Misspellings or "miscellings"-Non-verifiable and unknown cell lines in cancer research publications.

Reproducible laboratory research relies on correctly identified reagents. We have previously described gene research papers with wrongly identified nucleotide sequence(s), including papers studying miR-145. Manually verifying reagent identities in 36 recent miR-145 papers found that 56% and 17% of papers described misidentified nucleotide sequences and cell lines, respectively. We also found 5 cell line identifiers in miR-145 papers with misidentified nucleotide sequences and cell lines, and 18 cell line identifiers published elsewhere, that did not represent indexed human cell lines. These 23 identifiers were described as non-verifiable (NV), as their identities were unclear. Studying 420 papers that mentioned 8 NV identifier(s) found 235 papers (56%) that referred to 7 identifiers (BGC-803, BSG-803, BSG-823, GSE-1, HGC-7901, HGC-803, and MGC-823) as independent cell lines. We could not find any publications describing how these cell lines were established. Six cell lines were sourced from cell line repositories with externally accessible online catalogs, but these cell lines were not indexed as claimed. Some papers also stated that short tandem repeat (STR) profiles had been generated for three cell lines, yet no STR profiles could be identified. In summary, as NV cell lines represent new challenges to research integrity and reproducibility, further investigations are required to clarify their status and identities.

Does IPSS-R down staging before transplantation improve the prognosis of patients with Myelodysplastic neoplasms?

In MDS patients higher IPSS-R at transplant is associated with worse transplant outcome. Thus, it may seem beneficial to improve IPSS-R by therapeutic intervention prior to transplantation in order to "down-stage" the disease risk. However, there is no evidence to date to support this approach. A retrospective analysis of the EBMT transplant registry was performed to investigate the role of therapeutic interventions prior to transplantation with regard to changes in IPSS-R and transplant outcomes. A total of 1482 MDS patients with sufficient data to calculate IPSS-R at diagnosis and at time of transplantation were selected and analysed for transplant outcome in a multivariable Cox model including IPSS-R at diagnosis, treatment intervention, change in IPSS-R before transplant and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R change in untreated patients and moderately superior in chemotherapy-treated patients with improved IPSS-R at transplant. Improved IPSS-R after hypomethylating agents (HMA) or other therapies showed no beneficial effect. However, when IPSS-R progressed after chemotherapy, (HMA) or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R down staging or reduction of BM blasts after chemotherapy and no benefit for HMA or other treatments and thus question the role of prior therapy in MDS patients scheduled for transplantation. The model-based survival estimates should help inform decision making for both doctors and patients.

An Approach to Evaluate the Costs and Outputs of Academic Biobanks.

Academic biobanks commonly report sustainability challenges, which may be exacerbated by a lack of information on biobank value. To better understand the costs and supported outputs that contribute to biobank value, we developed a systematic, generalizable methodology to determine biobank inputs and publications arising from biobank-supported research. We then tested this in a small cohort (n = 12) of academic cancer biobanks in New South Wales, Australia. A proforma was developed to capture monetary and in-kind biobank costing data from biobank managers and publicly available sources. Participating biobanks were grouped and compared according to the following two classifications: open- versus restricted-access and high versus low total annual costs. Our methodology provides a feasible approach for capturing comprehensive costing data for a defined period. Characterization of biobanks using this approach showed that median total costs, as well as median staffing and in-kind costs, were comparable for open- and restricted-access biobanks, as were the quantity and journal impact metrics of supported publications. High- and low-cost biobanks supported similar median numbers of publications; however, high-cost biobanks supported publications with higher median journal impact factor and Altmetric scores. Overall, 9 of 10 biobanks had higher Field-Weighted Citation Impact scores than the global average for similar publications. This is the first tested, generalizable approach to analyze the costs and publications arising from biobank-supported research. By determining explicit cost and output data, academic biobanks, funders, and policymakers can engage in or support informed redirection of resourcing and/or benchmark setting with the aim of improving biobank support of research.

Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial.

BACKGROUND: A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population. METHODS: This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 µg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440. FINDINGS: Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. INTERPRETATION: Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Chronic myeloid leukemia diagnosed in pregnancy: management and outcome of 87 patients reported to the European LeukemiaNet international registry.

The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001-2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd-3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.

Verification of nucleotide sequence reagent identities in original publications in high impact factor cancer research journals.

Human gene research studies that describe wrongly identified nucleotide sequence reagents have been mostly identified in journals of low to moderate impact factor, where unreliable findings could be considered to have limited influence on future research. This study examined whether papers describing wrongly identified nucleotide sequences are also published in high-impact-factor cancer research journals. We manually verified nucleotide sequence identities in original Molecular Cancer articles published in 2014, 2016, 2018, and 2020, including nucleotide sequence reagents that were claimed to target circRNAs. Using keywords identified in some 2018 and 2020 Molecular Cancer papers, we also verified nucleotide sequence identities in 2020 Oncogene papers that studied miRNA(s) and/or circRNA(s). Overall, 3.8% (251/6647) and 4.0% (47/1165) nucleotide sequences that were verified in Molecular Cancer and Oncogene papers, respectively, were found to be wrongly identified. Wrongly identified nucleotide sequences were distributed across 18% (91/500) original Molecular Cancer papers, including 38% (31/82) Molecular Cancer papers from 2020, and 40% (21/52) selected Oncogene papers from 2020. Original papers with wrongly identified nucleotide sequences were therefore unexpectedly frequent in two high-impact-factor cancer research journals, highlighting the risks of employing journal impact factors or citations as proxies for research quality.

