'I just never wanted them to feel uncomfortable': Barriers to pharmacy-based identification and treatment of hepatitis C in Victoria, Canada.

Background: Canada is currently on target to reach the 2030 WHO goal of HCV elimination. Continued high rates of treatment are required to meet this goal. Novel models such as Tayside, Scotland pharmacy-based HCV screening and treatment have proven successful to engage people who use drugs (PWUD) in HCV therapy with a simplified, task-shifted cascade of care. This study seeks to determine whether these successes can be replicated at community pharmacies in Victoria BC. Methods: Four pharmacies who work with PWUD and provide opioid agonist therapy were trained to provide consent and perform point-of-care HCV antibody screening. They were supported by study nurse to link to HCV RNA testing when antibody positive patients were identified, with HCV treatment offered to RNA positive participants. Qualitative interviews were conducted with five pharmacy staff to explore experiences and feasibility of pharmacists in HCV care cascade. Results: Pharmacy staff completed 200 HCV OraQuick tests between October 2020 and June 2022: 65 HCV antibody positive, 29 HCV RNA negative (25 previously treated and 4 self-cleared). Of the 26 RNA positive participants, one is awaiting treatment, 25 people have started treatment, 22 achieving SVR. Although the onset of the COVID-19 pandemic was a fundamental barrier incorporating HCV testing at pharmacies, stigma related to HCV and illicit drug use continues to impact this process. Conclusions: This innovative pharmacy-based approach found people with limited connection to primary health care to test and treat HCV but requires more training and support to be more widely feasible.

Cytomegalovirus in children undergoing haematopoietic stem cell transplantation: a diagnostic and therapeutic approach to antiviral resistance.

Cytomegalovirus (CMV) is a ubiquitous virus which causes a mild illness in healthy individuals. In immunocompromised individuals, such as children receiving haematopoietic stem cell transplantation, CMV can reactivate, causing serious disease and increasing the risk of death. CMV can be effectively treated with antiviral drugs, but antiviral resistance is an increasingly common complication. Available therapies are associated with adverse effects such as bone marrow suppression and renal impairment, making the choice of appropriate treatment challenging. New agents are emerging and require evaluation in children to establish their role. This review will discuss established and emerging diagnostic tools and treatment options for CMV, including antiviral resistant CMV, in children undergoing haematopoietic stem cell transplant.

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.

Australia and New Zealand Transplant and Cellular Therapies (ANZTCT) position statement: COVID-19 management in patients with haemopoietic stem cell transplant and chimeric antigen receptor T cell.

Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.

Virological Outcomes After Switching to Abacavir/Lamivudine/Dolutegravir Combined with Adherence Support in People Living with HIV with Poor Adherence: A Phase IV, Multicentre Randomized Prospective Open Label Study (TriiADD-CTN 286).

Background: Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others. Objective: To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations. Methods: TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization. Results: In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, -17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers. Conclusion: Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations.

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

Cross-sectional comparison of age- and gender-related comorbidities in people living with HIV in Canada.

Because antiretroviral therapy (ART) is allowing people living with human immunodeficiency virus (PLWH) to survive longer, they are developing more age-related comorbidities. We evaluated the effects of age and gender on the burden of age-related comorbidities among PLWH. In this retrospective real-world study, de-identified data were extracted from the medical charts of 2000 HIV-positive adults on ART across 10 sites in Canada. The prevalence of age-related comorbidities was determined in 6 age subgroups (<30, 30-39, 40-49, 50-59, 60-69, and ≥70 years). The effects of gender on these comorbidities were also examined. Risks of cardiovascular disease and chronic kidney disease (CKD) were calculated using the Framingham and D:A:D equations. Most persons were White (68%), male (87%), and virologically suppressed (94%). The mean age was 50.3 years (57% aged ≥50 years), and mean CD4+ T-cell count was 616 cells/mm3. The most common comorbidities were neuropsychiatric symptoms (61%), overweight/obesity (43%), liver disease (37%), and dyslipidemia (37%). The mean number of comorbidities increased across age subgroups (P < .001). Across all age subgroups, the prevalence of hypertension (P = .04), dyslipidemia (P = .04), CKD (P = .03), bone fragility (P = .03), and depression (P = .02) differed between males and females. Both age (P < .001) and gender (P < .001) impacted cardiovascular disease and CKD risk. Age and gender influenced the burden, types, and risks of age-related comorbidities in PLWH in this Canadian cohort. These comorbidities should be diagnosed and treated in routine clinical practice.

Measurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions.

BACKGROUND: ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers. METHODS: Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines. RESULTS: ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001). CONCLUSIONS: MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL.

Treating people where they are: Nurse-led micro-elimination of hepatitis C in supported housing sites for networks of people who inject drugs in Victoria, Canada.

