ABSTRACT Introduction Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15–39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options. Methods We performed a retrospective review of patients aged 18–60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), primary mediastinal B‐cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18–39 years) and older adults (OAs) (aged 40–60). Results AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early‐stage and low‐risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced‐stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression‐free survival (PFS) and OS compared to OAs. Conclusion The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40–60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission

Importance:Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased risk of cardiovascular disease (CVD) events and mortality. However, there are no approved therapies for preventing or treating CHIP. Objective:To investigate whether low-dose aspirin might benefit older adults with CHIP for the primary prevention of CVD. Design, Setting, and Participants:This was a prespecified substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) double-blind, randomized clinical trial of daily low-dose aspirin vs placebo evaluating disability-free survival, which took place at primary and community care facilities in the US and Australia. Enrollment was from March 2010 to December 2014, and the randomized trial ended in June 2017. Community-dwelling Australian adults aged 70 years and older without a diagnosed cardiovascular event, atrial fibrillation, a serious intercurrent illness likely to cause death within the next 5 years, anemia, or a current or recurrent condition with a high risk of bleeding were included in the original study. Of 19 114 in the original trial, 11 402 were included in the substudy, and 9434 were included in the analysis. Follow-up for this substudy went through June 2022, with data analysis in February 2025. In-trial median (IQR) follow-up time was 4.6 (3.5-5.6) years, and posttrial observational follow-up was 8.7 (7.5-10.1) years from randomization. Interventions:Participants were randomized to aspirin, 100 mg, daily or placebo. Main Outcomes and Measures:CHIP was measured in blood specimens collected at trial entry. Major adverse cardiovascular events (MACEs), including fatal and nonfatal ischemic stroke, nonfatal myocardial infarction and coronary heart disease death, and clinically significant bleeding were adjudicated by independent expert committees blinded to trial-group assignments. Results:A total of 9434 participants (median [IQR] age, 73.7 [71.6-77.1] years; 5067 [54%] female) provided a sample at baseline for analysis, 2124 of whom (23%) had CHIP at variant allele fraction (VAF) ≥2%, with 532 (5.6%) at ≥10% VAF. CHIP was not associated with increased risk of MACEs at 2% to 10% VAF (adjusted hazard ratio [aHR], 0.84, 95% CI, 0.68-1.03; P = .09) or ≥10% VAF (aHR, 0.80, 95% CI, 0.57-1.12; P = .19). However, CHIP was associated with increased risk of clinically significant bleeding (2%-10% VAF: aHR, 1.24; 95% CI 1.02-1.51; P = .03; ≥10% VAF: aHR, 1.21; 95% CI, 0.85-1.73; P = .28). There was no evidence of a differential effect of aspirin according to presence of CHIP on MACEs (without CHIP: HR, 0.91; 95% CI, 0.72-1.16; 2%-10% VAF: HR, 1.40; 95% CI, 0.77-2.53; ≥10% VAF: HR, 1.33; 95% CI, 0.52-3.37; heterogeneity P = .35) or clinically significant bleeding (without CHIP: HR, 1.64; 95% CI, 1.22-2.30; 2%-10% VAF: HR, 1.45; 95% CI, 0.82-2.57; ≥10% VAF: HR, 1.41; 95% CI, 0.49-4.07; heterogeneity P = .91). Conclusion and Relevance:In this secondary analysis of a randomized clinical trial of daily low-dose aspirin in healthy adults 70 years and older, CHIP was not associated with higher CVD risk. However, participants with CHIP had a greater risk of clinically significant bleeding. There was no evidence that participants with CHIP were more likely than those without CHIP to benefit or experience more harm from aspirin when used for primary prevention of CVD events. Trial Registration:ClinicalTrials.gov Identifier: NCT01038583.

