Journal articles on the topic 'Blood donors – Australia'
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1
Rooks, Kelly, Clive R. Seed, Jesse J. Fryk, Catherine A. Hyland, Robert J. Harley, Jerry A. Holmberg, Denese C. Marks, Robert L. P. Flower, and Helen M. Faddy. "Mitigating the Risk of Transfusion-Transmitted Dengue in Australia." Journal of Blood Transfusion 2016 (November 13, 2016): 1–6. http://dx.doi.org/10.1155/2016/3059848.
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Dengue viruses (DENV 1–4) are a risk to transfusion safety, with several transfusion-transmitted (TT) cases reported globally. DENV 1–4 are endemic in over 100 countries, with seasonal outbreaks occurring in northeastern Australia. To mitigate TT-DENV risk in Australia, fresh blood components are not manufactured from donors returning from any area (domestic/overseas) with known dengue transmission. Alternatively, TT-DENV risk may be mitigated using an appropriate blood donor screening assay. We aimed to determine the rate of dengue infection in donors during dengue outbreaks in Australia. Plasma samples were collected from blood donors during local dengue outbreaks. All samples were tested for the presence of DENV RNA and selected samples were tested for DENV antigen (nonstructural protein 1, NS1) with two assays. No donors residing in high risk areas had detectable levels of DENV RNA or NS1 and no cases of DENV viremia were detected in blood donors residing in areas of Australia experiencing DENV outbreaks. Definitive conclusions could not be drawn from this study; however, the lack of detection of DENV RNA or antigen in donations suggests that the current risk of TT-DENV is low and maintaining the fresh component restriction for “at-risk” donors is appropriate.
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Speicher, David J., Jesse J. Fryk, Victoria Kashchuk, Helen M. Faddy, and Newell W. Johnson. "Human Herpesvirus 8 in Australia: DNAemia and Cumulative Exposure in Blood Donors." Viruses 14, no. 10 (October 3, 2022): 2185. http://dx.doi.org/10.3390/v14102185.
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Human herpesvirus 8 (HHV-8), the causative agent of Kaposi’s sarcoma, multicentric Castleman’s disease and primary effusion lymphoma, predominantly manifests in immunocompromised individuals. However, infection in immunocompetent individuals does occur. The prevalence of HHV-8 exposure in blood donors from non-endemic countries ranges between 1.2% and 7.3%. Nothing was known about the prevalence in Australian blood donors. Therefore, this study investigated the active and cumulative exposure of HHV-8 in this cohort. Plasma samples (n = 480) were collected from eastern Australian blood donors and were tested for HHV-8 DNA by qPCR, and for HHV-8 antibodies by two different ELISAs. Samples initially positive on either ELISA were retested in duplicate on both, and on a mock-coated ELISA. Any samples positive two or three out of the three times tested on at least one ELISA, and repeat negative on the mock-coated ELISA, were assigned as repeat positive. None of the 480 samples tested contained HHV-8 DNA. Serological testing revealed 28 samples (5.83%; 95% CI: 3.74−7.93%) had antibodies to HHV-8. There was no difference (p > 0.05) in seropositivity between sex or with increasing age. This is the first study to show serological evidence of cumulative HHV-8 exposure and no HHV-8 DNAemia within a select blood donor population in Australia. Our molecular and serological data is consistent with published results for blood donors residing in HHV-8 non-endemic countries, which shows the prevalence to be very low.
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Reinicke, V., H. Poulsen, O. Banke, and E. Dybkjaer. "THE SIGNIFICANCE OF AUSTRALIA-ANTIBODY IN BLOOD DONORS." Acta Pathologica Microbiologica Scandinavica Section B Microbiology and Immunology 81B, no. 6 (August 15, 2009): 753–56. http://dx.doi.org/10.1111/j.1699-0463.1973.tb02271.x.
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Wood, Robyn, and Richard Pembrey. "Blood supply protection: how much is enough?" Microbiology Australia 26, no. 1 (2005): 10. http://dx.doi.org/10.1071/ma05010.
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The delivery and maintenance of a safe blood supply are imperative for Australia?s security and medical advancement. Practices such as the use of voluntary nonremunerated donors (1927), and early coordination to identify optimal testing regimes, e.g. for Hepatitis B virus (HBV) 1975, Human Immunodeficiency virus (HIV) 1985 and Hepatitis C virus (HCV) 1990, have ensured the Australian public are at minimal risk of exposure to unsafe blood. However, the AIDS epidemic did reveal significant flaws and weaknesses in our delivery of a safe blood supply, unfortunately with some devastating ramifications. Since that time, public tolerance of adverse events following receipt of infectious donations is very low. Does Australia now have a safe blood supply, and is safety assured against future potential catastrophes?
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Lopez, Genghis H., Brett Wilson, Robyn M. Turner, Glenda M. Millard, Nicole S. Fraser, Naomi M. Roots, Yew-Wah Liew, Catherine A. Hyland, and Robert L. Flower. "Frequency of Mia (MNS7) and Classification of Mia-Positive Hybrid Glycophorins in an Australian Blood Donor Population." Transfusion Medicine and Hemotherapy 47, no. 4 (November 14, 2019): 279–87. http://dx.doi.org/10.1159/000504026.
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Background: MNS blood group system genes GYPA and GYPB share a high degree of sequence homology and gene structure. Homologous exchanges between GYPA and GYPB form hybrid genes encoding hybrid glycophorins GP(A-B-A) and GP(B-A-B). Over 20 hybrid glycophorins have been characterised. Each has a distinct phenotype defined by the profile of antigens expressed including Mia. Seven hybrid glycophorins carry Mia and have been reported in Caucasian and Asian population groups. In Australia, the population is diverse; however, the prevalence of hybrid glycophorins in the population has never been determined. The aims of this study were to determine the frequency of Mia and to classify Mia-positive hybrid glycophorins in an Australian blood donor population. Method: Blood samples from 5,098 Australian blood donors were randomly selected and screened for Mia using anti-Mia monoclonal antibody (CBC-172) by standard haemagglutination technique. Mia-positive red blood cells (RBCs) were further characterised using a panel of phenotyping reagents. Genotyping by high-resolution melting analysis and DNA sequencing were used to confirm serology. Result: RBCs from 11/5,098 samples were Mia-positive, representing a frequency of 0.22%. Serological and molecular typing identified four types of Mia-positive hybrid glycophorins: GP.Hut (n = 2), GP.Vw (n = 3), GP.Mur (n = 5), and 1 GP.Bun (n = 1). GP.Mur was the most common. Conclusion: This is the first comprehensive study on the frequency of Mia and types of hybrid glycophorins present in an Australian blood donor population. The demographics of Australia are diverse and ever-changing. Knowing the blood group profile in a population is essential to manage transfusion needs.
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Wong, Dodd, Kiely, Carroll, and Whyte. "Characteristics of hepatitis C-positive blood donors in Victoria, Australia." Transfusion Medicine 9, no. 1 (January 1999): 15–19. http://dx.doi.org/10.1046/j.1365-3148.1999.009001015.x.
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Linnen, Jeffrey M., Elizabeth Vinelli, Ester C. Sabino, Leslie H. Tobler, Catherine Hyland, Tzong-Hae Lee, Daniel P. Kolk, et al. "Dengue viremia in blood donors from Honduras, Brazil, and Australia." Transfusion 48, no. 7 (July 2008): 1355–62. http://dx.doi.org/10.1111/j.1537-2995.2008.01772.x.
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Polizzotto, Mark N., Erica M. Wood, Helen Ingham, and Anthony J. Keller. "Choosing Donors Wisely. Reducing the Risk of Transfusion-Transmissible Viral Infection through Blood Donor Selection: The Australian Experience 2000–2006." Blood 110, no. 11 (November 16, 2007): 2910. http://dx.doi.org/10.1182/blood.v110.11.2910.2910.
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Abstract Selection of voluntary donors who are at low risk of transfusion-transmissible viral infection (TTVI) is central in maintaining the safety of the blood supply. Evaluation of the effectiveness of donor selection and the dynamics of the process may offer opportunities to further improve transfusion safety. We analysed the impact of donor selection on the relative prevalence of TTVIs in all allogeneic donations in Australia between July 2000 and June 2006. We further explored the donor selection process where donors were found to have a TTVI despite pre-donation screening. Donors repeat reactive for a TTVI were offered counselling and confidential interview where potential infective risk exposures were reassessed, and disclosure of risk exposures at initial screening re-evaluated. 6,274,144 donations were received during the study period and tested for HCV, HBV, HIV, and HTLVI/II; of these, 1449 (0.02%) were repeat reactive for at least one TTVI and were discarded. Twenty-nice (2.5%) positive donors were not contactable or declined interview, giving an interview participation rate of 98.5%; all 1449 positive donors are included in the prevalence analysis. This comprised 605 (42%) positive for Hepatitis B; 818 (56%) positive for Hepatitis C; 18 (1%) positive for HIV; and 20 (1%) positive for HTLVI/II. The prevalence of HBV in accepted donors was at least 50 times lower than that in the Australian population; for HCV, 75 times lower; and HIV for 350 times lower. In new donors the prevalence was at least 6 times lower for HBV, 12 times lower for HCV and 140 times lower for HIV. In 1158 of 1420 donors interviewed (80%) an infective risk was identified; 509 donors (44%) had more than one risk. The most common identified were country of birth and parental ethnicity (N=682, 26% of reported risks); tattoos/piercings (N=448, 18%); and intravenous drug use (N=302, 12%). Other common risks included surgery or endoscopy (201 donors, 8%); receipt of blood products (N=144, 6%); and other blood contact, such as following sporting injuries (N=232, 10%). High-risk sexual contacts were uncommon risk exposures, but disproportionately significant in donors with HIV. Many of the identified risk exposures were temporally remote. The relative importance of risks varied significantly between TTVIs. In 302 cases (21%) disclosure of the identified risk exposures at pre-donation screening would have resulted in donor deferral. The proportion of positive donations which would not have been accepted had exposures been reported accurately was 3% for HBV; 35% for HCV; 39% for HIV; and 5% for HTLVI/II. Factors influencing non-disclosure included the temporal remoteness or isolated nature of the exposure, belief behaviour was not high-risk (eg, that needles were not shared during drug use), and perceptions that laboratory testing rendered disclosure unnecessary. Concerns about privacy or confidentiality of personal information were uncommon. These findings affirm the effectiveness of current stringent donor selection criteria in reducing the residual risk of TTVI. Ongoing donor education regarding the importance of risk disclosure is required. The development of screening criteria for use with emerging infections also offers continued opportunity for further improvements in transfusion safety.
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J. Kokani, Dr Mayur, and Dr Chiragkumar B. Menapara. "Seroprevalence of Australia antigen (HbsAg) among blood donors in local population." Tropical Journal of Pathology and Microbiology 4, no. 7 (November 30, 2018): 512–17. http://dx.doi.org/10.17511/jopm.2018.i07.06.
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Patel, Dr Kamini, Dr Sunita Mistry, Dr Kamlesh Shah, and Dr Niraj Patel. "Seroprevalence of Australia antigen (HbsAg) among blood donors in local population." Tropical Journal of Pathology and Microbiology 5, no. 11 (November 30, 2019): 942–47. http://dx.doi.org/10.17511/jopm.2019.i11.17.
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Hoad, Veronica C., Philip Kiely, Clive R. Seed, Elvina Viennet, and Iain B. Gosbell. "An Outbreak of Japanese Encephalitis Virus in Australia; What Is the Risk to Blood Safety?" Viruses 14, no. 9 (August 31, 2022): 1935. http://dx.doi.org/10.3390/v14091935.
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A widespread outbreak of Japanese encephalitis virus (JEV) was detected in mainland Australia in 2022 in a previous non-endemic area. Given JEV is known to be transfusion-transmissible, a rapid blood-safety risk assessment was performed using a simple deterministic model to estimate the risk to blood safety over a 3-month outbreak period during which 234,212 donors attended. The cumulative estimated incidence in donors was 82 infections with an estimated 4.26 viraemic components issued, 1.58 resulting in transfusion-transmission and an estimated risk of encephalitis of 1 in 4.3 million per component transfused over the risk period. Australia has initiated a robust public health response, including vector control, animal control and movement, and surveillance. Unlike West Nile virus, there is an effective vaccine that is being rolled-out to those at higher risk. Risk evaluation considered options such as restricting those potentially at risk to plasma for fractionation, which incorporates additional pathogen reduction, introducing a screening test, physicochemical pathogen reduction, quarantine, post donation illness policy changes and a new donor deferral. However, except for introducing a new deferral to potentially cover rare flavivirus risks, no option resulted in a clear risk reduction benefit but all posed threats to blood sufficiency or cost. Therefore, the blood safety risk was concluded to be tolerable without specific mitigations.