To achieve the World Health Organization's goal of eliminating hepatitis C (HCV) by 2030 requires enhanced HCV testing and treatment among people who use drugs (PWUD). Micro-elimination of HCV is a strategy to target HCV testing and treatment efforts to specific segments of the population. From February to December 2018 nurses initiated a "seek & treat" micro-elimination approach, increasing outreach and removing barriers to accessing HCV treatment in a clinic setting by testing and treating individuals, including PWUD, where they live. The aim of this study was to evaluate the proportion of clients with HCV antibodies and HCV RNA and the response to direct acting agent (DAA therapy) among people who live at or have social connections to local supportive housing sites through this nurse-led micro-elimination project in Victoria, Canada. A chart review of electronic medical records and case management documentation was used to collect relevant data of participants treated with DAA therapy, identified through specific housing site testing and outreach interventions. In total, 180 people were tested for HCV antibodies, 72 (40%) were antibody positive: 51 (28%) were RNA positive, 13 (7%) had spontaneously cleared and 8 (4%) had been previously treated. Of the 51 that were currently living with HCV, 43 people were started on treatment, 39 have achieved sustained virologic response (SVR). By providing treatment to clients in their homes and with their friends, clinicians have been able to treat clients, including those with limited contact with the health care system.

Factors associated with 60-day adherence to "safer supply" opioids prescribed under British Columbia's interim clinical guidance for health care providers to support people who use drugs during COVID-19 and the ongoing overdose emergency.

AIMS: In March 2020, British Columbia issued Risk Mitigation Guidance (RMG) to support prescribing of pharmaceutical alternatives to illicit drugs, in order to reduce risk for COVID-19, overdose, and withdrawal among people who use drugs. This study evaluated factors associated with 60-day adherence to novel opioid alternatives prescribed at an inner-city health centre in Victoria, Canada. METHODS: A chart review was conducted to collect data on sociodemographic information, medical histories, and follow-up services among all clients prescribed novel opioid alternatives from March 2020-August 2020 (n = 286). Bivariable and multivariable regression were used to identify independent and adjusted factors associated with 60-day adherence. RESULTS: Overall, 77% of 286 clients were still receiving opioids after 60 days of follow-up. Medications included hydromorphone (n = 274), sustained-release oral morphine (n = 2), and oxycodone (n = 9). The adjusted odds of 60-day adherence to novel opioid alternatives were significantly higher for those receiving a mental health medication (aOR = 3.49, 95%CI = 1.26, 11.00), a higher maximum daily dosage of RMG prescriptions (aOR = 1.03 per mg increase, 95%CI = 1.01, 1.04), and those with continuous receipt of OAT (aOR = 6.25, 95%CI = 2.67, 15.90). CONCLUSIONS: Higher dosages and co-prescription of mental health medications and OAT may help support better adherence to this form of prescriber-based "safer supply". Further work is needed to identify optimal prescribing practices and the longer term impacts of differing implementation scenarios.

Reinfection following successful direct-acting antiviral therapy for HCV infection among people attending an inner-city community health centre in Victoria, Canada.

BACKGROUND: Studies of HCV reinfection following direct-acting antiviral (DAA) therapy among PWID have been limited by short follow-up and small case numbers. This study evaluated the incidence of HCV reinfection following successful DAA therapy among people attending an inner-city community health centre in Victoria, Canada. METHODS: In this observational study, participants treated with DAA therapy between November 2014 and December 31, 2019 were included. Retrospective chart review was performed to assess demographics, recent injecting drug use at treatment initiation (previous six months), opioid agonist treatment (OAT), and HIV. Endpoints included sustained virologic response (SVR), HCV reinfection, and mortality. RESULTS: Of 482 participants initiating DAA treatment, 30% were female, 46% were receiving OAT, 49% had recent injection drug use, 15% had HIV/HCV coinfection, and 22% had cirrhosis. Treatment completion was 97% (468/482; 12 discontinued therapy, and 2 died during treatment). SVR was 87% (418/482). Outcomes among those who completed treatment but did not achieve SVR (n=53), included loss to follow-up (n=11), HCV RNA for SVR testing not completed (n=18), viral relapse (n=6), reinfection (n=5) and viral recurrence (n=5, unable to distinguish viral relapse from reinfection), and death (n=7). The rate of HCV reinfection was 3.6/100 person-years (95% confidence interval [CI] 2.4-5.5; 22 cases; 602 person-years follow-up). Factors associated with an increased risk of HCV reinfection included recent injection drug use (adjusted relative risk [aRR] 8.55, 95% CI 1.98-36.96) and HIV co-infection (aRR 2.35, 95% CI 1.01-5.44). Fifty-five people died (overdose, n=19) during (n=2) or following (n=53) therapy (7.4/100 person-years; 95% CI 5.6-9.6). CONCLUSION: This study demonstrates ongoing reinfection among a marginalized population at an inner-city community health centre, with higher rates among those with HIV and recent injecting drug use. The rates of reinfection and mortality highlight the importance of integrating HCV care with strategies to address drug-related harms.