BACKGROUND:Sickle cell disease (SCD) is an inherited condition that impairs red blood cell function, posing a substantial health burden on patients. As the prevalence of SCD in Australia rises due to migration, discussions surrounding treatment and management strategies are becoming more prominent. AIMS:Australia lacks a dedicated study on the prevalence and economic implications of SCD. In this study, we estimate the economic burden of SCD in Australia from the perspective of the Australian healthcare system. METHODS:We performed a cost-of-illness study by using a bottom-up approach to estimate resource use per patient from a national registry with unit costs from national sources, and a top-down estimate of the prevalence of SCD in Australia using stratification by ancestry. RESULTS:We estimated the prevalence of SCD in Australia in 2021 to be 8485 patients, the cost per patient per year to be AU$13 975 and the total cost to the Australian healthcare system to be approximately AU$119 million per year. Factors influencing costs were age, interventions and frequency of hospital visits for vaso-occlusive crises. Prevalence had the greatest influence on results in the sensitivity analysis. CONCLUSIONS:While the estimated prevalence of SCD in Australia resulted in a relatively small total cost, the per patient annual cost of SCD remains high. This cost of SCD is anticipated to increase alongside migration and improved treatment. There are policies that could enhance patients' quality of life, thereby mitigating both economic and health burdens.

BACKGROUND:Treatment of chronic lymphocytic leukaemia (CLL) has evolved significantly with the advent of targeted agents. Real-world analysis of patients with CLL provides a better understanding of treatment efficacy and toxicity and informs planning of future trials; however, Australasian studies are limited. AIMS:Here we describe the demographics, disease characteristics, treatment and outcome for CLL patients enrolled in the Australia and New Zealand Lymphoma and Related Diseases Registry (LaRDR). METHODS:This study included 365 patients aged ≥18 years with CLL diagnosed between January 2016 and May 2023. RESULTS:Median age at diagnosis was 68 years, with 65% being male. Median follow-up was 15.2 months (range 0-78). 11q, 13q, 17p deletions and trisomy 12 were detected in 12%, 54%, 11% and 14% respectively. During the period of follow-up, 38% of patients commenced first-line therapy. The use of Bruton's Tyrosine Kinase inhibitors and B-cell lymphoma 2 inhibitors increased more than 10-fold following regulatory approval in 2020. Two-year progression-free and overall survival, measured from commencement of first-line therapy, were 67% (95% CI 55-76) and 87% (95% CI 78-93) respectively. CONCLUSION:The increasing use of targeted agents largely reflected availability; however, continuing use of chemoimmunotherapy following regulatory approval of targeted agents was noted in 29% of patients in 2022.

Description: Optimal transfusion strategies for patients with acute myocardial infarction (AMI) are uncertain. The aim of this guideline is to provide recommendations for red blood cell transfusion in patients with AMI. Methods: These guidelines are based on evidence from randomized controlled trials of patients presenting with AMI and assigned to 2 different transfusion strategies (restrictive or liberal) based on hemoglobin concentrations or hematocrit levels before receipt of a transfusion. A meta-analysis of eligible trials was performed using Cochrane methods. The international panel followed GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods to summarize evidence and formulate recommendations. This guideline's primary perspective is that of the patient, including medical, financial, and psychological effects, with secondary consideration of health care system issues, particularly conservation of the limited and costly blood supply. Recommendation: For hospitalized patients with AMI, the panel suggests a liberal red cell transfusion strategy when the hemoglobin concentration is less than 10 g/dL (conditional recommendation, low-certainty evidence). A restrictive strategy of 7 to 8 g/dL may result in increased mortality in patients with AMI. The direction of the recommendation for the liberal strategy was based on the great importance of mortality for patients. The conditional recommendation was based on the low certainty of evidence and the competing consideration of blood supply conservation. Clinicians should adopt mitigation strategies to reduce potential adverse events associated with a liberal transfusion strategy, and all transfusion decisions should incorporate the clinical context rather than solely the hemoglobin concentration.

