Financial Toxicity and Quality of Life in Patients Undergoing Stem-Cell Transplant Evaluation: A Single-Center Analysis.

PURPOSE: We investigated the prevalence of financial toxicity in a population undergoing hematopoietic cell transplantation (HCT) evaluation and measured its impact on post-transplant clinical and health-related quality-of-life outcomes. MATERIALS AND METHODS: This was a prospective study in patients undergoing evaluation for allogeneic HCT between January 1, 2018, and September 23, 2020, at a large academic medical center. Financial health was measured via a baseline survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey. The cohort was divided into three groups: none (grade 0), mild (grade 1), and moderate-high financial toxicity (grades 2-3). Health-related quality of life outcomes were measured at multiple time points. Multivariate logistic regression analysis evaluated factors associated with financial toxicity. Kaplan-Meier curves and log-rank tests was used to evaluate overall survival (OS) and nonrelapse survival. RESULTS: Of 245 patients evaluated for transplant, 176 (71.8%) completed both questionnaires (median age was 57 years, 63.1% were male, 72.2% were White, and 39.2% had myelodysplastic syndrome, 38.1% leukemia, and 13.6% lymphoma). At initial evaluation, 83 (47.2%) patients reported no financial toxicity, 51 (29.0%) with mild, and 42 (23.9%) with moderate-high financial toxicity. Patients with financial toxicity reported significant cost-cutting behaviors, including reduced spending on food or clothing, using their savings, or not filling a prescription because of costs (P < .0001). Quality of life was lower in patients with moderate-high financial toxicity at 6 months (P = .0007) and 1 year (P = .0075) after transplant. Older age (>62; odds ratio [OR], 0.33 [95% CI, 0.13 to 0.79]; P = .04) and income ≥$60,000 in US dollars (USD) (OR, 0.17 [95% CI, 0.08 to 0.38]; P < .0001) were associated with lower odds of financial toxicity. No association was noted between financial toxicity and selection for transplant, OS, or nonrelapse mortality. CONCLUSION: Financial toxicity was highly correlated with patient-reported changes in compensatory behavior, with notable impact on patient quality of life after transplant.

Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients.

INTRODUCTION: In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. METHODS: We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. RESULTS: There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p<0.0001). There were no significant differences in overall average collection rates between the autologous HCT patients in the contemporaneous control and historical control groups (36% vs 32%, p = 0.2760). CONCLUSION: Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection.

Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains- physical, cognitive, nutritional, and psychological-at 2 time points prior to HCT-new patient evaluation (NPE) and sign-off (SO)-between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.

Cognitive impairment in candidates for allogeneic hematopoietic stem cell transplantation.

Hematopoietic cell transplant (HCT) is an increasingly common and curative treatment strategy to improve survival among individuals with malignant and nonmalignant diseases, with over one million HCTs having been performed worldwide. Neurocognitive dysfunction is a common and untoward consequence of HCT for many recipients, although few studies have examined the profile of neurocognitive impairments in HCT or their association with clinical features, such as frailty, or the incidence of pre-HCT neurocognitive impairments across all ages, which may influence post-HCT neurocognitive impairments. We examined the pattern and correlates of pre-transplant neurocognitive dysfunction in a prospective sample of adults undergoing HCT. Neurocognition was assessed using the Montreal Cognitive Assessment Battery. Frailty was assessed using the Short Physical Performance Battery. Linear regression analysis was used to examine the associations between neurocognitive performance and frailty. Neurocognitive screening profiles were also examined by partitioning MoCA into domain scores, including Executive Function and Memory. We also examined the associations between neurocognition, frailty, and clinical outcomes, including length of transplant hospitalization and survival. One hundred and ten adults were evaluated across a wide age range (range: 19-75; mean age = 54.7 [SD = 14.1]). Neurocognitive performance tended to fall below published normative levels (mean MoCA = 25.5 [SD = 4.1]), with 17% of participants demonstrating impaired performance compared with medical normative data (MoCA ≤ 22) and 34% exhibiting impaired performance relative to healthy samples (MoCA ≤ 25). Mild impairments (MoCA ≤ 25) were common across age ranges, including middle-aged patients (23% for age < 50; 35% for age 50-60, 41% for age ≥ 60), particularly for items assessing Executive Function. Greater levels of frailty associated with lower neurocognitive screening scores (r = -0.29, P < 0.01) and Executive Functioning (r = -0.24, P < 0.01), whereas greater age was associated with poorer Memory performance only (r = -0.33, P < 0.01). Greater levels of frailty prior to transplant associated with longer length of stay (ß = 0.10, P = 0.046), but were not associated with survival. Neurocognitive impairments are common among adults undergoing HCT and the pattern of performance varies by age. Pre-transplant frailty is associated with neurocognitive functioning and may portend worse post-transplant early clinical outcomes.

