eviQ Cancer Treatments Online: Providing evidence-based information to improve cancer patient outcomes.

AIM: To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users. METHODS: A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users. RESULTS: In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022.  eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided. CONCLUSION:  eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored.

Mental Health Service Contact Following Cancer Diagnosis and Associations with Cancer Mortality: Results from a Linked Population-Based Study of Adolescents and Young Adults in New South Wales.

Purpose: To assess the mental health conditions, as indicated by mental health service contact in adolescents and young adults (AYAs) diagnosed with cancer in New South Wales (NSW) and associations with cancer mortality. Methods: In 3998 NSW AYAs diagnosed with cancer in 2005-2017, mental health service contacts were obtained from hospital inpatient records and specified medical and pharmaceutical insurance claims. Odds of postcancer mental health contact were assessed by precancer mental contacts using logistic regression adjusted for sociodemographic and cancer characteristics. The risk of cancer-specific mortality related to postcancer mental health contacts was estimated using competing risk regression. Results: The prevalence of mental health service contacts in the 5 years postcancer diagnosis was 27.0%, higher than the corresponding precancer prevalence of 21.4%. The most common mental health conditions were depression and anxiety. The odds of having a mental health contact postcancer diagnosis were higher in patients with a precancer mental health service contact (adjusted odds ratio 5.69, confidence intervals [95% CIs]: 4.90-6.75). The 5-year cancer-specific survival was 87.9% (95% CI: 85.8-89.8) for patients with a mental health service contact postcancer, which was lower than the 93.9% (95% CI: 93.0-94.7) for patients without this contact. The subhazard ratio (SHR) for cancer mortality in patients having mental health service contact postcancer diagnosis was 1.67 (95% CI: 1.29-2.15), adjusted for sociodemographic characteristics, cancer stage, and precancer mental health status. Conclusion: The prevalence of mental health service contact increased after a cancer diagnosis. Mental health care should be a continued priority for AYA cancer patients, particularly for high-risk groups.

Hopes, concerns, satisfaction and regret in a precision medicine trial for childhood cancer: a mixed-methods study of parent and patient perspectives.

BACKGROUND: Paediatric precision oncology aims to match therapeutic agents to driver gene targets. We investigated whether parents and patients regret participation in precision medicine trials, particularly when their hopes are unfulfilled. METHODS: Parents and adolescent patients completed questionnaires at trial enrolment (T0) and after receiving results (T1). Parents opted-in to an interview at T1. Bereaved parents completed a questionnaire 6-months post-bereavement (T1B). We analysed quantitative data with R and qualitative data thematically with NVivo, before integrating all data for interpretation. RESULTS: 182 parents and 23 patients completed T0; 108/182 parents and 8/23 patients completed T1; 27/98 bereaved parents completed T1B; and 45/108 parents were interviewed. At enrolment, participants held concurrent hopes that precision medicine would benefit future children and their child. Participants expressed concern regarding wait-times for receipt of results. Most participants found the trial beneficial and not burdensome, including bereaved parents. Participants reported high trial satisfaction (median scores: parents: 93/100; patients: 80/100). Participants expressed few regrets (parent median scores: parents: 10/100; bereaved parents: 15/100; patient regret: 2/8 expressed minimal regret). CONCLUSIONS: Even when trial outcomes did not match their hopes, parents and patients rarely regretted participating in a childhood cancer precision medicine trial. These data are critical for integrating participants' views into future precision medicine delivery.

Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial.

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia's first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care.

Parents' expectations, preferences, and recall of germline findings in a childhood cancer precision medicine trial.

BACKGROUND: Germline genome sequencing in childhood cancer precision medicine trials may reveal pathogenic or likely pathogenic variants in cancer predisposition genes in more than 10% of children. These findings can have implications for diagnosis, treatment, and the child's and family's future cancer risk. Understanding parents' perspectives of germline genome sequencing is critical to successful clinical implementation. METHODS: A total of 182 parents of 144 children (<18 years of age) with poor-prognosis cancers enrolled in the Precision Medicine for Children with Cancer trial completed a questionnaire at enrollment and after the return of their child's results, including clinically relevant germline findings (received by 13% of parents). Parents' expectations of germline genome sequencing, return of results preferences, and recall of results received were assessed. Forty-five parents (of 43 children) were interviewed in depth. RESULTS: At trial enrollment, most parents (63%) believed it was at least "somewhat likely" that their child would receive a clinically relevant germline finding. Almost all expressed a preference to receive a broad range of germline genomic findings, including variants of uncertain significance (88%). Some (29%) inaccurately recalled receiving a clinically relevant germline finding. Qualitatively, parents expressed confusion and uncertainty after the return of their child's genome sequencing results by their child's clinician. CONCLUSIONS: Many parents of children with poor-prognosis childhood cancer enrolled in a precision medicine trial expect their child may have an underlying cancer predisposition syndrome. They wish to receive a wide scope of information from germline genome sequencing but may feel confused by the reporting of trial results.

Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study.

INTRODUCTION: Identifying an underlying germline cancer predisposition (CP) in a child with cancer has potentially significant implications for both the child and biological relatives. Cohort studies indicate that 10%-15% of paediatric cancer patients carry germline pathogenic or likely pathogenic variants in cancer predisposition genes, but many of these patients do not meet current clinical criteria for genetic testing. This suggests broad tumour agnostic germline testing may benefit paediatric cancer patients. However, the utility and psychosocial impact of this approach remain unknown. We hypothesise that an approach involving trio whole-genome germline sequencing (trio WGS) will identify children and families with an underlying CP in a timely fashion, that the trio design will streamline cancer risk counselling to at-risk relatives if CP was inherited, and that trio testing will not have a negative psychosocial impact on families. METHOD AND ANALYSIS: To test this, we present the Cancer PREDisposition In Childhood by Trio sequencing study (PREDICT). This study will assess the clinical utility of trio WGS to identify CP in unselected patients with cancer 21 years or younger in New South Wales, Australia. PREDICT will perform analysis of biological parents to determine heritability and will examine the psychosocial impact of this trio sequencing approach. PREDICT also includes a broad genomics research programme to identify new candidate genes associated with childhood cancer risk. ETHICS AND DISSEMINATION: By evaluating the feasibility, utility and psychosocial impact of trio WGS to identify CP in paediatric cancer, PREDICT will inform how such comprehensive testing can be incorporated into a standard of care at diagnosis for all childhood cancer patients. TRIAL REGISTRATION NUMBER: NCT04903782.

Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, with a median follow-up of 21.5 months and 33.3 months, respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.

The Voices of Stakeholders Involved in Precision Medicine: The Co-Design and Evaluation of Qualitative Indicators of Intervention Acceptability, Fidelity and Context in PRecISion Medicine for Children With Cancer in Australia.

We report a novel approach of amalgamating implementation outcomes of acceptability and fidelity alongside context as a new way of qualitatively evaluating implementation outcomes and context of a precision medicine intervention. A rapid qualitative online proforma was co-designed with stakeholders and sent to a purposive sample of healthcare professionals involved in an early-phase clinical trial intervention. Data were analysed using Framework Analysis. A total of 24 out of 68 proformas were returned. Although some participants raised concerns about drug medication access issues, the main intervention was well accepted and understood across professional groups. Comprehension was enhanced through exposure to specialist multidisciplinary meeting arrangements. In conclusion, a rapid data collection tool and framework are now available to assess readily measurable, qualitative indicators of acceptability, fidelity of receipt and contextual fit within the dynamic precision medicine context.

What's in a Name? Parents' and Healthcare Professionals' Preferred Terminology for Pathogenic Variants in Childhood Cancer Predisposition Genes.

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; 'faulty gene,' 'altered gene,' 'gene change,' and 'genetic variant,' analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred 'gene change,' 'altered gene,' or 'genetic variant' (n = 8/25). Parents least preferred 'faulty gene' (n = 18/25). Half the genetics professionals most preferred 'faulty gene' (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred 'genetic variant' (n = 11/29) and least preferred 'faulty gene' (n = 19/29). Participants across all groups perceived 'faulty gene' as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families' preferred terminology, while providing accurate explanations regarding implications of genetic findings.

Rethinking Blood Testing in Pediatric Cancer Patients: A Quality Improvement Approach.

Introduction: The overuse of blood tests burdens the healthcare system and can detrimentally impact patient care. Risks of frequent blood sampling include infection and clinician-induced anemia, which can negatively impact patients and their families. Pediatric cancer patients are particularly vulnerable as they are immunocompromised with a small blood volume. Four blood tests had become a daily practice. Therefore, we aimed to reduce the number of blood tests taken per bed day within the inpatient pediatric cancer unit by 15% within 8 months. Methods: This quality improvement project combined several strategies to reduce test frequency and empower clinicians on the rationale for blood test ordering. Recommendations were developed collaboratively presented in a summary table. Targeted behavior-change methodology built engagement and momentum for the change. All clinicians were challenged to STOP and THINK about why a test is necessary for each patient. The primary outcome measure was the frequency of the tests taken per bed day. Frequency was compared between pre- and postimplementation plus follow-up periods across 2019-2021. Results: 26,941 blood tests were captured in 1,558 admissions. The intervention led to an overall blood test reduction of 37% over 8 months. Liver Function Tests were the standout, with a 52% decrease in test frequency. Conclusions: A strategy incorporating education and culture change, combined with clear guidance on testing frequency, significantly reduced the ordering frequency of blood tests without increased patient harm.

