Hematopoietic Stem Cell Transplant Population Research Articles

A novel psychosocial virtual reality intervention (BMT-VR) for patients undergoing hematopoietic stem cell transplantation: Pilot randomized clinical trial design and methods

BackgroundAlthough patients undergoing hematopoietic stem cell transplantation (HSCT) must cope with psychological distress and isolation during an extended transplant hospitalization, psychosocial interventions to address these unmet needs are lacking. Virtual reality offers an innovative modality to deliver a patient-centered psychosocial intervention to address psychosocial needs of patients undergoing HSCT. However, there are currently no supportive care interventions leveraging virtual reality in patients undergoing HSCT. ObjectiveTo describe the methods of a randomized clinical trial (RCT) to assess the feasibility and preliminary efficacy of a self-administered, virtual reality-delivered psychosocial intervention (BMT-VR) to improve psychological distress and quality of life (QOL) for patients hospitalized for HSCT. MethodsThis study entails a single-center RCT of BMT-VR compared to usual transplant care in 80 patients hospitalized for HSCT. Adult patients with hematologic malignancies hospitalized for autologous or allogeneic HSCT are eligible. BMT-VR includes psychoeducation about the HSCT process, psychosocial skill building to promote effective coping and acceptance, and self-care and positive psychology skills to promote post-HSCT recovery. The primary aim is to assess the feasibility defined a priori as ≥60% of eligible patients enrolling in the study, and of those enrolled and randomized to the BMT-VR, ≥ 60% completing 4/6 BMT-VR modules. Secondary objectives include assessing the preliminary effects on psychological distress and QOL. DiscussionThis is the first RCT of a virtual reality-delivered psychosocial intervention for the HSCT population. If deemed feasible, a future larger multi-site clinical trial can evaluate the efficacy of BMT-VR on outcomes for patients hospitalized for HSCT.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p=.03) to engage in teeth brushing (56/62=90%) compared to baseline (61/81=75%). Mean days of OM decreased from 11.3 to 9days; patients who received PBM were less likely (p<.001) to be discharged on total parental nutrition (TPN) (11/62=18%) compared to baseline (50/82=61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p=.02) for those who received PBM (median cost=$31,229.87 vs. $37,370.66). PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Impact of self-directed exercise intervention in a minority rich, hematopoietic stem cell transplant (HSCT) inpatient population at high risk for sarcopenia and falls.

390 Background: Extended hospitalizations in the adult HSCT population increase patients’ risk for deconditioning and sarcopenia. Sarcopenia negatively impacts overall survival in adult HSCT patients (Armenian et al, 2019) and is strongly associated with falls among older adults (Yeung et al, 2019; Marques A &amp; Queirós C., 2018; Wheatley et al, 2021). Methods: In a safety net, minority rich, academic medical center in suburban NYC, stationary pedals were placed inside patient rooms in a 31-bedded inpatient HSCT unit starting Q4 2020. Intentional, inpatient room placement prevented additional risk of infectious exposures to COVID-19 in late 2020-2021, allowed for safe access to pedals from a seated position in chairs inside patient rooms, and provided insight into self-directed exercise participation. Attending MDs, PAs and RNs encourage HSCT patients to utilize stationary pedals up to 3 times daily, while usage remains self-directed. Direct observation of patient pedal usage and patient-verbalized interest in participation reflects positive acceptance and consistent usage since implementation. Results: 2019-2023 Midas Event Reporting data was reviewed by the author. Total numbers of Weak/Impaired Gait patient falls decreased in the post-implementation period: 19 falls at baseline versus 13 falls in 2021, 11 falls in 2022, and 3 falls in Q1 2023. Pre-intervention 2019 data indicates 63.3% of falls are among Weak/Impaired Gait patients. (2020 falls data is not included due to unit closures during the COVID-19 pandemic). Post-intervention 2021-2023 data reveals a mean of 51.2% of falls are in Weak/Impaired Gait patients, indicating a 12.1% decline in falls in the post-intervention period of 2.25 years. Conclusions: Sarcopenia and inpatient falls impact patient outcomes (i.e., injuries, extended hospitalizations, and survival) and are financially burdensome. Each inpatient fall, whether injurious or not, costs hospitals approximately 35,000 (Dykes et al, 2023). Reductions in numbers of inpatient falls at this institution are potentially associated with the following hospital cost savings: 210K in 2021, 280K in 2022 and a projected 245K in 2023. Reduction in sarcopenia during extended hospitalizations, when reviewed alongside the financial impact of inpatient falls, supports the ongoing implementation of self-directed exercises in this population. Next steps include self-directed use of resistance bands, chair-based and bed-based stretches, and utilizing self-tracking devices to record exercise duration. (Full references available upon request).

