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Background. The Coronavirus disease 2019 (COVID-19) pandemic negatively impacted nursing students' opportunity to gain experience through clinical placement, potentially threatening their readiness for practice and their clinical competence. The aim of this study was to explore whether and to what extent the thirdyear undergraduate nursing students perceived that their readiness for practice was impacted by changes to clinical placement and classroom learning implemented in response to the COVID-19 pandemic. Study design. Cross-sectional study. Methods. The study was conducted in a university of North-western Italy that provides nursing education across five sites. All sites stopped in-person classroom learning at the beginning of March 2020, but each site was free to decide whether to continue in-person clinical placement based on the local epidemiological situation. All 228 third-year nursing students who completed their degree by June 2020 were invited to participate. Data were collected via online questionnaire, which included the question "What impact do you think that COVID-19 safety measures employed by your nursing programme had on your readiness for practice?" Answers were given on a 5-point Likert scale (none, minimal, moderate, major, and severe). Explanatory variables were collected at the individual, nursing programme, and university site levels. Results. A total of 126 (response rate 55.3%) nursing students completed the questionnaire. Overall, 84 (66.7%) perceived that COVID-19 safety measures had a moderate to severe impact on their readiness for practice. These students often had lower grade point averages (p=0.037) and received no clinical placement during the pandemic (72.6% vs 90.5% of students who reported no or minimal impact, p=0.022). Average duration of third-year clinical placement was also lower among these students, though it was not statistically significant. No differences emerged at the university site level. Conclusions. Despite important advances in technology-based educational activities, clinical placement remains the best educational strategy to allow nursing students to feel prepared to work effectively during a pandemic. [ABSTRACT FROM AUTHOR]

Post-transplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GvHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear.We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into four groups: Group I (CNI + MTX or MMF), Group II (CNI + MTX or MMF + ATG), Group III (PTCy + ATG + CNI), and Group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade II-IV [HR 0.6, p=0.01] and grade III-IV acute GvHD [HR 0.2, p=0.001] as well as all grade chronic GvHD [HR 0.5, p=0.007] and moderate-severe chronic GvHD [HR 0.4, p=0.001] compared to CNI+MTX (or MMF) containing regimens. PTCy did not increase relapse risk; PTCy reduced NRM [HR 0.3, p<0.002], leading to improved GvHD-free/relapse-free survival (GRFS) [HR 0.4, p<0.001]. PTCy was also associated with improved overall survival [HR 0.56, p=0.01]. Bloodstream infections are increased with PTCy [HR: 1.5, p=0.001]. The addition of ATG to PTCy did not further improve the GRFS and was associated with a higher incidence of clinically significant Cytomegalovirus (CMV) [HR 2.16, p=0.002] and Epstein-Barr virus reactivation (EBV) [HR 9.5, p<0.001] and a numerical increase in NRM [HR 1.7, p=0.2]. PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted., (Copyright © 2024 American Society of Hematology.)

Objective: To synthesize evidence assessing the effectiveness of quality improvement (QI) interventions in reducing hospital service use from nursing homes (NHs)., Design: Systematic review and meta-analysis of randomized controlled trials (RCTs), controlled before-after (CBA), uncontrolled before-after (UBA), and interrupted time series studies. Searches were conducted in MEDLINE, CINAHL, The Cochrane Library, Embase, and Web of Science from 2000 to August 2023 (PROSPERO: CRD42022364195)., Setting and Participants: Long-stay NH residents (>30 days)., Methods: Included QI interventions using a continuous and data-driven approach to assess solutions aimed at reducing hospital service use. Risk of bias was assessed using JBI tools. Delivery arrangements and implementation strategies were categorized through EPOC taxonomy., Results: Screening of 14,076 records led to the inclusion of 22 studies describing 29 QI interventions from 6 countries across 964 NHs. Ten studies, comprising 4 of 5 RCTs, 3 of 4 CBAs, and 1 of 12 UBAs were deemed to have a low risk of bias. All but 3 QI interventions used multiple component delivery arrangements (median 6; IQR 3-8), focusing on the "coordination of care and management of care processes" alone or combined with "changes in how, when, where, and