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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 (β = 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.

The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; therefore, probiotics may be a low-risk, easily implementable modality to reduce risk of COVID-19, particularly in areas with low vaccine availability/uptake. In this study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lactobacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤ 7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes. Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4% vs. 42.9%, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8% vs. 15.4%, p = 0.17). This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤ 7 days post-COVID-19 exposure. This initial work may inform future COVID-19 prevention studies worldwide, particularly in underdeveloped nations where Lactobacillus probiotics have previously been utilized to reduce non-COVID infectious-morbidity. Trial registration: ClinicalTrials.gov, NCT04399252, Date: 22/05/2020 https://clinicaltrials.gov/ct2/show/NCT04399252

Single-agent, high-dose melphalan continues to be the most commonly used conditioning regimen for transplantation-eligible patients with multiple myeloma undergoing autologous stem cell transplantation. The timing of melphalan administration with respect to stem cell infusion has not been clearly defined. Many institutions require a minimum of 24 hours between melphalan administration and stem cell infusion; however, some institutions have adopted shorter intervals based on melphalan's short half-life. Some studies have suggested that shortening the interval between melphalan administration and stem cell infusion may contribute to delays in engraftment, but this correlation has not been clearly evaluated or defined. This multicenter retrospective cohort study evaluated the times to neutrophil and platelet engraftment in patients who received stem cells at least 24 hours after melphalan (≥24 hours cohort) compared with those who received stem cells within 24 hours of melphalan (24 hours cohort. The study included a total of 723 adult patients, 502 patients in the ≥24 hours cohort and 221 in the24 hours cohort, treated at 3 transplantation centers between January 1, 2016, and September 30, 2019. Patient characteristics were summarized using descriptive statistics. The Fisher exact test was used to compare nominal categorical variables between the 2 cohorts, and the nonparametric van der Waerden test or Mood median test was used to compare ordinal or continuous variables. The median time to neutrophil engraftment was 12 days for both the ≥24 hours cohort (interquartile range [IQR], 11 to 12 days) and the24 hours cohort (IQR, 11 to 13 days) (P = .07). The median time to platelet engraftment was 19 days for both the ≥24 hours cohort (IQR, 17 to 22 days) and24 hours cohort (IQR, 17 to 20 days) (P = .25). The median time between melphalan administration and stem cell infusion in the24 hours cohort was 18 hours, with a minimum time of 12 hours. The existing literature has not clearly defined the impact of the timing between melphalan administration and stem cell infusion on engraftment in autologous transplantation. The ability to safely shorten the interval between chemotherapy and transplantation could increase logistical flexibility and/or decrease the length of hospital stay. This large multicenter retrospective study did not identify a statistical or clinical impact on engraftment when melphalan was infused24 hours or ≥24 hours before autologous stem cell infusion.

We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States. By using 16S ribosomal gene sequencing, we assessed fecal microbiota composition and diversity, as measured by the inverse Simpson index. At both centers, the diversity of early pretransplant fecal microbiota was lower in patients than in healthy controls and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to those with allo-HCT. Above-median fecal intestinal diversity in the periengraftment period was associated with decreased risk of death or progression (progression-free survival hazard ratio, 0.46; 95% confidence interval, 0.26-0.82; P = .008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and posttransplant outcomes should be undertaken.

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: 1.26; 95% confidence interval: 1.03–1.54) and acute GVHD mortality (hazard ratio: 1.63; 95% confidence interval: 1.08–2.46), but not chronic GVHD diagnosis (hazard ratio: 1.04; 95% confidence interval: 0.84–1.28) or chronic GVHD mortality (hazard ratio: 0.88; 95% confidence interval: 0.53–1.45). 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.

Patients undergoing allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) require extensive hospitalizations or daily clinic visits for the duration of their transplantation. Home HCT, wherein patients live at home and providers make daily trips to the patient's residence to perform assessments and deliver any necessary interventions, may enhance patient quality of life and improve outcomes. We conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life. This case-control study evaluated patients who received home HCT at Duke University in Durham, North Carolina, from November 2012 to March 2018. Each home HCT patient was matched with 2 controls from the same institution who had received standard treatment based on age, disease, and type of transplant for outcomes comparison. Clinical outcomes were abstracted from electronic health records, and quality of life was assessed via Functional Assessment of Cancer Therapy-Bone Marrow Transplant. Clinical outcomes were compared with Student's t-test or Fisher's exact test (continuous variables) or chi-square test (categorical variables). Quality of life scores were compared using the Student t-test. All analyses used a significance threshold of 0.05. Twenty-five patients received home HCT, including 8 allos and 17 autos. Clinical outcomes were not significantly different between the home HCT patients and their matched controls; home HCT patients had decreased incidence of relapse within 1 year of transplantation. Pre-HCT quality of life was well preserved for autologous home HCT patients. This Phase I study demonstrated that home HCT can be successfully implemented in the United States. There was no evidence that home HCT outcomes were inferior to standard-of-care treatment, and patients undergoing autologous home HCT were able to maintain their quality of life. A Phase II randomized trial of home versus standard HCT is currently underway to better compare outcomes and costs.

