Hematologic Malignancy: Who Cares in the End? A Retrospective Cohort Study of Markers of Quality End-of-Life Care.

BACKGROUND: Early palliative care is increasingly used in solid organ malignancy but is less established in patients with hematologic malignancy. Disease-related factors increase the demand for hospitalization, treatment, and supportive care in patients with hematologic malignancy. The terminal phase of illness in patients with hematologic malignancy can be difficult to predict, resulting in complexities in establishing a standard for quality end-of-life care. METHODS: This is a retrospective single-center cohort study of adult patients with hematologic malignancy who died between October 2019 and July 2022. Patients were identified, and disease characteristics, therapy, and outcomes were extracted from medical records. Descriptive statistics are reported and univariate analyses were performed across a range of factors to assess for associations. RESULTS: A total of 229 patients were identified, with a median age of 77 years and 35% female. In the final 30 days of life, 65% presented to the emergency department, 22% had an ICU admission, 22% had an invasive procedure, 48% received cytotoxic therapy, 61% received a RBC transfusion, and 46% received a platelet transfusion. Use of intensive chemotherapy was particularly associated with hospitalization and ICU admission. A total of 74% referred to palliative care, with a median time from referral to death of 13 days. Of these patients, one-third were referred within the last 5 days of life. In terms of place of death, 54% died in the acute hospital setting and 30% in hospice, with a median hospice length of stay of 4 days. CONCLUSIONS: These findings highlight the need for further research into quality indicators for end of life in hematologic malignancy and earlier integration of specialist supportive and palliative care in both inpatient and outpatient settings.

A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.

BACKGROUND: For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings. METHOD: We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews. RESULTS: Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions. CONCLUSIONS: Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.

Activity and toxicity of intramuscular 1000 iu/m2 polyethylene glycol-E. coli L-asparaginase in the UKALL 2003 and UKALL 2011 clinical trials.

In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m2 was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart. Post-induction, non-high-risk patients (Regimens A, B) received 1-2 doses in delayed intensification (DI) while high-risk Regimen C patients received 6-10 PEG-EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase-related toxicity and ASNase-associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144-307 iu/l), 265 iu/l (165-401 iu/l) and 292 iu/l (194-386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient -9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG-EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing.

It doesn't stop at validation: patient reported outcome measures require ongoing and iterative development.

Patient reported outcomes (PROs) are a pillar of modern-day patient-centered care and clinical trials. PROs complement clinical information with the patient's own report about their experiences of health, without influence or interpretation by other people. However, choosing an appropriate PRO measure from the many available remains challenging for clinicians and researchers. One of the common pitfalls in instrument selection is that the instrument is often developed with a different patient population than the group being cared for or researched. This difference can result in salient items of importance to the patients, being under-reported or missed altogether. We highlight, through the reporting of some of our own data, that PRO instrument development does not stop with a validation study and we provide suggestions for future research for further improvement in this space.

Arthritis-related work outcomes experienced by younger to middle-aged adults: a systematic review.

OBJECTIVE: The aim of this review was to systematically identify, appraise and synthesise evidence on work-related outcomes experienced by younger to middle-aged adults (aged 16-50 years) with arthritis. METHODS: Eligible studies were identified in Medline, PsycINFO, Embase and CINAHL in January 2020. Quantitative and qualitative studies containing self-reported data on work-related outcomes on younger/middle-aged adults with arthritis were included. Quality assessment was undertaken using validated quality appraisal tools from the Joanna Briggs Institute. RESULTS: Thirty-four studies were identified for inclusion. Work outcomes were organised around five themes: (1) arthritis-related work productivity outcomes, (2) arthritis-related work participation outcomes, (3) other arthritis-related workplace outcomes, (4) barriers to work participation associated with arthritis and (5) enablers to work participation associated with arthritis. Arthritis was associated with work limitations on the Workplace Activity Limitations Scale (average scores ranging from 5.9 (indicating moderate workplace difficulty) to 9.8 (considerable workplace difficulty)), and higher work disability prevalence rates (range: 6%-80%) relative to healthy populations. Arthritis was not associated with decreased absenteeism on the Work Productivity and Activity Impairment Questionnaire (mean (SD) 7.9% (14.0%)), indicating low levels of absenteeism, similar to healthy populations. As work outcomes were commonly binary, person-centred (qualitative) perspectives on barriers and enablers augmented the quantitative findings. CONCLUSION: Arthritis is commonly associated with poorer work outcomes for younger/middle-aged adults relative to healthy populations. Additional research focusing solely on the workplace needs of younger/middle-aged population groups is required to inform tailored interventions and workplace support initiatives to maximise productive working years.

EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications.

The EBF1-PDGFRB gene fusion accounts for <1% of B-cell precursor acute lymphoblastic leukemia (ALL) cases and occurs within the Philadelphia-like ALL subtype. We report 15 EBF1-PDGFRB-positive patients from childhood ALL treatment trials (ALL 97/99, UKALL 2003, UKALL 2011) in the United Kingdom. The fusion arose from interstitial deletion of 5q33 (n = 11), balanced rearrangement (n = 2), or complex rearrangement (n = 2). There was a predominance of females (n = 11), median age of 12 years, and median white blood cell count of 48.8 × 10(9)/L. Among 12 patients who achieved complete remission on earlier trials (ALL 97/99 and UKALL 2003), 10 were positive for minimal residual disease (MRD) at the end of induction, and 7 relapsed 18 to 59 months after diagnosis. The majority (9 of 12) remained alive 6 to 9 years after diagnosis. There are reports of EBF1-PDGFRB-positive patients who are refractory to conventional chemotherapy who achieve complete response when treated with the tyrosine kinase inhibitor imatinib. These findings have prompted screening for EBF1-PDGFRB in patients entered onto the current UKALL 2011 trial for whom induction therapy failed, who did not achieve remission by day 29, or who remained MRD positive (>0.5%) at week 14. Two UKALL 2011 patients, positive for EBF1-PDGFRB, received imatinib; 1 died 6 months after a matched unrelated bone marrow transplant as a result of undefined encephalopathy, and the other remained in remission 10 months after diagnosis.

Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia.

Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < .001). TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P < .001) and 2.15 (1.32-3.48, P = .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P = .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at www.clinicaltrials.org as #ISCRTN45724312.

A Randomized Controlled Trial of an Additional Funding Intervention to Improve Clinical Trial Enrollment.

Background: A low proportion of adults with cancer are recruited to clinical trials. Cancer Council Victoria provides funding to clinical trial sites through its statewide Cancer Trials Management Scheme (CTMS). Historically, there appeared to be a relationship between budget-allocated funding and the number of patients recruited. A randomized controlled trial was conducted to test whether additional funding in 2013 would increase trial recruitment. Methods: A total of 18 trial centers ("sites") received usual CTMS funds, whereas 16 intervention sites received usual funds plus additional funds, proportional to recruitment in 2011; additional payments to sites in the intervention group ranged from $6,750 to $234,000 AUD (≈$6,750-$234,000 USD at the time). This represented an average 11.8% (interquartile range [IQR], 8.0%, 12.3%) increase in sites' budgets. Sites were required to use the funds with the aim of increasing recruitment. The study end point was the number of new participants recruited to trials in 2013. An online survey assessed strategies used to increase recruitment. Results: The median number of new trial recruits per site in 2013 was 21 (IQR, 5-39) in the control arm and 12.5 (IQR, 3.5-44.5) in the intervention arm. The ratio of new trial recruitment numbers at the intervention sites compared with control sites in 2013, adjusting for respective 2012 numbers and institution type, was 0.99 (95% CI, 0.69, 1.43; P=.96). The survey revealed most intervention sites used funding to increase staffing. Conclusions: Additional funding at a site level did not lead to a contemporaneous increase in trial recruitment.

Patient and caregiver satisfaction of a palliative care chronic diseases clinic during COVID lockdowns.