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis.

Letermovir has changed the game of primary prophylaxis against cytomegalovirus (CMV) for hematopoietic stem cell transplant (HSCT) and more recently, solid organ transplant recipients. This is largely due to letermovir's similar efficacy in protecting against CMV reactivation and disease, along with its superior safety profile, notably reduced myelotoxicity, and lack of renal dose adjustment compared to standard agents like valganciclovir. This review will describe the potential benefits and clinical considerations of letermovir as prophylaxis among transplant recipients, with a focus on recent evidence describing nonviral outcomes of CMV. Recent evidence has demonstrated improved safety (e.g., less myelosuppression) and tolerability with no difference in rates of CMV infection or disease in kidney transplant recipients given letermovir compared to valganciclovir. Real-world studies and meta-analyses in HSCT populations have explored various nonviral outcomes with letermovir use. Letermovir prophylaxis was associated with reduced mortality, lower rates of graft versus host disease, delayed CMV immune reconstitution, improved tolerability with extended durations, and decreased healthcare utilization. Letermovir is an effective antiviral agent for CMV prevention and has demonstrated enhanced safety, which may allow for extended durations of primary prophylaxis among transplant recipients along with other improved clinical outcomes by mitigating the indirect effects of CMV.

Attenuated immunogenicity of SARS-CoV-2 vaccines and risk factors in stem cell transplant recipients: a meta-analysis.

Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination isdiminished in hematopoietic stem cell transplant (HSCT) recipients. To summarize current evidence and identify risk factors for attenuated responses, 5 electronic databases were searchedsince database inceptions through 12 January 2023 for studies reporting humoral and/or cellular immunogenicity of SARS-CoV-2 vaccination in the HSCT population. Using descriptive statistics and random-effects models, extracted numbers of responders and pooled odds ratios (pORs) with 95% confidence intervals (CIs) for risk factors of negative immune responses were analyzed (PROSPERO: CRD42021277109). From 61 studies with 5906 HSCT recipients, after 1, 2, and 3 doses of messenger RNA (mRNA) SARS-CoV-2 vaccines, the mean antispike antibody seropositivity rates (95% CI) were 38% (19-62), 81% (77-84), and 80% (75-84); neutralizing antibody seropositivity rates were 52% (40-64), 71% (54-83), and 78% (61-89); and cellular immune response rates were 52% (39-64), 66% (51-79), and 72% (52-86). After 2 vaccine doses, risk factors (pOR; 95%CI) associated with antispike seronegativity were male recipients (0.63; 0.49-0.83), recent rituximab exposure (0.09; 0.03-0.21), haploidentical allografts (0.46; 0.22-0.95), <24months from HSCT (0.25; 0.07-0.89), lymphopenia (0.18; 0.13-0.24), hypogammaglobulinemia (0.23; 0.10-0.55), concomitant chemotherapy (0.48; 0.29-0.78) and immunosuppression (0.18; 0.13-0.25). Complete remission of underlying hematologic malignancy (2.55; 1.05-6.17) and myeloablative conditioning (1.72; 1.30-2.28) compared with reduced-intensity conditioning were associated with antispike seropositivity. Ongoing immunosuppression (0.31; 0.10-0.99) was associated with poor cellular immunogenicity. In conclusion, attenuated humoral and cellular immune responses to mRNA SARS-CoV-2 vaccination are associated with several risk factors among HSCT recipients. Optimizing individualized vaccination and developing alternative COVID-19 prevention strategies are warranted.