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Solaas, Marit Hornberg. "Frequency of the Australia-SH Antigen and Antibody among Norwegian Blood Donors." Scandinavian Journal of Haematology 7, no. 6 (April 24, 2009): 506–8. http://dx.doi.org/10.1111/j.1600-0609.1970.tb01938.x.
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Klamer, Guy, Jessica Sue, Kap-Hyoun Ko, Annette Trickett, Phillip Johnson, and Ngaire Elwood. "Abstract 26 HLA Analysis of the Australian Cord Blood Banks: How Diverse Are Donors?" Stem Cells Translational Medicine 11, Supplement_1 (September 1, 2022): S31. http://dx.doi.org/10.1093/stcltm/szac057.026.
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Abstract Introduction The network of public cord blood banks (CBB) in Australia, known as AusCord, is comprised of CBB located in Brisbane, Sydney, and Melbourne. The network stores almost 37,000 cord blood units (CBU) and has released more than 1,300 for transplantation. Objective The objectives of this study were (1) to determine the relative diversity of HLA allele subtypes, tissue types, and haplotypes at each of the banks and between the banks and (2) to identify common tissue types and haplotypes that could be utilized for clinical research and development of third party cell therapy products. Methods HLA data was obtained for 36,782 CBU stored in the AusCord inventory. To standardize data format, high-resolution typing was converted to 2-digit typing. HLA allele subtypes were ranked from most to least common. A subset of Indigenous Australian and Pacific Islander HLA allele subtypes was interrogated to determine whether increased frequency correlated with declared ethnicity. Tissue types were separated into CBU that had HLA-A, HLA-B, HLA-C, and HLA-DRB1 typing (21,815 total) and CBU that did not have HLA-C typing (36,782 total). CBU tissue types were interrogated in 3 separate groups: searchable, searched, and released inventory. Haplotypes were confirmed where maternal typing was available (3,105 CBU). Results Ethnicity screening for donors and strategic location of collection sites servicing ethnic minority communities resulted in banking of Indigenous Australian and Pacific Islander HLA. At a bank and network level, there was a similar frequency of specific HLA subtypes; however, when considering the tissue types, there was vast diversity (~75% unique with 8 allele typing). Whilst there is diversity, there was also a fraction of the inventory that exhibited repetitive tissue types that could be utilized for clinical research. Discussion The study demonstrates that cord blood collections are able to boost storage of diverse tissue types in, and unique to, a multicultural population such as Australia. This finding can guide policy development and funding, as well as operational decisions at the CBB. Furthermore, CBB are well positioned to support research and development activity aimed at discovery of new applications for cord blood units through supply of GMP grade cryopreserved products exhibiting common tissue types and haplotypes.
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Garg, Amit X., Jennifer B. Arnold, Meaghan Cuerden, Christine Dipchand, Liane S. Feldman, John S. Gill, Martin Karpinski, et al. "The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study." Canadian Journal of Kidney Health and Disease 9 (January 2022): 205435812211294. http://dx.doi.org/10.1177/20543581221129442.
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Background: Living kidney donation is considered generally safe in healthy individuals; however, there is a need to better understand the long-term effects of donation on blood pressure and kidney function. Objectives: To determine the risk of hypertension in healthy, normotensive adults who donate a kidney compared with healthy, normotensive non-donors with similar indicators of baseline health. We will also compare the 2 groups on the rate of decline in kidney function, the risk of albuminuria, and changes in health-related quality of life. Design, Participants, and Setting: Prospective cohort study of 1042 living kidney donors recruited before surgery from 17 transplant centers (12 in Canada and 5 in Australia) between 2004 and 2014. Non-donor participants (n = 396) included relatives or friends of the donor, or donor candidates who were ineligible to donate due to blood group or cross-match incompatibility. Follow-up will continue until 2021, and the main analysis will be performed in 2022. The anticipated median (25th, 75th percentile, maximum) follow-up time after donation is 7 years (6, 8, 15). Measurements: Donors and non-donors completed the same schedule of measurements at baseline and follow-up (non-donors were assigned a simulated nephrectomy date). Annual measurements were obtained for blood pressure, estimated glomerular filtration rate (eGFR), albuminuria, patient-reported health-related quality of life, and general health. Outcomes: Incident hypertension (a systolic/diastolic blood pressure ≥ 140/90 mm Hg or receipt of anti-hypertensive medication) will be adjudicated by a physician blinded to the participant’s donation status. We will assess the rate of change in eGFR starting from 12 months after the nephrectomy date and the proportion who develop an albumin-to-creatinine ratio ≥3 mg/mmol (≥30 mg/g) in follow-up. Health-related quality of life will be assessed using the 36-item RAND health survey and the Beck Anxiety and Depression inventories. Limitations: Donation-attributable hypertension may not manifest until decades after donation. Conclusion: This prospective cohort study will estimate the attributable risk of hypertension and other health outcomes after living kidney donation.
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Best, Denisse, Kevin Burrage, Pamela Burrage, Diane Donovan, Shamila Ginige, Tanya Powley, Bevan Thompson, and James Daly. "Probabilistic mathematical modelling to predict the red cell phenotyped donor panel size." PLOS ONE 17, no. 11 (November 11, 2022): e0276780. http://dx.doi.org/10.1371/journal.pone.0276780.
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In the last decade, Australia has experienced an overall decline in red cell demand, but there has been an increased need for phenotyped matched red cells. Lifeblood and mathematicians from Queensland universities have developed a probabilistic model to determine the percentage of the donor panel that would need extended antigen typing to meet this increasing demand, and an estimated timeline to achieve the optimum required phenotyped (genotyped) panel. Mathematical modelling, based on Multinomial distributions, was used to provide guidance on the percentage of typed donor panel needed, based on recent historical blood request data and the current donor panel size. Only antigen combinations determined to be uncommon, but not rare, were considered. Simulations were run to attain at least 95% success percentage. Modelling predicted a target of 38% of the donor panel, or 205,000 donors, would need to be genotyped to meet the current demand. If 5% of weekly returning donors were genotyped, this target would be reached within 12 years. For phenotyping, 35% or 188,000 donors would need to be phenotyped to meet Lifeblood’s demand. With the current level of testing, this would take eight years but could be performed within three years if testing was increased to 9% of weekly returning donors. An additional 26,140 returning donors need to be phenotyped annually to maintain this panel. This mathematical model will inform business decisions and assist Lifeblood in determining the level of investment required to meet the desired timeline to achieve the optimum donor panel size.
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Costantino, Valentina, Mallory J. Trent, John S. Sullivan, Mohana P. Kunasekaran, Richard Gray, and Raina MacIntyre. "Serological Immunity to Smallpox in New South Wales, Australia." Viruses 12, no. 5 (May 18, 2020): 554. http://dx.doi.org/10.3390/v12050554.
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The re-emergence of smallpox is an increasing and legitimate concern due to advances in synthetic biology. Vaccination programs against smallpox using the vaccinia virus vaccine ceased with the eradication of smallpox and, unlike many other countries, Australia did not use mass vaccinations. However, vaccinated migrants contribute to population immunity. Testing for vaccinia antibodies is not routinely performed in Australia, and few opportunities exist to estimate the level of residual population immunity against smallpox. Serological data on population immunity in Australia could inform management plans against a smallpox outbreak. Vaccinia antibodies were measured in 2003 in regular plasmapheresis donors at the Australian Red Cross Blood Service from New South Wales (NSW). The data were analysed to estimate the proportion of Australians in NSW with detectable serological immunity to vaccinia. The primary object of this study was to measure neutralising antibody titres against vaccinia virus. Titre levels in donor samples were determined by plaque reduction assay. To estimate current levels of immunity to smallpox infection, the decline in geometric mean titres (GMT) over time was projected using two values for the antibody levels estimated on the basis of different times since vaccination. The results of this study suggest that there is minimal residual immunity to the vaccinia virus in the Australian population. Although humoral immunity is protective against orthopoxvirus infections, cell-mediated immunity and immunological memory likely also play roles, which are not quantified by antibody levels. These data provide an immunological snapshot of the NSW population, which could inform emergency preparedness planning and outbreak control, especially concerning the stockpiling of vaccinia vaccine.
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M Ashshi, Ahmed, Saad Alghamdi, Adel G. El-Shemi, Sabir Almdani, Bassem Refaat, Amr M. Mohamed, Hani O. Ghazi, Esam I. Azhar, and Faisal A. Al-Allaf. "Seroprevalence of Asymptomatic Dengue Virus Infection and Its Antibodies Among Healthy/Eligible Saudi Blood Donors: Findings From Holy Makkah City." Virology: Research and Treatment 8 (January 1, 2017): 1178122X1769126. http://dx.doi.org/10.1177/1178122x17691261.
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Background: Threat to blood transfusion–transmitted dengue virus (DENV) and its antibodies has recently emerged worldwide. Dengue fever is an endemic disease in Saudi Arabia, particularly in its Western region. The aim of this study was to estimate the seroprevalence of asymptomatic DENV infection and its antibodies among eligible Saudi blood donors. Methods: Serum samples from 910 healthy/eligible adult male Saudi blood donors, who reside in Holy Makkah City of Saudi Arabia, were collected between March 2015 and August 2016 and screened for the detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM and IgG antibodies using commercial enzyme-linked immunosorbent assay kits (Panbio, Brisbane, QLD, Australia). Results: Among the tested donors, 48 (5.3%) were seropositive for DENV-NS1 antigen, whereas 50 (5.5%) and 354 (38.9%) were seropositive for anti-DENV IgM and IgG antibodies, respectively. Seropositivity for DENV-NS1 antigen and/or anti-DENV IgM antibody among the tested donors reflects their ongoing asymptomatic viremic infectious stage with DENV during their donation time, whereas high prevalence of anti-DENV IgG seropositivity reflects the high endemicity of dengue disease in this region of Saudi Arabia. Conclusions: These results show high prevalence of asymptomatic DENV infection and its antibodies among Saudi blood donors, raising the importance of establishing blood screening for dengue disease at different blood donation services and units in Saudi Arabia to improve the guarantee of blood transfusions and to control DENV dissemination.
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Broderick, Pia, and Iain Walker. "Donor Gametes and Embryos: Who Wants to Know What about Whom, and Why?" Politics and the Life Sciences 20, no. 1 (March 2001): 29–42. http://dx.doi.org/10.1017/s0730938400005165.
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Many treatments for infertility require the use of donated gametes or embryos. Arguments have been made that all parties involved (donors, recipients, and children) should have open access to information about one another. The present article reports a survey of attitudes of 77 donors and 327 recipients in the state of Western Australia. Donors and recipients endorsed a register of nonidentifying information, but were less keen on a register of identifying information. They believed that medical personnel should have access to such registers, and that donors and recipients (but not children) should have access to nonidentifying, but not identifying, information. Typically, the sort of information respondents wanted to access pertained to health status and physical characteristics. Overwhelmingly, both donors and recipients saw gamete and embryo donation as more like blood donation than like adoption.
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Sampson, Brett G., Steven R. Wilson, Mark E. Finnis, Alison M. Hodak, Philippa N. Jones, Stephanie L. O’Connor, and Marianne J. Chapman. "A Quality Control Study of the Adherence to Recommended Physiological Targets for the Management of Brain-Dead Organ Donors in South Australian Intensive Care Units." Progress in Transplantation 28, no. 4 (September 16, 2018): 386–89. http://dx.doi.org/10.1177/1526924818800053.
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Background: The Australian and New Zealand Intensive Care Society and the Australasian Transplant Coordinators Association provide recommendations on the physiological management of brain-dead donors. Problem statement: How often physiological targets are prescribed for brain-dead donors in Australian intensive care units (ICUs), and how well these compare to recommended targets is unknown. It is also unknown how often recommended targets are achieved, irrespective of prescribed targets. Methods: We performed a retrospective, observational quality control study in 81 adult (>18 years) brain-dead donors to describe how often physiological targets were prescribed, comparing these to current guidelines. We determined the proportion of observations within the recommended target range, irrespective of any prescribed target. We aimed to identify poor adherence to recommended targets to guide future quality improvement initiatives. Outcomes: Seventy-four (91%) donors had at least 1 prescribed physiological target written on the ICU chart, with a median of 2 (range 2-5), and a maximum of 13 targets. Prescribed targets appeared to adhere well with recommended targets. Most recommended physiological targets were met irrespective of any prescribed target. However, one-quarter of serum sodium observations and one-third of blood glucose levels were above the recommended target. Implications for practice: Quality improvement initiatives are required to improve the prescription of physiological targets in brain-dead donors in South Australia. Serum sodium and serum glucose targets were not met. However, this most likely reflects the need for current guidelines to be updated in line with current evidence.