Importance:The role of low-dose aspirin (LDA) in cancer prevention among older adults is unclear. Identifying individuals likely to experience benefit or harm is crucial for guiding personalized prevention strategies. Objective:To identify subgroups of the older population who may benefit most from LDA for cancer prevention by developing and validating an effect score model, including individual characteristics such as clonal hematopoiesis of indeterminate potential (CHIP) and other factors, to predict the individualized treatment effects (ITEs) of LDA in cancer incidence. Design, Setting, and Participants:This comparative effectiveness study is a nonprespecified secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial conducted between 2010 and 2014. Australian community-dwelling ASPREE participants (aged ≥70 years) provided biospecimen samples for CHIP testing. CHIP was measured in 18 genes using a targeted sequencing assay. Analyses were conducted between May 2023 and July 2025. Exposures:LDA (100 mg per day) or placebo. Main Outcomes and Measures:The primary outcome was overall cancer incidence at 5 years. Twelve candidate models for predicting ITEs were assessed; the final model was selected to maximize cancer risk reduction and internally validated using bootstrapping. Participants were grouped into treatment-favorable (ITE >0) and treatment-unfavorable (ITE <0) subgroups based on the final predictive model. Results:A total of 9350 participants were included in the analysis (median age, 73.7 [IQR, 71.6-77.1] years; 5021 females [53.7%]) to LDA (4667 [49.9%]) or placebo (4683 [50.1%]). The median follow-up was 4.5 (IQR, 3.3-5.5) years. Factors associated with LDA benefit included older age, nonsmoking status, CHIP with a variant allele frequency of 10% or greater, family history of cancer, and lower body mass index. CHIP was the strongest predictor of benefit. Personalized treatment based on the model improved 5-year absolute cancer risk reduction by a median of 2.3% (IQR, 0.7%-3.7%) compared with a treat-all approach (LDA to all participants). LDA was associated with lower cancer risk (hazard ratio [HR], 0.85 [95% CI, 0.72-1.00]) in the treatment-favorable subgroup and higher cancer risk (HR, 1.14 [95% CI, 0.95-1.38]) in the treatment-unfavorable subgroup (P = .02 for heterogeneity). Conclusions and Relevance:The findings of this study suggest significant heterogeneity in the effectiveness of LDA for cancer prevention among older adults, with CHIP identified as a key predictive factor. Further study is needed to fully understand the implications of these findings. Trial Registration:ClinicalTrials.gov Identifier: NCT01038583.

The presence of a single large site of disease or so-called tumor ‘bulk’ in lymphoma has been variably associated with outcomes and influenced management decisions. However, challenges arise in using bulk as a prognosticator due to varied definitions across different lymphoma subtypes but also within studies of each subtype, increased utility of positron emission tomography in decision-making and recent incorporation of novel therapies. We analyzed data from the Australasian Lymphoma Registry regarding presence and influence of bulk on outcomes and treatment decisions in six key subtypes: diffuse large B-cell, follicular, marginal zone, T-cell, Hodgkin and Burkitt lymphoma. Of the 5,090 eligible patients identified between 2016-2025, 88% had documented information on the presence of bulk (registry definition >5 cm). Patients with bulk were more likely to receive systemic chemotherapy alone, and less likely to have localized treatment alone (radiotherapy and/or surgery), compared to those without bulk. Bulk was associated with inferior overall survival in patients with diffuse large B-cell lymphoma, and superior overall survival in those with Hodgkin lymphoma, in the univariate analyses. Exploratory analyses using disease-specific bulk definitions from clinicians practicing in Australia and New Zealand showed inferior progression-free survival in patients with diffuse large B-cell lymphoma (bulk >7.5 cm) and inferior overall survival in those with Burkitt lymphoma (bulk >10 cm), but not other subtypes. We demonstrated real-world evidence of management heterogeneity for patients with bulk, with potential prognostic implications. International standardization of the definition of bulk is urged for uniform utility in positron emission tomography-based and molecular prognostication across clinical studies. Trial registered with the Australian New Zealand Clinical Trials Registry: ANZCTRN12617000050358.

BACKGROUND:Alpha-gal syndrome (AGS) is caused by IgE antibodies against the alpha-gal oligosaccharide, which is structurally similar to the Group B antigen. Recent case reports of severe allergic transfusion reactions (ATRs) in Group O patients receiving Group B plasma and platelets raise the possibility of a new adverse event, herein called transfusion-related AGS (TRAGS). The primary goal of this study was to assess the frequency of Groups B and AB plasma and platelet transfusions to Group O patients. STUDY DESIGN AND METHODS:In this multi-site retrospective study, participating sites submitted the numbers of platelet and plasma transfusions administered during a 2-year period categorized by patient and product ABO group. RESULTS:Fourteen sites from 10 countries participated. Group O patients received Group AB for an average of 9.9% (range 2.8%-29.2%) of plasma transfusions and Group B for 3.2% (0%-12.8%). AB plasma transfusion to Group O patients represented 4.5% (0.9%-14.6%) of the total plasma transfused; Group B 1.4% (0%-5.1%). Group O patients received Group AB for an average of 1.5% (range 0%-5.9%) of platelet transfusions and Group B for 4.1% (0%-14.2%). AB platelet transfusion to Group O patients represented 0.6% (0%-2.7%) of the total platelets transfused; Group B platelets were 1.8% (0%-6.7%). DISCUSSION:Evidence supporting the possibility of a new adverse event, TRAGS, is accumulating. This study quantifies how often Group O patients may be exposed to Group B antigen in Group B or AB plasma and/or platelet transfusions, providing an estimate of the scope of potential risk for TRAGS.

