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Rapid Response Systems have been introduced in the last decade to increase patient safety and decrease the rate of cardiorespiratory arrest on the hospital wards and readmission to the intensive care units. In this article we share our experience at the Hospital for Sick Children in Toronto on implementation and evolution of a pediatric rapid response team; the process, barriers, and ongoing challenges. [ABSTRACT FROM AUTHOR]

The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.17 trial evaluated a dose-intensive chemotherapy approach using a single cycle of inpatient R-DICEP (rituximab, dose-intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol-specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R-DICEP or to 3 cycles of R-GDP. The overall response rate (ORR) was 65.6% for R-DICEP and 48.6% for R-GDP. The ASCT rate was 71.9% versus 54.3%, and 1-year progression-free survival rate was 42% versus 32%, respectively, for R-DICEP versus R-GDP. Although the improvement in ORR for R-DICEP versus R-GDP exceeded the pre-specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3-5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Very late relapse (VLR) occurring >5 years after initial diagnosis is an uncommon event in the management of Hodgkin lymphoma (HL). Limited information regarding risk factors and optimal therapy is available., Patients and Methods: We reviewed patients treated for HL at Princess Margaret Cancer Centre, Toronto, Ontario Canada between January 01, 1999 and 31 December 31, 2018., Results: Thirty-two patients experienced VLR. Median time to first relapse was 7.2 years. Most patients were treated with CMT both at initial diagnosis and relapse. Male gender (P = .04) and increased age at initial diagnosis (P = .008; HR 1.09 (95% CI: 1.02-1.15)) were identified as risk factors for inferior survival on univariate analysis. Stage, histology, treatment modality and risk assessment at diagnosis or relapse did not have a significant impact on survival outcomes. ASCT at first relapse had no impact on time to second progression (HR 1.72; 95% CI, 0.35-8.53; P = .51) or overall survival from first relapse (HR 1.55; 95% CI, 0.3-8.03; P = .6)., Conclusion: Our data aligns with the limited information available in VLR HL suggesting the negative impact of age and male gender on this rare event. Additionally, our data did not show benefit of ASCT at first relapse in terms of survival outcomes in this population, though this analysis is limited by small sample size. Further study of optimal therapy to prevent and treat VL in the era of novel agents is critical., Competing Interests: Disclosure The authors declare not conflicts of interest regarding this study., (Copyright © 2023. Published by Elsevier Inc.)

Background: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data., Methods: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020)., Results: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange., Conclusions: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To understand the impact of therapy sequencing on progression-free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low-dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting., Methods: We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second-line therapy, 575 patients were included., Results: Patients treated with LM had statistically similar 2nd PFS when re-exposed to lenalidomide in second-line therapy compared to those receiving non-lenalidomide-containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second-line therapy than their non-LM counterparts., Conclusion: Our data suggest that patients progressing on LM who receive lenalidomide-containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non-lenalidomide-containing second-line regimens. Identification of patients mostly likely to benefit from further lenalidomide-containing therapy is paramount., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Intravenous (IV) compounding safety has garnered recent attention as a result of high-profile incidents, awareness efforts from the safety community, and increasingly stringent practice standards. New research with more-sensitive error detection techniques continues to reinforce that error rates with manual IV compounding are unacceptably high. In 2014, our team published an observational study that described three types of previously unrecognized and potentially catastrophic latent chemotherapy preparation errors in Canadian oncology pharmacies that would otherwise be undetectable. We expand on this research and explore whether additional potential human failures are yet to be addressed by practice standards., Methods: Field observations were conducted in four cancer center pharmacies in four Canadian provinces from January 2013 to February 2015. Human factors specialists observed and interviewed pharmacy managers, oncology pharmacists, pharmacy technicians, and pharmacy assistants as they carried out their work. Emphasis was on latent errors (potential human failures) that could lead to outcomes such as wrong drug, dose, or diluent., Results: Given the relatively short observational period, no active failures or actual errors were observed. However, 11 latent errors in chemotherapy compounding were identified. In terms of severity, all 11 errors create the potential for a patient to receive the wrong drug or dose, which in the context of cancer care, could lead to death or permanent loss of function. Three of the 11 practices were observed in our previous study, but eight were new. Applicable Canadian and international standards and guidelines do not explicitly address many of the potentially error-prone practices observed., Conclusion: We observed a significant degree of risk for error in manual mixing practice. These latent errors may exist in other regions where manual compounding of IV chemotherapy takes place. Continued efforts to advance standards, guidelines, technological innovation, and chemical quality testing are needed.

Background: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data., Methods: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided., Results: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations., Conclusions: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)