CMR) after successively trying a methotrexate-based regimen combined with orelabrutinib or whole-brain radiotherapy and encountered intracranial hemorrhage during orelabrutinib treatment. Ultimately, the patient achieved CMR after one cycle of acalabrutinib in combination with temozolomide, teniposide, liposomal doxorubicin, dexamethasone, and rituximab (TEDDi-R). Following another cycle of TEDDi-R treatment, he has been receiving acalabrutinib maintenance up to now and remained in CMR.
View Article and Find Full Text PDFManaging novel therapies and concomitant medications in chronic lymphocytic leukemia: key challenges.
Front Pharmacol
January 2025
Clinic of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia.
The treatment of chronic lymphocytic leukemia (CLL) consists of the continuous use of Bruton tyrosine kinase inhibitors (BTKis) such as ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib, or Bcl-2 inhibitors, such as venetoclax. Overall survival (OS) and progression-free survival (PFS) of CLL patients are significantly improved with the use of these therapies. Adverse effects (AEs) that can occur during treatment and the presence of pre-existing comorbidities in patients can influence subsequent treatment outcomes and, consequently, OS and PFS.
View Article and Find Full Text PDFDifferentiation of the chronic lymphocytic leukemia response to ibrutinib and acalabrutinib treatment by single-cell MALDI-TOF MS imaging.
J Pharm Biomed Anal
March 2025
Clinical Institute of Laboratory Diagnostics, University Hospital Centre Osijek, J. Huttlera 4, Osijek 31 000, Croatia; Faculty of Medicine Osijek, JJ Strossmayer University of Osijek, J. Huttlera 4, Osijek 31 000, Croatia. Electronic address:
Ibrutinib and acalabrutinib, Bruton's tyrosine kinase inhibitors (BTKi) used for chronic lymphocytic leukemia (CLL) treatment, aim the same target but their off-target effects are different. The aim of this study was to use single-cell MALDI TOF mass spectrometry imaging to compare the CD19+ lymphocytes' mass spectra in untreated and ibrutinib- or acalabrutinib-treated subjects in order to better understand the therapeutic effect of BTKi. 180 cells from 9 male subjects divided in 3 groups (untreated, ibrutinib-treated and acalabrutinib-treated) were analyzed using MALDI-TOF mass spectrometry analyzer.
View Article and Find Full Text PDFImpact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia.
Elife
December 2024
Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, United States.
Inhibition of Bruton's tyrosine kinase (BTK) has proven to be highly effective in the treatment of B-cell malignancies such as chronic lymphocytic leukemia (CLL), autoimmune disorders, and multiple sclerosis. Since the approval of the first BTK inhibitor (BTKi), Ibrutinib, several other inhibitors including Acalabrutinib, Zanubrutinib, Tirabrutinib, and Pirtobrutinib have been clinically approved. All are covalent active site inhibitors, with the exception of the reversible active site inhibitor Pirtobrutinib.
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