by whom health care is delivered." The most frequently used implementation strategies were educational meetings (n = 25) and materials (n = 20). The meta-analysis of 11 studies showed a significant reduction in "all-cause hospital admissions" for QI interventions compared with standard care (rate ratio, 0.60; 95% CI, 0.41-0.87; I 2  = 99.3%), with heterogeneity due to study design, QI intervention duration, type of delivery arrangements, and number of implementation strategies. No significant effects were found for emergency department (ED) visits or potentially avoidable hospitalizations., Conclusions and Implications: The study provides preliminary evidence supporting the implementation of QI interventions seeking to reduce hospital admissions from NHs. However, these findings require confirmation through future experimental research., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM)., Design: Retrospective cohort study (2014-2022)., Setting: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center., Patients: Adult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy., Interventions: None., Main Variables of Interest: We analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU., Results: We included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76-0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary., Conclusions: In this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%., Clinical Trial Registration: NCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/)., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Letermovir, a novel anti-cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high-risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high-risk patients. Thirty two (82%) patients received anti-thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41-56) after HCT and was administered for a median duration of 77 days (range, 46-90). A single breakthrough CMV reactivation was noted in this high-risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23-59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment-related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty-nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III-IV acute graft-versus-host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non-relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022. Using propensity score matching, we compared transplant outcomes between 2 well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n = 46) or fludarabine-busulfan with total body irradiation (FBT200) (n = 92). A scoring system based on patient age, Karnofsky performance score, and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m 2 ) or high-dose (42 g/m 2 ) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the 2 groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P = .61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and antithymocyte globulin (ATG). Patients who received FT had a superior 2-year overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1 to 81.2) versus 44.5% (95% CI: 34 to 54.4), hazard ratio (HR): 0.43, 95% CI: 0.22 to 0.84 (P = .013). In multivariate analysis (MVA), only the use of fresh grafts (P = .02) and FT (P = .01) were associated with improved OS. FT was associated with superior 2-year relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6 to 77.9) versus 39.1% (95% CI: 29.1 to 49.1), HR: 0.44 (95% CI: 0.24 to 0.81), P = .008. In MVA, the use of fresh grafts (P = .03) and FT (P = .009) were associated with improved RFS. Recipients of FT demonstrated superior 2-year graft-versus-host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8 to 72.8) versus 35.1% (95% CI: 25.5 to 45). In MVA, only FT was associated with superior GRFS (P = .02). FT recipients exhibited markedly superior 1-year event-free survival compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9 to 54.2) versus 9.2% (95% CI: 4.4 to 16.3), HR: 0.47 (95% CI: 0.30 to 0.72), P < .001) and MVA (P = .004). FT was associated with lower 1-year nonrelapse mortality compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0 to 21.8) versus 29.7% (95% CI: 20.6 to 39.3), HR: 0.41 (95% CI: 0.17 to 0.96), P = .04) and MVA (P = .04). Our study utilized propensity score matching to demonstrate superiority of treosulfan- over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m 2 ., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Poor treatment adherence and lack of self-care behaviors are significant contributors to hospital readmissions of people with heart failure (HF). A transitional program with non-invasive telemonitoring may help sustain patients and their caregivers to timely recognize signs and symptoms of exacerbation. We will conduct a Randomized Clinical Trial (RCT) to evaluate the feasibility and acceptability