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Iga, Timothy, D. V. Babona, and G. T. Nurse. "Province of Origin of Hepatitis B Surface Antigen Carriers Among Blood Donors in Port Moresby." Asia Pacific Journal of Public Health 3, no. 3 (July 1989): 237–41. http://dx.doi.org/10.1177/101053958900300311.
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A paper published in the Medical Journal of Australia in 1972 gave a breakdown of Port Moresby blood donors by HBS Ag carrier status and area of origin. It has lately become possible to test whether such geographical subsamples provide reliable evidence of the carrier status in the home areas, and it appears that, except for the Islands provinces, they do not. Traditional lifestyles conduce to the maintenance and spread of the virus, which is much more prevalent in the provinces than in the capital.
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Sharplin, Kirsty M., David Ritchie, David Gottlieb, Ian Bilmon, Shyam Panicker, Glen A. Kennedy, Cameron Curley, et al. "An Australasian Bone Marrow Transplant Registry (ABMTR) Study of the Trends and Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Hodgkin Lymphoma between 2009-2019: Relapse Remains the Most Common Cause of Death Post Transplantation." Blood 136, Supplement 1 (November 5, 2020): 36–37. http://dx.doi.org/10.1182/blood-2020-138684.
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An Australasian Bone Marrow Transplant Registry (ABMTR) Study of the Trends and Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Hodgkin Lymphoma between 2009-2019: Relapse remains the most common cause of death post transplantation Introduction: Hodgkin Lymphoma (HL) is an eminently curable disease, with 80% of cases achieving cure with first line therapies. There are a subset of patients who relapse and require salvage therapy including autologous stem cell transplant and more recently novel agents such as brentuximab vedotin (BV) and the PD-1 inhibitors. The latter are less toxic and achieve durable responses but are not considered curative for most (LaCasce et al., 2019). In Australia BV and PD-1 inhibitors were approved in December 2013 and September 2017 respectively. Allogeneic HSCT offers a graft vs lymphoma (GVL) effect that may contribute to long term survival in some patients (Peggs et al., 2005). The introduction of reduced intensity conditioning (RIC) has seen improved outcomes with an OS of 67% (59-74%) and Progression Free Survival (PFS)of 45% (35-56%) (Rashidi et al., 2016) Patients and methods: Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic transplant for HL between 2009 and 2019. The Kaplan Meier method was used to calculate OS and PFS with log rank test for comparison. Multivariable Cox proportional hazards models were used to identify associations with OS. We divided the patients into 5 year cohorts to compare transplant outcomes over time. Results: A total of 149 patients from 16 sites in Australia and New Zealand were included. The median age at time of transplant was 31 years (range 19-61) and the majority were male (60%). Seventy-five percent of patients had undergone previous autologous HSCT with data missing for 22%. Median follow up was 75 months (range 4.7-137.1). Forty five percent of patients were in complete remission (CR), 34% in partial remission and 15% relapsed/primary refractory (RR) at the time of HSCT with information missing in 4%. The majority of donors were matched unrelated donors (47%) and sibling donors were used for 37% of patients, haploidentical in 11% and umbilical cord blood in 5%. Reduced intensity conditioning was used in 86% of patients and in vivo T cell depletion with ATG or alemtuzumab was used in 27%. Acute GVHD occurred in 53/149 (30%) of which 31% was grade III-IV. In patients who survived beyond 100 days, the incidence of chronic GVHD was 38%, of which 53% was preceded by some form of aGVHD. Non-relapse mortality (NRM) at 100 days was 8% with 5/12 of these patients dying from aGVHD. Two-year OS and PFS were 75% and 49% respectively. A period effect was not detected with no significant difference in OS (p=0.8) nor PFS (0.2) based on transplant year (figure 1a & 1b). Multivariate analysis of factors associated with OS identified age at transplant of >40 (HR 3.24, 95% CI 1.71-6.15, p<0.001) and RR disease at time of transplant (HR 3.07, 95% CI 1.44-6.54, p=0.004) with a higher risk of death. The numbers of HSCT performed each year are illustrated in figure 1c, with a larger proportion of patients in CR from 2014 onward. Post-transplant relapse occurred in 38% of patients (figure 1d)with a median time to relapse of 8.5 months (range 0.2 -42). Forty-eight percent (27/56) of patients who relapsed post HSCT were in CR at the time of HSCT. Of those who relapsed, 37% died due to progressive disease with no evidence of chronic GVHD. Relapse was the most common cause of death (37%) Conclusion: Although the rates of HSCT for HL in Australia and New Zealand have not varied over the past decade despite the availability of novel agents, there is a larger proportion of patients in CR prior to transplant. Survival outcomes for HL post HSCT are comparable to those reported internationally. Despite a higher percentage of patients transplanted in CR in later years, relapse post HSCT remains the major cause of death. Further studies to examine strategies to prevent or treat relapse of HL post-allograft are needed. Disclosures Sharplin: Novartis: Other: FUnded to attend Australian Haematology Conference . Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Spencer:AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Celgene, Janssen and Takeda: Speakers Bureau. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad:Abbvie: Honoraria; Novartis: Honoraria.
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Polonsky, Michael, Kate Francis, and Andre Renzaho. "Is removing blood donation barriers a donation facilitator?" Journal of Social Marketing 5, no. 3 (July 13, 2015): 190–205. http://dx.doi.org/10.1108/jsocm-08-2014-0054.
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Purpose – The aim of this study was to assess whether the removal of blood donation “barriers” facilitates blood donation intentions, using a sample of African migrants, and to identify the implications for social marketing. African migrants are currently under-represented as blood donors in Australia. Some members of the African community have unique donation needs that can only be served by this community. Design/methodology/approach – Interviews were conducted with 425 people from the African community in Victoria and South Australia. Factor analysis was performed on the barriers and the removal of barriers. Item groupings for both constructs differed, suggesting that barriers and their removal are not necessarily opposite constructs. Findings – The cultural society factor was negatively associated with blood donation intention (i.e. a barrier), whereas engagement and overcoming fear were positively associated with blood donation intention (i.e. facilitators). Cultural issues and lack of understanding were not seen to impede blood donation. Additionally, the removal of cultural barriers did not facilitate increases in blood donation intentions. Thus, the removal of barriers may not be sufficient on their own to encourage donation. Research limitations/implications – This only examines the issue with regards to whether the removal of barriers is a facilitator of blood donation with one group of migrants, and relationships may vary across other migrant and non-migrant groups. Practical implications – Policymakers often use social marketing interventions to overcome barriers as a way of facilitating blood donation. This research suggests that removing barriers is indeed important because these barriers impede people considering becoming blood donors. However, the findings also suggest that the removal of barriers is insufficient on its own to motivate blood donations (i.e. the removal of barriers is a hygiene factor). If this is the case, social marketing campaigns need to be multifaceted, removing barriers as well as leveraging facilitators, simultaneously. Social implications – This work identified that the impact of barriers and their removal may facilitate effective social marketing campaigns in differing ways, in the context of blood donation. Originality/value – How barriers and their removal impact social marketing activities (i.e. blood donation behaviour) has generally not been explored in research.
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Jangi, Majid, Mahmoud Tara, and Kolsoum Deldar. "DETERMINE THE IMPORTANT OF KIDNEY TRANSPLANTATION ITEMS IN SELECTED COUNTRIES AND IRAN (APPLICATION REGISTRY)." Medical Technologies Journal 1, no. 4 (November 29, 2017): 126–27. http://dx.doi.org/10.26415/2572-004x-vol1iss4p126-127.
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Introduction:
In many cases a kidney transplant is effective treatment for advanced chronic kidney disease and ESRD patients. There are multiple items to identify candidates for a kidney transplant. So one of the problems, considerable differences in factors, because of the vastness and the variety of factors affecting them.The purpose of this study is to provide a comparative analysis of kidney transplantation items in selected countries and Iran in order to choose the most important items that will be used in iran.
Methods:
The study was carried out in 2015 using a comparative review method in United States, Australia, Croatia and Iran. The countries have the largest number of kidney transplants on their continent in 2014. Items in two categories (Candidate’s items and Donor’s items) was gathered from last version guidelines and execute delphi rounds and focus group(feasibility) to choose the important criteria in 3 iran’s medical centers. Data analyzed by Excel 2015.
Results:
Total items of candidate was twenty that five items, including “duration of dialysis”, “blood type”, “previous transplant history”, “age“ and “HLA” were considered as items affecting transplant in all three countries. Iran just included two items (duration of dialysis and blood type). After Delphi rounds and accessibility study, sexteen items were remain to gathering in iran.
Total items of donor was thirteen that three items, including “blood type”, “age“ and “HLA” were considered as items affecting transplant in all three countries. Iran just included 2 items (hepatit and blood type). After Delphi rounds and feasibility study, 11 items were remain to gathering in Iran.
Croatia that adherence Euro guideline in kidney transplantation had maximum candidate’s items and United states has maximum donors items that involving in kidney transplantation
Conclusion:
Kidney transplantation items determine the amount of readiness kidney transplant candidates and the quality of the kidney donor. In iran this items did not intended to be the comparison candidates and just “duration of dialysis” was criterion. While in America, Europe and Australia the readiness of candidate and the quality of the kidney donor is based on the items scoring and matching.
One of the deleted items as a result of feasibilty study in Iran was the HLA typing test. Due to the long time and high cost, there is no possibility of collecting it.
projected is if Iran involved items in queues waiting for a transplant candidates, they will receive graft survival rate better than before.
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Pasricha, Sant-Rayn, Denese C. Marks, Hannah Salvin, Tania Brama, Anthony J. Keller, Joanne Pink, and Joanna Speedy. "Postdonation iron replacement for maintaining iron stores in female whole blood donors in routine donor practice: results of two feasibility studies in Australia." Transfusion 57, no. 8 (May 18, 2017): 1922–29. http://dx.doi.org/10.1111/trf.14173.
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Couban, Stephen, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cynthia L. Toze, Morel Rubinger, Jeff H. Lipton, et al. "A Canadian Blood and Marrow Transplant Group (CBMTG) Randomised Trial Comparing G-CSF Mobilized Peripheral Blood Versus G-CSF Stimulated Bone Marrow In Recipients Of Sibling Allografts For Hematologic Malignancies." Blood 122, no. 21 (November 15, 2013): 709. http://dx.doi.org/10.1182/blood.v122.21.709.709.
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Abstract G-CSF mobilized peripheral blood (G-PB) allografts lead to faster hematologic recovery than marrow grafts, but with more chronic GvHD(cGvHD). We hypothesized that G-CSF stimulated marrow (G-BM) may result in faster hematological recovery with less cGvHD. Methods We conducted a Phase III randomised multicenter trial of matched sibling G-PB vs G-BM allografts in adults with hematologic malignancies. The primary endpoint was time to treatment failure defined as the first occurrence of extensive cGvHD, relapse or death from any cause. Thirteen centers in Canada, Saudi Arabia, U.S., Australia and New Zealand enrolled patients. Adaptive stratification (minimization) balanced treatment groups by center, disease, disease risk and conditioning. Donors received G-CSF 5 mg/kg/d sc for 4 or 5 days and underwent apheresis on Day 5 and, if necessary, on Day 6 or marrow harvest on Day 5. Eligible recipients between 16 and 65 years received myeloablative conditioning and cyclosporine/methotrexate as GvHD prophylaxis. The study began before widespread adoption of the NIH GvHD consensus guidelines so cGvHD was characterized as limited or extensive. Immunophenotyping and functional assays performed on donor cells were correlated with incidence of cGvHD. Results Between 2007 and 2012, 230 sibling donor-recipients were randomized to receive either a G-PB or G-BM allograft; 3 randomized to G-PB and 4 to G-BM were inevaluable (4 relapsed before transplant, 1 donor withdrew before collection, 1 recipient withdrew consent and 1 was ineligible (non-myeloablative conditioning)). Indication for allograft was AML (109; 49%), ALL (57; 25%); MDS/MPD(31; 14%), CML(13; 6%), lymphoproliferative disorder(NHL/MCL/CLL)(12; 5%) and biphenotypic leukemia(1). 77(70%)(G-PB) and 71(63%)(G-BM) recipients had low-risk disease (AML or ALL in CR1, RA, RARS, CML in 1st CP). Donor and recipient ages, sex and CMV immune status were balanced between groups. Donors tolerated mobilization well although one donor (G-PB) died of a cardiac event while receiving G-CSF. Median nucleated cells per kg were 7.59x108 (2.73-18.64) and 5.92x108 (0.94-13.23) in the G-PB and G-BM arms respectively (P<0.0001). Median CD34 cells per kg were 5.50x106 (2.03-23.94) and 3.22x106 (0.29-8.71) respectively (P<0.0001). 94% of G-PB donors underwent 1 apheresis. Median volume of harvested G-BM was 1127mL (350-1731mL). With a median follow-up of 36 months (range 9.6-48), using Cox proportional hazards multivariable modelling adjusted for the 4 minimization factors, time to treatment failure did not differ significantly between arms (HR 0.91; 95% CI 0.68-1.22; P= 0.52). There was a significantly delayed time to onset of overall cGvHD in the G-BM arm (HR=0.66; 95% CI 0.46-0.95; P=0.03) but time to onset of extensive cGvHD did not differ significantly between arms (HR=0.76; 95% CI 0.52-1.10; P=0.15). Other results are shown below: Evaluation of donor immune populations showed that IFNg+ CD4 T cells and CD56bright NK cells were protective against cGvHD in G-PB and G-BM recipients. In contrast, specific B cell populations consistent with memory or exhausted B cells were associated with cGvHD in G-PB recipients (CD19+CD27+, p=0.05, CD19+ CD21lo, p=0.009) but not in G-BM. Conclusions In this large prospective randomized trial, the primary endpoint of time to treatment failure did not differ between G-PB and G-BM. OS and RFS were also not significantly different between arms. Neutrophil and platelet recovery were slower by a median of 3 days with G-BM. However, time to overall cGvHD was significantly delayed in G-BM recipients with non-significant trends of less acute and less extensive cGvHD with G-BM. cGvHD correlated with different cell populations in G-PB and G-BM suggesting that donor source can influence the mechanism of cGvHD. Further analyses are underway to determine the clinical impact of these differences. Disclosures: No relevant conflicts of interest to declare.