COVID-19 vaccination in children and adolescents aged 5 years and older undergoing treatment for cancer and non-malignant haematological conditions: Australian and New Zealand Children's Haematology/Oncology Group consensus statement.

INTRODUCTION: The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults. RECOMMENDATIONS: Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion. ENDORSED BY: The Australian and New Zealand Children's Haematology/Oncology Group.

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium.

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (<0.1%) by centralized flow cytometry and 84% (n = 16) successfully proceeded to hematopoietic stem cell transplant. Two-year overall survival was 75.6% [95%CI: 47.3%, 90.1%] for MRD-negative patients vs. 17.9% [95%CI: 4.4%, 38.8%] for those with residual disease (p < .001). Twelve subjects (34%) had known epigenetic alterations with 8 (67%) achieving a CR, 7 (88%) of whom were MRD negative. Correlative pharmacodynamics demonstrated the biologic activity of decitabine and vorinostat and identified specific gene enrichment signatures in nonresponding patients. Overall, this therapy was well-tolerated, biologically active, and effective in pediatric patients with R/R AML, particularly those with epigenetic alterations.

Rationalised premedication practice for blood product transfusions: A single-centre quality initiative.

AIM: Blood and platelets are scarce resources that are an essential part of the supportive care for paediatric cancer patients. There are many inherent risks involved with transfusions including acute transfusion reactions (ATRs). Following an initial ATR, prophylactic medications are commonly given prior to subsequent transfusions. However, there are risks with medication administration as well as negative implications for the health system. Our aim was to prevent the automatic prescribing of premedications prior to blood and platelet transfusions for ATRs. We hypothesised this would not increase the risk of harm. METHODS: Our intervention was to eliminate automatic prescribing of intravenous corticosteroids and intravenous promethazine prior to a transfusion. This was approached through a behaviour change model and the implementation of recommended prescribing guidelines. Three Plan Do Study Act (PDSA) cycles refined the guidelines to align with clinicians' needs and build support through co-design. Data gathered on individual patients receiving transfusions and reaction rates during the trial were compared to international data. RESULTS: A total of 100 patients received a transfusion during the trial. Eleven patients either had a previous reaction or experienced their first reaction during this time. All patients followed the guidelines and had either no premedication or an oral antihistamine premedication. There were no breakthrough reactions using oral antihistamines. The overall reaction rate was 1.33%, which aligns with the reported data on ATRs internationally. CONCLUSION: A restricted prescribing approach to pharmaceutical cover prior to blood and platelet transfusions can be implemented effectively in a paediatric cancer population, without an increase in the risk of harm to the patients.

ESCAPE-Allergy: Evaluating screening for children and adolescents with penicillin allergy.

AIM: Penicillin allergy labels are frequently encountered in children and are associated with significant harms. Most children are falsely labelled and can safely tolerate a penicillin but delabelling strategies are underutilised and paediatric-specific resources are lacking. The aim of this study was to evaluate an allergy assessment tool for children in hospital. METHODS: We evaluated a paediatric-adapted penicillin allergy assessment tool, using an online survey of clinicians in a tertiary paediatric hospital, with 10 hypothetical potential penicillin allergy or adverse reaction cases (including non-allergy reactions). For each case, respondents were asked to use the tool to assign a reaction phenotype and recommend management. We determined the tool's sensitivity, specificity and acceptability to end users. RESULTS: We evaluated 30 complete survey responses from senior and junior medical staff, nurses and pharmacists. The tool's overall sensitivity was 80.7% (95% confidence interval (CI) 74.2-87.1%) for assigning the correct reaction phenotype and 85.3% (95% CI 79.4-91.3%) for appropriate management. The tool had high sensitivity for identifying immediate hypersensitivity reactions at 95.6% (95% CI 90.2-100%). Most respondents agreed or strongly agreed that they would use the tool in their practice (22/30, 73.3%). CONCLUSION: This survey evaluated a paediatric-adapted penicillin allergy assessment tool in a tertiary paediatric hospital among multidisciplinary clinician groups. The tool performed well overall and had high safety in identifying immediate hypersensitivity reactions. Further research to support implementation of allergy assessment and delabelling programmes among children is required.

Infection-Related Mortality in Adults and Children Undergoing Allogeneic Hematopoietic Cell Transplantation: An Australian Registry Report.

