Publications by authors named "L M Bohannon"

24 Publications

Female Sex is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplant.

Transplant Cell Ther 2021 Jun 16. Epub 2021 Jun 16.

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtct.2021.06.012DOI Listing
June 2021

Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.

Transplant Cell Ther 2021 May 12. Epub 2021 May 12.

Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtct.2021.05.002DOI Listing
May 2021

Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol.

BMJ Open 2021 05 5;11(5):e047069. Epub 2021 May 5.

Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA

Introduction: The 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 (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 Analysis: In 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 Dissemination: This 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 Number: NCT04399252.
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http://dx.doi.org/10.1136/bmjopen-2020-047069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102858PMC
May 2021

Assessing the Feasibility of a Novel mHealth App in Hematopoietic Stem Cell Transplant Patients.

Transplant Cell Ther 2021 Feb 13;27(2):181.e1-181.e9. Epub 2020 Dec 13.

Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtct.2020.10.017DOI Listing
February 2021

Chlorhexidine Gluconate Bathing Reduces the Incidence of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 Mar 7;27(3):262.e1-262.e11. Epub 2021 Jan 7.

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, North Carolina. Electronic address:

Bloodstream infections (BSIs) occur in 20% to 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. 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 1 year of data without CHG bathing (2016) and 2 years of data when CHG was used on the HCT unit (2017 and 2018). Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: high (>75%), medium (50% to 75%), low (1% to 49%), and none (0%). 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 = .003), laboratory-confirmed BSI (LCBI; P = .03), central line-associated BSI (P = .04), and mucosal barrier injury LCBI (MBI-LCBI; P = .002). Multivariate analysis confirmed a significant effect of CHG bathing on clinically significant BSI (P = .023) and MBI-LCBI (P = .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. Adherence to daily CHG bathing significantly decreases the rate of bloodstream infection following HCT.
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http://dx.doi.org/10.1016/j.jtct.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010223PMC
March 2021