BACKGROUND:Real-world data on treatment outcomes for elderly transplant-ineligible patients with newly diagnosed multiple myeloma are limited. The difference in treatment subsidization in Australia compared with New Zealand enables comparison of bortezomib-cyclophosphamide-dexamethasone (VCd), lenalidomide-bortezomib-dexamethasone (VRd) with Rd maintenance, and continuous Rd. METHODS:Using data from the ANZ Myeloma and Related Diseases Registry, we evaluated 1092 patients over 70 years of age between February 2013 and February 2024. Those who received Rd, VRd or VCd induction, and did not undergo an autologous stem cell transplant were included. RESULTS:Overall response rates were 85.6%, 73.7%, and 91.5% for VCd, Rd, and VRd, respectively (P < 0.001). At a median follow-up of 37 months, VRd showed the longest median progression-free survival (PFS) of 27.5 months, compared to 23.7 months for Rd and 20.5 months for VCd (P = 0.01). After adjustment, PFS for VRd and Rd remained superior compared to VCd. Rd patients had the longest median time to next treatment (35.1 months), compared to 28.7 months for VRd and 20.1 months for VCd. Overall survival (OS) was superior with VRd (P = 0.039), with 3-year survival rates of 80% for VRd, 67% for Rd, and 67% for VCd. However, multivariate analysis did not show a significant difference in OS. CONCLUSION:Our study confirms VRd demonstrates superior PFS compared to Rd and VCd, but was underpowered to detect a significant difference in OS. More prospective real-world studies are needed to establish the optimal choice of induction therapy balancing efficacy and toxicity for this cohort in resource limited settings.

Platelet transfusion is a frequent procedure with benefits and risks. To provide recommendations in adult and pediatric populations in whom platelet transfusions are commonly performed. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was applied to findings from 21 randomized trials and 13 observational studies in contexts of limited randomized clinical trial data. Transfusion strategies using fewer (restrictive) vs greater (liberal) amounts of platelets were compared. Evidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations. Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture. Because definitions of restrictive strategies varied across trials, recommendations reflect practical guidance. The following recommendations are strong recommendations with high/moderate–certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding patients receiving chemotherapy or undergoing allogeneic stem cell transplant, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. For consumptive thrombocytopenia in neonates without major bleeding, platelet transfusion is recommended when platelet count is less than 25 × 103/μL. In patients undergoing lumbar puncture, platelet transfusion is recommended when platelet count is less than 20 × 103/μL. In patients with consumptive thrombocytopenia due to Dengue without major bleeding, platelet transfusion is not recommended. The following recommendations are conditional recommendations with low/very low–certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended. In adults with consumptive thrombocytopenia without major bleeding, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing central venous catheter placement in compressible anatomic sites, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing interventional radiology, platelet transfusion is recommended when platelet count is less than 20 × 103/μL for low-risk procedures and less than 50 × 103/μL for high-risk procedures. For adults undergoing major nonneuraxial surgery, platelet transfusion is recommended when platelet count is less than 50 × 103/μL. For patients without thrombocytopenia undergoing cardiovascular surgery in the absence of major hemorrhage, including those receiving cardiopulmonary bypass, platelet transfusion is not recommended. For nonoperative intracranial hemorrhage in adults with platelet count greater than 100 × 103/μL, including those receiving antiplatelet agents, platelet transfusion is not recommended. A consistent pattern of evidence supports the implementation of restrictive platelet transfusion strategies. Restrictive strategies reduce risk of adverse reactions, mitigate platelet shortages, and reduce costs. It is good practice to consider overall clinical context and alternative therapies in the decision to perform platelet transfusion.