Incidence of Bloodstream Infections after Hematopoietic Stem Cell Transplantation for Hurler Syndrome

Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder characterized by the deficiency of the alpha-L-iduronidase enzyme necessary for the degradation of glycosaminoglycans (GAG) in the lysosome. Hurler syndrome is the most severe form of MPS I, manifesting as multiorgan dysfunction, cognitive delay, and death, usually within ten years if left untreated. Hematopoietic stem cell transplantation (HSCT) is the optimal treatment option, providing a permanent solution to enzyme deficiency and halting cognitive decline; however, the HSCT complications transplantation-associated thrombotic microangiopathy (TA-TMA) and graft-versus-host disease (GVHD) are known risk factors for bloodstream infection (BSI). BSI is a serious complication of HSCT, contributing to poor outcomes and transplantation-related morbidity. There are little data evaluating BSI after HSCT in the Hurler syndrome population. We performed a retrospective analysis of patients with Hurler syndrome who underwent HSCT at our center between 2013 and 2020 to determine the incidence of BSI within the first year post-transplantation. Patient BSI data were collected through the first year post-HSCT. Variables including patient demographics and transplantation-related characteristics were collected, including information on BSI and mortality. Twenty-five patients with a total of 28 HSCTs were included in the analysis; the majority (n=17; 68%) were male, with a median age of 1.1 years (interquartile range, .35 to 1.44 years) at the time of transplantation. The most common graft source was cord blood (n=15; 54%), followed by bone marrow (n=13; 46%), with the majority from matched unrelated donors (n=14; 52%) and mismatched unrelated donors (n=13; 44%). Sixteen BSIs were diagnosed in 12 patients (48%). Most infections (n=7; 43.8%) were diagnosed in the first 20 days post-transplantation, with fewer infections observed at later time points. Seven of the 9 Hurler patients diagnosed with TA-TMA (78%) also had a BSI. The incidence rate of BSIs in Hurler patients (n=12; 48%) was higher than the rates reported in the general pediatric HSCT population at 1-year post-transplantation (15% to 35%). Given the high rate of both TA-TMA and a BSI in Hurler patients, we suspect a possible correlation between the 2. Additionally, due to the time it takes for GAG levels to normalize post-HSCT in Hurler patients, it is reasonable to suspect that the high BSI rates in these patients are linked to their Hurler diagnosis. These findings bring awareness to possible disease-related factors contributing to high BSI rates in the Hurler population post-HSCT.

An Algorithm Addressing the Problem of Overdiagnosis of Clostridioides difficile Infections in Hematopoietic Stem Cell Transplantation Recipients: Effects on C. difficile Infection Rates and Patient Outcomes

Diarrhea of other causes and Clostridioides difficile colonization are common in patients hospitalized for hematopoietic stem cell transplantation (HSCT). It has been well recognized that these issues tend to decrease the specificity of stool testing for C. difficile infection (CDI). The best way to address this problem is uncertain. In September 2018, we initiated a project with the goal of addressing the apparent problem of overdiagnosis of CDIs in our HSCT population. Using the quality improvement tool Model for Improvement, we introduced a C. difficile stool testing and CDI diagnosis algorithm with the aim of decreasing unnecessary inpatient CDI diagnoses and treatments. In this study, we examined the effects of the algorithm. We reviewed all HSCT admissions for the 2 years before introduction of the algorithm and the subsequent 3 years, recording all stool submissions for C. difficile determination and CDI. At the close of the study, we recruited our advanced practice providers (APPs) to review all CDIs following algorithm initiation and provide feedback on the ease of use of the algorithm and potential improvements to the overall process. Stool submissions for C. difficile determination decreased from 38.0/1000 to 20.6/1000 inpatient days (P < .001) and CDI diagnoses decreased from 5.5/1000 to 2.4/1000 days (P=.007). Patients admitted for a first allogeneic HSCT, first autologous HSCT, or HSCT readmission showed similar proportionate reductions. No detrimental effects on hospital length of stay, overall survival, progression-free survival, rate of readmission post-HSCT, incidence of acute graft-versus-host disease, or incidence of recurrent CDI were noted following algorithm introduction. A strategy of education, monitoring/feedback, and ease of algorithm access proved effective in inducing provider compliance. APPs rated the algorithm high on ease of use. We conclude that the use of an algorithm defining criteria for C. difficile testing, diagnosis, and treatment was associated with significantly decreased CDI diagnoses on a HSCT inpatient unit without apparent adverse effects.