Good Engraftment but Quality and Donor Concerns for Cryopreserved Hemopoietic Progenitor Cell Products Collected During the COVID-19 Pandemic.

Changes to donor availability, collection center capacity, and travel restrictions during the early phase of the COVID-19 pandemic led to routine cryopreservation of most unrelated donor products for hematopoietic transplantation prior to the recipient commencing the conditioning regimen. We investigated the effect of this change on unrelated donor product quality and clinical outcomes. Product information was requested from transplantation centers in Australia and New Zealand and clinical outcome data from the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). In total, 191 products were collected between April 1, 2021, and September 30, 2021, and most (74%) were from international collection centers. Median post-thaw CD34 recovery was 78% (range 25% to 176%) and median post-thaw CD34 viability was 87% (range 34% to 112%). Median time to neutrophil recovery was 17 days (interquartile range 10 to 24 days), and graft failure occurred in 6 patients (4%). These clinical outcomes were similar to those of "fresh" unrelated donor transplants reported to the ABMTRR in 2019. However, recipient transplantation centers reported problems with 29% of products in the form of damage during transit, low cell dose, inadequate labeling, missing representative samples, or missing documentation. These problems were critical in 7 cases (4%). At last follow-up, 22 products (12%) had not been infused. Routine cryopreservation of unrelated donor hemopoietic progenitor cell products has enabled safe continuation of allogeneic transplant services during the COVID-19 pandemic. However, practices for product tracing, documentation, and transportation can be optimized, and measures to reduce the incidence of unused unrelated donor product are required.

Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab.

We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19-directed chimeric antigen receptor T-cell therapy despite prior blinatumomab exposure. Inferior 2-year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A-rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B-ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.

Epidemiology and outcome for viremia in children undergoing bone marrow transplant: A retrospective cohort study.

INTRODUCTION: Viral infections pose a serious risk for children undergoing hematopoietic stem cell transplant (HSCT). There are few published case series of prevalence, risk factors, and outcomes examining multiple viruses simultaneously, and no pediatric Australasian data published to date. We describe the real-life experience of viremia in pediatric HSCT in a single tertiary center. METHODS: All episodes of viremia in children undergoing HSCT between 2000 and 2018 were identified by matching HSCT patients' unique identification numbers with positive blood polymerase chain reaction (PCR) results for human adenovirus (HAdV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV-6). Paper or electronic charts and electronic pathology results were used to extract the study variables. RESULTS: Viremia was detected in 177/445 (39.8%) HSCT episodes, of which 46% were allogeneic and 19% autologous transplants. Viremia was disseminated in 96 (21.6%) episodes, with 80 (18%) having more than one virus. HAdV was detected in 108 (24.3% of total episodes) and frequently in autologous transplants, CMV in 71 (16.0%), EBV in 60 (13.5%), and HHV-6 in 38 (8.5%). Of 174 children, 19 (10.9%) died of a viral-associated cause, with viral mortality highest in CMV (18.3%), lowest in HHV-6 (2.6%) with HAdV and EBV similar (6.6% and 6.7%). Adenoviral (but not other virus) dissemination was significantly associated with lower lymphocyte count at time of first detection. CMV dissemination and death were significantly associated with initial and highest CMV viral loads (copies/mL). CONCLUSION: This study presents the first pediatric-specific Australasian data for viremia in HSCT. Findings may help guide clinicians in prophylaxis and treatment decisions.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.

Diagnosis and management of severe combined immunodeficiency in Australia and New Zealand.

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.

Exploring nurse-led HIV Pre-Exposure Prophylaxis in a community health care clinic.

OBJECTIVES: Gay, bisexual, and other men who have sex with men (gbMSM) are 131 times more likely to acquire HIV compared with other Canadian men. Pre-Exposure Prophylaxis (PrEP) for HIV has the potential to reduce or eliminate disparities in HIV acquisition among key affected populations. This paper aims to discuss the feasibility and utility of a nurse-led PrEP program administered by the Cool Aid Community Health Centre (CACHC) in Victoria, British Columbia as a public health PrEP program was initiated. DESIGN, SAMPLE AND MEASUREMENTS: A retrospective chart review of 124 gbMSM patients accessing PrEP at CACHC in 2018 collected information on patient demographics, STI testing results, and PrEP prescription pick-ups at 3 time points. RESULTS: Ninety-nine (79.8%) patients have continued on PrEP, as defined as having picked up their second 90-day PrEP prescription. Both older age and having an Sexually Transmitted Infection after PrEP enrolment were significantly associated with staying on PrEP; decreased risk perceptions contributed most to clinic-level discontinuance. Very few patients who stayed on PrEP have transitioned to their own General Practitioner. CONCLUSIONS: Patients appear to recognize their risk and are continuing on PrEP to reduce their risk of HIV. As evidenced by ability to recruit and maintain patients, we conclude that nurse-led PrEP at community health centres supports access and uptake of essential health services to optimize individual and population health.

Development of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines.

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.

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.