STRUCTURED ABSTRACTImportanceThe COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, supplemental strategies to mitigate the spread and severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to infections, including respiratory tract infections, may be reduced by probiotic interventions; therefore, probiotics may be a low-risk, widely implementable modality to mitigate risk of COVID-19 disease, particularly in areas with low vaccine availability and/or uptake.ObjectiveTo determine whether daily probiotic Lactobacillus rhamnosus GG (LGG) is effective in preventing development of symptoms of illness within 28 days of COVID-19 exposure.DesignThis randomized, double-blind, placebo-controlled trial across the United States (PROTECT-EHC) enrolled in 2020-2021. Participants were followed for 60 days.SettingDescribe the study setting to assist readers to determine the applicability of the report to other circumstances, for example, multicenter, population-based, primary care or referral center(s), etc.ParticipantsParticipants included individuals ≥ 1 year of age with a household contact with a recent (≤ 7 days) diagnosis of COVID-19. 182 participants were enrolled and randomized during the study period.InterventionParticipants were randomized to receive daily oral LGG or microcrystalline cellulose placebo for 28 days.Main Outcomes and MeasuresThe primary outcome was development of symptoms within 28 days of exposure to a COVID-19-infected household contact. Stool was collected to evaluate for changes in microbiome structure.Results182 participants were enrolled and randomized during the study period. Intention-to-treat analysis showed that participants randomized to LGG were less likely to develop symptoms versus those randomized to placebo (26.4% vs. 42.9%, p=0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank p=0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8% vs. 15.4%, p=0.17). LGG was well-tolerated with no increased side effects versus placebo. Placebo recipients were more likely to stop the study product, temporarily or permanently, due to symptoms attributed to the study product (5.5% vs. 0%, p = 0.02).Conclusions and RelevanceOur study suggests that LGG is well-tolerated and is associated with prolonged time to development of COVID-19 infection, reduced incidence of symptoms, and changes to gut microbiome structure when used as post-exposure prophylaxis within 7 days after exposure. This preliminary work may inform the approach to prevention of COVID-19, particularly in underdeveloped nations where Lactobacillus probiotics have already been utilized to reduce non-COVID sepsis and infectious-morbidity. This study was limited by its remote format, which necessitated a primary endpoint of self-reported symptoms rather than laboratory-confirmed infection; further laboratory-based studies are needed to further define the efficacy of LGG in preventing COVID-19 infection, especially in larger populations and including comparison of pre-exposure vs. post-exposure prophylaxis.Trial registrationClinicalTrials.gov, NCT04399252, https://clinicaltrials.gov/ct2/show/NCT04399252KEY POINTSQuestionIs daily probiotic Lactobacillus rhamnosus GG (LGG) effective in preventing development of symptoms of illness compatible with COVID-19 within 28 days of COVID-19 exposure compared to placebo?FindingsIn this randomized clinical trial that included 182 participants, the proportion who developed symptoms was 26.4% with LGG versus 42.9% with placebo, a significant difference.MeaningLGG probiotic may protect against the development of symptoms when used as post-exposure prophylaxis within 7 days after COVID-19 exposure.

Lactose can fuel GVHD Allogeneic hematopoietic cell transplantation (allo-HCT) is used to treat certain hematopoietic malignancies, but patients have a risk of developing graft-versus-host disease (GVHD). Stein-Thoeringer et al. performed a large-scale analysis of more than 1300 patients treated with allo-HCT across four clinical centers (see the Perspective by Zitvogel and Kroemer). High levels of bacteria from the Enterococcus genus were associated with greater incidence of GVHD and mortality. Lactose appears to provide a substrate for Enterococcus growth, and patients with a lactose-malabsorption genotype had a greater abundance of Enterococcus. A lactose-free diet limited Enterococcus growth, reduced the severity of GVHD, and improved survival in gnotobiotic mouse models. Science , this issue p. 1143 ; see also p. 1077

BACKGROUND: Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplant (alloHSCT), defined as those living ≥5 years post-transplant, is significantly lower compared to that of the age-matched general population despite a relatively low primary disease relapse rate >2 years post-transplant. Among several factors, patient sex is increasingly recognized as a prognostic indicator of long-term survival. OBJECTIVE: We examined the influence of patient sex and donor-recipient sex matching on overall survival in a landmark analysis of long-term survivors. STUDY DESIGN: Using our institutional database supplemented with individual patient record review, we retrospectively investigated the relative influence of recipient sex and donor-recipient sex matching on outcomes of long-term survivors receiving alloHSCT between 1994 – 2014. RESULTS: Over this 20-year period, 247 met inclusion criteria for analysis; males and females had similar demographic and treatment characteristics. However, significantly more deaths after the 5-year landmark occurred in male recipients. Interestingly, donor sex did not have a significant impact on overall survival in multivariate analysis, and differences in overall survival of donor-recipient sex pairs was driven by recipient sex. In addition to recipient sex, only cGVHD retained significance as a covariate with impact on overall survival in multivariate analysis. Men experienced slightly higher, but non-significant, rates and increased severity of cGVHD, and a greater percentage of cGVHD-related mortality as compared to females. CONCLUSION: In this long-term survival analysis of alloHSCT adult patients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplant. This outcome is independent of other common pre-transplant prognostic indicators such as donor sex or performance status at transplant. Inferior survival for males is consistent with survival outcomes described in transplant literature. Gathering evidence suggests a biologic basis for long-term sex-determined outcomes, possibly due to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Larger studies are warranted to validate these retrospective clinical results.