of a 6-month supportive intervention for patients discharged home after cardiac decompensation. Forty-five people aged 65 years and over will be randomized to either receive a supportive intervention in addition to standard care, which combines nurse-led telephone coaching and a home-based self-monitoring vital signs program, or standard care alone. Four aspects of the feasibility will be assessed using a mixed-methods approach: process outcomes (e.g., recruitment rate), resources required (e.g., adherence to the intervention), management data (e.g., completeness of data collection), and scientific value (e.g. 90- and 180-day all-cause and HF-related readmissions, self-care capacity, quality of life, psychological well-being, mortality, etc.). Participants will be interviewed to explore preferences and satisfaction with the intervention. The study is expected to provide valuable insight into the design of a definitive RCT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Acute graft versus host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplant (HCT) and is associated with significant morbidity and mortality. Steroid refractory aGVHD (SR-aGVHD) carries a particularly grim prognosis. Ruxolitinib has shown promise for treatment of SR-aGVHD in a phase 3 trial; however, safety and efficacy data outside of the clinical trial setting is lacking. We performed a multicenter retrospective study to examine the response to ruxolitinib and its efficacy in patients with SR-aGVHD. We included 59 patients treated with ruxolitinib for SR-aGVHD between 2015 and 2022. Of these 59 patients, 36 patients (61.0%) achieved a complete (CR) or partial response (PR) at 28 days, while 31 patients (52.5%) obtained a CR/PR at day 56. Patients that achieved a CR or PR at day 28 had a higher rate of overall survival (OS; 69.2%), compared with patients that did not (31.6%; p = 0.037). OS at 12 months was 41.5%, with a median OS duration of 5.3 months. Failure free survival (FFS) at 12 months was 29.1%, with a median FFS of 2.6 months. Overall, this real-world experience data support ruxolitinib as the standard of care for SR-aGVHD in a non-controlled trial population., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In 2015, dual T cell depletion with antithymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) combined with cyclosporine A (CsA) replaced our prior institutional graft-versus-host disease (GVHD) prophylaxis regimen of 4.5 mg/kg ATG, CsA, and mycophenolate mofetil (MMF) (ATG-based) in 10/10 HLA-matched unrelated donor (MUD) peripheral blood allogeneic hematopoietic stem cell transplantation (allo-HCT). The initial ATG dose of 4.5 mg/kg [ATG(4.5)/PTCy] was reduced to 2 mg/kg [ATG(2)/PTCy] in 2018. This study compares the results obtained from 444 adults undergoing MUD allo-HCT at our institution who received ATG(4.5)/PTCy (n = 127) or ATG(2)/PTCy (n = 223) with those who received ATG-based prophylaxis without PTCy (n = 84). The rates of grade II-IV and grade III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 1 year were 35.7%, 21.6%, and 14.7%, respectively, in patients receiving ATG-based prophylaxis without PTCy; 16.5%, 4.9%, and 4.3% in patients receiving ATG(4.5)/PTCy; and 23.3% (P = .004), 8.0% (P < .001), and 14.1% (P =.006) in patients receiving ATG(2)/PTCy. One-year overall survival (OS), nonrelapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) were 69.8%, 25.3%, and 52.0%, respectively, for patients receiving ATG-based prophylaxis without PTCy; 82.7%, 17.3%, and 59.8% for patients receiving ATG(4.5)/PTCy; and 78.3% (P = .446), 14.7% (P = 101), and 56.2% (P = .448) for patients receiving ATG(2)/PTCy. On univariate analyses, the use of ATG(2)/PTCy was associated with a lower risk of NRM (hazard ratio, .54; P = .023) compared with the use of ATG-based prophylaxis without PTCy. ATG(2)/PTCy prophylaxis effectively prevents GVHD and is associated with comparable relapse risk, OS, and GRFS as seen with ATG(4.5)/PTCy and ATG-based prophylaxis without PTCy., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Blinatumomab, a bispecific monoclonal antibody, effectively controls refractory B cell acute lymphoblastic leukemia (ALL) and promotes measurable residual disease (MRD) negativity. This study investigated the impact of pretransplant blinatumomab on allogeneic hematopoietic cell transplantation (HCT) outcomes in B cell ALL patients., Methods: We analyzed the effect of pretransplant blinatumomab on transplant outcomes of 117 adults undergoing allogeneic HCT for B cell ALL at Princess Margaret Hospital, Toronto, between 2010 and 2021. Outcomes assessed included overall survival (OS), graft-versus-host disease and relapse-free survival (GRFS), cumulative incidences of relapse (CIR), and nonrelapse mortality (NRM)., Results: The