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Heidelberg, Australia

Banerjee A.,MIMR PHI Institute of Medical Research | Banerjee A.,Monash University | Mifsud N.A.,Monash University | Bird R.,Haematology | And 11 more authors.
British Journal of Haematology | Year: 2015

Summary: The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies. © 2014 John Wiley & Sons Ltd. Source


Herbrecht R.,Hopital de Hautepierre | Cernohous P.,Cell Therapeutics | Engert A.,University of Cologne | Le Gouill S.,Hematology Service | And 7 more authors.
Annals of Oncology | Year: 2013

Background: Pixantrone is an aza-anthracenedione with enhanced, preclinical antitumor activity and reduced cardiotoxicity compared with doxorubicin. Patients and methods: We compared the efficacy and toxic effect of CPOP-R (substituting pixantrone for doxorubicin) against CHOP-R in untreated, diffuse large B-cell lymphoma (DLBCL) patients. The primary objective was to demonstrate non-inferiority of CPOP-R by complete response/complete response unconfirmed (CR/CRu) rate. Results: The CR/CRu rate for CPOP-R was 75% versus 84% for CHOP-R. Three-year overall survival was lower for CPOP-R (69% versus 85%) (P = 0.029). Median progression-free survival (PFS) was not reached for CPOP-R and was 40 months for CHOP-R [HR 95% confidence interval (CI) = 1.02 (0.60, 1.76), P = 0.934]. Fewer CPOP-R patientsdeveloped congestive heart failure (CHF) (0% versus 6%, P = 0.120), >20% declines in ejection fraction (2% versus 17%, P = 0.004), or elevations in troponin-T (P = 0.003). Conclusions: CPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL. © The Author 2013. Source


Andersen S.,Royal Brisbane and Womens Hospital | Kennedy G.,Clinical Haematology | Kennedy G.,University of Queensland | Banks M.,Royal Brisbane and Womens Hospital
Clinical Nutrition ESPEN | Year: 2015

Background and aims: Nutritional support during allogeneic haematopoietic progenitor cell transplantation (HPCT) is imperative to prevent malnutrition and poorer patient outcomes. However, there is little literature on the most efficacious approach, leading to wide variation in the use of enteral (EN) and parenteral (PN) feeding across HPCT units. This study aimed to determine the tolerability and efficacy of EN versus PN in patients undertaking allogeneic HPCT. Methods: A randomised controlled trial was conducted from September 2011 to January 2013. Patients were randomized to receive either EN (nasogastric) or PN if nutrition support was required, however those with severe gastro-intestinal toxicity, including severe mucositis, were excluded from randomisation. If patients did not tolerate the type of feeding given they were swapped to the alternate route. Results: Nine patients were able to be randomized between EN (n = 5) and PN (n = 4). The patients randomized to EN all required changing to PN due to gastro-intestinal intolerance (p ≤ 0.01). None of the patients receiving PN required changing to EN. Conclusions: This study demonstrates that due to the significant gastrointestinal toxicity, EN was not feasible to commence when oral intake became inadequate. This study was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Number ACTRN12611001084976. © 2015 European Society for Clinical Nutrition and Metabolism. Source


Tran H.,Haemostasis Thrombosis Unit | Joseph J.,St. Vincents Hospital | Young L.,Clinical Haematology | Mcrae S.,Haemophilia Treatment Center | And 4 more authors.
Internal Medicine Journal | Year: 2014

New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or 'reverse' the anticoagulant effects for urgent invasive procedures. © 2014 Royal Australasian College of Physicians. Source


Siderov J.,Cancer Services | Duggan J.,Clinical Haematology
Journal of Oncology Pharmacy Practice | Year: 2010

Arsenic trioxide in the treatment of acute promyelocytic leukaemia is relatively safe with minimal side effects. Dental toxicities associated with its use are uncommon. We describe the first case report of toothache associated with arsenic trioxide. A 45-year-old male with relapsed APL was commenced on a treatment schedule of all-trans-retinoic acid 20mg four times a day for 14 days concurrent with a 10mg intravenous infusion of arsenic trioxide for 28 days. After 14 doses of the 6th cycle of treatment he experienced severe acute pain in various parts of the oral cavity. Extensive examination including an orthodontic review concluded there was no indication that the pain symptoms were due to a dental or endodontic cause. Four days after completing his 6th cycle the pain completely resolved. The mechanism of this adverse event remains unclear. Physicians with patients receiving arsenic trioxide with unexplained toothache should consider the arsenic as the cause of the pain. © 2010 SAGE Publications. Source

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