IntroductionThe COVID-19 pandemic has proven to be an unprecedented challenge to worldwide health, and strategies to mitigate the spread and severity of COVID-19 infection are urgently needed. Emerging evidence suggests that the composition of the gut microbiome and modification of microbial ecology via probiotics can affect susceptibility to a wide range of infections, including respiratory tract infections. In this study, we aim to evaluate the effects of the probiotic Lactobacillus rhamnosus GG (LGG) versus placebo on COVID-19 infection status and the gut microbiome in subjects with a household contact who has tested positive for COVID-19.Methods and analysisIn this double-blinded, randomised, placebo-controlled trial, we will randomise 1132 subjects having a household contact who has recently (≤7 days) tested positive for COVID-19 to daily oral LGG or placebo for 28 days. We hypothesise that taking LGG as a probiotic will protect against COVID-19 infection and reduce the severity of disease in those who become infected (primary endpoint: decreased symptoms), and will be associated with beneficial changes in the composition of the gut microbiome. Stool samples and nasal swabs will be collected to evaluate the microbiome by 16S rRNA sequencing and the presence of SARS-CoV-2 by PCR, respectively. We will also conduct multivariate analysis of demographic, behavioural, temporal, and other variables that may predict development of symptoms and other outcomes.Ethics and disseminationThis trial is conducted under a Food and Drug Administration Investigational New Drug for LGG, has received ethics approval by the institutional review board of Duke University and enrolment has begun. We plan to disseminate the results in peer-reviewed journals and at national and international conferences.Trial registration numberNCT04399252.

Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.

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 age50; 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 (β = 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.

BACKGROUND: Bloodstream infections (BSIs) occur in 20-45% of inpatient autologous and allogeneic hematopoietic cell transplant (HCT) patients. Daily bathing with the antiseptic chlorhexidine gluconate (CHG) has been shown to reduce the incidence of BSIs in critically ill patients although very few studies include HCT patients or have evaluated the impact of compliance on effectiveness. METHODS: We conducted a prospective cohort study with historical controls to assess the impact of CHG bathing on the rate of BSIs and gut microbiota composition among adults undergoing inpatient HCT at the Duke University Medical Center. We present one year of data without CHG bathing (2016) and two years of data when CHG was used on the HCT unit (2017-2018). Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: High (>75%), Medium (50-75%), Low (1-49%), and None (0%). RESULTS: Among 192 patients, univariate trend analysis demonstrated that increased CHG usage was associated with decreased incidence of clinically-significant BSI, defined as any BSI requiring treatment by the medical team (High-8% BSI, Medium-15.2%, Low-15.6%, No CHG-30.3%, p=0.003), laboratory-confirmed BSI (LCBI, p=0.03), central line-associated BSI (CLABSI, p=0.04), and mucosal barrier injury BSI (MBI-LCBI, p=0.002), Multivariate analysis confirmed a significant effect of CHG bathing on clinically-significant BSI (p=0.023) and mucosal barrier injury BSI (MBI-LCBI, p=0.007), without consistently impacting gut microbial diversity. Benefits of CHG bathing were most pronounced with >75% daily usage, and there were no adverse effects attributable to CHG. CONCLUSIONS: Adherence to daily CHG bathing significantly decreases the rate of bloodstream infection following HCT.

Hematopoietic stem cell transplantation (HCT) is a curative treatment option for patients with hematologic conditions but presents many complications that must be managed as a complex, chronic condition. Mobile health applications (mHealth apps) may permit tracking of symptoms in HCT. In seeking strategies to manage the complexities of HCT, our team collaborated with Sicklesoft, Inc., to develop an mHealth app specifically for HCT patients to allow for daily evaluation of patient health, Technology Recordings to better Understand Bone Marrow Transplantation (TRU-BMT). The primary value of this application is that of potentially enhancing the monitoring of symptoms and general health of patients undergoing HCT, with the ultimate goal of allowing earlier detection of adverse events, earlier intervention, and improving outcomes. To first evaluate patient interest in mHealth apps, we designed and administered an interest survey to patients at the 2017 BMT-InfoNet reunion. As a follow-up to the positive feedback received, we began testing the TRU-BMT app in a Phase 1 pilot study. Thirty patients were enrolled in this single-arm study and were given the TRU-BMT mHealth app on a smartphone device in addition to a wearable activity tracker. Patients were followed for up to 180 days, all the while receiving daily app monitoring. Adherence to TRU-BMT was approximately 30% daily and 44% weekly, and greater adherence was associated with increased meal completion, decreased heart rate, and shorter hospital stay. TRU-BMT assessments of symptom severity were significantly associated with duration of hospital stay and development of chronic graft-versus-host disease. Our findings suggest that using TRU-BMT throughout HCT is feasible for patients and established a proof-of-concept for a future randomized control trial of the TRU-BMT application in HCT. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.

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.

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.

BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.)

