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Background Risk of nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT) is high. Patient-level clinical prediction models such as the HCT–comorbidity index (HCT-CI) help identify those at increased risk for NRM, but the independent contribution of social determinants of health on HCT outcomes is not well characterized. Methods This study included 1602 patients who underwent allogeneic HCT between 2013 and 2019 at City of Hope. Census tract–level social vulnerability was measured using the social vulnerability index (SVI). Fine-Gray multivariable regression evaluated the association between SVI and 1-year NRM. Subgroup analysis examined risk of NRM across combined SVI and HCT-CI categories and by race and ethnicity. Results Cumulative incidence of 1-year NRM after HCT was 15.3% (95% confidence interval [CI] = 13.6% to 17.1%). In multivariable analysis, patients in the highest SVI tertile (highest social vulnerability) had a 1.4-fold risk (subdistribution hazard ratio [sHR] = 1.36, 95% CI = 1.04 to 1.78) of NRM compared with individuals in the lower tertiles; patients in the highest SVI tertile who also had elevated (≥3) HCT-CI scores had the highest risk (sHR = 1.81, 95% CI = 1.26 to 2.58) of 1-year NRM (reference: lower SVI tertiles and HCT-CI < 3). High social vulnerability was associated with risk of 1-year NRM in Asian (sHR = 2.03, 95% CI = 1.09 to 3.78) and Hispanic (sHR = 1.63, 95% CI = 1.04 to 2.55) but not non-Hispanic White patients. Conclusions High social vulnerability independently associated with 1-year NRM after HCT, specifically among minority populations and those with a high comorbidity burden at HCT. These findings may inform targeted approaches for needs assessment during and after HCT, allowing for timely interventions to improve health outcomes in at-risk patients. [ABSTRACT FROM AUTHOR]

Background: Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors' mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality.Methods: We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976-2014. Statistical tests were two-sided.Results: The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors.Conclusion: Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT. [ABSTRACT FROM AUTHOR]

Background: High intensity treatments such as hematopoietic cell transplantation (HCT) can be curative for patients with hematologic malignancies, but this needs to be balanced by the high risk of nonrelapse mortality (NRM) during the first 2 years after HCT. Sarcopenia (low muscle mass) is associated with physical disability and premature mortality in individuals with nonmalignant diseases and may be a predictor of NRM and poor overall survival in patients undergoing HCT.Methods: This was a retrospective cohort study of 859 patients with acute leukemia or myelodysplastic syndrome who underwent a first HCT as adults (≥18 years) between 2007 and 2014. Sarcopenia was assessed from pre-HCT abdominal computed tomography scans. Two-year cumulative incidence of NRM was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained and adjusted for relevant covariates. Kaplan-Meier method was used to examine overall survival. All statistical tests were two-sided.Results: Median age at HCT was 51 years (range = 18-74 years); 52.5% had a high [≥3] HCT-comorbidity index; 33.7% had sarcopenia pre-HCT. Sarcopenia was an independent predictor of higher NRM risk (hazard ratio = 1.58, 95% CI = 1.16 to 2.16) compared with patients who were not. The 2-year incidence of NRM approached 30% in patients with sarcopenia and high (≥3) HCT-comorbidity index. Patients with sarcopenia had on average a longer hospitalization (37.2 days vs 31.5 days, P < .001) and inferior overall survival at 2 years (55.2%, 95% CI = 49.5% to 61.0% vs 66.9%, 95% CI = 63.0% to 70.8%, P < .001).Conclusions: Sarcopenia is an important and independent predictor of survival after HCT, with potential additional downstream impacts on health-economic outcomes. This information can be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT. [ABSTRACT FROM AUTHOR]

Background. VCL-CB01, a candidate cytomegalovirus (CMV) DNA vaccine that contains plasmids encoding CMV phosphoprotein 65 (pp65) and glycoprotein B (gB) to induce cellular and humoral immune responses and that is formulated with poloxamer CRL1005 and benzalkonium chloride to enhance immune responses, was evaluated in a phase 1 clinical trial. Methods. VCL-CB01 was evaluated in 44 healthy adult subjects (22 CMV seronegative and 22 CMV seropositive) 18-43 years old. Thirty-two subjects received 1- or 5-mg doses of vaccine on a 0-, 2-, and 8-week schedule, and 12 subjects received 5-mg doses of vaccine on a 0-, 3-, 7-, and 28-day schedule. Results. Overall, the vaccine was well tolerated, with no serious adverse events. Local reactions included mild to moderate injection site pain and tenderness, induration, and erythema. Systemic reactions included mild to moderate malaise and myalgia. All reactions resolved without sequelae. Through week 16 of the study, immunogenicity, as measured by enzyme-linked immunosorbant assay and/or ex vivo interferon (IFN)-γ enzyme-linked immunospot assay, was documented in 45.5% of CMV-seronegative subjects and in 25.0% of CMV-seropositive subjects who received the full vaccine series, and 68.1% of CMV-seronegative subjects had memory IFN-γ T cell responses at week 32. Conclusion. The safety and immunogenicity data from this trial support further evaluation of VCL-CB01. [ABSTRACT FROM AUTHOR]