median follow-up was 36 months. Thirty-one participants (26.5%) received blinatumomab. Blinatumomab group had higher proportions of individuals with high disease risk index, primary induction failure and was more likely to receive dual T cell depletion with antithymocyte globulin and post-transplant cyclophosphamide. Two-year OS, GRFS, NRM, and CIR in the blinatumomab and nonblinatumomab groups were, respectively: 65.4% versus 45.6% (P = .05), 42.2% versus 17.3% (P = .01), 3.2% versus 43.0% (P = .007) and 34.4% versus 14.4% (P = .02). Blinatumomab was associated with a lower incidence of day-100 grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD): 27.5% versus 56.7% (P = .009), and 10.9% versus 34.7% (P = .04), respectively. Multivariate analysis confirmed the association between pretransplant blinatumomab and improved OS and NRM., Conclusions: Pretransplant blinatumomab is associated with improved OS and lower risk of NRM in B cell ALL patients undergoing allogeneic HCT, likely reflecting lower burden of treatment-related toxicity in this population. Larger prospective trials are warranted to validate our findings., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRD pos ) post-induction. MRD pos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRD neg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRD pos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRD pos intermediate-risk AML patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA. Among these patients, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0. The study reported a median follow-up of 32 months (range 0.3-61.64) for survivors. The cumulative incidence of grade II-IV and grade III-IV acute GVHD at day +100 was 26.3% and 9.5%, respectively. Moderate/severe chronic GVHD at 1 year was 19.9%. The 2-year overall survival (OS) was 49.4%, with a relapse-free survival (RFS) of 44.6%. In multivariate analysis, older patients, and those with high/very-high disease risk indices (DRI) were at higher risk for worse OS and higher non-relapse mortality (NRM). The study confirms that using PTCy and ATG (4.5 mg/kg), alongside CsA is safe and effective in preventing GVHD when using peripheral blood as the stem cell source in haploidentical hematopoietic cell transplantation (haplo-HCT)., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The objective of this scoping review is to explore how wearable technology is being used to care for older adults in long-term care facilities., Introduction: The use of digital health technologies to support care delivery in long-term care facilities for older adults has grown significantly in recent years, especially since the COVID-19 pandemic. Wearable technology refers to devices worn or attached to the body that can track a variety of health-related data, such as vital signs, falls, and sleep patterns. Despite the evidence that wearable devices are playing an increasing role in older adults' care, no review has been conducted on how wearable technology is being used in long-term care facilities., Inclusion Criteria: This review will consider studies that include people aged over 65, with any health condition or level of disability, who live in long-term care facilities. Primary and secondary studies using quantitative, qualitative, and mixed methods study designs will be included. Dissertations and policy documents will also be considered., Methods: Data sources will include comprehensive searches of electronic databases (MEDLINE, Embase, CINAHL, and Scopus), gray literature, and reference scanning of relevant studies. Two independent reviewers will screen titles, abstracts, and full texts of the selected studies. Data extraction will be performed using a tool developed by the researchers. Data will be mapped and analyzed. Descriptive frequencies and content analysis will be included, along with the tabulated results, which will be used to present the findings with regard to the review objectives., Review Registration: Open Science Framework https://osf.io/r9qtd., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 JBI.)

Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes., Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation., Results: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR., Conclusions: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%-60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post-imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Graft-versus host disease (GVHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). Although corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus-host disease (cGVHD), approximately one-half of cGVHD patients are refractory to corticosteroid therapy. The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photopheresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGVHD. Using propensity score matching (PSM), treatment outcomes were compared between ECP-treated patients (n = 74) and a historical cohort of cGVHD patients treated with BAT (n = 132). By adjusting for unbalanced risk factors between the groups, including GVHD severity at the start of therapy, acute GVHD history, and baseline corticosteroid dose, 62 patients were balanced and selected for PSM. In the PSM cohort, the ECP group showed a 12-month failure-free survival (FFS) rate of 70.1% versus 32.5% in the BAT group (P < .0001; hazard rate [HR], .214), and 93.1% 12 months' overall survival (OS) rate of 93.1% versus 68.1% in the BAT group (P = .0249; HR, .3811); multivariate analysis confirmed ECP's superior FFS and OS compared with BAT. Generalized linear model analysis showed faster tapering of corticosteroids and higher rates of prednisone discontinuation in the ECP versus BAT PSM groups in the first 6 months. The ECP group also had a higher percentage of prednisone discontinuation, by 6% at month 0, by 14.9% at month 3, and by 22.5% at month 6. The current study demonstrates superior FFS, OS, and steroid tapering efficacy for ECP compared with BAT as third-line therapy or beyond in cGVHD patients., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The HCT Frailty Scale is an easy prognostic tool composed of (a) Clinical Frailty Scale; (b) Instrumental Activities of Daily Living; (c) Timed-up-and-Go test; (d) Grip Strength; (e) Self-Health Rated Questionnaire; (f) Falls tests; (g) Albumin and C-reactive protein levels. This scale was designed to classify allogeneic hematopoietic cell transplant (alloHCT) candidates into fit, pre-frail and frail groups, irrespective of age. This study evaluates the ability of this frailty classification to predict overall survival (OS) and non-relapse mortality (NRM) in adult patients of all ages, in a prospective sample of 298 patients transplanted between 2018 and 2020. At first consultation, 103 (34.6%) patients were fit, 148 (49.7%) pre-frail, and 47 (15.8%) were frail. The 2-year OS and NRM of the three groups were 82.9%, 67.4%, and 48.3% (P < 0.001), and 5.4%, 19.2%, and 37.7% (P < 0.001). For patients younger than 60 years (n = 174), the 2-year OS and NRM of fit, pre-frail, and frail groups were 88.4%, 69.3% and 53.1% (P = 0.002), and 5.8%, 22.8%, and 34.8% (P = 0.005), respectively; and in patients older than 60 (n = 124), OS and NRM were 75.5%, 63.8% and 41.4% (P = 0.006), and 4.9%, 16.4%, and 42.1% (P = 0.001). In conclusion, frailty predicted worse transplant outcomes in both younger and older adults., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Pre-transplant pulmonary function testing (PFT) is essential before allogeneic hematopoietic stem cell transplant (HCT), yet the optimal cutoff value for affecting transplant outcomes remains poorly defined., Study Design: Retrospective analysis of pre-HCT PFT data from 605 consecutive patients at the Princess Margaret Cancer Centre between January 1, 2004 and December 31, 2013 used binary recursive partitioning to identify cutoff values for overall survival (OS) as an endpoint of transplant outcomes. These values were compared to HCT comorbidity index (HCT-CI) FEV 1 cutoffs for OS, cumulative incidence of relapse and non-relapse mortality., Results: FEV 1  ≥ 81% was the identified cutoff point. The OS rate at 3 years showed 49.8% (FEV 1  ≥ 81%) vs. 36.6% (<81%, p < .001). For HCT-CI cutoffs, the OS rate at 3 years for FEV 1  ≥ 80%, 66%-80% and ≤65% were 49.0%, 38.1% and 37.6% (p = .011), respectively. Multivariate analysis confirmed that FEV 1  ≥ 81% predicted reduced mortality (HR 0.682, p = .001). Subgroup analysis showed both FEV 1  ≥ 81% and FEV 1 by HCT-CI cutoffs may stratify patients according to OS and NRM risk in subgroups receiving myeloablative, but not reduced intensity conditioning., Conclusion: FEV 1  ≥ 81% can predict OS and NRM in our cohort and is potentially simpler when risk stratifying patients undergoing allogeneic HCT, particularly those receiving myeloablative conditioning., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Extracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection., Methods: We evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes., Results: With a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively., Conclusion: ECP is an effective treatment option for heavily pre-treated cGvHD patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34 + cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: The literature comparing outcomes between myeloablative (MAC) and reduced intensity conditioning (RIC) for acute myeloid leukemia (AML) is conflicting., Methods: We retrospectively analyzed 451 patients who underwent allogenic hematopoietic cell transplantation (alloHCT) for