Ionizing-radiation causes acute radiation syndrome leading to hematopoietic, gastrointestinal and cerebrovascular injuries. Substantial federal efforts have been made to develop therapeutic radioprotectants for routine clinical use, however it remains a long-standing and unresolved problem. We investigated a population of mice that recovered from high-dose radiation to live normal lifespans. These elite-survivors harbored distinct gut microbiota that developed post-radiation and protected against radiation-induced damage and death in germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with post-radiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy who also displayed milder gastrointestinal dysfunction. Metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The concentrations of these metabolites correlated with long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in pro-inflammatory responses. The novelty of our work lies in the first identification of gut microbiota and downstream metabolites in providing protection against lethal radiation. Furthermore, our work provides a comprehensive omics dataset at the bacteria and metabolite levels that is of broad interest and serves as a powerful resource and example for the identification of actionable therapeutic targets derived from microbiome studies.

Introduction: Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplant (allo-HCT) is significantly lower compared to that of the age-matched general population, despite a relatively low primary disease relapse rate >2 years post-transplant. Long-term transplant-related complications instead account for most mortality in this patient population. These include chronic graft-versus-host disease (cGVHD), infection, organ failure, and secondary cancers. In addition, gender is emerging as a critical determinant of outcome in the immediate post-transplant setting. However, less is known regarding gender effects on outcomes of long-term survivors. We retrospectively investigated the impact of recipient gender and donor-recipient gender mismatch on outcomes of long-term survivors of allo-HCT. Methods: We performed a retrospective analysis using Duke University's Adult Blood and Marrow Transplant database, supplemented by individual patient chart review. Inclusion criteria consisted of long-term survivors of first allo-HCT, excluding syngeneic, between 1995 - 2015 for a hematologic malignancy. A long-term survivor is defined as having been alive with documented follow-up to at least five years following allo-HCT. Patient characteristics were summarized as count (%) for categorical variables and median (interquartile range) for continuous variables. Fisher's exact tests or t-tests were used to compare difference between groups. Overall survival was estimated using the Kaplan-Meier method and multivariable Cox proportional hazard model. Patients who had received cord blood allograft were excluded from donor-recipient gender survival analyses. SAS version 9.4 (SAS Institute, Cary, NC) and R 3.5.0 were used to perform statistical analyses. Results: Over this 20-year period, 1103 patients underwent allo-HCT, with 247 (22%) meeting inclusion criteria. Of these 247, males and females had similar demographic and treatment characteristics (Table 1). However, significantly more deaths after the 5-year landmark occurred in male recipients (Figure 1, p value=0.003). To estimate whether this was due to the general population-wide shorter life expectancy for males, we performed Kaplan-Meier estimates of survival for patients aged < 50 years at transplant and aged ≥ 50 years at transplant, with similar results for both groups (Figure 2, p value=0.006). Interestingly, donor gender did not have a significant impact on overall survival in multivariate analysis (Table 2), and differences in overall survival of donor-recipient gender pairs was driven by patient gender (Figure 3, p value =0.007). A separate multivariate analysis of interaction between donor-recipient gender pairs further demonstrated that significant differences in overall survival were due to patient gender (Table 3). In addition to patient gender, only cGVHD retained significance as a covariate with impact on overall survival in multivariate analysis (Table 2, Table 3). Men experienced slightly higher rates and increased severity of cGVHD, and a greater percentage of cGVHD-related mortality as compared to females, though these findings were not statistically significant (Table 1). Conclusion: In this long-term survival analysis of allo-HCT adult patients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplant. This outcome is independent of other common pre-transplant prognostic indicators such as donor gender or performance status at transplant. Inferior survival for males is consistent with survival outcomes described in another large and fully risk annotated HCT cohort, and in solid organ transplants such as lung and kidney. Gathering evidence suggests a biologic basis for long-term gender-determined outcomes, possibly due to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Male patients should be counseled on their possible increased long-term risk. Prospective and larger studies are warranted to validate these retrospective clinical results. Disclosures Rizzieri: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; abbvie: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Acrobiotech: Membership on an entity's Board of Directors or advisory committees.

Background Gastrointestinal (GI) toxicity and acute graft versus host disease (GVHD) are significant morbidities associated with allogeneic hematopoietic stem cell transplantation (HSCT). The somatostatin analogue Octreotide ameliorates mucosal injury from radiation damage in pre-clinical mouse models. We hypothesized that administration of the longer-acting synthetic somatostatin analogue, Pasireotide, in the peri-transplant period would decrease acute GI toxicity and acute GVHD related to allogeneic HSCT. Methods Adult patients who underwent matched allogeneic HSCT with myeloablative conditioning were eligible for this study. Exclusion criteria included severe cardiac and endocrine abnormalities. Pasireotide was administered at 0.9mg twice daily from the day before conditioning began to day +4. The co-primary endpoints were 1) Acute GI toxicity, defined as GI toxicity occurring from the day prior to conditioning to day +30, and 2) Acute GVHD. Results were compared with 50 historical controls matched by Transplant diagnosis, Donor, Graft, GVHD prophylaxis, and Conditioning regimen. Results 36 patients were consented for the study, 25 patients received the study drug (5 screen failures, 1 insurance denial, 3 withdrew consent, 1 switched trials, 1 enrolled at an alternate center without available follow-up). There was no difference in Acute GI toxicity, which occurred in all patients in both the Pasireotide and Control groups. Grade 3 or 4 GI toxicity was similar, occurring in 20 patients (80%) in the Pasireotide group and 35 patients (70%) in the Control group. Specific GI toxicities varied in incidence between the Control and Pasireotide study groups (Figure 1), most notable for numerically higher rates of the expected toxicities abdominal pain, bloating, and vomiting in the Pasireotide group. Other common toxicities that occurred in the Pasireotide and Control groups are listed in Figure 1. There was no significant difference in incidence of overall Acute GVHD or Acute GI GVHD (Figure 2). The subset of patients who received Total Body Irradiation (TBI) conditioning had numerically lower Acute GVHD in the Pasireotide group (5/9, 55%) compared to the Control group (16/20, 80%), however this was not statistically significant (Fisher's Exact Test, p=0.21); these patients also had a lower rate of combined upper and lower GI GVHD (3/9, 33% in the Pasireotide group versus 11/20, 55% in the Control group), though this was not statistically significant (Fisher's Exact Test, p=0.43). Conclusions In this Phase 2 study, the somatostatin analogue Pasireotide did not decrease GI toxicity in allogeneic HSCT; however, in the subset of patients who received TBI conditioning, there was a numerically (but not statistically) significant decrease in overall and GI Acute GVHD. Further study in a larger cohort of patients undergoing TBI conditioning is warranted.