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Pentecost, Robin, Denni Arli, and Sharyn Thiele. "It’s my choice! Investigating barriers to pro-social blood donating behaviour." Marketing Intelligence & Planning 35, no. 2 (April 3, 2017): 243–58. http://dx.doi.org/10.1108/mip-03-2016-0055.
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Purpose The purpose of this paper is to investigate barriers to pro-social behaviour in the form of blood donating using self-determination theory. Design/methodology/approach Respondents were recruited through intercepts at a major international university and at points within the community in a capital city in Australia. Sampling was conducted over a three-week period resulting in a sample of 617 respondents. Findings Results show intrinsic motivations positively influence intentions towards blood donation, self-identity, and locus of control. Further, despite positively influencing other factors, external regulation positively influenced amotivation indicating the more likely people feel pressured to donate blood, the less likely they will be motivated to donate blood. Originality/value This would suggest one way to influence more people to become donors is to place greater focus on the positive emotional feelings they derive from the act of donating blood and the control they have over that donation. Using external regulation strategy which often suggests people “must” or “have-to” donate blood may be limiting blood donation numbers.
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Komarova, Tatiana, Daniel McKeating, Anthony V. Perkins, and Ujang Tinggi. "Trace Element Analysis in Whole Blood and Plasma for Reference Levels in a Selected Queensland Population, Australia." International Journal of Environmental Research and Public Health 18, no. 5 (March 6, 2021): 2652. http://dx.doi.org/10.3390/ijerph18052652.
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The levels of trace elements in whole blood and plasma have been widely used for assessing nutritional status and monitoring exposure and can vary widely in populations from different geographical regions. In this study, whole blood samples (n = 120) and plasma samples (n = 120) were obtained from healthy donors attending the Red Cross Blood Bank (Queensland Red Cross Blood Service), which provided information for age and sex. There were 71 males (age range: 19–73 years) and 49 females (age range: 18–72 years) for whole blood samples, and 59 males (age range: 19–81 years) and 61 females (age range: 19–73 years) for plasma samples. The main aim of the study was to provide information on blood reference levels of 21 trace elements (Ag, Al, As, Bi, Br, Cd, Co, Cr, Cu, Hg, I, Mn, Mo, Ni, Pb, Sb, Se, Tl, U, V, Zn) in Queensland. The study also aimed to assess differences in trace element blood levels between males and females and the effect of age. The trace element levels in blood samples were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and the standard reference materials of Seronorm (Trace Elements Whole Blood) and UTAK (Trace Elements Serum) were used for quality control and assurance. The study found wide variations of trace element levels in whole blood and plasma, and generally the levels were comparable to other countries. No detectable levels were found for Bi, Cr, U and V in whole blood, but V levels were found in plasma samples. There were significant differences between males and females for whole blood Cu (p < 0.001), I (p = 0.009), Tl (p = 0.016) and Zn (p = 0.016). Significant differences were also found for plasma Cu (p < 0.001) and Se (p = 0.003) between males and females. There were trends of increased levels of blood Pb, Se and Zn with age. The study has provided further information on a wide range of trace elements in blood as reference levels for Queensland and Australia which are currently lacking.
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Dean, Melinda M., Melanie Dunford, Robert L. Flower, and Helen M. Faddy. "Biological markers of infection may assist in the identification of early stage viral infection and serve as a surrogate biomarker to identify asymptomatic Ross River or Barmah Forest virus infection." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 124.36. http://dx.doi.org/10.4049/jimmunol.196.supp.124.36.
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Abstract Background and Aims Although Ross River virus (RRV) and Barmah Forest virus (BFV) pose a risk to transfusion safety, in Australia, blood donations are not screened for either. RRV and BFV pathogenesis is poorly understood; however, mannose binding lectin (MBL) levels have been associated with RRV disease severity. We investigated biological markers to identify early stages of infection in asymptomatic RRV or BFV infection. Methods Samples from 7001 blood donations from donors at risk for RRV and/or BFV were tested for anti-RRV (IgM) and/or anti-BFV (IgM). MBL level was assessed in 139 anti-RRV (IgM) positive samples, 143 anti-BFV (IgM) positive samples and clinical samples (10 RRV, 10 BFV). MCP-1, MIG, TNF-α, IFN-α, IFN-γ, IL-8, IL-10 and IP-10 were quantified in these samples and 50 seronegative samples. Results Anti-RRV (IgM) was detected in 2.3%, and anti-BFV (IgM) in 2.4%, of donations, consistent with asymptomatic infection. MBL deficiency was not associated with seropositivity, but higher MBL levels were evident in RRV patients. IP-10, MIG, MCP-1 and IL-8 were elevated in RRV patients and IFN-γ, MCP-1 and IL-8 higher in BFV patients. For both anti-RRV (IgM) and anti-BFV (IgM) positive donations, IL-8 was elevated compared to IgM negative donors. All statistical analysis unpaired T-test, 95% CI. Conclusions Asymptomatic RRV or BFV infection occurs in blood donors. The frequency of MBL deficiency was similar between samples from clinical and presumed asymptomatic RRV or BFV infection. Measurement of IL-8 may assist in the identification of early stage viral infection and function as a surrogate biomarker for early stage RRV or BFV infection.
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Hyland, Catherine A., Roy Douglas, Rita Mazzocchi, and Ian F. Young. "Surrogate testing for non-A, non-B hepatitis in Queensland, Australia: An ALT microtitre tray method for screening blood donors." Pathology 20, no. 3 (1988): 271–74. http://dx.doi.org/10.3109/00313028809059506.
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Maritz, Leo, Nicholas J. Woudberg, Amber C. Bennett, Andreia Soares, Florian Lapierre, Justin Devine, Matti Kimberg, and Patrick J. Bouic. "Validation of high-throughput, semiquantitative solid-phase SARS coronavirus-2 serology assays in serum and dried blood spot matrices." Bioanalysis 13, no. 15 (August 2021): 1183–93. http://dx.doi.org/10.4155/bio-2021-0065.
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Aim: Serological assays for the detection of anti-SARS coronavirus-2 (SARS-CoV-2) antibodies are essential to the response to the global pandemic. A ligand binding-based serological assay was validated for the semiquantitative detection of IgG, IgM, IgA and neutralizing antibodies (nAb) against SARS-CoV-2 in serum. Results: The assay demonstrated high levels of diagnostic specificity and sensitivity (85–99% for all analytes). Serum IgG, IgM, IgA and nAb correlated positively (R2 = 0.937, R2 = 0.839, R2 = 0.939 and R2 = 0.501, p < 0.001, respectively) with those measured in dried blood spot samples collected using the hemaPEN® microsampling device (Trajan Scientific and Medical, Victoria, Australia). In vitro SARS-CoV-2 pseudotype neutralization correlated positively with the solid phase nAb signals in convalescent donors (R2 = 0.458, p < 0.05). Conclusion: The assay is applicable in efficacy studies, infection monitoring and postmarketing surveillance following vaccine rollout.
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Di Ciaccio, Pietro R., Matthew Greenwood, Glen A. Kennedy, Sam Milliken, David Gottlieb, David Ritchie, Duncan Purtill, et al. "Allogeneic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma Can Achieve Durable Remissions: An Australasian Bone Marrow Transplant Recipient Registry Study." Blood 136, Supplement 1 (November 5, 2020): 18–19. http://dx.doi.org/10.1182/blood-2020-139076.
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Introduction A majority of patients with diffuse large B cell lymphoma (DLBCL) will be cured with frontline chemoimmunotherapy, however a significant number of patients will relapse. Although autologous haematopoietic stem cell transplantation (autoHCT) may lead to sustained survival in some relapsing patients, long term survival with relapsed DLBCL is approximately 25% (Larouche et al., J Clin Oncol 2010;28(12):2094). Allogeneic HCT (alloHCT) is a potential treatment strategy in some DLBCL patients with relapsed disease. We performed a retrospective national registry study to examine alloHCT practice and outcomes for DLBCL in Australia and New Zealand in the modern era. Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving an alloHCT for DLBCL between January 2009 and December 2019. Survival was analysed using the Kaplan-Meier method, with comparisons between the transplant periods 2009-2014 and 2015-2019 performed using the log-rank test. Both univariate and Cox proportional hazards regression were performed to determine significant risk factors for transplant outcome. The following risk factors were analysed for impact on outcomes: age, transplant before 2015, previous autoHCT, remission status at transplant, use of myeloablative conditioning (MAC), haploidentical donor (HD) and use of T cell depletion (TCD). Results A total of 154 patients were included in the analysis. The median age was 52 years (range 19-71) and 68% were male. Disease status at transplant was complete remission (CR) in 49%, partial response in 31% and stable or progressive disease in 17% (missing data in 3%). Fifty-five per cent had undergone a previous autoHCT. Approximately equal proportions of donors were HLA-matched siblings or matched unrelated (45% and 46% respectively) and 9% were HDs. MAC was utilised in 26%, and TCD in 24% (alemtuzumab in 3%, anti-thymocyte globulin in 21%) (data missing in 12%). The median times to neutrophil engraftment and platelet engraftment were 16 and 18 days respectively. Non-relapse mortality (NRM) at 1-year and 5-years was 20% (95%CI 7-30%) and 26% (95%CI: 13-38%). The 100-day cumulative incidence of grade II to IV acute graft versus host disease was 15% (95%CI 5-31%). The 3-year cumulative incidence of chronic graft versus host disease (cGVHD) was 56% (95%CI 46-65%) (figure 1). The median duration of follow up for the cohort was 3.98 years (range 0-9.64 years). Median overall survival (OS) post-transplant was 4.01 years, with 5-year OS of 47% (95%CI 38-56%) and 10-year OS of 40% (95%CI 26-54%) (figure 2). The 5-year relapse free survival (RFS) was 45% (95%CI 26-50%) (figure 3). The cumulative incidence of relapse (CIR) was 21% at 1 year and 32% at four years, however relapses were not seen after this point, suggesting a subpopulation with durable remissions (figure 4). On univariate analysis, TCD was associated with both reduced incidence of cGVHD (HR 0.35 95%CI 0.19-0.66, p=0.012) and increased NRM (HR 2.10 95%CI 0.88-4.99 p=0.043). These associations were maintained on multivariate analysis (MVA) (HR 0.29 95%CI 0.16-0.76, p=0.011; HR 2.19 95%CI 1.02-4.70, p=0.045) (figures 5, 6). TCD did not impact on RFS. The vast majority of TCD was given in unrelated donor alloHCTs. CR at time of transplant was associated with improved RFS on univariate analysis (HR 1.65 95%CI 1.04-2.64, p=0.034), however this association was not seen on MVA. No other analysed risk factors impacted OS, RFS, NRM, CIR or GVHD rates on either univariate or MVA. An average of 14 alloHCTs were performed each year, with a trend towards increasing annual numbers over time. There was a significant increase in the proportion of haploidentical transplants between 2009 and 2019 (p=0.003), though total numbers were low (n=14). There was no significant change over time for the use of MAC, TCD, nor in OS, RFS or NRM. Conclusion There has been an increase in the rates of alloHCT with HDs for DLBCL in Australia and New Zealand over the past decade. Survival and relapse rates are relatively favourable compared to the published literature, with sustained remissions observed (5 and 10-year OS of 47% and 40% respectively). TCD is associated with reduced cGVHD rates, as well as increased NRM. Ongoing reporting of alloHCT outcomes in DLBCL is important given the emerging role of novel therapies such as bispecific monoclonal antibodies and chimeric antigen receptor T cell therapy. Figure 1 Disclosures Di Ciaccio: Jansen: Honoraria, Other: travel and accomodation grant. Greenwood:Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Spencer:Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy. Arthur:Royal North Shore Hospital: Current Employment. Hamad:Novartis: Honoraria; Abbvie: Honoraria.