OBJECTIVES: To assess the quality assurance of a specialist palliative care clinic focused on chronic diseases and explore the satisfaction and acceptability of the telemedicine model amongst patients and caregivers. METHODS: A cross-sectional 23-item survey was developed by the clinical team, approved by ethics and distributed to patients and caregivers. Data collection ran between September 2021 and February 2022, and SPSS was used for data analysis. Demographics were collected from hospital records. RESULTS: Thirty-five surveys were returned. The cohort had a median age of 82 years, and the most common primary diagnosis was renal failure. Participants rated telemedicine as easier to access than face-to-face appointments due to convenience. Telemedicine was rated highly for future utility, with video consultations being perceived as more useful than telephone consultations. Participants responded overwhelmingly well towards the clinic. DISCUSSION: Findings demonstrated high levels of satisfaction with the Supportive Care Clinic model and for telemedicine. However, logistical challenges and the desire for face-to-face appointments were also identified. The study highlights the importance of offering a range of modalities for patient engagement in healthcare services and suggests that telemedicine should complement, rather than replace, face-to-face consultations. Future investigations should explore patient and caregiver sentiment towards telemedicine platforms alongside patient deterioration.

PeRsOnaliSed care Planning for oldER people with frailty (PROSPER): protocol for a randomised controlled trial.

BACKGROUND: Frailty is common in older age and is characterised by loss of biological reserves across multiple organ systems. These changes associated with frailty mean older people can be vulnerable to sudden, dramatic changes in health because of relatively small problems. Older people with frailty are at increased risk of adverse outcomes including disability, hospitalisation, and care home admission, with associated reduction in quality of life and increased NHS and social care costs. Personalised Care Planning offers an anticipatory, preventative approach to supporting older adults to live independently for longer, but it has not been robustly evaluated in a population of older adults with frailty. METHODS: Following an initial feasibility study, this multi-centre, individually randomised controlled trial aims to establish whether personalised care planning for older people improves health-related quality of life. It will recruit 1337 participants from general practices across Yorkshire and Humber and Mid-Mersey in the North of England. Eligible patients will be aged 65 and over with an electronic frailty index score of 0.21 or above, living in their own homes, without severe cognitive impairment and not in receipt of end-of-life care. Following confirmation of eligibility, informed consent and baseline data collection, participants will be individually randomised to the PeRsOnaliSed care Planning for oldER people with frailty (PROSPER) intervention or usual care in a 2.6:1 allocation ratio. Participants will not be blinded to allocation, but data collection and analysis will be blinded. The intervention will be delivered over 12 weeks by a Personal Independence Co-ordinator worker based within a voluntary sector organisation, Age UK. The primary outcomes are health-related quality of life, measured using both the physical and mental components of the Short-Form 12 Item Health Questionnaire at 12 months after randomisation. Secondary outcomes comprise activities of daily living, self-management capabilities and loneliness, admission to care homes, hospitalisations, and health and social care resource use at 12 months post randomisation. Parallel cost-effectiveness and process evaluations will be conducted alongside the trial. DISCUSSION: The PROSPER study will evaluate the effectiveness and cost-effectiveness of a personalised care planning approach for older people with frailty and inform the process of its implementation. TRIAL REGISTRATION: ISRCTN16123291 .  Registered on  28 August 2020.

Inhibition of carbonic anhydrase activity modifies the toxicity of doxorubicin and melphalan in tumour cells in vitro.

Carbonic anhydrase IX (CA IX) is a hypoxia-regulated enzyme, overexpressed in many types of human cancer. CA IX is involved in pH homeostasis, contributing to extracellular acidification and tumourigenesis. Acidification of the extracellular milieu can impact upon cellular uptake of chemotherapeutic drugs by favouring weak acids (e.g. melphalan), but limiting access of weak bases (e.g. doxorubicin). We investigated whether alterations of CA IX activity affected anti-cancer drug uptake and toxicity. CA inhibitor acetazolamide (AZM) enhanced doxorubicin toxicity but reduced melphalan toxicity in cell lines that highly expressed CA IX under anoxic conditions (HT29 and MDA435 CA9/18). The toxicity changes reflected modification of passive drug uptake. AZM did not alter toxicity or uptake in cells with low CA IX activity (HCT116 and MDA435 EV1). AZM lowered intracellular pH in HT29 and MDA435 CA9/18 cells under anoxic conditions. CA IX activity has chemomodulatory properties and is an attractive target for anti-cancer therapy.

