ORCID Profile
0000-0002-5759-6162
Current Organisations
UNSW Sydney
,
Cancer Institute NSW
,
Sydney Childrens Hopsital
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Publisher: American Society of Hematology
Date: 29-05-2018
DOI: 10.1182/BLOODADVANCES.2018016956
Abstract: Children receiving BuFlu for nonmalignant conditions experienced less toxicity than those receiving BuCy, but survival was comparable. Children with malignancy had shorter postrelapse survival with BuFlu than BuCy transplant-related mortality and relapse were similar.
Publisher: JMIR Publications Inc.
Date: 25-10-2017
Publisher: JMIR Publications Inc.
Date: 04-05-2018
DOI: 10.2196/RESPROT.9258
Publisher: Wiley
Date: 16-08-2022
DOI: 10.1111/JPC.15698
Abstract: Blood and platelets are scarce resources that are an essential part of the supportive care for paediatric cancer patients. There are many inherent risks involved with transfusions including acute transfusion reactions (ATRs). Following an initial ATR, prophylactic medications are commonly given prior to subsequent transfusions. However, there are risks with medication administration as well as negative implications for the health system. Our aim was to prevent the automatic prescribing of premedications prior to blood and platelet transfusions for ATRs. We hypothesised this would not increase the risk of harm. Our intervention was to eliminate automatic prescribing of intravenous corticosteroids and intravenous promethazine prior to a transfusion. This was approached through a behaviour change model and the implementation of recommended prescribing guidelines. Three Plan Do Study Act (PDSA) cycles refined the guidelines to align with clinicians' needs and build support through co-design. Data gathered on in idual patients receiving transfusions and reaction rates during the trial were compared to international data. A total of 100 patients received a transfusion during the trial. Eleven patients either had a previous reaction or experienced their first reaction during this time. All patients followed the guidelines and had either no premedication or an oral antihistamine premedication. There were no breakthrough reactions using oral antihistamines. The overall reaction rate was 1.33%, which aligns with the reported data on ATRs internationally. A restricted prescribing approach to pharmaceutical cover prior to blood and platelet transfusions can be implemented effectively in a paediatric cancer population, without an increase in the risk of harm to the patients.
Publisher: Springer Science and Business Media LLC
Date: 09-10-2023
Publisher: American Society of Hematology
Date: 26-10-2023
Abstract: Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay of transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs - FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2 - bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remained unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (the Heptad, PU.1, CTCF, and STAG2) in HSPC subsets (HSC-MPP, CMP, GMP, MEP) and found that TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs such as PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type-specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of specific TF complexes was at least partially regulated by features encoded in specific DNA sequence motifs. Taken together, this study provides a comprehensive characterisation of the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying datasets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analysing aberrant regulatory networks in leukemic cells.
Publisher: Wiley
Date: 24-09-2020
DOI: 10.1002/PBC.28715
No related grants have been discovered for Tracey O'Brien.