IMPORTANCE:. Blood transfusions are a common and potentially lifesaving intervention in ICU patients but are associated with harm and often transfused inconsistently with guidelines. However, it is not well known how ICU transfusion practice has recently changed and if there is variation in transfusion practice. OBJECTIVES:. To describe blood transfusion practices in ICU, the variation in practice across sites, and to compare transfusion practices against national guidelines and with prior published practice. DESIGN, SETTING, AND PARTICIPANTS:. A prospective, multicenter, binational, observational study conducted in 40 Australian and New Zealand ICUs from October 2021 to July 2022. All adult (≥ 18 yr) ICU patients admitted over 1 week were included and followed until ICU discharge or 28 days. MAIN OUTCOMES AND MEASURES:. Types of transfusion, thresholds and reasons for transfusions, the use of viscoelastic hemostatic assays (VHAs), variation in transfusion practice across sites, and changes in transfusion practice over time. RESULTS:. Of 927 patients, 217 (23.4%) received a blood transfusion during their ICU admission—192 (20.7%) received RBCs, 63 (6.8%) received platelets, 49 (5.3%) received fresh frozen plasma (FFP), and 29 (3.1%) received cryoprecipitate. Massive transfusion protocols were implemented nine times for six patients (0.7%). VHA were used in 25 of 268 (9.3%) non-RBC transfusions. Compared with national guidelines, 89.0% of RBC transfusions, 30.3% of platelet, 27.4% of FFP, and 20.0% of cryoprecipitate transfusions were consistent. Compared with ICU transfusion practices in 2008, after adjusting for confounding variables, ICU patients who received RBC and FFP were transfused more units each, and variation in total transfusions across sites increased for RBC, platelets, and FFP. CONCLUSIONS AND RELEVANCE:. Blood transfusions are common in ICU, but the practice is heterogeneous and frequently inconsistent with national guidelines, and the number of units transfused per patient has increased. More evidence is required.

BACKGROUND AND AIMS:Guidelines recommend against routine initiation of low-dose aspirin in older adults for primary prevention of atherosclerotic cardiovascular disease events. This study aimed to estimate long-term and post-trial effects of aspirin on major adverse cardiovascular events (MACE) and major haemorrhage using extended follow-up of participants from the ASPREE trial. METHODS:In-trial (2010-17) and post-trial (2017-22) data were analysed. At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial. RESULTS:Of the 19 114 participants randomized (9525 aspirin, 9589 placebo), 15 668 without in-trial MACE consented to post-trial follow-up. No long-term benefit of randomization to aspirin was observed for MACE for the entire in-trial and post-trial period [hazard ratio (HR) 1.04, 95% confidence interval (CI) .94, 1.15]. However, during the post-trial period (median 4.3 years), there was a higher rate of MACE (HR 1.17, 95% CI 1.01, 1.36) in those randomized to aspirin compared with placebo. Over the entire period, a higher rate of major haemorrhage was observed in the randomized aspirin group compared with placebo (HR 1.24, 95% CI 1.10, 1.39). CONCLUSIONS:The present study provides novel evidence concerning long-term MACE and haemorrhage following aspirin use in initially healthy older adults. The finding of no long-term MACE benefit needs to be considered in clinical decision-making if aspirin is being considered for use in this context.

ABSTRACT:Patients with chronic lymphocytic leukemia (CLL) often experience infections due to immune suppression and/or dysregulation. Hypogammaglobulinemia is a key contributor to immunosuppression in CLL, and immunoglobulin replacement therapy (IgRT) is commonly given to prevent infections. However, the benefit of IgRT in preventing serious infections in CLL remains unclear. This study aimed to describe IgRT treatment patterns in a large, real-world cohort of patients with CLL, and explore the association between IgRT and serious infections. We conducted a retrospective longitudinal study of linked hospital data, including 6217 patients with CLL between 2008 and 2022 in Victoria, Australia. Kaplan-Meier survival analyses were performed to estimate survival, infection incidence, and IgRT use. Cox survival analyses explored associations between infections and IgRT in patients receiving regular prophylactic IgRT. Over the 14-year follow-up, the monthly proportion of patients experiencing serious infections doubled, while the proportion of patients receiving any IgRT quadrupled. The median time to death from CLL diagnosis was 10 years, and patients with serious infections had a higher mortality rate (0.090 [95% confidence interval (CI), 0.074-0.110]) vs those without (0.008 [95% CI, 0.007-0.009]). In total, 753 patients (12.1%) received IgRT, and 524 (8.4%) received IgRT regularly. In patients who received regular IgRT, infection incidence was higher during periods of IgRT (0.056 [95% CI, 0.052-0.060]) compared with periods without IgRT (0.038 [95% CI, 0.035-0.042]). Serious infections were associated with not only IgRT initiation and reinitiation, but also cessation. Further research is needed to evaluate the causal relationship between IgRT and infections in this population.