The gut microbiota influences development1–3 and homeostasis4–7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11–14. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota—together and over time—on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity. Influence of the gut microbiome on the human immune system is revealed by systems analysis of vast clinical data from decades of electronic health records paired with massive longitudinal microbiome sequencing.

The gut microbiota influences the development and homeostasis of the mammalian immune system1–3, can alter immune cell compositions in mice4–7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8–12. Still, our understanding of how the microbiota modulates circulatory immune cells remains limited, particularly in humans where a lack of manipulative experiments makes inference challenging. Here we overcome this challenge by studying hundreds of hospitalized—and closely monitored—bone marrow transplantation patients as they recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously over time with unprecedented resolution. We analyzed daily changes in white blood cell counts from 2,235 patients, and 10,680 longitudinal fecal microbiota samples to identify bacterial genera consistently associated with those changes. Bayesian inference and validation across different patient cohorts revealed consistent associations between intestinal bacteria and peripheral immune cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks between peripheral immune cells. The quantification of validated microbiota associations enabled us to contrast the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism, and this way estimate the microbiota potential to alter peripheral immune cell dynamics directly in patients. Our analysis establishes and quantifies the link between the intestinal microbiota and immune cell dynamics in humans, with implications for microbiota-driven modulation of immunity and immunotherapies that rely on circulatory immune cells.

e19373 Background: Increasing healthcare costs often result in many individuals and families foregoing required care, delaying care, or non-adhering to prescribed medication. Hematopoietic cell transplantation (HCT) is a highly specialized procedure that has the potential to adversely affect the socioeconomic well-being of patients and their family. Financial well-being in patients undergoing evaluation for HCT has been inadequately studied. In this prospective cohort study, we examined financial toxicity in a cohort of patients being considered for HCT at the Duke Adult Bone Marrow Transplant Clinic. Methods: This is a prospective cohort review of patients age ≥18 years undergoing evaluation for allogeneic HCT between 1/1/2017 – 1/1/2020. Patients that completed a baseline financial health survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey were included. Financial health was measured via baseline survey and financial distress was assessed via the validated COST-FACIT measure. The primary outcome was financial distress. Results: Of 157 consecutive patients, 112 (71.3%) completed financial toxicity assessments. Of these, 63.4% were male, had a mean age of 61.0, were predominantly white (74.4%), and majority had household incomes less than $90,000 (53.7%). Primary diagnosis at screening was leukemia (35.4%) and myelodysplastic neoplasm (31.7%). Overall, 94.5% noted an inability to see a physician in the prior year due to cost, 76.8% had not filled a prescription due to cost, 73.2% reduced spending on basics like food or clothing to pay for cancer care, 69.5% borrowed money or used a credit card to pay for cancer care, 54.9% used all or a portion of their savings to pay for cancer care, and 54.9% reduced spending on leisure activities like vacations, eating out, or movies to pay for cancer care. Overall, 31 (37.8%) respondents noted mild financial distress while 26 (34.1%) noted moderate-to-high financial distress. Conclusions: Previous studies in the solid tumor and hematological malignancy fields have noted similar results in financial toxicity. However, this is the first study of its kind to demonstrate prevalent financial toxicity present in a cohort of patients undergoing evaluation for HCT. Early interventions by physician and social work led teams may benefit patients who are at risk for financial distress. Future directions include investigating factors associated with high financial toxicity in HCT, and whether financial distress is related to worse outcomes after transplant.