AML in complete remission (CR) with either RIC (n = 331) or MAC (n = 120) with the use of dual T-cell depletion as graft-versus-host disease (GVHD) prophylaxis., Results: Univariate analysis demonstrated nonrelapse mortality (NRM) at 2 years was 19.1% for MAC and 22.5% for RIC (p = .44). Two-year cumulative incidence of relapse (CIR) was 19.8% for MAC and 24.5% for RIC (p = .15). Two-year overall survival (OS) was 61% and 53% for MAC and RIC, respectively (p = .02). Two-year graft-versus-host disease relapse-free survival (GRFS) was 40.8% for MAC and 33.7% for RIC (p = .30). A propensity score-matched analysis was done matching patients for age, HLA match, in vivo T-cell depletion, and Disease Risk Index (DRI). Two-year OS was 67% for MAC, 66% for RIC (p = .95). A subgroup analysis identified that matched related donor transplants benefit from MAC with OS at 2 years 82.6% versus 57.3% for RIC (p = .006)., Conclusions: In the matched-related donor setting, MAC regimens may offer superior survival. Overall, for our cohort of predominantly in vivo T-cell depleted patients the outcomes of MAC and RIC were similar., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Quality improvement interventions are a promising strategy for reducing hospital services use among nursing home residents. However, evidence for their effectiveness is limited. It is unclear which characteristics of the quality improvement intervention and activities planned to facilitate implementation may promote fidelity to organisational and system changes. This systematic review and meta-analysis will assess the effectiveness of quality improvement interventions and implementation strategies aimed at reducing hospital services use among nursing home residents., Methods and Analysis: The MEDLINE, CINAHL, Cochrane Library, Embase and Web of Science databases will be comprehensively searched in September 2023. The eligible studies should focus on the implementation of a quality improvement intervention defined as the systematic, continuous approach that designs, tests and implements changes using real-time measurement to reduce hospitalisations or emergency department visits among long-stay nursing home residents. Quality improvement details and implementation strategies will be deductively categorised into effective practice and organisation of care taxonomy domains for delivery arrangements and implementation strategies. Quality and bias assessments will be completed using the Quality Improvement Minimum Quality Criteria Set and the Joanna Briggs Institute Critical Appraisal Tools.The results will be pooled in a meta-analysis, by combining the natural logarithms of the rate ratios across the studies or by calculating the rate ratio using the generic inverse-variance method. Heterogeneity will be assessed using the I 2 or H 2 statistics if the number of included studies will be less than 10. Raw data will be requested from the authors, as required., Ethics and Dissemination: Ethical approval is not required. The results will be published in a peer-review journal and presented at (inter)national conferences., Prospero Registration Number: CRD42022364195., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Allogeneic stem cell transplant (allo-HSCT) patients are at risk of malnutrition and weight loss from impaired oral intake resulting from gastrointestinal toxicities, dysgeusia, and psychological effects., Methods: A retrospective review of 264 adult patients transplanted at Princess Margaret Cancer Centre who achieved relapse-free survival up to 3 months after allo-HSCT was performed., Results: Overall incidence of patients who experienced WL (WL) ≥ 10% from HSCT to 3-month post-transplant was 45.9% and from HSCT to 6 months was 56.6%. Patients with ≥ 10% WL from allo-HSCT at 3 months and 6 months had similar 2-year overall survival (OS) compared to those with < 10% WL, 55.7% vs 62.8% (HR = 1.38, p = 0.11) and 71.1% vs 77.2% (HR = 1.37, p = 0.27), respectively. Patients with ≥ 10% WL 3 and 6 months from allo-HSCT also had similar 2-year relapse-free survival (RFS) compared to those with < 10% WL, 48.1% vs 55.8% (HR = 1.26, p = 0.22), and 62.7% vs 69.8% (HR = 1.29, p = 0.31), respectively. The 2-year transplant-related mortality (TRM) was higher for those with ≥ 10% WL from allo-HSCT to 3 months, 35.4% vs 16.9% (HR = 2.39, p = 0.0007) and 6 months, 22% vs 8% (HR = 3.1, p = 0.0034). Although statistical significance was not observed for OS or RFS, patients who experienced ≥ 10% WL 3- and 6-months post allo-HSCT experienced higher 2-year TRM. These results highlight the importance of early intervention and close monitoring of weight post allo-HSCT., Conclusion: Approaches to WL post allo-HSCT should be multifaceted and include members of the interdisciplinary team in order to