BACKGROUND:Evidence guiding optimal transfusion practice for patients with myelodysplastic syndromes (MDS) is lacking. Many patients have concurrent cardiac disease. Data on practice are sparse. We aimed to describe the use of red blood cell (RBC) transfusion and the prevalence of cardiac comorbidities in patients with MDS within Australia's largest public hospital network to better understand real-world practices and outcomes. METHODS:We conducted a retrospective cohort study of patients aged ≥18 years with MDS, MDS/myeloproliferative overlap neoplasm or chronic myelomonocytic leukemia admitted from 2016 to 2018 to determine RBC transfusion-related endpoints. RESULTS:One hundred and seventy-nine patients (median age 78 years, 61.5% male) were included, with a median follow-up of 46 weeks. Of these, 102 (57.0%) received RBC transfusion. Transfused patients had lower presenting Hb (87 vs. 105 g/L, p < 0.0001), higher rates of cardiac disease (29.4% vs. 12.9%, p = 0.009) and 5-azacytidine use (31.4% vs. 13.0%, p = 0.004). Sixty-five patients (36.3%) received outpatient RBC transfusions, with a median of 2 units RBC per transfusion and 14 days between transfusions. The median pre-transfusion Hb was 80 g/L (IQR 74-86 g/L). Forty patients (22.4%) had evidence of cardiac disease, with similar pre-transfusion Hb for patients with and without cardiac disease (median Hb 79 g/L vs. 81 g/L, p = 0.1). DISCUSSION:Patients with MDS frequently require RBC transfusion, and restrictive transfusion strategies predominate despite many patients having cardiac comorbidities. Further research is needed to address optimal transfusion strategies in such patients and associated cardiac outcomes.

Importance:Platelet transfusion is a frequent procedure with benefits and risks. Objective:To provide recommendations in adult and pediatric populations in whom platelet transfusions are commonly performed. Evidence Review:Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was applied to findings from 21 randomized trials and 13 observational studies in contexts of limited randomized clinical trial data. Transfusion strategies using fewer (restrictive) vs greater (liberal) amounts of platelets were compared. Findings:Evidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations. Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture. Because definitions of restrictive strategies varied across trials, recommendations reflect practical guidance. The following recommendations are strong recommendations with high/moderate-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding patients receiving chemotherapy or undergoing allogeneic stem cell transplant, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. For consumptive thrombocytopenia in neonates without major bleeding, platelet transfusion is recommended when platelet count is less than 25 × 103/μL. In patients undergoing lumbar puncture, platelet transfusion is recommended when platelet count is less than 20 × 103/μL. In patients with consumptive thrombocytopenia due to Dengue without major bleeding, platelet transfusion is not recommended. The following recommendations are conditional recommendations with low/very low-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended. In adults with consumptive thrombocytopenia without major bleeding, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing central venous catheter placement in compressible anatomic sites, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing interventional radiology, platelet transfusion is recommended when platelet count is less than 20 × 103/μL for low-risk procedures and less than 50 × 103/μL for high-risk procedures. For adults undergoing major nonneuraxial surgery, platelet transfusion is recommended when platelet count is less than 50 × 103/μL. For patients without thrombocytopenia undergoing cardiovascular surgery in the absence of major hemorrhage, including those receiving cardiopulmonary bypass, platelet transfusion is not recommended. For nonoperative intracranial hemorrhage in adults with platelet count greater than 100 × 103/μL, including those receiving antiplatelet agents, platelet transfusion is not recommended. Conclusions And Relevance:A consistent pattern of evidence supports the implementation of restrictive platelet transfusion strategies. Restrictive strategies reduce risk of adverse reactions, mitigate platelet shortages, and reduce costs. It is good practice to consider overall clinical context and alternative therapies in the decision to perform platelet transfusion.