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Lynch, Sean A., Kanta Subbarao, Siddhartha Mahanty, Bridget E. Barber, Eileen V. Roulis, Lia van der Hoek, James S. McCarthy, and Kirsten M. Spann. "Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia." Viruses 13, no. 8 (August 16, 2021): 1618. http://dx.doi.org/10.3390/v13081618.
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The COVID-19 pandemic has highlighted the importance of understanding the immune response to seasonal human coronavirus (HCoV) infections such as HCoV-NL63, how existing neutralising antibodies to HCoV may modulate responses to SARS-CoV-2 infection, and the utility of seasonal HCoV as human challenge models. Therefore, in this study we quantified HCoV-NL63 neutralising antibody titres in a healthy adult population using plasma from 100 blood donors in Australia. A microneutralisation assay was performed with plasma diluted from 1:10 to 1:160 and tested with the HCoV-NL63 Amsterdam-1 strain. Neutralising antibodies were detected in 71% of the plasma samples, with a median geometric mean titre of 14. This titre was similar to those reported in convalescent sera taken from individuals 3–7 months following asymptomatic SARS-CoV-2 infection, and 2–3 years post-infection from symptomatic SARS-CoV-1 patients. HCoV-NL63 neutralising antibody titres decreased with increasing age (R2 = 0.042, p = 0.038), but did not differ by sex. Overall, this study demonstrates that neutralising antibody to HCoV-NL63 is detectable in approximately 71% of the healthy adult population of Australia. Similar titres did not impede the use of another seasonal human coronavirus (HCoV-229E) in a human challenge model, thus, HCoV-NL63 may be useful as a human challenge model for more pathogenic coronaviruses.
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Di Ciaccio, Pietro R., David Ritchie, Glen A. Kennedy, Sam Milliken, Duncan Purtill, David Gottlieb, Travis Perera, et al. "Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma Can Achieve Durable Remission and Myeloablative Conditioning Is Associated with Inferior Survival: An Australasian Bone Marrow Transplant Recipient Registry Study." Blood 136, Supplement 1 (November 5, 2020): 7–8. http://dx.doi.org/10.1182/blood-2020-139057.
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Introduction Mantle cell lymphoma (MCL) is a mature B lymphoproliferative disorder with a frequently aggressive clinical course. Although the response rates in patients eligible for conventional chemoimmunotherapy are high, relapses are virtually inevitable, with a median overall survival (OS) of three to five years. For some patients allogeneic stem haematopoietic cell transplantation (alloHCT) is a potential therapeutic option. AlloHCT for MCL has been associated with long term overall survival (OS) of around 40%, with high rates of non-relapse mortality (NRM) of 20-40% and relapse rates of 20-30% (Urbano-Ispizua et al., Biol Blood Marrow Transplant 2015;21:1746, Robinson et al., Leukemia 2015;29:464). Whilst there is evidence of a graft-versus-lymphoma effect in MCL, it has not been shown to translate into improved OS. We performed a retrospective national registry study to examine alloHCT practice and outcomes for MCL in Australia and New Zealand in the modern era. Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving an alloHCT for MCL between January 2009 and December 2019. This time range was chosen to capture the era of widespread rituximab use. Survival, relapse and toxicities of alloHCT were investigated, as well as transplant trends over time. Survival was analysed using the Kaplan-Meier method, with comparisons between the transplant periods 2009-2014 and 2015-2019 performed using the log-rank test. Cox proportional hazards regression was performed to determine significant risk factors for transplant outcome. The following risk factors were analysed for impact on outcomes: age, transplant before 2015, previous autologous HCT (autoHCT), remission status at transplant, use of myeloablative conditioning (MAC), haploidentical donor and use of T cell depletion (TCD). Results A total of 86 patients were included in the analysis. The median age was 56 (range 39-71). There was a male predominance with only 12% female patients. At the time of transplant, 51% were in complete remission, 26% had a partial response and 20% had stable or progressive disease (data missing in 3%). Sixty-seven percent had undergone previous autoHCT. The majority of donors were HLA-matched siblings (51%), followed by HLA-matched-unrelated (42%) and haploidentical (7%). Myeloablative conditioning was utilised in 14%, and T-cell depletion (TCD) in 24%. The median times to neutrophil engraftment (>0.5x109/L) and platelet engraftment (>20x109/L) were 16 and 20 days respectively. NRM at 1 and 5 years was 23% (95% confidence interval [95%CI] 10-39%) and 30% (95%CI 15-48%) respectively. The 100-day cumulative incidence of grade II to IV acute GVHD was 29%. The 3-year cumulative incidence of chronic GVHD was 27%. The median duration of follow up was 4.17 years (range 0-9.6 years). Median OS was 4.2 years, with an estimated 5-year OS of 47% (95%CI 35-58%) and 10-year OS of 23% (95%CI 8-43%) (figure 1). Five-year relapse free survival (RFS) was 38% (95%CI 26-50%) (figure 2). The cumulative incidence of relapse (CIR) was 20% at 1 year and 33% at 4 years, with a flattening of the curve after this point (figure 3). On multivariate analysis (MVA), the use of myeloablative conditioning (MAC) was associated with inferior RFS (hazard ratio 2.33; 95%CI 1.05-5.17; p=0.038) and OS (hazard ratio 3.11; 95%CI 1.39-7.00; p=0.006) (figure 4). No risk factors on MVA impacted NRM or CIR. Chronic GVHD was not associated with RFS or CIR. An average of nine alloHCTs were performed each year. There was an increase in the proportion of haploidentical transplants between 2009-2014 and 2015-2019 (4% to 10%). There was no significant change over time in OS, RFS or NRM, or in the use of MAC or TCD. Conclusion There has been no significant change in the rates of alloHCT for MCL in Australia and New Zealand over the past decade. Trends show an increasing utilisation of haploidentical donors. Overall outcomes were comparable to those previously published with favourable OS and durable remissions seen in a subset of patients. MAC was associated with inferior OS and RFS, however the cause for this is unclear given the lack of association with NRM or CIR. Ongoing reporting of alloHCT outcomes in MCL is important given the emerging role of novel therapies, such as Bruton tyrosine kinase inhibitors, bispecific T cells and CAR-T cell therapy. Figure 1 Disclosures Di Ciaccio: Jansen: Honoraria, Other: travel and accomodation grant. Greenwood:MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad:Novartis: Honoraria; Abbvie: Honoraria.
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Hirani, Rena, Ibrahim Tohidi-Esfahani, Phillip Mondy, and David O. Irving. "An analysis on the fate of a selection of blood products derived from cytomegalovirus-seronegative donors at three tertiary referral hospitals in Australia." Transfusion 58, no. 3 (December 17, 2017): 669–76. http://dx.doi.org/10.1111/trf.14459.
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Cutting, Rachel B., Angela C. Webster, Nicholas B. Cross, Heather Dunckley, Ben Beaglehole, Ian Dittmer, John Irvine, et al. "AcceSS and Equity in Transplantation (ASSET) New Zealand: Protocol for population-wide data linkage platform to investigate equity in access to kidney failure health services in New Zealand." PLOS ONE 17, no. 8 (August 25, 2022): e0273371. http://dx.doi.org/10.1371/journal.pone.0273371.
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Background Kidney transplantation is considered the ideal treatment for most people with kidney failure, conferring both survival and quality of life advantages, and is more cost effective than dialysis. Yet, current health systems may serve some people better than others, creating inequities in access to kidney failure treatments and health outcomes. AcceSS and Equity in Transplantation (ASSET) investigators aim to create a linked data platform to facilitate research enquiry into equity of health service delivery for people with kidney failure in New Zealand. Methods The New Zealand Ministry of Health will use patients’ National Health Index (NHI) numbers to deterministically link individual records held in existing registry and administrative health databases in New Zealand to create the data platform. The initial data linkage will include a study population of incident patients captured in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), New Zealand Blood Service Database and the Australia and New Zealand Living Kidney Donor Registry (ANZLKD) from 2006 to 2019 and their linked health data. Health data sources will include National Non-Admitted Patient Collection Data, National Minimum Dataset, Cancer Registry, Programme for the Integration of Mental Health Data (PRIMHD), Pharmaceutical Claims Database and Mortality Collection Database. Initial exemplar studies include 1) kidney waitlist dynamics and pathway to transplantation; 2) impact of mental illness on accessing kidney waitlist and transplantation; 3) health service use of living donors following donation. Conclusion The AcceSS and Equity in Transplantation (ASSET) linked data platform will provide opportunity for population-based health services research to examine equity in health care delivery and health outcomes in New Zealand. It also offers potential to inform future service planning by identifying where improvements can be made in the current health system to promote equity in access to health services for those in New Zealand.
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Clancy, Leighton Edward, Emily Blyth, Barbara Withers, Jane Burgess, Renee Simms, Chun Kei Kris Ma, Kenneth P. Micklethwaite, and David Gottlieb. "Therapeutic Infusion of Partially HLA-Matched Third-Party Virus-Specific T Cells in HSCT Patients with Refractory Viral Infection." Blood 124, no. 21 (December 6, 2014): 3835. http://dx.doi.org/10.1182/blood.v124.21.3835.3835.
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Abstract Introduction Adoptive transfer of donor derived virus specific T cells (VST) can be effective therapy for infections in allogeneic HSCT recipients. However, this is not a practical strategy to treat acute infections due to the time required to prepare products and potential unavailability of transplant donors. To overcome this, treatment with cryopreserved partially HLA-matched T cells from third-party donors is being investigated. A recent report described disease resolution using cells matched at only one or two HLA alleles (Leen et al., (2013) Blood 121(26):5113-23). This less stringent requirement for matching would allow a small bank of cells to provide most patients with a therapeutic product. We describe the establishment of a virus specific T cell bank in Australia with centralized manufacturing by the Westmead Hospital BMT laboratory. The bank has been used to treat patients in multiple states in a Phase I clinical trial to treat patients who have failed antiviral pharmacotherapy. Aim To assess the safety and feasibility of treatment with partially HLA-matched VSTs derived from third-party donors for refractory cytomegalovirus (CMV), Epstein-Barr Virus (EBV), or adenoviral (AdV) infection in allogeneic HSCT patients. Methods We generated a bank of cryopreserved VSTs from peripheral blood or G-CSF mobilized stem cell product of healthy donors. Products were generated by co-culturing PBMC with dendritic cells loaded with overlapping peptides covering CMV pp65, AdV hexon or EBV BZLF1, LMP2A and EBNA1 proteins. Cultures were re-stimulated once with peptide loaded DC and cultured for 14 days with IL-2. Products were assessed for phenotype, sterility and specificity by MHC multimer staining where applicable or production of interferon-gamma in response to peptides by flow cytometry. Patients with persistent viral reactivation/infection after 2 weeks of standard therapy were eligible to receive up to 4 fortnightly infusions of 2x107 cells/m2partially HLA matched (minimum 1/6) CMV, EBV, or AdV specific T cells, and were followed for up to 12 months. Results T cell products were expanded from 25 donors to create a bank of 177 bags of VSTs (75 CMV, 47 AdV and 55 EBV). CMV specific products were predominantly T cells (mean 95.8±3%) with a higher proportion of CD8+ compared to CD4+ T cells (mean 66.6±23.9% versus 20.1±6.2%). Specificity was mapped by MHC multimer staining to epitopes restricted to common HLA types including HLA-A*0101, HLA-A*0201, HLA-A*2402, HLA-B*0702 and HLA-B*3501. AdV specific T cells had a higher proportion of CD4+ T cells (mean 64.6±23.8% versus 34.2±20.1% CD8 T cells). Specificity was mapped to CD8 epitopes restricted to HLA-A*0101 and HLA-A*2402 as well as 10 CD4 T cell epitopes restricted to three HLA-DRB1 alleles (DRB1*0301, DRB1*0701, DRB1*1501). EBV specific products contained a mix of CD8+ and CD4+T cells (mean 38.9%±18% AND 42.5±23.1% respectively). The antigen specificity of EBV products showed high variability between donors. Dominant responses to known MHC class I restricted epitopes were infrequent though responses were mapped to HLA-A*0201 and HLA-A*2402 restricted LMP2A epitopes, a HLA-B*0801 restricted BZLF1 epitope and a HLA-B*0702 restricted EBNA1 epitope. Based on HLA frequency analysis in the Australian recipient population we estimate 94%, 89% and 74% of patients would have access to a CMV, AdV and EBV specific product respectively with the current bank. To date nine patients have received VSTs, with median follow-up of 5.5 months (0-12 months). All patients had treatment resistant CMV after a median of 26 days (19-116 days) prior therapy. Six patients received a single infusion and 3 patients received 2, 3 and 4 infusions respectively. HLA matching ranged from 2-4/6 HLA match. There were no instances of 24hr infusion related toxicity. Follow-up data is available for 7 patients. One patient with chronic hepatitis C developed abnormal liver function tests 3 months post-infusion. One patient died from presumed progressive CMV disease 6 months post-enrolment. Five patients achieved a best response of CMV PCR negativity (2 with complete resolution of CMV-colitis). One patient has shown >50% reduction in CMV copy number over 3 weeks. Conclusion The infusion of third party CMV specific T cells is a promising therapy that offers the advantage of rapid availability, centralized manufacturing and relatively low cost per dose when produced on a large scale. Disclosures No relevant conflicts of interest to declare.