decrease TRM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)-based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Established first-line therapy for chronic graft-versus-host disease (cGvHD) comprises corticosteroids with/without calcineurin inhibitors, but about half of cGvHD patients are refractory to corticosteroid therapy. The present study retrospectively analyzed treatment outcomes in 426 patients and undertook a propensity-score matching (PSM) analysis between ruxolitinib (RUX) treated group and a historical group of cGvHD patients treated with best available treatment (BAT). PSM process adjusted unbalanced risk factors between the 2 groups, including GvHD severity, HCT-CI score, and treatment line, extracting 88 patients (44 in BAT/RUX groups each) for final analysis. In PSM subgroup, RUX group showed 74.7% 12 months' FFS rate vs 19.1% for BAT group (p < 0.001), whereas 12 months' OS rates were 89.2% and 77.7%, respectively. Multivariate analysis for FFS confirmed RUX superiority over BAT together with HCT-CI score 0-2 vs ≥3. For OS, RUX was superior to BAT, while age ≥60 years and severe grade cGvHD adversely impacted OS. In PSM subgroup, at months 0, 3, and 6, 4.5%, 12.2% and 22.2% more patients in RUX group could discontinue prednisone compared to BAT group, respectively. In conclusion, the current study showed that for FFS, RUX was superior to BAT as second-line therapy or beyond in cGvHD patients after therapy failure., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Chronic graft-versus-host disease (cGVHD) is a common cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Tyrosine kinase inhibitors (TKIs), including ruxolitinib, imatinib, and ibrutinib, have shown promising efficacy in cGVHD treatment., Method: A total of 43 patients who developed cGVHD and received at least one line of TKI therapy for cGVHD treatment were evaluated retrospectively. The overall response, clinical benefit (CB), corticosteroid dose reduction, failure-free survival (FFS), and overall survival (OS) were assessed., Result: A total of 62 lines of TKI therapy were evaluated, including ruxolitinib (n = 18), ibrutinib (n = 13), and imatinib (n = 31). With a 12-month median follow-up duration, 19/58 (32.8%), 20/41 (48.7%), and 17/29 (58.6%) responded to TKI therapy at 3, 6, and 12 months, respectively. The CB was observed in 80% of patients over time, allowing prednisone dose reduction in all 3 TKIs. The FFS rate at 12 months was higher in the imatinib (71%) and ruxolitinib groups (67%) than in the ibrutinib group (46%), while the OS rate at 12 months was similar among the three groups at 96%-100% in patients. In the sclerotic GVHD patient subgroup (n = 39), the overall response rate gradually increased over time. Ruxolitinib appeared to be as effective as imatinib and gradually improved the photographic range of motion score in sclerotic GVHD patients., Conclusion: TKI drugs ruxolitinib, imatinib, and Ibrutinib are effective and feasible for cGVHD treatment. Ruxolitinib is as effective as imatinib for sclerotic GVHD.

Allogeneic hematopoietic stem cell transplant (HCT) has improved survival for patients with acute myeloid leukemia (AML), especially for those at high risk of relapse. However, relapse remains the leading cause of treatment failure post-HCT, occurring in around 35-45% of patients, and leading to dismal outcomes. Strategies to reduce relapse risk are urgently needed, especially in the early post-transplant period before activation of the graft-versus-leukemia (GVL) effect. Maintenance therapy is a course of treatment given post-HCT with the expectation of reducing relapse risk. While there are currently no therapies approved for maintenance therapy for AML after HCT, there are a number of studies and ongoing investigations examining the role of maintenance therapies that include targeted agents against FLT3-ITD, BCL2, or IDH mutations, hypomethylating agents, immunomodulatory therapies and cellular therapies. In this review, we discuss the mechanistic and clinical data for post-transplant maintenance therapies in AML and strategies for maintenance therapy for AML after HCT., (© 2023. Japanese Society of Hematology.)

Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other acute myeloid leukemia-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (P=0.969), relapse incidence (P=0.600) or non-relapse mortality (P=0.570). Donor CHIP did not impair neutrophil (P=0.460) or platelet (P=0.250) engraftment, the rates of acute (P=0.490), or chronic graft-versus-host disease (P=0.220). No significant difference was noted for secondary malignancy following HSCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HSCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pretransplant evaluation of donors prior to stem cell donation.