Patient Perceived Financial Burden in Haematological Malignancies: A Systematic Review.

Advances in scientific understanding have led to novel therapies and improved supportive care for many patients with haematological malignancies. However, these new drugs are often costly, only available at centralised health care facilities, require regular specialist reviews and lengthy treatment regimens. This leads to a significant financial burden. Understanding the impact of financial burden on haematological patients is important to appreciate the urgency of alleviating this systemic issue. METHOD: Eligible studies were identified by systematically searching Medline, PsycINFO, CINAHL and Embase. Self-reported data reported in both quantitative and qualitative studies that described the financial burden for patients with haematological malignancies were included. Quality appraisal of the included studies was undertaken using the Joanna Briggs Institute tools. A narrative synthesis was employed. For quantitative studies, outcomes were extracted, tabulated and categorised to find similarities and differences between the studies. For qualitative studies, quotations, codes and themes were extracted and then clustered. An inductive approach derived qualitative themes. RESULTS: Twenty studies were identified for inclusion. Of the quantitative studies most (83%) employed un-validated researcher-generated measures to assess financial burden. Between 15-59% of patients experienced a financial burden. Out-of-pocket expenditure was frequent for clinical appointments, prescription and non-prescription medication, and travel. Financial burden was associated with a worsening quality of life and living in metropolitan areas, but there was no evidence for impact on survival. Patient-centred experiences from the qualitative inquiry complemented the quantitative findings and five themes were determined: familial or household impact; reliance on others; barriers to care due to cost; and barriers to accessing financial assistance and sources of out-of-pocket expenses. CONCLUSION: The impacts of financial burden are yet to be fully appreciated in haematological malignancies, exacerbated by the heterogeneous methods employed by researchers. Future work should focus on identifying the long-term ramifications of financial burden for patients and should trial interventions to reduce its prevalence and patient impacts.

Do patients with haematological malignancies suffer financial burden? A cross-sectional study of patients seeking care through a publicly funded healthcare system.

BACKGROUND: It is increasingly appreciated that some patients with cancer will experience financial burden due to their disease but little is known specifically about patients with haematological malignancies. Therefore, this study aimed to measure financial toxicity experienced by patients with haematological malignancies in the context of a publicly funded health care system. METHOD: All current patients diagnosed with leukaemia, lymphoma or multiple myeloma, from two major metropolitan health services in Melbourne, Australia were invited to complete a survey capturing; patient demographics, employment status, income sources, financial coping and insurances, OOP expenses and self-reported financial toxicity using a validated measure. RESULTS: Of the 240 people approached, 113 (47 %) participated and most had leukaemia (62 %). Forty-seven (42 %) participants experienced some degree of financial toxicity using the Comprehensive Score for financial toxicity (COST) instrument. On multivariate linear regression, older age (>65 years, p = 0.007), higher monthly income (>$8000, p = 0.008), not having and being forced into unemployment or early retirement (p < 0.001) remained significantly associated with less financial toxicity. CONCLUSION: Financial toxicity is present in Australian haematology patients and those at higher risk may be patients of working age, those without private health insurance and patients that have been forced to retire early or have become unemployed due to their diagnosis.

Do patients with haematological malignancies suffer financial burden? A cross-sectional study of patients seeking care through a publicly funded healthcare system.