BACKGROUND:Convalscent plasma (CP) was identified as a potential therapy for COVID-19 available early in the pandemic. AIMS:To evaluate CP for the treatment of hospitalised adults with COVID-19 within the Australasian COVID-19 Trial (ASCOT). METHODS:ASCOT is an investigator-initiated, international, open-label, randomised clinical trial. Adult patients hospitalised with confirmed SARS-CoV-2 within 12 days of symptom onset and not receiving intensive respiratory or vasopressor/inotropic support were randomised to two units of CP or standard care. The primary outcome was the proportion of participants who died or required intensive respiratory support (invasive or non-invasive ventilation) or vasopressors/inotropic support in the 28 days after randomisation. The trial steering committee decided to discontinue the study in January 2021 in response to external evidence suggesting the futility of CP. RESULTS:Between May and November 2020, 33 participants were enrolled from eight sites across Australia and New Zealand. At baseline, nine (53%) in standard care and seven (47%) in CP arms required supplemental oxygen, three participants (all in the CP arm) required non-invasive ventilation or high-flow oxygen and over half were taking dexamethasone. The primary outcome was met by 23.5% (4/17) of standard care and 7% (1/15) of CP participants. One serious adverse event was reported in the CP arm, which was deemed not treatment-related. CONCLUSION:Fewer participants allocated to CP died or required new intensive respiratory or vasopressors/inotropic support in the 28 days after randomisation compared to standard care. However, our trial was stopped early in response to external evidence, and our sample size was small, limiting any definitive conclusions regarding the efficacy or safety of CP.

Tumour 'bulk' has historically been considered an important prognostic marker and clinical tool to guide treatment in patients with lymphoma. However, its use and definitions in trial designs varies significantly and it is unclear how this has influenced the relevance of bulk in contemporary practice. This comprehensive literature review evaluated the definitions, applications and prognostic impact of bulk in phase 3 randomised trials in four major lymphoma subtypes. Overall, 87 studies were identified across follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma (HL) with a wide range of bulk thresholds employed (5cm, 6cm, 7cm, 7.5cm, 10cm and >1/3 mediastinal mass ratio (MMR)). The most common threshold was: FL; 7cm (58%), DLBCL; 7.5cm and 10cm (44% each), PTCL; 7.5cm (66%) and HL; 1/3 MMR (91%). Bulk threshold was used by trials to determine eligibility (66%), stratification (24%), as a prognostic risk factor (37%) and decision tool for risk-adapted treatment e.g. radiotherapy (29%), however bulk definitions used for these varied both between, and within, lymphoma subtypes, and even within single trials in 25%. Thirty-two studies incorporated bulk in prognostic analyses with only five showing significance for differential survival outcomes. Our analysis demonstrates high inconsistency in thresholds defining tumour bulk and use of bulk in phase 3 lymphoma trials across eligibility, stratification, therapeutic risk-adaptation plus prognostication. This highlights an urgent need for international consensus on definitions of bulk within trials to improve its prognostic and predictive value and refine its application in clinical practice.

BACKGROUND:Blood transfusion is a common medical intervention. For patients with acute critical bleeding, large volume "massive" transfusion (MT) is required, and is potentially life-saving. However, the evidence-base for transfusion practice, particularly for critical bleeding/MT management, is relatively weak, and has confounded the development of clinical best practice recommendations. AIM:The aim was to address this evidence gap by building the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). We describe how data collection, standardisation and interoperability of data sourced from multiple electronic information systems are managed, and share the lessons learned. INNOVATION:The ANZ-MTR is a database of routine electronic hospital admission information, laboratory test results, transfusion records and outcomes of adults (18 years and older) who have received a MT for any cause of acute critical bleeding, including trauma, major surgery, obstetric or gastrointestinal haemorrhage. Source data are provided by participating hospitals and are harmonised by the registry. Since its launch in 2011, the ANZ-MTR has captured over 9200 MT episodes from 29 hospitals.What can be learned from this case:Effective communication with all custodians of the source data has been fundamental to the success of the registry. A preeminent outcome of this success is the current expansion of the registry to become the National Transfusion Dataset, which will capture comprehensive data for all transfusions.Implications for health information management practice:The ANZ-MTR illustrates that complex and varied arrays of routinely collected clinical and hospital administrative data from multiple electronic information systems can be consolidated into a resource-rich clinical database.