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Abadir, Edward, Jad Othman, John Kwan, David J. Gottlieb, Glen A. Kennedy, Ashish Bajel, Richard Doocey, et al. "Peripheral Blood Haploidentical Allogeneic Stem Cell Transplantation in Older Adults with AML/MDS Demonstrates Excellent Long Term Overall Survival, Results from the Australasian Bone Marrow Transplant Recipient Registry." Blood 138, Supplement 1 (November 5, 2021): 2929. http://dx.doi.org/10.1182/blood-2021-149939.
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Abstract Background: Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HCT) is an established therapy using alternative donors for patients with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS). There is a limited body of evidence for older patients undergoing Haplo-HCT in AML and MDS. Studies describing Haplo-HCT in older patients have used a high proportion of bone marrow (BM) derived grafts and a variety of conditioning regimens. In this setting, Haplo-HCT demonstrates acceptable Non-Relapse Mortality (NRM) and chronic Graft Versus Host Disease (cGVHD) rates of less than 10% (Ciurea. Biology of Blood and Marrow Transplantation. 2018 Jun 1;24(6):1232-6.). In Australia and New Zealand, Haplo-HCT is predominantly performed using peripheral blood (PB). We performed a retrospective national registry study to examine the outcomes of Haplo-HCT using PB in older patients. Methods: Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB Haplo-HCT for AML/MDS between January 2010 and July 2020. Cumulative incidence functions were used for engraftment, CMV reactivation, acute GVHD, chronic GVHD, relapse, and NRM. The competing risk for engraftment, CMV reactivation and GVHD was death. Relapse and NRM were competing risks for each other. Overall survival (OS), relapse-free survival (RFS), and composite GVHD and RFS (GRFS) were calculated using Kaplan-Meier analyses. The impact of pre-transplant factors on these endpoints was analyzed using Cox regression. Results: A total of 44 patients were included in the analysis. The median follow-up time was 734 days. The median age was 68 (range 65-74) with a median Karnofsky Performance Status of 90. Thirty patients (68.2%) had AML while 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was non-myeloablative fludarabine, cyclophosphamide and TBI (73.8%), the remainder of the patients received either melphalan or busulfan based regimens, the majority were reduced intensity with only 2 patients undergoing myeloablative conditioning. All patients received post-transplant cyclophosphamide and mycophenolate mofetil with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporin (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients, at a median of 18 days while platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of CMV reactivation and CMV disease were 52.5% and 5.1% at 1 year The incidence of Grade 2-4 aGVHD was 18.2%. The incidence of cGVHD at 2 years was 40.7%, with extensive cGVHD occurring in 17.7% of patients. The incidences of relapse and NRM at 2 years were 8.8%. and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year OS was 74%. RFS and GRFS at 2 years was 70% and 48% (Figure 1). Recipient age, donor age or disease type (AML vs MDS) had no significant impact on OS or GRFS. Conclusion: These results confirm the safety and effectiveness of Haplo-HCT for AML/MDS in older patients. The rates of cGVHD were higher than expected given the lower rates reported in other studies using PTCy GVHD prophylaxis. Haplo-HCT using a PB graft demonstrates good long-term disease control with reasonable rates of NRM and cGVHD for older patients with AML/MDS. Figure 1 Figure 1. Disclosures Bajel: Abbvie, Amgen, Novartis, Pfizer: Honoraria; Amgen: Speakers Bureau. Perera: Abbvie: Speakers Bureau; BMS: Speakers Bureau. Greenwood: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Dyer, Wayne B., Sarah L. Pett, John S. Sullivan, Sean Emery, David A. Cooper, Anthony D. Kelleher, Andrew Lloyd, and Sharon R. Lewin. "Substantial Improvements in Performance Indicators Achieved in a Peripheral Blood Mononuclear Cell Cryopreservation Quality Assurance Program Using Single Donor Samples." Clinical and Vaccine Immunology 14, no. 1 (October 18, 2006): 52–59. http://dx.doi.org/10.1128/cvi.00214-06.
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ABSTRACT Storage of high-quality cryopreserved peripheral blood mononuclear cells (PBMC) is often a requirement for multicenter clinical trials and requires a reproducibly high standard of practice. A quality assurance program (QAP) was established to assess an Australia-wide network of laboratories in the provision of high-quality PBMC (determined by yield, viability, and function), using blood taken from single donors (human immunodeficiency virus [HIV] positive and HIV negative) and shipped to each site for preparation and cryopreservation of PBMC. The aim of the QAP was to provide laboratory accreditation for participation in clinical trials and cohort studies which require preparation and cryopreservation of PBMC and to assist all laboratories to prepare PBMC with a viability of >80% and yield of >50% following thawing. Many laboratories failed to reach this standard on the initial QAP round. Interventions to improve performance included telephone interviews with the staff at each laboratory, two annual wet workshops, and direct access to a senior scientist to discuss performance following each QAP round. Performance improved substantially in the majority of sites that initially failed the QAP (P = 0.002 and P = 0.001 for viability and yield, respectively). In a minority of laboratories, there was no improvement (n = 2), while a high standard was retained at the laboratories that commenced with adequate performance (n = 3). These findings demonstrate that simple interventions and monitoring of PBMC preparation and cryopreservation from multiple laboratories can significantly improve performance and contribute to maintenance of a network of laboratories accredited for quality PBMC fractionation and cryopreservation.
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Phan, Ngoc Minh Hien, Helen M. Faddy, Robert L. Flower, Wayne J. Dimech, Kirsten M. Spann, and Eileen V. Roulis. "Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors." Viruses 13, no. 7 (June 30, 2021): 1275. http://dx.doi.org/10.3390/v13071275.
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Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors’ plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. An analysis of the genetic diversity of eight HBV small surface genes from our 16 samples was conducted and compared with HBV sequences from NCBI of 164 international (non-Australian) blood donors. Genotypes A–D were identified in our samples. The region of HBV small surface gene that contained the sequence encoding the ‘a’ determinant had a greater genetic diversity than the remaining part of the gene. No escape mutants or OBI-related variants were observed in our samples. Variant call analysis revealed two samples with a nucleotide deletion leading to truncation of polymerase and/or large/middle surface amino acid sequences. Overall, we found that HBV small surface gene sequences from Australian donors demonstrated a lower level of genetic diversity than those from non-Australian donor population included in the study.
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Mifsud, Nicole, Amina Ismail, Elisha de Valle, Andrew Spencer, Sushrut S. Patil, George Grigoriadis, and Raffi Gugasyan. "The Effect of Granulocyte-Colony-Stimulating Factor (G-CSF) on T Cell Polarization in Vitro: A Direct Comparison Between Nivestim® and Neupogen®." Blood 124, no. 21 (December 6, 2014): 5803. http://dx.doi.org/10.1182/blood.v124.21.5803.5803.
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Abstract Introduction Recombinant granulocyte colony stimulating factor (G-CSF) such as filgrastin (NeupogenÒ) is widely used to mobilize peripheral blood stem cells (PBSC) in healthy donors prior to allogeneic stem cell transplantation (all-SCT). In comparison to the bone marrow harvest, the G-CSF mobilized graft has a higher content of donor-derived T cells, the primary mediators of acute graft versus host disease (aGvHD). However, the incidence of aGvHD is identical suggesting a modulatory effect of Neupogen on T cells. The differentiation of allo-T cells to a T-helper 1 (Th1) phenotype polarizes the cells to produce IFN-g and IL-2, and this in turn promotes the development of GvHD. Conversely, recent evidence suggests that T-helper 2 (Th2) cells that produce IL-4 and IL-10 protects against GvHD. In healthy donors, G-CSF (NeupogenÒ) has been shown to decrease IFN-g and increase IL-4 production. A finding that is also observed under specific stimulatory condition in vitro. The recent patent expiry on G-CSF (Neupogen®) has prompted the development of alternative forms of G-CSF – called biosimilars. These molecules are structurally equivalent but their biological mode of action is currently under review. However, biosimilar G-CSF has not been accepted for routine stem cell mobilization in healthy donors primarily due to a lack of data about their safety in this cohort. In addition, no data exists of their influence on T cell modulation, which will potentially have a significant effect on aGvHD in the recipient. The primary objective of this study was to investigate the in vitro effects of Nivestim®, a biosimilar G-CSF that has been approved by the Therapeutic Goods Administration in Australia, and compared to the reference product filgrastim (Neupogen®) on human CD4+ T cells obtained from healthy volunteers. Results PBMC from 10 healthy volunteers, were cultured in the presence of Nivestim® or Neupogen® (both at 100 ng/ml), and stimulated 24 hrs later with either (1) anti-CD3 MoAb; (2) Phytohaemagglutin (PHA) or (3) PMA plus Ionomycin. The effects of Nivestim® and Neupogen® were examined on Th1 and Th2 cytokine profiles (IFN-g and IL-4 respectively), Th-specific transcriptional regulators, and T cell proliferation and survival. Our findings showed that CD4+ T cells from PBMC cultures produced significant levels of IFN-g following T cell activation. However, in the presence of Nivestim® or Neupogen®, the production of IFN-g was notably reduced and IL-4 levels were increased. These findings were consistent regardless of whether the T cell receptor was stimulated directly, or by-passed through the activation of proximal signaling molecules. Conclusion Whilst this pattern of Th2 polarization was not observed for all healthy volunteers, the biological effects of Nivestim® was comparable to Neupogen® in all cases. These findings have established that Nivestim® has an immunomodulatory effect on Th1/Th2 polarization in vitro that is equivalent to the reference product Neupogen®. Our findings will assist in facilitating Nivestim’s use for stem cell mobilization in healthy donors. Disclosures Mifsud: Hospira: Research Funding. Ismail:Hospira: Research Funding. de Valle:Hospira: Research Funding. Spencer:Hospira: Research Funding. Patil:Hospira: Research Funding. Grigoriadis:Hospira: Research Funding. Gugasyan:Hospira: Research Funding.
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Lwin, Yadanar, Simon Zhao-Xiong He, Andrew Spencer, Duncan Purtill, Ashley Mcewan, Peter Browett, Andrew Butler, et al. "An Update of Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era." Blood 134, Supplement_1 (November 13, 2019): 5719. http://dx.doi.org/10.1182/blood-2019-126547.