Challenges and Opportunities in Antimicrobial Stewardship among Hematopoietic Stem Cell Transplant and Oncology Patients.

Antimicrobial stewardship programs play a critical role in optimizing the use of antimicrobials against pathogens in the era of growing multi-drug resistance. However, implementation of antimicrobial stewardship programs among the hematopoietic stem cell transplant and oncology populations has posed challenges due to multiple risk factors in the host populations and the infections that affect them. The consideration of underlying immunosuppression and a higher risk for poor outcomes have shaped therapeutic decisions for these patients. In this multidisciplinary perspective piece, we provide a summary of the current landscape of antimicrobial stewardship, unique challenges, and opportunities for unmet needs in these patient populations.

Bone Mineral Densitometry Diagnostic Yield Remains High Beyond 10 Years Post Allogeneic Stem Cell Transplant

Introduction: Reduced bone mineral density is a complication following allogeneic hematopoietic stem cell transplant (HSCT) resulting from the complex interplay of pre-, peri- and post- HSCT factors. Whilst guidelines recommend baseline bone mineral density (BMD) testing within a year of HSCT, evidence on the optimal timing and interval of post HSCT BMD assessment limited, and literature suggests heterogeneity in the management of abnormal results. Published literature to date largely focuses on the incidence of osteopenia and osteoporosis, within 5 years post transplant. The extent of the problem in long term post HSCT survivors remains largely unknown. The population . Here we present long-term data on bone mineral deficiency in HSCT patients from Westmead Hospital, Sydney, Australia. Method: A retrospective analysis of patients with a history of hematological malignancy who attended the long term follow up (LTFU) HSCT clinic between January 2013 and April 2022 at Westmead Hospital in Sydney, Australia, was undertaken. Patients required at least one BMD report to be included in the analysis. Data was collected from patient medical records and descriptive analysis undertaken. Timing of first post HSCT BMD was categorised as <12 months, 13-24 months, 25-36 months, 37-48 months, 49-60 months, 61-120 months, or >120 months. Bone mineral deficiency was defined according to the World Health Organization (WHO) criteria, with osteopenia at a T-score of <-1.0 to -2.5, and osteoporosis at a T-score of <-2.5. Results: Of the 355 patients who attended the clinic, 86% (305 patients) had at least one BMD study between 6 months and 36 years post transplant, with a total of 414 studies performed. Osteoporosis or osteopenia was reported in 59% of all patients undergoing their first post HSCT BMD, irrespective of the time-point post HSCT at which the BMD was performed. The median T-score for patients diagnosed with osteopenia was -1.8 (range -2.5 to -1.1), and for those with osteoporosis was -3.0 (range -4.1 to -2.6). Patient age at time of diagnosis of bone mineral deficiency ranged from 19 to 76 years. Amongst the 57 patients who had their first BMD more than 10 years post HSCT, 55.9% had evidence of osteoporosis or osteopenia, similar to the rate detected in patients having first BMD within 12 months of transplant (61.3%, n=80). Conclusion: This the largest report of the ongoing diagnostic yield of BMD in long term follow up post HSCT. Osteoporosis or osteopenia was identified in almost 60% of patients at first BMD post transplant, even when the first bone density assessment occurred beyond 10 years post transplant. The stability in detection rates over time could indicate that a bone-loss-causing insult occurs at the time of HSCT and does not necessarily progress after transplant. However longitudinal studies are required for confirmation. Osteoporosis is found at first BMD assessment in up to 15% of patients underlining the importance of interventions to optimise post-transplant bone health. Our data is limited by selection bias towards patients who continued to attend the LTFU clinic, but the diagnosis of new cases beyond 10 years post transplant highlights the importance of ongoing monitoring of BMD in the post HSCT population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

DNA Methylation Research in Autologous Hematopoietic Stem Cell Transplant Population.