Background Delirium is common among adults undergoing hematopoietic stem cell transplant (HCT), although the clinical predictors and neuroimaging correlates of postoperative delirium have not been adequately delineated. We therefore examined the frequency of delirium and neuroimaging correlates of post-HCT delirium in a retrospective cohort of 115 adults undergoing BMT. Methods Delirium was established using previously validated methods for retrospective identification of chart-assessed postoperative delirium. Chart reviews were independently conducted by a team including a HCT physician, a transplant psychiatrist, a transplant psychologist, and a psychiatry resident on consecutive allogeneic HCT patients who underwent neuroimaging assessments, transplanted between January, 2009 December, 2016Y. Neuroimaging markers of cortical volume loss and white matter hyperintensities were also recorded. Results One hundred fifteen patients were included, ranging in age from 20 to 74 (mean age = 49 [SD = 13]). Fifty-three patients (46%) developed post-HCT delirium. In an adjusted model, delirium incidence was associated with older age (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 treatment regimen intensity (OR = 6.37 [2.20, 18.45], P Conclusions Greater incidence of delirium following BMT was associated with greater age, microvascular burden, and more severe treatment regimen. Pre-HCT consideration of microvascular burden and other neuroimaging biomarkers of risk may be warranted.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HCT) provides a potential cure for a multitude of diseases but can result in high rates of morbidity and mortality. These outcomes have been associated with donor choice, with umbilical cord blood (UCB) perceived as an inferior option to matched related or matched unrelated donors (MRD/MUD) due to increased morbidity and mortality the first year after allo-HCT due to delayed engraftment and increased graft versus host disease (GvHD). At the same time, studies have shown that recipients of cells from younger donors do better, and UCB is the youngest donor cell source available. Given that UCB may have long-term benefits, we evaluated long-term survival in recipients of UCB vs. MRD/MUD in patients who had survived at least 1 year. Methods: This is a retrospective analysis of ≥1 year (≥365 days) survivors of first allo-HCT from the Duke Adult Bone Marrow Transplant (ABMT) program over a twenty year period from January 1, 1996 to December 31, 2015. Detailed clinical data was extracted from the Duke ABMT database and electronic medical record. Patients who either died or were lost to follow-up within 1 year of transplant were excluded. Also excluded were those who received an allo-HCT for a disease other than a hematologic malignancy and those who received haploidentical or mismatched adult cells, as these donor sources have been associated with worse outcomes and the goal was to compare UCB to MRD/MUD. Patient characteristics included gender, race, ethnicity, transplant diagnosis, transplant year, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), Karnofsky performance score (KPS) at transplant workup, age at transplant, donor cell characteristics, conditioning regimen, acute GvHD (aGvHD), date of relapse, and date of death. Chi-square tests or Fisher's exact tests were used to compare categorical variables, as appropriate, and Wilcoxon Rank Sum tests or t-tests were used to compare continuous variables, as appropriate. A Kaplan-Meier estimator was used to analyze overall survival. A Cox Proportional Hazard model with stepwise selection with significance of entry=0.1 and significance of stay=0.2 was used to evaluate the patient characteristics of age, gender, race, disease, KPS, conditioning type, history of aGvHD, and decade of transplant and adjusted for selected covariates to compare the two groups. Results: Over the 20-year study period, 848 patients received a first allo-HCT, of whom 456 (54%) survived at least 1 year post-HCT: 102 (22%) UCB and 354 (78%) MRD/MUD. UCB recipients were more likely to be younger (median 42 years vs. 50 years, p= Discussion: Among patients who survived at least 1 year post-HCT, those who received UCB had a significantly lower risk of mortality on univariate analysis than those who received adult cells. Though this finding was no longer statistically significant on multivariate analysis, there was a strong trend and the lack of statistical significance could be an effect of the small sample size. Additional research across larger populations (e.g. CIBMTR) is warranted to further explore the clinical characteristics and long-term health outcomes between the two groups, especially given the potential for newer UCB approaches such as ex-vivo expansion to decrease the early post-HCT morbidity and mortality associated with UCB and delayed engraftment. If other studies support improved long-term outcomes with UCB, those findings coupled with advances in UCB transplants may promote UCB as a donor source. Disclosures Gasparetto: Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