BACKGROUND: It is increasingly appreciated that some patients with cancer will experience financial burden due to their disease but little is known specifically about patients with haematological malignancies. Therefore, this study aimed to measure financial toxicity experienced by patients with haematological malignancies in the context of a publicly funded health care system. METHOD: All current patients diagnosed with leukaemia, lymphoma or multiple myeloma, from two major metropolitan health services in Melbourne, Australia were invited to complete a survey capturing; patient demographics, employment status, income sources, financial coping and insurances, OOP expenses and self-reported financial toxicity using a validated measure. RESULTS: Of the 240 people approached, 113 (47 %) participated and most had leukaemia (62 %). Forty-seven participants (42 %) experienced some degree of financial toxicity using the Comprehensive Score for financial toxicity (COST) instrument. On multivariate linear regression, older age (>65 years, p = 0.007), higher monthly income (>$8000, p = 0.008), not having and being forced into unemployment or early retirement (p < 0.001) remained significantly associated with less financial toxicity. CONCLUSION: Financial toxicity is present in Australian haematology patients and those at higher risk may be patients of working age, those without private health insurance and patients that have been forced to retire early or have become unemployed due to their diagnosis.

'If I don't work, I don't get paid': An Australian qualitative exploration of the financial impacts of acute myeloid leukaemia.

A cancer diagnosis can have significant financial impacts for patients, often resulting from unexpected out-of-pocket expenses and a reduced capacity to work. These financial implications have been well characterised quantitatively in common cancers. However, less is known about the lived experience of financial stress, particularly outside the United States and in rarer cancers. This study aimed to explore the perceived financial impact of acute myeloid leukaemia (AML)-a rare haematological malignancy where patients may be particularly vulnerable to financial stress due to the lengthy, specialised and centralised care. The findings provide insight into the patients' lived experience of the personal financial impact of the disease. This Australian qualitative study was undertaken with 11 adults in remission from AML and recruited from their treating hospital. Semi-structured interviews were transcribed, and data were managed using NVivo. Themes were identified through inductive and deductive analysis using open, axial and thematic coding. Four themes were identified: burden of AML-attributable costs (e.g. out-of-pocket parking and medication expenses); accommodating the AML-impact on paid work (e.g. early retirement and modifying job tasks); the consequence of financial strain from AML (e.g. using savings and accessing Government welfare) and concerns about the future and future familial financial burden (e.g. securing finances and worry about depleting financial resources). A reduction in or stopping work was perceived as the most burdensome to their current and future finances. The findings demonstrate people with AML experience financial difficulty even within a publically funded healthcare system. Opportunities exist for health services to alleviate some financial burden through reducing or abolishing parking fees for oncology patients and ensuring adequate access to social workers to facilitate access to Government welfare. Improving patients' financial difficulties contributes to improved quality of life, which is congruent to cancer survivorship.

Experiences of personal protective equipment by Australian healthcare workers during the COVID-19 pandemic, 2020: A cross-sectional study.

The aim of this study was to capture Australian frontline healthcare workers' (HCWs) experiences with personal protective equipment (PPE) during the COVID-19 pandemic in 2020. This was a cross-sectional study using an online survey consisting of five domains: demographics; self-assessment of COVID risk; PPE access; PPE training and confidence; and anxiety. Participants were recruited from community and hospital healthcare settings in Australia, including doctors, nurses, allied health professionals, paramedics, and aged care and support staff. Data analysis was descriptive with free-text responses analysed using qualitative content analysis and multivariable analysis performed for predictors of confidence, bullying, staff furlough and anxiety. The 2258 respondents, comprised 80% women, 49% doctors and 40% nurses, based in hospital (39%) or community (57%) settings. Key findings indicated a lack of PPE training (20%), calls for fit testing, insufficient PPE (25%), reuse or extended use of PPE (47%); confusion about changing guidelines (48%) and workplace bullying over PPE (77%). An absence of in-person workplace PPE training was associated with lower confidence in using PPE (OR 0.21, 95%CI 0.12, 0.37) and a higher likelihood of workplace bullying (OR 1.43; 95% CI 1.00, 2.03) perhaps reflecting deficiencies in workplace culture. Deficiencies in PPE availability, access and training linking to workplace bullying, can have negative physical and psychological impacts on a female dominant workforce critical to business as usual operations and pandemic response.

Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial.

