Background: Cytarabine is a nucleoside analog used in chemotherapy regimens for the treatment of multiple hematologic malignancies. One of the known adverse effects of cytarabine, particularly in patients receiving high-dose cytarabine (HDAC), is drug-induced fever. Multiple studies have demonstrated an increased risk of viridans group streptococcal bacteremia in patients who have received HDAC. For this reason, our institution and several other institutions across the country routinely include vancomycin as empiric coverage for patients who develop fever during HDAC, due to concern for resistance to cephalosporin monotherapy.
Materials And Methods: Patient demographic, diagnosis, treatment, and outcome information was collected by electronic chart review for each HDAC infusion from 2007 to August 2018 at the University of Iowa Stead Family Children's Hospital. If fever was documented during or within 24 hours of HDAC, additional information was collected regarding patient outcome and diagnostic testing.
Results: Of 208 HDAC administrations documented, patients developed fevers during the course on 82 occasions (39.4%). A median of 3 blood cultures per febrile period were obtained from time of fever onset during HDAC administration through >24 hours afebrile. One blood culture was positive for an oral flora organism determined by the microbiology lab report to be a likely contaminant. There were no other positive blood cultures in non-neutropenic or neutropenic patients.
Conclusion: Fever due to HDAC is relatively common but appears to frequently lack association with bacteremia during the time of HDAC administration. Broad-spectrum empiric antibiotic regimens including vancomycin may be unnecessary for these patients, particularly before they become neutropenic.
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http://dx.doi.org/10.1097/MPH.0000000000002073 | DOI Listing |
J Med Chem
January 2025
Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn institution, An der Immenburg 4, Bonn 53121, Germany.
Targeted protein degradation (TPD) represents a promising alternative to conventional occupancy-driven protein inhibition. Despite the existence of more than 600 E3 ligases in the human proteome, so far only a few have been utilized for TPD of histone deacetylases (HDACs), which represent important epigenetic anticancer drug targets. In this study, we disclose the first-in-class Fem-1 homologue B (FEM1B)-recruiting HDAC degraders.
View Article and Find Full Text PDFJ Med Chem
January 2025
Jiangsu Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Targeting the WDR5-MLL1 protein-protein interaction (PPI) is considered to be an effective approach for the treatment of MLL-rearranged leukemia. However, interfering with WDR5-MLL1 PPI reduces methylated H3K4 levels and induces a decline in acetylated H3 levels, which may contribute to the suboptimal cellular efficacy of WDR5 inhibitors. We observed that cotreatment with WDR5-MLL1 PPI and HDAC inhibitors augmented the antiproliferative effect in MV-4-11 cells.
View Article and Find Full Text PDFThe cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction.
View Article and Find Full Text PDFJAAD Case Rep
January 2025
Department of Dermatology, Columbia University Irving Medical Center, New York, New York.
J Transl Int Med
December 2024
Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Background And Objectives: Histone deacetylase (HDAC) families regulate various physical processes and the development of several diseases. The role of HDACs in asthma development and progression worths further investigation. This study aims to evaluate the effect of HDACs in a mouse model of asthma.
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