Introduction: Geriatric assessment (GA) is a multidimensional evaluation of patient health and function that may detect impairments not identified as part of routine care, predict treatment-related morbidity and mortality, and inform treatment plans. Given evidence of these benefits, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend GA for older candidates of hematopoietic stem cell transplantation (HCT). However, both older and younger HCT candidates will often receive multiple rounds of chemotherapy before HCT, leading to functional impairments in all age groups. Furthermore, HCT patients often experience a significant gap between when they are first evaluated and actually proceed to transplant (e.g., while a donor search is conducted), creating an opportunity to identify impairments and optimize function prior to transplant. Methods: To address this opportunity, we created a clinical pre-HCT optimization program (C-POP) to evaluate physical function, cognitive function, nutritional status, and mental health in all adults who were deemed potential candidates for allogeneic HCT by a HCT physician. We applied this standard of care program to all adult candidates for HCT, regardless of age, with the goal of identifying functional impairments and then referring patients to services to optimize those impairments prior to HCT. We defined impairments using validated measures and compared results to established norms or scoring, controlling for age and gender where appropriate (e.g., the cut-off for six-minute walk distance was adjusted for age, gender, height, and weight, while the cut-off for falls was any fall regardless of characteristics). Patients with impairments were referred to the appropriate supportive care (e.g., physical function impairment -> referral to physical therapy). Results were prospectively analyzed at new patient evaluation (NPE), which was the first time the patient met a HCT physician and sign-off, which occurred within a week before starting transplant. While the program is ongoing, we present here the results of patients evaluated between October 16th, 2017 and July 1st, 2019. Patients are divided into three pre-specified age groups: =60 years old, with results compared using a chi-squared test. Results: We evaluated 115 patients: 21 (18%) =60 years). There were no differences between the age groups in other demographics (gender, race, and ethnicity). At NPE, 93 (81%) met criteria for at least 1 impairment in physical function, cognitive function, nutritional status, or mental health; 62 (54%) met criteria for impairments in 2 or more areas. Surprisingly, patients =60 years (36/54, 67%) (p=0.03). Of those 115 patients, 52 (45%) proceeded to HCT, including 12 (57%) =60 years (p=0.75); of those patients who have not proceeded to HCT, 40 (35%) will never proceed to HCT (e.g., deemed not a candidate after functional evaluation or died of disease prior to HCT) while 23 (20%) are still awaiting HCT (e.g., donor search ongoing). Patients who proceeded to HCT were less likely to have mental health impairments (2/52, 4% vs. 9/40, 23%, p=0.006). Of the 52 who were seen at new patient evaluation and proceeded to transplant, 40 (77%) were seen at sign off. Of those who had impairments at NPE, 12/23 (52%) improved their physical function to normal limits, 4/9 (44%) improved their cognitive function, and 9/13 (69%) improved their nutritional status by the time of sign-off (of those who were seen at sign-off, none had mental health impairments at NPE). Discussion: These results demonstrate that younger as well as older candidates for HCT exhibit a high degree of functional impairment. However, this impairment could be amenable to improvement prior to HCT. These findings support application of GA to all HCT candidates regardless of age. We will investigate the effect of referred interventions (e.g., physical therapy, seeing a dietician) in improving functional impairments in future studies, as well as look at the effect of these findings on HCT outcomes. Disclosures Wiggins: Incyte, Inc.: Speakers Bureau. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Rizzieri:Millennium: Speakers Bureau; Novartis: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; TEVA: Consultancy; Spectrum: Consultancy; Kite Pharma: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

Introduction: While hematopoietic stem cell transplantation (HSCT) has great therapeutic potential, intensive conditioning regimens and variability in time to stem cell engraftment result in a period of pancytopenia and immunosuppression in which patients are vulnerable to infection. Bloodstream infections (BSIs) occur in 20-45% of inpatient autologous and allogeneic transplant patients, leading to prolonged hospitalization and increased mortality. One method of infection prevention is daily application of the antiseptic chlorhexidine gluconate (CHG). Daily CHG bathing, either with a CHG wash or with application of CHG-impregnated cloths, has been shown to reduce the incidence of all-cause hospital-acquired BSIs in critically ill patients, such as those in the ICU, though very few studies include HSCT patients. Methods: We conducted an observational cohort study to assess the impact of daily CHG bathing on the rate of BSIs among adults undergoing inpatient HSCT at the Duke University Medical Center. Patients were included if they were admitted for pre-transplant conditioning and inpatient monitoring for allogeneic or autologous HSCT from January 2016 through December 2018. CHG bathing was instituted in January 2017 for all patients admitted to the inpatient HSCT unit using 2% CHG-impregnated cloths (SAGE™), providing one year of data with no CHG bathing and two years of data with bathing. Patients were tracked from admission until unit discharge, transfer, or first infection. Laboratory-confirmed bloodstream infections (LCBI), central-line associated bloodstream infections (CLABSI), and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI) were determined per CDC/NHSN definitions. An additional variable of "clinically-significant infection" was recorded; this included both laboratory-confirmed BSIs and infections deemed significant by the treatment team but that did not meet CDC/NHSN criteria. For example, patients that were febrile, hypotensive, and treated with antibiotics, but with only one positive culture of a common commensal were deemed to have a clinically-significant BSI. Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: High (>75%), Medium (50-75%), Low (1-49%), and None (0%). Baseline characteristics and clinical outcomes between groups were compared via ANOVA, Chi-squared test, or Cochran-Armitage two-sided trend test. Multivariate analysis using the Fine-Grey subdistribution hazard model was conducted to compare time to all infection variables, accounting for the effects of CHG usage, antibiotic prophylaxis regimen, and type of transplant. Results: We evaluated 192 patients hospitalized for HSCT, including 118 (62%) allogeneic transplants and 74 (38%) autologous transplants. Of these, 25 (13%) had high CHG usage, 33 (17%) medium, 45 (23%) low, and 89 (46%) none. Demographics and transplant characteristics were evenly matched between the CHG usage groups with the exception that high usage groups were more likely to receive levofloxacin for antibiotic prophylaxis (p=0.003). Increased CHG usage was significantly associated with decreased incidence of clinically-significant infection (p=0.006), CLABSI (p=0.04), and MBI-LCBI (p=0.002) (Table 1). Multivariate analysis did not demonstrate a significant contribution of antibiotic prophylaxis regimen. No significant difference was found between CHG usage groups in median days to stem cell engraftment, incidence of febrile neutropenia or C. difficile infection, or rashes requiring medical treatment. There were no rashes attributable to CHG usage. Among patients who were VRE rectal swab negative on admission, there was a significant trend toward lower rates of VRE acquisition with increasing CHG usage (High CHG 13.6% vs No CHG 25.3%, p=0.02). Discussion: Increased CHG usage is associated with a significant trend toward lower rates of clinically-significant infection, CLABSI, MBI-LCBI, and VRE colonization in adult inpatients undergoing HSCT. Effects are most strongly seen at >75% daily CHG usage. There were no adverse effects due to CHG application. The significant decrease in MBI-LCBI with topical CHG suggests an interaction between the skin microbial environment and enteric organisms. Therefore, further research exploring the effects of CHG on the skin and gut microbiota is warranted. Disclosures Gasparetto: BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