Palliation of Intractable Cancer-Related Pain With Low-Dose Epidural Bupivacaine.

Introduction: Patients with advanced cancer nearing end of life often present with complex multifactorial pain. Although epidural analgesia is routinely used in inpatient hospital settings for targeted pain control, there is scant description in the literature of the use of low-dose epidural analgesia for relief of cancer-related pain at end of life. In this study, we present a case of difficult to control cancer-related rectal and pelvic pain in a patient who responded well in her last days of life to a low-dose bupivacaine epidural. Case Description: A 66-year-old woman presented for inpatient hospital admission for pain control from home hospice with intractable cancer-related pain from metastatic colorectal adenocarcinoma marked by extensive erosive lesions extending from the anterior perineum to the posterior rectum, with rectovaginal fistula. The patient reported poor tolerance of medications and described spiritual beliefs (based in Buddhism) that caused her and her family to prioritize maintaining a lucid, clear mind above nearly all else while seeking symptom management. The patient was so debilitated by pain at the time of presentation that she was bedbound in a quadruped position. Case Management and Outcome: After 2 weeks of poor pain control in the hospital with multiple failed attempts at palliation-including bilateral pudendal block, as well as opioids and other routine, but potentially sedating or deliriogenic, medications to treat her pain-the patient permitted administration of a low-dose bupivacaine epidural that significantly reduced her pain and allowed the patient to remain clear-headed up until the time of her death. Twenty-three days after admission, and 5 days after initiation of low-dose bupivacaine epidural for pain control, the patient died peacefully in the hospital. Conclusion: Low-dose epidural analgesia for cancer-related pain at end of life from malignancy involving the pelvis-perineum, rectum, or vagina-may be a viable option for patients, particularly those who wish to avoid the risk of somnolence or confusion from systemic opioids and other analgesics.

Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

Dexmedetomidine Continuous Infusion for Refractory Cancer Pain at End of Life: A Case Report.

Refractory cancer-related pain at end-of-life (EoL) is multifaceted and may require utilizing medications with different mechanism of actions beyond opioids. We report the successful use of dexmedetomidine in a 63-year old female with recurrent breast cancer and intractable left arm pain and swelling admitted to University of California, San Diego, Health (UC San Diego Health), palliative care unit. Patient's pain and agitation continued to persist and she declined clinically despite efforts to start methadone, continuous infusion opioids, continuous infusion lidocaine and intravenous chlorpromazine by the palliative care team. On hospital day (HD) 11 patient was started on dexmedetomidine continuous infusion for refractory pain per our protocol at UC San Diego Health. The next day the patient appeared much improved in terms of pain and agitation with grimacing and moaning completely resolved. She was able to have some lucid periods and interacting with her family. With the addition of dexmedetomidine to her pain regiment, the patient was able to peacefully die 5 days later. This case report highlights the clinical utility of demedetomidine in a palliative care unit for refractory pain at EoL.

Autologous hematopoietic cell transplantation for relapsed multiple myeloma performed with cells procured after previous transplantation-study on behalf of CMWP of the EBMT.

Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.

Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019.

Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy-based induction fell significantly, being largely replaced by bortezomib-based regimens. The two-year complete response rate increased from 22% to 42%. The five-year progression-free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.

Identification of human gene research articles with wrongly identified nucleotide sequences.

Nucleotide sequence reagents underpin molecular techniques that have been applied across hundreds of thousands of publications. We have previously reported wrongly identified nucleotide sequence reagents in human research publications and described a semi-automated screening tool Seek & Blastn to fact-check their claimed status. We applied Seek & Blastn to screen >11,700 publications across five literature corpora, including all original publications in Gene from 2007 to 2018 and all original open-access publications in Oncology Reports from 2014 to 2018. After manually checking Seek & Blastn outputs for >3,400 human research articles, we identified 712 articles across 78 journals that described at least one wrongly identified nucleotide sequence. Verifying the claimed identities of >13,700 sequences highlighted 1,535 wrongly identified sequences, most of which were claimed targeting reagents for the analysis of 365 human protein-coding genes and 120 non-coding RNAs. The 712 problematic articles have received >17,000 citations, including citations by human clinical trials. Given our estimate that approximately one-quarter of problematic articles may misinform the future development of human therapies, urgent measures are required to address unreliable gene research articles.

Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3-ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation.

FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3-ITD patients referred for allogeneic stem cell transplantation (allo-SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3-ITD AML patients who underwent allo-SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes. Median patient age was 49 years and median follow-up duration was 36 months. Two-year leukemia-free survival (LFS) and incidence of relapse were 54% and 31.6%, respectively. Non-relapse mortality was experienced by 14.4% with a 2-year overall survival (OS) of 60.1%. On multivariate analysis, LFS was significantly lower in patients with intermediate and adverse risk cytogenetics compared with those with favorable risk cytogenetics, (hazard ratio [HR] = 1.48, 95% confidence interval [CI], 1.06-2.06; p = .02), and (HR = 01.65, 95% CI, 1.13-2.40; p = .009), respectively. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16-2.61; p = .008) with a trend toward lower OS in patients with intermediate risk cytogenetics compared to those with favorable risk cytogenetics (HR = 1.43, 95% CI, 1.00-2.05; p = .052). In addition, adverse risk patients and intermediate risk patients experienced higher relapse rates compared with favorable risk patients (HR = 1.83, 95% CI, 1.13-2.94; p = .013 and HR = 1.82, 95% CI, 1.19-2.77; p = .005). Overall, cytogenetic studies aid in refinement of risk stratification in transplanted FLT3-ITD AML patients.

Rare germline variants in childhood cancer patients suspected of genetic predisposition to cancer.

Identification of cancer-predisposing germline variants in childhood cancer patients is important for therapeutic decisions, disease surveillance and risk assessment for patients, and potentially, also for family members. We investigated the spectrum and prevalence of pathogenic germline variants in selected childhood cancer patients with features suggestive of genetic predisposition to cancer. Germline DNA was subjected to exome sequencing to filter variants in 1048 genes of interest including 176 known cancer predisposition genes (CPGs). An enrichment burden analysis compared rare deleterious germline CPG variants in the patient cohort with those in a healthy aged control population. A subset of predicted deleterious variants in novel candidate CPGs was investigated further by examining matched tumor samples, and the functional impact of AXIN1 variants was analyzed in cultured cells. Twenty-two pathogenic/likely pathogenic (P/LP) germline variants detected in 13 CPGs were identified in 19 of 76 patients (25.0%). Unclear association with the diagnosed cancer types was observed in 11 of 19 patients carrying P/LP CPG variants. The burden of rare deleterious germline variants in autosomal dominant CPGs was significantly higher in study patients versus healthy aged controls. A novel AXIN1 frameshift variant (Ser321fs) may impact the regulation of ß-catenin levels. Selection of childhood cancer patients for germline testing based on features suggestive of an underlying genetic predisposition could help to identify carriers of clinically relevant germline CPG variants, and streamline the integration of germline genomic testing in the pediatric oncology clinic.

Vignettes to Illustrate the Value of Tumor Biobanks in Cancer Research in Canada.

Background: Tumor biobanks are a common research infrastructure. As a collection of biospecimens and annotated data collected to support a multitude of research projects, biobanks facilitate access to materials that are the critical fuel for the generation of data in up to 40% of cancer research publications. However, quantifying how to measure biobanks' impact and their value on the field of cancer research discoveries and findings, has not been well elucidated. Methods: We have used a qualitative case study approach to illustrate the impact of tumor biobanks. We assessed the impact of three research studies published between 2010 and 2012 that required easily accessible "classic" biobanks. Each study utilized preassembled collections of tumor biospecimens with associated patient outcomes data at the outset of the research project. We compared the resulting journal impact factor, altmetric and field-weighted citation impact factor scores for each article to a set of six "benchmark" articles that represent cancer research and treatment discoveries from the same time period and two sentinel scientific discovery articles. Results: We developed a value model using a literature search and design-thinking methodologies to illustrate the contributions of these "classic" model biobanks to these research studies. Assessment of the three example articles supported by biobanks demonstrates that the output can have impact that is comparable to the impact of a set of benchmark articles describing milestones in the field of cancer research and cancer care. Conclusions: These case studies illustrate the value of the sustained investment of funds, planning, time, and effort on the part of the biobanks before the conduct of the research study to be able to ultimately support high-value research. The "value" model will enable further discussion around impact and may be useful in better delineating qualitative metrics of biobank value in the future.

In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

Impact of early candidemia on the long-term outcome of allogeneic hematopoietic stem cell transplant in non-leukemic patients: an outcome analysis on behalf of IDWP-EBMT.

We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p < 0.0001), and 100-day OS was lower (HR 3.22, p < 0.0001) than that of patients without candidemia. After a median follow-up of 4.3 years, 5-year OS, NRM, and RM for patients with and without candidemia were 50.5% vs. 60.8%, p < 0.0001, 28.2% vs.18.8%, p < 0.0001, and 25.3% vs. 27.2%, p = 0.4, respectively. In conclusion, in non-leukemic transplant patients, the occurrence of an early episode of candidemia is rare but it is still associated with a negative effect on the outcome.

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.