Despite increased sophistication in DNA methylation (DNAm) measurement and methods, conducting studies in specific populations such as the hematopoietic stem cell transplant (HCT) population, presents unique challenges and study design considerations. In this article, we explain the motivation for investigating DNAm in the HCT population, highlighting important study design features and key findings in a longitudinal prospective pilot study of DNAm in 32 patients undergoing autologous HCT in Central Virginia, USA. We also discuss limitations and challenges to generating robust results. We observed that HCT does not prevent high-quality DNA from being extracted from whole blood for DNAm research and that longitudinal prospective studies that span pre- and 2-months post-HCT are feasible. Critically, we did not observe significant impacts of cancer diagnosis, time since transplant, age, or chromosomal sex on overall DNAm data dimensionality. These observations demonstrate that while extreme care is required to ensure generalizable, accurate, and interpretable results, researchers should not avoid HCT-DNAm research simply for fear that the transplant procedure or presence of a cancer diagnosis will prevent meaningful conclusions from being drawn. DNAm is an attractive biomarker that is understudied in patients undergoing HCT and needs to expand to improve precise prediction of HCT outcomes.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13-3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91-0.99], P = .02), lower bicarbonate (OR 0.94 [0.88-0.99], P = .035), and higher creatinine (OR 1.91 [1.23-2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48-3.94], P < .001), opioids (OR 2.94 [1.67-5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30-1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34-2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33-1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2-301.7], P < .001), bloodstream infection (OR 4.59 [2.46-8.57], P < .001), and pneumonia (OR 9.76 [5.01-19.00], P < .001). Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Respiratory Viral Infections in the Pediatric Hematopoietic Stem Cell Transplant Population: Progression to Lower Respiratory Tract Disease.

Respiratory viral infections (RVIs) are important complications in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT); however, risk factors for lower respiratory tract infections (LRTIs) are not well characterized. The aim of this study was to determine risk factors for the progression to LRTIs in pediatric patients with respiratory symptoms who underwent HSCT. This retrospective study included 87 pediatric patients with respiratory symptoms who underwent HSCT. Respiratory viral polymerase chain reaction samples were obtained from all patients. The evaluated data included risk factors to progression to LRTIs, long-term pulmonary complications, transplantation-related mortality, and overall survival. Viral pathogens were detected in 31 (48.4%) patients with upper respiratory tract infections and 13 (56.5%) patients with LRTIs. There was a statistically significant difference between the groups in engraftment delay and lymphocytopenia. Also it was determined that engraftment delay (odds ratio: 7.46 [95% CI, 1.99 to 27.86]; P = 0.003) and COVID-19 infection had statistically significant effects on overall survival in general (odds ratio: 8.06 [95% CI, 2.63 to 24.64]; P <0.001]). Not only host and transplant-related factors but also viral agent type were found to be effective in progression to LRTIs. As the available therapy for respiratory viral infections remains limited, the focus should be on the prevention of infection.

An mHealth App to Promote Adherence to Immunosuppressant Medication and Track Symptoms in Children After Hematopoietic Stem Cell Transplant: Protocol for a Mixed Methods Usability Study.

BackgroundIn the United States, poor adherence accounts for up to 70% of all medication-related hospital admissions, resulting in $100 billion in health care costs annually. In pediatrics, adherence is largely dependent on caregivers. In a high-risk hematopoietic stem cell transplant (HSCT) population, caregivers are isolated with their child due to infection risk and must manage challenging treatment regimens at home, often with limited time and support. Complex behavioral interventions, typically employed to address adherence, are difficult to deliver and manage in the context of these daily tasks. The most successful adherence interventions, and thus improved clinical outcomes, have included mobile health (mHealth) reminder approaches and a direct measure of adherence.ObjectiveThis is a 3-phase project, with this protocol describing phase 2, to determine the usability and feasibility of an mHealth app (BMT4me) designed to promote adherence to immunosuppressant medication and to track symptoms among children who received HSCT.MethodsThis study uses an iterative convergent mixed methods design to develop and assess the usability and feasibility of an adherence digital health intervention. We will recruit 15 caregivers of pediatric patients receiving HSCT to complete user testing. Qualitative and quantitative data will be integrated to enhance and expand upon study findings.ResultsEnrollment began in September 2021 and is ongoing. A total of 7 caregivers have enrolled. We anticipate completion by fall 2022. We anticipate high usability scores and a better understanding of unique features within the app that are needed for HSCT families post transplant. To date, usability scores among enrolled participants are greater than 70%. Feedback from qualitative interviews is being used to further adapt the app by adding specific weekly logs, call provider options, and voice to text.ConclusionsThis protocol describes a mixed methods usability and feasibility study to develop and implement a smartphone app for caregivers of children receiving HSCT. The app was designed to improve immunosuppressant adherence and to track symptoms in the acute phase post discharge. Study findings will inform further refinement of the app and the feasibility of a pilot randomized controlled trial examining efficacy on clinical outcomes.Trial RegistrationClinicalTrials.gov NCT04976933; https://clinicaltrials.gov/ct2/show/NCT04976933International Registered Report Identifier (IRRID)DERR1-10.2196/39098