The outcomes of allogeneic hematopoietic cell transplantation (HCT) in older patients are not well defined. We retrospectively analyzed the outcomes of 332 patients, with the median age of 65 years (range, 60-76), between 2014 and 2019. We categorized them to 3 age groups (G): G1, 60-65 years (n = 175); G2, > 65-70 years (n = 127); and G3, > 70 years (n = 30). The median length of hospitalization during the initial HCT period was 30 days, with a significant difference when stratified by age (p = 0.049). Overall, 183 (58.7%) patients were re-hospitalized within the first 6 months post HCT, and 60 (21.6%) in the second 6-month period. The 2-year OS was 56% in G1, 53% in G2, and 34% in G3 (p = 0.05). The 2-year event-free survival (EFS) was 54% for G1, 49% for G2, and 31% for G3 (p = 0.04). Non-relapse mortality (NRM) at 2 years was 25% in G1, 36% in G2, and 52% in G3 (p = 0.008). In multivariable analysis, patients aged 60-65 years had significantly better EFS (p = 0.04) and had a trend toward lower NRM (p = 0.05) than those aged > 70 years. Re-admission in the first 6 months post HCT had a significant impact on OS, EFS, and NRM. HCT-specific comorbidity index > 3 had significantly affected NRM. Finally, age had a significant influence on length of hospitalization during HCT. In conclusion, patients aged > 70 years have an inferior EFS and higher NRM. This likely related to higher rate of re-admissions due to infectious complications (84%)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Chronic graft-versus-host disease (cGVHD) is a serious immune-mediated complication after allogeneic haematopoietic stem cell transplantation (HSCT), but in patients with malignancy, cGVHD development is associated with superior survival. Lack of reliable biomarkers and clinical underreporting means there is insufficient understanding of cGVHD clinical outcomes and balance between cGVHD treatment and maintaining beneficial graft-versus-tumour effects., Methods: We performed a Swedish population-wide registry study following patients who underwent allogeneic HSCT 2006-2015. cGVHD status was retrospectively classified using a real-world method based on the timing and extent of systemic immunosuppressive treatment., Results: cGVHD incidence among patients surviving ≥6 months post-HSCT (n = 1246) was 71.9%, significantly higher than previously reported. 5-year overall survival in patients surviving ≥6 months post-HSCT was 67.7%, 63.3%, and 65.3%, in non-, mild, and moderate-severe cGVHD, respectively. Non-cGVHD patients had a mortality risk almost five-fold higher compared to moderate-severe cGVHD patients 12-months post-HSCT. Moderate-severe cGVHD patients had greater healthcare utilization compared with mild and non cGVHD patients., Conclusion: cGVHD incidence was high among HSCT survivors. Non-cGVHD patients had higher mortality during the first 6 months of follow-up; however, moderate-severe cGVHD patients had more comorbidities and healthcare utilization. This study highlights the urgent need for new treatments and real-time methods to monitor effective immunosuppression after HSCT., Competing Interests: Janssen Global Services provided financial support for the study. No other grants or funding was received from any other party. The funding was used for study design, ethical application submission, study protocol development, patient level data access, statistical analyses and publication related work. All statistical analyses were performed by SDS Life Science. Parexel and Schain Research supported the study team with medical writing. The funder also contributed with scientific resources to perform administrative tasks throughout study execution. Frida Schain, Thomas Webb and Nishan Sengupta were employed by Janssen Global Services at the time of the study and received salary from their employer during the study period. Nurgul Batyrbekova received salary from SDS Life Science and Janssen Global Services provided SDS with consultancy fees for statistical services in line with the study protocol. The other authors (Igor Novitzky-Basso, Mats Remberger, Armand Keating and Jonas Mattson) received no specific funding for this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Novitzky-Basso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This prospective study designs an HCT Frailty Scale to classify alloHCT candidates into groups of frail, pre-frail, and fit, and to be implemented in the first consultation at no additional cost. The present scale is composed of the following eight variables: Clinical Frailty Scale, Instrumental Activities of Daily Living, Timed Up and Go Test, Grip Strength, Self-Health Rated, Falls, Albumin, and C-Reactive Protein. The Frailty score of a patient is the weighted sum of scores for each item, with weights assigned according to the hazard ratios of a multivariable Cox proportional hazards model estimated and validated with data on OS as the dependent variable, and the scores of the eight variables as explanatory ones, from 298 adults split into training (n = 200) and validation (n = 98) sets. For clinical use, the scale scores were transformed into three categories: scale score ≤1: fit; 15.5 frail. The estimated probabilities of 1-year OS in each group of frailty, were, respectively: 83.7%, 48.5%, and 16.5% (p < 0.001). In the validation cohort, the respective values were 90.3%, 69.5%, and 46.2% (p < 0.001). Pending further external validations, the HCT Frailty Scale is a low cost-highly informative prognostic signal of outcomes at the pre-transplant stage., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)