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Aim: Although allogeneic stem cell transplant (alloSCT) remains the only curative option for myelofibrosis, novel therapeutic agents, the application of new prognostic scoring systems and the emergence of molecular genetic analysis have lead to a new management landscape in myelofibrosis. In view of these recent advances, we aimed to review national practice in transplanting myelofibrosis patients and its outcomes. Methods: A retrospective study was conducted using the Australasian Bone Marrow Transplant Registry (ABMTRR) data on patients who underwent alloSCT for myelofibrosis at Australian/New Zealand transplant centres between 2006 and 2017. Participating centres completed an online questionnaire and responses were reviewed centrally by the ABMTRR. Results: 142 patients underwent alloSCT for myelofibrosis, primary (n=94) or secondary (n=48) (Table 1). 52% had HLA-identical sibling donors and 45% had matched unrelated donors (UD). Median follow-up was 51.8 months (range: 3.1-148). Cytogenetic abnormalities were identified in 29% of 120 patients who were tested pretransplant. JAK2 mutation testing was performed in 74% of patients whilst other mutations (CALR, MPL, EZH2, IDH, SRSF2, ASXL1) were rarely tested (1.4-8.4%). Only 4.2% of patients had next generation sequencing. Before transplant, 16% had splenectomy or splenic irradiation and 54 patients (38%) received JAK 1/2 inhibitors (JAKi), of whom 92.5% had Ruxolitinib. Median time to neutrophil engraftment was 20 (range: 10-43) days whereas median platelet recovery time was 28 (range: 13-230) days. 9 patients (6.3%) had primary graft failure and 11 patients (7.7%) had secondary graft failure. 60% had chimerism studies using cytogenetic or molecular techniques at 3 months post transplant; 63% of those assessed achieved complete (≥95%) donor chimerism. CMV reactivation was detected in 32% and 10% had sinusoidal obstruction syndrome. The cumulative incidence of grade II-IV acute GvHD was 21.4% and grade III-IV acute GvHD was 8.7%. The cumulative incidences of limited and extensive chronic GvHD at 5 years were 11.1% and 18.1% respectively. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GvHD free progression free survival was 54% at 1 year and 42% at 5 years (Figure 1). The cumulative incidence of non-relapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, use of an UD was a significant independent unfavourable risk factor for OS (HR 2.26, 95%CI 1.17- 4.33, p=0.015) and NRM (HR 3.02, 95%CI 1.36-6.71, p=0.007), while splenic irradiation/splenectomy resulted in shortened neutrophil (HR 1.88, 95%CI 1.00-3.54, p=0.05) and platelet recovery time (HR 2.13, 95%CI 1.12-4.05, p=0.02). Use of UD significantly increased the incidence of grade II-IV acute GvHD in multivariate analysis (HR 5.66, 95%CI 1.99-16.11, p=0.001) whereas use of antithymoglobulin or alemtuzumab significantly reduced it (HR 0.27, 95% CI 0.09-0.79, p=0.017). Neither use of JAKi prior to alloSCT nor presence of JAK2 mutation had a significant impact on OS or NRM. 9 patients underwent a second alloSCT for myelofibrosis and median length of time from the first transplant was 22 (range: 1-132) months. 4 patients were transplanted for disease relapse and 3 patients for graft failure. For the second transplant cohort, NRM at day 100 and 1 year were 11.1% (95% CI, 0.4%-40.6%) and 33.3% (95% CI, 6.6%-64%) respectively, while 1-year and 5-year OS were 66.6% (95% CI, 42%-100%) and 44.4% (95% CI, 21.4%-92.2%). Conclusion: Survival rates in alloSCT for myelofibrosis in this Australasian cohort were comparable to international studies. There is a rise in the numbers of patients treated with JAKi pretransplant (Figure 2). Although this does not appear to have any effect on transplant outcomes, reduced symptom burden associated with increasing use of pre-transplant JAKi may increase the numbers of patients considered eligible for alloSCT. Although splenectomy/splenic irradiation had a positive impact on engraftment, it did not improve the survival outcomes. Our results show a negative influence of UD on OS and NRM, possibly related to an increased incidence of acute GVHD in the UD group. In light of the rise in utilization of alloSCT in the management of myelofibrosis, there is a need for further prospective studies incorporating molecular testing and the new comprehensive clinical-molecular myelofibrosis transplant scoring system. Disclosures Spencer: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Specialised Therapeutics Australia: Consultancy, Honoraria. Purtill:MSD: Honoraria; Novartis: Honoraria, Other: Travel for speaking and advisory boards; Gilead: Honoraria, Other: Travel for speaking and advisory boards; Janssen: Honoraria. Browett:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Achillion: Research Funding; Beigene: Research Funding. Szer:Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; Prevail Therapeutics: Honoraria, Other: Travel, Research Funding. Ritchie:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria. Greenwood:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gottlieb:Merck: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Novartis: Consultancy; University of Sydney: Employment; Haemalogix P/L: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Yong, Michelle K., Shio Yen Tio, Jake Valentine, Joe Sasadeusz, Lynette C. Y. Chee, Ashish Bajel, David Ritchie, and Monica Slavin. "The Economic and Health Utilization Cost of Clinically Significant Cytomegalovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation." Blood 134, Supplement_1 (November 13, 2019): 3437. http://dx.doi.org/10.1182/blood-2019-128227.
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Introduction Understanding the economic impact of managing allogeneic hematopoietic stem cell transplant (HSCT) recipients with cytomegalovirus (CMV) is important for future planning within institutional transplant programs. CMV remains the most frequent viral infection following HSCT of which the clinical impact on transplant outcomes has been well described. However, much less is known about the impact of CMV on health resource utilisation, re-admissions and hospital costs. In addition to antiviral therapy, there are nursing, medical and pharmacy costs to consider. We therefore undertook a study to evaluate the clinical and economic burden of CMV infection following HSCT in a large Australian transplant centre operating under a universal health care system. Methods A retrospective single centre study at the Royal Melbourne Hospital, Melbourne, Australia was performed on all consecutive allogeneic HSCT recipients between January 2015 to December 2017. CMV pre-emptive monitoring using quantitative CMV plasma viral load was performed twice weekly from time of transplant to 100 days or longer in the presence of graft versus host disease. Clinically significant CMV (csCMV) was defined as patients receiving anti-CMV treatment, often with a plasma CMV viral load >400 IU/ml. Throughout the study period, the first line anti-CMV therapy was ganciclovir; either as oral valganciclovir for outpatient management in asymptomatic patients or IV ganciclovir as an inpatient for patients with concerns about oral absorption. Second-line therapy was IV foscarnet. Hospital costing data for the first and subsequent re-admissions for the first 12 months were obtained from the business intelligence unit. Financial year costing was available for FY2015/2016 to FY2017/2018. Ethics was approved by the Melbourne Health Human Ethics Review Committee (HREC 2017.368). Results A total of 255 patients underwent alloHSCT with a median age of 51 years (IQR 40-59) with the most common underlying diagnoses being AML (41%), ALL (11%) and MDS (11%) (Table 1). Thirty-one percent of transplants used myeloablative conditioning, 54% had unrelated donors and 3% had an umbilical cord source. Pre-transplant recipient CMV seropositivity was 62% (n=158), of whom 139 had detectable CMV viremia and 104 (40.8%) experienced clinically significant CMV (csCMV). The median duration of CMV treatment was 33 days (IQR 21-63). Re-admission to hospital within the first 12 months of HSCT occurred in 78.4%. There was a greater number of admissions observed in csCMV patients compared to no csCMV (median 3 vs 2 admissions, p=0.001) with the duration of admitted days within the first 12 months being significantly greater in csCMV patients compared to no csCMV (median 65 vs 36 days, p<0.00001). The mean total cost of treating patients with csCMV for the first 12 months compared to the total cost for patients not requiring CMV treatment was A$196,822 (US$147,616) and A$114503 (US $85,877) (p<0.0001), respectively. Therefore the crude attributable mean cost of treating csCMV was A$82,319 (US$61,739) per patient for the first 12 months of HSCT. The greatest significant contributory costs were from pharmacy A$17,807 (US$13,355), nursing A$16,944 (US$12,708) and medical A$5,898 (US$4,423). Conclusions The health care cost and resource utilisation of treating CMV infection following an allogeneic HSCT is substantial and places a heavy burden on limited health resources. In this study, patients experiencing csCMV had an increased number and longer total duration of admissions days compared to patients who did not require CMV treatment. Interventions aimed at reducing the burden of CMV in alloHSCT recipients are required. Disclosures Yong: Merck Ltd: Honoraria. Bajel:AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: travel funding. Ritchie:Sanofi: Honoraria; Novartis: Honoraria; Imago: Research Funding; Beigene: Research Funding; Takeda: Research Funding; BMS: Research Funding; Pfizer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Slavin:Merck Ltd: Honoraria, Research Funding.
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Curnow, Jennifer L., Marie-Christine Morel-Kopp, Ninfa Rojas, Margaret Aboud, and Christopher Ward. "Patients with the Antiphospholipid Syndrome (APLS) Show Hypercoagulability Due to Hypofibrinolysis and Increased Fibrin Generation, but Thrombin Generation Is Variable." Blood 112, no. 11 (November 16, 2008): 3833. http://dx.doi.org/10.1182/blood.v112.11.3833.3833.
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Abstract We have previously demonstrated hypercoagulability utilizing a global haemostatic assay, the Overall Haemostatic Potential (OHP) in a heterogenous population of patients with a demonstrable lupus anticoagulant. Our aim in this study was to determine whether the OHP assay demonstrated a persistent hypercoagulable state in a well-defined prospective population with APLS and whether global assays were able to predict the occurrence of thrombotic complications. Informed consent was obtained and blood was collected on three occasions, three months apart from 54 patients with APLS, recruited from Haematology clinics at Royal North Shore Hospital, Sydney, Australia between May 2005 and November 2007. Clinical data was collected including history of prior and subsequent thrombotic events. Two control groups consisted of 200 healthy blood donors and 20 patients with autoimmune disorders, but no history of thrombosis. Assays performed were PT, INR, APTT, FVIIIc, lupus anticoagulant assay (LAC), anticardiolipin antibodies (ACLA), b2-glycoprotein1 antibodies (B2GP1), a thrombin generation assay (Calibrated Automated Thrombogram, CAT) and the OHP assay which utilizes thrombin (0.03 IU/ml) and rt-PA (350 ng/ml) to trigger fibrin generation and fibrinolysis, respectively, in platelet poor plasma. Change in optical density in microtitre wells is measured over 60 minutes. Statistical analysis involved calculation of means, SD, T-tests and paired T-tests utilizing SPSS v16.0. Fifty percent of APLS patients were male, compared with 10% of the autoimmune control group. APLS had been diagnosed on the basis of persistent antiphospholipid antibodies and at least one thrombotic event: VTE (n=46), ATE (n=6) or recurrent late miscarriage (n=2). Number of thrombotic events prior to study entry ranged form 1 to 6 per patient, with 49/66 events unprovoked. Samples from APLS patients on anticoagulation (OAC, n=35) were analysed separately from those not anticoagulated (n=19). Global assay results for samples collected at different time points were stable, with no significant differences on paired T-test. APLS patients had significantly shorter PT, higher fibrinogen, increased fibrin generation and reduced fibrinolysis parameters (p<0.001), compared with healthy donors. The autoimmune control group also showed hypercoagulable OHP parameters compared with healthy donors (p<0.001), with assay results comparable to those in APLS patients, not on OAC. The only thrombin generation assay parameter significantly increased in APLS patients, not on OAC, compared with controls was peak thrombin (266 vs 298 nM, p=0.016). However thrombin generation was significantly suppressed in those on OAC (p<0.001). Only one patient had recurrent DVT during the study. The OHP assay identifies a hypercoagulable state in APLS patients with reduced fibrinolysis and increased fibrin generation, even when anticoagulated. The calibrated automated thrombogram (CAT) showed increased peak thrombin generation in APLS patients not on OAC but endogenous thrombin potential (ETP) was not significantly elevated. Thrombin generation was suppressed by OAC therapy. These global assays show differential results in patients with APLS. More prolonged follow up will be necessary to determine whether the assays predict recurrent thrombotic events and are useful in risk stratification of APLS patients.
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Zheng, Xinyuan. "An Analysis of Blood Donating Rate in Australia, Influential Factors and Recommendations to Increase the Rate." Asian Journal of Social Science Studies 4, no. 4 (November 6, 2019): 24. http://dx.doi.org/10.20849/ajsss.v4i4.667.
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Based on the information from the research of the red cross, it can be known there is a low value for the average blood donating rate in Australia, which is around 3%, which means the population for the blood donating are more insufficiency, it may lack of the blood in the blood bank for the injured person use, especially in the emergency such as earthquake, traffic and so on. Consequently, there is no doubt that the quantity of blood and the amount of blood donor need be increased in Australian Red Cross (ARCBS).The purpose of this group assignment is to analysis the survey data that provided, find the server relevant questions about the blood donating, using the SPSS software and reasonable test to examine them. For instance, find the relevant information about donating such as whether the male or female more frequency to donating blood, the possible reason of people choose to donating blood, the reason of the donators encourage their friends and family to donate blood, which publication are more effective, the personally or the media appeal and so on. Finally, it will provide several suitable solutions and reasonable recommendations to ARCBS based on the test results and answer of the questions, in order to help the ARCBS broaden the blood donor base.
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Pasricha, Sant-Rayn S., Zoe McQuilten, Mark Westerman, Anthony Keller, Elizabeta Nemeth, Tomas Ganz, and Erica M. Wood. "Iron Deficiency without Anemia In Premenopausal Blood Donors Is Associated with Future Deferral From Whole Blood Donation." Blood 116, no. 21 (November 19, 2010): 1110. http://dx.doi.org/10.1182/blood.v116.21.1110.1110.