Peer support in patients with hematologic malignancies: a systematic review

Peer support has been utilized and associated with clinical outcomes (e.g., improved mood) in patients with solid malignancies. However, to date, there is minimal literature examining peer support among patients with hematologic malignancies and/or patients who have undergone hematopoietic stem cell transplantation (HSCT). In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we completed a systematic review using five databases to assess the relationship between peer support and clinical outcomes (e.g., distress, physical symptoms) among patients with hematologic malignancies or HSCT recipients. The eight included studies examined peer support in a total of 574 patients. Four intervention studies highlighted the potential benefits of peer support, such as improved physical symptoms. Two studies, one interventional and one cross-sectional, highlighted the need for more empirically based peer support interventions in the HSCT population. Among patients with hematologic malignancies and/or HSCT recipients, there is a dearth of literature examining the association between peer support and outcomes, although few studies have described a positive association between peer support and better health outcomes. More randomized controlled studies are needed to better understand the role of peer support and peer support interventions on outcomes in these vulnerable populations.

192 - Xylitol in the Pediatric Hematopoietic Stem Cell Transplant Population: Quality Initiative to Decrease Bloodstream Infections

192 - Xylitol in the Pediatric Hematopoietic Stem Cell Transplant Population: Quality Initiative to Decrease Bloodstream Infections

Multiple Breath Washout Testing to Identify Pulmonary Chronic Graft Versus Host Disease in Children After Hematopoietic Stem Cell Transplantation

Pulmonary chronic graft versus host disease (p‐cGvHD) is a highly morbid, late complication of hematopoietic stem cell transplantation (HSCT). The 2014 National Institutes of Health cGvHD consensus criteria require a tissue biopsy or a drop in spirometry (with other features) to establish the diagnosis of p‐cGvHD. Unfortunately, children are often incapable of performing spirometry, which can delay the diagnosis of this condition. Multiple breath washout testing (MBW) can detect abnormal pulmonary physiology in older children and adults after HSCT, but its feasibility and utility have not been assessed in younger children and in those who cannot perform spirometry. In this study, we assess the feasibility and sensitivity of MBW to detect p‐cGvHD in children as young as 3 years of age after HSCT. We performed a cross-sectional analysis of children age 3 to 18 years, between 100 days and 5 years after allogenic HSCT. Participants were recruited from the HSCT population at BC Children's Hospital (Vancouver, Canada). All participants attempted nitrogen MBW, and children age 6 years and over attempted spirometry. Nonparametric statistical techniques were used; descriptive statistics used median (interquartile range [IQR]) and group medians were compared using Wilcoxon rank‐sum test. Twenty‐six children, median age 11.0 (range 3.6‐18.5) years, were recruited a median of 26.4 (IQR 15.7, 51.8) months after HSCT. Six of the 26 children (23%) had a clinical diagnosis of p‐cGvHD. MBW was successful in all (26/26, 100%) participants. The lung clearance index (LCI; the primary outcome of MBW) was higher in those with a history of p‐cGvHD (median 11.8 [IQR 9.6, 18.7]) than in those with no history of cGvHD (median 7.7 [IQR 7.1, 8.0]; P = .001) or a history of extrapulmonary cGvHD (median 7.5 [IQR 6.9, 7.6], P = .007). A threshold LCI = 9 resulted in a sensitivity of 100% and specificity of 90% for the correct identification of clinically diagnosed p‐cGvHD using MBW (area under the receiver operator characteristic curve is 0.97 [95% confidence interval 0.80, 0.99]). Spirometry was successful in most (17/26, 65%) participants. Similar to LCI, forced expiratory volume in 1 second (FEV1)/ forced vital capacity could distinguish between p‐cGvHD and no cGvHD (P = .02) and extrapulmonary cGvHD (P = .01). FEV1 alone could not distinguish between either of these groups (P = .87, P = .24 respectively). MBW is feasible in young children after HSCT and in those who cannot perform spirometry. LCI has high discriminative power for correctly identifying p‐cGvHD, but these preliminary results require confirmation in a larger validation cohort.