BACKGROUND: Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens. METHODS: This open-label randomised trial was undertaken in 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1-18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk, intermediate-risk, and standard-risk groups on the basis of duration of first complete remission, site of relapse, and immunophenotype. All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. Neither patients nor those giving interventions were masked. After three blocks of therapy, all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease (≥10(-4) cells) received an allogenic stem-cell transplant. Standard-risk and intermediate-risk patients with postinduction low minimal residual disease (<10(-4) cells) continued chemotherapy. The primary outcome was progression-free survival and the method of analysis was intention-to-treat. Randomisation was stopped in December, 2007 because of differences in progression-free and overall survival between the two groups. This trial is registered, reference number ISCRTN45724312. FINDINGS: Of 239 registered patients, 216 were randomly assigned to either idarubicin (109 analysed) or mitoxantrone (103 analysed). Estimated 3-year progression-free survival was 35·9% (95% CI 25·9-45·9) in the idarubicin group versus 64·6% (54·2-73·2) in the mitoxantrone group (p=0·0004), and 3-year overall survival was 45·2% (34·5-55·3) versus 69·0% (58·5-77·3; p=0·004). Differences in progression-free survival between groups were mainly related to a decrease in disease events (progression, second relapse, disease-related deaths; HR 0·56, 0·34-0·92, p=0·007) rather than an increase in adverse treatment effects (treatment death, second malignancy; HR 0·52, 0·24-1·11, p=0·11). INTERPRETATION: As compared with idarubicin, mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia, a potentially useful clinical finding that warrants further investigation. FUNDING: Cancer Research UK, Leukaemia and Lymphoma Research, Cancer Council NSW, and Sporting Chance Cancer Foundation.

Characterising experiences with acute myeloid leukaemia using an Instagram content analysis.

Instagram has more than one billion monthly users, which presents a unique research opportunity particularly in rare diseases or hard to reach populations. This study focuses on acute myeloid leukaemia, a rare haematological malignancy and aims to characterise who posts acute myeloid leukaemia-related content and the type of content created. The findings can provide information and a method for future studies, particularly those focused on online or social media based interventions. Acute myeloid leukaemia-related Instagram posts were identified by searching specific and relevant hashtags (#). A content analysis systematically classified themes in the data. A convenience sample of 100 posts (138 photos) were manually extracted and coded. Data are described using descriptive statistics and demonstrated by qualitative examples. The most frequent users in our sample were patients (66%), patient support networks (24%) and professional organisations (10%). Patients who were communicating their health update (31%) were the most frequently posted content and 25% of these posts described a symptom experience. Our findings demonstrate that patients and their support networks are frequenting Instagram and therefore may be able to receive and benefit from tailored intervention, however there is an identified gap in health-organisations participating in this virtual online community.

Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY).

PURPOSE: Acute myeloid leukemia (AML) is a rare hematologic malignancy accounting for 0.8% of new cancer diagnoses in Australia. High mortality and morbidity affect work productivity through workforce dropout and premature death. This study sought to estimate the productivity loss attributable to AML in the Australian population over 10 years and to estimate the costs of this productivity loss. Productivity was measured using productivity-adjusted life years (PALYs), a similar concept to quality-adjusted life years, but adjusts for the productivity loss attributable to disease, rather than impaired health. MATERIALS AND METHODS: Dynamic life tables modeled the Australian working population (age 15-65 years) between 2020 and 2029. The model population had two cohorts: those with and without AML. Differences in life years, PALYs, and costs represented the health and productivity impact of AML. Secondary analyses evaluated the impact of different scenarios. RESULTS: Over the next 10 years, there will be 7,600 years of life lost and 7,337 PALYs lost because of AML, amounting to Australian dollars (AU$) 1.43 billion in lost gross domestic product ($971 million in US dollars). Secondary analyses highlight potential savings of approximately AU$52 million if survival rates were improved by 20% and almost AU$118 million in savings if the return-to-work rates increased by 20% on the current estimates. CONCLUSION: Our study demonstrates that even in low-incidence cancer, high mortality and morbidity translate to profound impacts on years of life, productivity, and the broader economy. Better treatment strategies are likely to result in significant economic gains. This highlights the value of investing in research for improved therapies.

Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials.

AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. RESULTS: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL. CONCLUSION: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. TRIAL REGISTRATION: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.