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Abstract Abstract 1110 Introduction: Iron deficiency is a risk of blood donation, especially for premenopausal females. Iron depletion may also be associated with diminished wellbeing. Blood donors developing anemia must be deferred from donation and referred for medical review. Iron deficiency is thus both a risk to individual donors and the national blood supply. How iron depletion affects donor health remains poorly understood, and there are few published data on predictors of donor deferral. We sought to (1) identify factors associated with donor iron depletion, including whether depletion was associated with health and/or with subsequent deferral from blood donation; and (2) evaluate whether iron indices, including serum hepcidin levels, could predict subsequent deferral. Methods: Non-anemic, premenopausal, eligible female whole blood donors were recruited, completed the SF-36 health survey and had samples taken for serum ferritin and serum hepcidin (ELISA) prior to donation. After a minimum of 6 months, records were reviewed to identify whether donors had returned for subsequent donation; any change in hemoglobin (Hb) and deferral for anemia was documented. Results: Of 261 non-anemic donors, 22.6% had ferritin<15ng/mL (“iron depletion”) at baseline. This was associated with number of donations over previous 12 months (OR 1.95 per donation, P<0.001). At baseline, 27.6% donors had serum hepcidin<18ng/mL. There was no association between iron depletion and impaired health as measured by SF-36 (linear regression: log(ferritin) versus physical, mental & general health, vitality and social functioning scores, all P>0.10). After a minimum 6 months follow-up, 150 (58.1%) donors had returned for donation. Baseline Hb and ferritin was similar between donors who did and did not return for donation (P=0.37 & P=0.17 respectively). The following analysis relates only to returning donors: mean Hb was lower at follow-up (131.3g/L) than baseline (133.7g/L)(P<0.01, t-test); anemia (Hb<120g/L) developed in 8.1% (Hb<120g/L), and this was associated with baseline iron depletion (OR 20.3, P<0.001). Deferrals due to anemia occurred in 10/150 (6.7%): 9 (90%) of these donors had baseline ferritin<15ng/mL, compared with 30/140 (21.4%) of those not deferred (OR 33.0, P<0.001). Baseline Hb was higher in donors not deferred (mean 134.5g/L) compared with those deferred (mean 124.4g/L)(P<0.0005, t-test). Both ferritin (AUCROC=0.88) and Hb (AUCROC=0.87) were useful predictors of subsequent deferral due to anemia. Ferritin<15ng/mL had sensitivity 90% and specificity 78.6% in predicting deferral. Serum hepcidin also predicted future deferral (AUCROC=0.81): hepcidin<18ng/mL had sensitivity 90% and specificity 71.4% in predicting deferral. Conclusions: Iron deplete donors are more likely to develop anemia and be deferred from future donations. Donor iron depletion is associated with number of previous donations. Although we did not find iron depletion without anemia to be associated with concurrent health impairment, development of anemia in donors is a major potential adverse health outcome. Screening for iron depletion using rapid or point-of-care assays of iron status may offer opportunities to alleviate subsequent anemia and deferral through early intervention, to improve donor health, reduce deferrals and contribute to sufficiency of national blood supplies. Prevention of donor iron deficiency is a high priority for the Australian Red Cross Blood Service and is being addressed through donor education, research and investigation of iron replacement strategies. Disclosures: Westerman: Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees. Nemeth:Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees. Ganz:Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees.
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Roy, Jean, Tony Panzarella, Stephen Couban, Félix Couture, Gerald M. Devins, Mohamed Elemary, Stephen Ronan Foley, et al. "Less Chronic Graft-Versus-Host Disease, Immunosuppressive Therapy and Better Survival after Anti-Thymocyte Globulin in Unrelated Donor Stem Cell Transplant Recipients: Longer Follow-up of a Multicentre Cell Therapy Transplant Canada Randomized Trial." Blood 134, Supplement_1 (November 13, 2019): 875. http://dx.doi.org/10.1182/blood-2019-123275.
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Background: We previously reported that pretreatment with rabbit anti-thymocyte globulin (ATG) decreases the use of immunosuppressive therapy (IST) and occurrence of chronic graft-versus-host disease (GVHD) 12 months after allogeneic stem cell transplantation from unrelated donors. We hypothesized these benefits would persist beyond 12 months with a positive clinical impact on patients. Methods: Phase 3, multicentre, open-label, randomized controlled trial at 10 centres in Canada and one in Australia. Patients aged 16-70 years with a hematological malignancy, a matched (HLA-A, B, C and DRB1) or 1-antigen/allele mismatched unrelated donor were eligible. Myeloablative, nonmyeloablative or reduced intensity conditioning regimens were permitted according to center clinical preference. Patients were randomized to receive or not to receive rabbit ATG (Thymoglobulin®, Sanofi Canada) as part of their conditioning. GVHD prophylaxis included either cyclosporine or tacrolimus plus methotrexate or mycophenolate mofetil. The ATG arm received 0.5, 2.0, 2.0 mg/kg of ATG on days -2, -1 and +1, respectively. Analyses were on a modified intention-to-treat basis for patients actually transplanted. Primary endpoint was freedom from all systemic IST without resumption up to 24 months after transplantation. Secondary endpoints included survival, relapse, non-relapse mortality, incidence and symptoms of chronic GVHD according to Lee scale and quality of life using different questionnaires including the Center for Epidemiologic Studies Depression (CES-D) scale. We also aimed to evaluate the recently described endpoints of graft-versus-host disease and relapse-free survival (GRFS) and chronic graft-versus-host disease and relapse-free survival (CRFS) in each cohort. This trial was registered at ISRCTN (#29899028) and clinicaltrials.gov (#NCT01217723). Results: Between 06/2010 and 07/2013, 203 patients were randomized and 196 available for end-points analysis, including 99 patients in the ATG group and 97 in the No ATG (control) group. Datalock was performed on April 1, 2019. The cumulative incidence of chronic GVHD at 24 months was significantly lower in ATG recipients (26.3% versus 41.2%, p=0.032). Similarly, more than twice patients in the ATG group were free from IST at 24 months (adjusted OR of 3.49 [95% CI : 1.60-7.60]; p = 0.002). Most patients retained the same IST status from 12 to 24 months (74.7% in the ATG and 81.4% in the control group). Symptoms of chronic GVHD were also significantly less prevalent in patients receiving ATG, with scores by Lee scale of 13.57 (SE : 1.47) versus 19.90 (SE : 2.15); p=0.017. In contrast, we observed no difference in non-relapse mortality (ATG : 21.2% versus No ATG : 30.9%; p=0.14) and relapse (ATG : 16.2% versus No ATG : 17.5%; p=0.73). Of note, there was no increase in relapse in those receiving either myeloablative or non-myeloablative conditioning (Gray's test p = 0.66 and 0.29, respectively). ATG had a positive impact on survival (Figure 1), with an overall survival at 12 months of 74.8% (SE : 4.4) compared with 64.9% (SE : 4.8) in the control group (adjusted HR 0.56 [95% CI : 0.35-0.90; p=0.017). This benefit of ATG on survival persisted at 24 months, with 70.7% of patients in the ATG group and 53.6% in the control group being alive (p=0.018). GRFS at 12 and 24 months were significantly better in the ATG group, with 45.4% and 37.4% of patients alive and free of ever having had GVHD versus 24.7% and 17.5%, respectively (p = 0.0034). CRFS led to similarly better results in ATG recipients at 12 (57.6%) and 24 (48.5%) months (p=0.01; Figure 2). Depressive symptoms were less frequently reported in the ATG group, the mean CES-D scores being 10.39 (SE : 1.29) compared with 14.63 (SE : 1.48) in the No ATG group (p=0.034). There were no statistically significant differences in other patient-reported outcomes. Conclusions: Pretreatment with rabbit ATG in combination with standard acute GVHD prophylaxis provides long term benefits consisting of decreases in chronic GVHD incidence, use of IST, depression and improved survival. Our trial is the first to demonstrate both a survival advantage and improvement in quality of life in patients receiving ATG for chronic GVHD prophylaxis. Our data support that ATG should be included in the preparative regimens of all unrelated donor transplant recipients receiving standard acute GVHD prophylaxis. Disclosures Roy: Celgene: Consultancy, Honoraria, Research Funding; ExCellThera: Patents & Royalties: Royalties from sales of UM171, Research Funding; Amgen Canada: Honoraria; Janssen Canada: Honoraria; Sanofi Canada: Research Funding. Foley:Celgene: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Speakers Bureau. Kuruvilla:Janssen: Research Funding; Roche: Research Funding; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Karyopharm: Consultancy; Merck: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Amgen: Honoraria; Astra Zeneca: Honoraria; BMS: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; Novartis: Honoraria; Roche: Honoraria; Seattle Genetics: Honoraria. Lee:AstraZeneca: Research Funding; Incyte: Research Funding; Syndax: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Kadmon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Popradi:Sanofi Canada: Consultancy, Honoraria. Walker:Kiadis Pharma: Other: Grant funding via institution (as a principal investigator). OffLabel Disclosure: Rabbit ATG (Sanofi) for chronic GVHD prophylaxis.
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Meijers, Joost, Rapeephan Maude, Direk Limmathurotsakul, Nicholas Day, Sharon Peacock, Tom Poll, Willem Wiersinga, and Gavin Koh. "Diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis)." Thrombosis and Haemostasis 106, no. 12 (2011): 1139–48. http://dx.doi.org/10.1160/th11-07-0504.
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SummaryDiabetes is associated with a disturbance of the haemostatic balance and is an important risk factor for sepsis, but the influence of diabetes on the pathogenesis of sepsis remains unclear. Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Southeast Asia and northern Australia. We sought to investigate the impact of pre-existing diabetes on the coagulation and fibrinolytic systems during sepsis caused by B. pseudomallei. We recruited a cohort of 44 patients (34 with diabetes and 10 without diabetes) with culture-proven melioidosis. Diabetes was defined as a pre-admission diagnosis of diabetes or an HbA1c>7.8% at enrolment. Thirty healthy blood donors and 52 otherwise healthy diabetes patients served as controls. Citrated plasma was collected from all subjects; additionally in melioidosis patients follow-up specimens were collected seven and ≥28 days after enrolment where possible. Relative to uninfected healthy controls, diabetes per se (i.e. in the absence of infection) was Characterised by a procoagulant effect. Melioidosis was associated with activation of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2 and fibrinogen concentrations were elevated; PT and PTT prolonged), suppression of anti-coagulation (antithrombin, protein C, total and free protein S levels were depressed) and abnormalities of fibrinolysis (D-dimer and plasmin-antiplasmin complex [PAP] were elevated). Remarkably, none of these haemostatic alterations were influenced by pre-existing diabetes. In conclusion, although diabetes is associated with multiple abnormalities of coagulation, anticoagulation and fibrinolysis, these changes are not detectable when superimposed on the background of larger abnormalities attributable to B. pseudomallei sepsis.
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Cheng, A., C. R. Seed, S. Ismay, and A. J. Keller. "Malaria antibody testing of Australian blood donors." Vox Sanguinis 100, no. 2 (January 11, 2011): 252–53. http://dx.doi.org/10.1111/j.1423-0410.2010.01373.x.
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Branch, Songee L., and Paul N. Levett. "Evaluation of Four Methods for Detection of Immunoglobulin M Antibodies to Dengue Virus." Clinical Diagnostic Laboratory Immunology 6, no. 4 (July 1, 1999): 555–57. http://dx.doi.org/10.1128/cdli.6.4.555-557.1999.
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ABSTRACT Dengue has become hyperendemic in many islands of the Caribbean region. The performance in a diagnostic laboratory of four commercial assays for detection of immunoglobulin M (IgM) antibodies was evaluated. Sera from 62 patients with dengue virus infection were studied. These included 18 patients from whom dengue virus type 2 was isolated in a 1997 outbreak (specimens collected a mean of 14 days after onset of symptoms), 8 patients with dengue hemorrhagic fever (mean time after onset, 11 days), and 36 patients in whom dengue was previously confirmed by serology (mean time after onset, 10 days). Thirty serum specimens from blood donors in a country where dengue is not endemic were used as negative controls. The methods evaluated were two IgM-capture enzyme-linked immunosorbent assays (ELISA) (MRL Diagnostics, Cypress, Calif., and PanBio, Queensland, Australia), a dot ELISA dipstick assay (Integrated Diagnostics, Baltimore, Md.), and a rapid immunochromatographic assay for dengue IgG and IgM (PanBio IC). IgG antibodies were also detected by an ELISA method (MRL Diagnostics). The sensitivities of the four assays were as follows: MRL Diagnostics IgM ELISA, 98.4%; PanBio IgM ELISA, 85.5%; Integrated Diagnostics IgM dot ELISA, 96.8%; and PanBio IC, 83.9%. The specificities of all tests were 100%. Evidence of secondary dengue was found in all patients with dengue hemorrhagic fever and in 83% of the remaining patients. The MRL Diagnostics IgM ELISA appears to be more sensitive than the PanBio IgM ELISA, and this may be significant when IgM titers are low, particularly in patients with secondary dengue infections. The dot ELISA dipstick assay is equally sensitive and may be more appropriate for use in laboratories with lower workloads.
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Lucky, Tarana T. A., Clive R. Seed, Daniel Waller, June F. Lee, Ann McDonald, Handan Wand, Stephen Wroth, et al. "Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors." Transfusion 54, no. 7 (April 10, 2014): 1739–49. http://dx.doi.org/10.1111/trf.12554.
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