Background: The hypomethylating agents (HMAs) azacitidine and decitabine have been increasingly used in the frontline setting for elderly and/or unfit patients with acute myeloid leukemia (AML). While these therapies are oftentimes used in the palliative setting, HMAs have also been used with curative intent in some patients, as a bridge to allogeneic hematopoietic cell transplantation (HCT). It is well known that 4-6 cycles of HMA therapy can be necessary to achieve a response; however, it is still common in practice for treating physicians to stop HMAs earlier when a rapid response is not observed. Few studies have investigated time to response in the setting of frontline HMA treatment for AML. Methods: We retrospectively evaluated all patients who were initiated on frontline HMAs for AML at our institution from September 2013 to April 2018. HMAs were administered without dose reduction or treatment delays. Responses were evaluated and categorized as hematologic response (HR; defined by neutrophils > 1000/µL, platelets > 100k/µL, transfusion independence, and no peripheral blasts), complete remission (CR), CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), and no response. Patient, cytogenetic, and treatment characteristics were summarized and described. We evaluated patients exhibiting a response before receiving 4 cycles of HMA therapy ("early" responders) and compared these patients to those achieving a response after receiving at least 4 cycles of HMA ("late" responders). The Kaplan-Meier method estimated overall survival (OS). Odds of early response were estimated with logistic regression models. Results: During the study period, 137 patients received frontline HMAs. 122 (89.1%) patients received azacitidine, and 15 (10.9%) were treated with decitabine. Mean age at HMA start was 70.1 years (range 39.8-94.3). Most patients (62.8%) were male, and most (77.4%) were Caucasian. 21 (15.3%) patients were NCCN favorable-risk, 52 (38.0%) were intermediate-risk, and 64 (46.7%) were poor-risk. At first testing, 21.4% of the patients were positive for the FLT3/ITD mutation, 0.8% the FLT3/TKD mutation, and 21.4% the NPM1 mutation. Some patients received concomitant therapies along with the HMA; these included hydroxyurea, lenalidomide, and sorafenib. Median survival in the entire population was 11.6 (95% CI 8.3, 15.2) months. Overall response rate (ORR) was 60.6%. Among responders, 80.7% achieved HR as their first response; 19.3% were first noted to have marrow responses (1.2% CR, 4.8% CRp, and 13.3% CRi). Most patients did not undergo bone marrow evaluation to assess response. Among responding patients, 60.2% responded "early", whereas 39.8% responded "late". Median overall survival was 15.2 (9.3, 17.7) months in early responders, and 22.2 (11.7, 38.9) months in late responders. There was no difference in survival between the groups (p=0.108, log-rank test; Figure 1), although there was a trend toward improved survival in late responders. Nineteen patients underwent allogeneic HCT. Time to response was not associated with odds of receiving HCT (p=0.812). Conclusions: HMAs have a high ORR as frontline therapy in elderly and unfit AML patients. Among AML patients receiving frontline HMAs, later responders have equivalent survival to earlier responders. Physicians should consider exercising patience when treating AML patients with HMAs. These findings warrant validation in a larger, prospective study. Figure. Figure. Disclosures Avalos: Juno: Membership on an entity's Board of Directors or advisory committees. Grunwald:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Janssen: Research Funding; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medtronic: Equity Ownership.

Background: Financial Toxicity (FT) is increasingly recognized as a major contributor to morbidity and mortality in a variety of cancers. Treatment of acute leukemia is associated with heavy healthcare utilization and high costs. The purpose of this study was to define rates, risk factors, and mortality implications for FT in patients with acute leukemia using patient reported data. Methods: All patients seen at the Levine Cancer Institute, a tertiary hospital-based leukemia practice, were surveyed prior to each visit over a six-month period. All patients were aged ≥18 years and were diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 4 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Demographic data and disease characteristics were abstracted from the medical record. Model selection was carried out using logistic regression to identify factors impacting the incidence of financial toxicity. Correlation of numerical financial toxicity scores with PROMIS scores and with mortality data was assessed using linear regression. Results: Of the 106 patients, 58 (54%) met the definition of exhibiting FT. The factors associated with incidence of FT included: age, race, and insurance type. The odds of FT in those patients 4 compared to patients with FT scores Conclusions: Patients with acute leukemia represent an extremely vulnerable population for financial toxicity with rates of distress even higher than other reported malignancies. Urgent interventions are indicated in this population. Disclosures Grunwald: Medtronic: Equity Ownership; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Janssen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Symanowski:Five Prime Therapeutics: Other: Data Safety Monitoring Board ; Boston Biomedical: Other: Data Safety Monitoring Board ; Eli Lily & Co: Other: Data Safety Monitoring Board; Immatics: Other: Data Safety Monitoring Board.

7033Background: Outcomes for patients (pts) with RR-AML are poor, with limited treatment options. Salvage HMA therapy has been explored for RR-AML but is often considered palliative. We examined re...