Mobile Application to Identify Cancer Treatment-Related Financial Assistance: Results of a Randomized Controlled Trial.

PURPOSE: Insured patients with cancer face high treatment-related, out-of-pocket (OOP) costs and often cannot access financial assistance. We conducted a randomized, controlled trial of Bridge, a patient-facing app designed to identify eligible financial resources for patients. We hypothesized that patients using Bridge would experience greater OOP cost reduction than controls. METHODS: We enrolled patients with cancer who had OOP expenses from January 2018 to March 2019. We randomly assigned patients 1:1 to intervention (Bridge) versus control (financial assistance educational websites). Primary and secondary outcomes were self-reported OOP costs and subjective financial distress 3 months postenrollment. In post hoc analyses, we analyzed application for and receipt of financial assistance at 3 months postenrollment. We used chi-square, Mann-Whitney tests, and logistic regression to compare study arms. RESULTS: We enrolled 200 patients. The median age was 57 years (IQR, 47.0-63.0). Most patients had private insurance (71%), and the median household income was $62,000 in US dollars (USD) (IQR, $36,000-$100,000 [USD]). Substantial missing data precluded assessment of primary and secondary outcomes. In post hoc analyses, patients in the Bridge arm were more likely than controls to both apply for and receive financial assistance. CONCLUSION: We were unable to test our primary outcome because of excessive missing follow-up survey data. In exploratory post hoc analyses, patients who received a financial assistance app were more likely to apply for and receive financial assistance. Ultimately, our study highlights challenges faced in identifying measurable outcomes and retaining participants in a randomized, controlled trial of a mobile app to alleviate financial toxicity.

Clinical and Neuroimaging Correlates of Post-Transplant Delirium.

Delirium is common among adults undergoing hematopoietic stem cell transplantation (HCT), although the clinical and neuroimaging correlates of post-HCT delirium have not been adequately delineated. We therefore examined the frequency of delirium and neuroimaging correlates of post-transplant delirium in a retrospective cohort of 115 adults undergoing neuroimaging after allogeneic HCT. Delirium was established using previously validated methods for retrospective identification of chart-assessed postprocedural delirium. Chart reviews were independently conducted by a multidisciplinary team with expertise in HCT, psychiatry, and psychology on consecutive allogeneic HCT patients who underwent neuroimaging assessments and transplantation at a single center between January 2009 and December 2016. Neuroimaging markers of white matter damage and brain volume loss were also recorded. In total, 115 patients were included, ranging in age from 20 to 74 years (mean [SD] age, 49 [13]). Fifty-three patients (46%) developed post-HCT delirium. In an adjusted model, delirium incidence was associated with older age (odds ratio [OR], 1.92 [1.28, 2.87] per decade, P = .002), greater severity of white matter hyperintensities (OR, 1.95 [1.06, 3.57], P = .031), and conditioning intensity (OR, 6.37 [2.20, 18.45], P < .001) but was unrelated to cortical atrophy (P = .777). Delirium was associated with fewer hospital-free days (P = .023) but was not associated with overall survival (hazard ratio, 0.95 [0.56, 1.61], P = .844). Greater incidence of delirium following HCT was associated with greater age, microvascular burden, and conditioning intensity. Pre-HCT consideration of microvascular burden and other neuroimaging biomarkers of risk may be warranted.

Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Certain anaerobic bacteria are important for maintenance of gut barrier integrity and immune tolerance and may influence the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center retrospective cohort study of allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 children and adults who developed febrile neutropenia between 7 days before and 28 days after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n = 491) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, cefepime, or ceftazidime; n = 723). We performed metagenomic sequencing of serial fecal samples from 36 pediatric patients to compare the effects of specific antibiotics on the gut metagenome. Receipt of anaerobic antibiotics was associated with higher hazards of acute gut/liver GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.03 to 1.54) and acute GVHD mortality (HR, 1.63; 95% CI, 1.08 to 2.46), but not chronic GVHD diagnosis (HR, 1.04; 95% CI: .84 to 1.28) or chronic GVHD mortality (HR, .88; 95% CI, .53 to 1.45). Anaerobic antibiotics resulted in decreased gut bacterial diversity, reduced abundances of Bifidobacteriales and Clostridiales, and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome. Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment. Our findings demonstrate that exposure to anaerobic antibiotics is associated with increased risks of acute gut/liver GVHD and acute GVHD mortality after allogeneic HSCT. Use of piperacillin-tazobactam or carbapenems should be reserved for febrile neutropenia cases in which anaerobic or multidrug-resistant infections are suspected.