Infection-related mortality (IRM) is the most common non-relapse-related cause of death reported after allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies. This report provides the first account of IRM in adults and children undergoing HCT in Australia. Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry database, associated with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death, including infectious etiology and causative organisms, were extracted from the database for adults and children for analysis. At day +100 and 1 year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children, IRM was the leading cause of post-HCT mortality at day +100 at 2.5% and the second highest cause of post-HCT mortality at 1 year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of antithymocyte globulin (ATG) or alemtuzumab, donor-positive/recipient-negative cytomegalovirus (CMV) serostatus, and acute graft-versus-host disease were significant risk factors for IRM. However, in children, age >5 years, acute lymphocytic leukemia as the primary disease, and mismatched unrelated or haploidentical donor source were predictive of IRM. Of the deaths in which an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to post-transplantation lymphoproliferative disorder (PTLD). The most common organisms were Pseudomonas spp, Enterococcus spp, Candida spp, Aspergillus spp, and CMV. In children where an infectious etiology was reported (64%), 13% were attributed to bacteria, 26% to fungus, 45% to viruses, and 16% to PTLD. This report highlights that IRM was the leading cause of death early post-HCT in Australia. Strategies to reduce IRM, such as individualized pre-transplantation infection risk assessment, rapid diagnostics, and prevention management strategies should be explored to determine whether these outcomes can be improved. In addition, improving the completeness and accuracy of reported data, particularly for infectious pathogens, could assist in directing management strategies to reduce IRM in HCT.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders.

BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.

Addition of Thiotepa to Total Body Irradiation and Cyclophosphamide Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia.

Total body irradiation (TBI)/cyclophosphamide (CY) is a standard-of-care conditioning regimen in allogeneic hematopoietic stem cell transplant (HSCT) for pediatric acute lymphoblastic leukemia (ALL). This study sought to identify whether the addition of thiotepa (TT) to TBI/CY improves HSCT outcomes for pediatric patients with ALL. A retrospective analysis was performed on 347 pediatric ALL patients who underwent HSCT between 1995 and 2015, with 242 receiving TBI/CY/TT and 105 patients receiving TBI/CY. There were no statistical differences in age, donor source, or complete remission status between the 2 groups. Comparison of the TBI/CY/TT versus TBI/CY groups demonstrated no difference in transplant-related mortality at 1 (11% versus 11%), 5 (13% versus 16%), or 10 years (16% versus 16%). There was lower relapse in the TBI/CY/TT group at 1 (14% versus 26%), 5 (24% versus 36%), 10 (26% versus 37%), and 15 years (26% versus 37%) (P= .02) but was not statistically significant on multivariate analysis. The TBI/CY/TT group showed a trend toward improved disease-free survival (DFS) at 5 (59% versus 47%), 10 (56% versus 46%), and 15 years (49% versus 40%) (P = .05) but was not statistically significant on multivariate analysis. Comparing overall survival at 5 (62% versus 53%), 10 (57% versus 50%), and 15 years (50% versus 44%) demonstrated no statistical difference between the 2 groups. The addition of thiotepa to TBI/CY demonstrated no increase in transplant-related mortality for pediatric ALL HSCT but was unable to demonstrate significant benefit in disease control. Minimal residual disease status remained the key risk factor impacting both relapse and DFS. More studies are warranted to better clarify the benefits of using thiotepa in conditioning for ALL HSCT.

Development of an implementation and evaluation strategy for the Australian 'Zero Childhood Cancer' (Zero) Program: a study protocol.

INTRODUCTION: Effective implementation of a research Program requires an actionable plan to guide execution. To assess the actionability and success of that plan, both scientific and implementation elements must be taken into account. The aim of this study is to assess the 'Zero Childhood Cancer Personalised Medicine Program' (the Zero Program), an Australian first-ever and most comprehensive personalised medicine programme for children with high-risk or relapsed cancer, in terms of its structure, process and implementational effect. METHODS AND ANALYSIS: We will assess Program delivery mechanisms. The development of the implementation and evaluation strategy will concentrate on the work of the Zero Program as a complex whole. This includes the structure of collaborative links across stakeholder groups involved in Program development and delivery, changes to collaborative relationships over time and the impact of group working on Program outcomes. We are applying a mixed-methods design including: a rapid ethnography (observations of stakeholder interactions and informal conversations), Program professionals' completion of a rapid health implementation proforma and a social network analysis. Formative evaluations of the implementation science effects, applying feedback techniques, for example, Formative Evaluation Feedback Loops and the Zero Program professionals' feedback, will determine where Program tailoring may be needed. A repeat of the social network analysis downstream will examine network changes over time, followed by an expert panel using the expert recommendations for implementing change to assess the integration of implementation strategies into the Program structure. A summative evaluation of the Program will bring the research elements together, leading to comprehensive data triangulation and determining the sustainability and implementational effects of Program delivery. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by Hunter New England Research Ethics Committee, New South Wales, Australia (approval ref: 2019/ETH12025). Knowledge translation will be achieved through publications, reports and conference presentations to healthcare professionals, patients, families and researchers. TRIAL REGISTRATION: NCT03336931; Pre-results.