Caregivers' Experience of Medication Adherence Barriers during Pediatric Hematopoietic Stem Cell Transplant: A Qualitative Study.

Medications are critical for reducing morbidity and mortality risk in pediatric hematopoietic stem cell transplant (HCT). Nonetheless, medication adherence is suboptimal in this population. Identifying and managing barriers to medication management (i.e., medication barriers) is a key component of supporting medication adherence. However, understanding how medication barriers uniquely impact the pediatric HCT population and which barriers characterize each treatment stage remain unclear. Therefore, this study examined caregiver-perceived medication barriers over the course of pediatric HCT. Semi-structured qualitative interviews and demographic questionnaires were completed by 29 caregivers of children (≤12 years) who had received an HCT in the past 24 months and were either still admitted to, or had been discharged from, the hospital. Grounded methodology revealed 21 qualitative themes grouped into 6 hierarchical categories. Findings reflected barriers to be present across HCT treatment but to differ based on treatment stage with only child medication refusal being a consistent barrier across all stages. Barriers were particularly prevalent after hospital discharge post-HCT when caregivers assumed full responsibility for medication management. In addition, families approaching hospital discharge often lacked insight about these post-discharge barriers such that they did not report anticipating the range of barriers described by caregivers who had already been discharged from the hospital and taken on full responsibility for medication management. Findings support the benefit of medication barrier assessment across HCT treatment. These results suggest that families may benefit from intervention to address the specific barriers they experience around medication adherence especially during the post-HCT outpatient period.

Age Adjusted Comorbidity Risk Index Does Not Predict Outcomes in an Autologous Hematopoietic Stem Cell Transplant Population

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to prognosticate morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplantation. Recently, the HCT-CI was updated to include an age component (HCT-CI-age). Although other studies have validated this tool in allogeneic stem cell transplant recipients, it has never been studied in an autologous transplant patient population. We retrospectively reviewed 181 patients who underwent their first autologous hematopoietic stem cell transplant. We aimed (1) to assess whether an HCT-CI score of 3 or greater is associated with greater mean transplant hospital days, greater total hospital days, or greater risk of intensive care unit (ICU) utilization and (2) whether age influences any of these responses independent of HCT-CI. There were 136 patients with an HCT-CI score of 3 or higher and 45 with a score less than 3. The length of initial transplant hospitalization in days was not statistically significant (15.6 v 16.4 days, P = 0.38). Utilizing spline modeling prediction curves, transplant hospital days were estimated to increase from a mean of 15.5 days for a patient with 4 comorbidities to a mean of 22.7 days for a patient with 8 comorbidities. Age made no significant impact on any of the outcomes. The HCT-CI, with or without age, in an autologous stem cell transplantation did not predict length of hospitalization or utilization of the ICU. Patients with higher-HCT-CI scores at baseline may incrementally utilize more resources, and this should be explored in a larger cohort population.

Enterococcus Intestinal Domination is Associated with Increased Mortality in the Acute Leukemia Chemotherapy Population.

Enterococcus intestinal domination (EID), a state of dysbiosis wherein enterococci comprise ≥30% abundance within the microbiota, has been associated with Enterococcus bacteremia, graft-versus-host disease, and mortality in the allogeneic hematopoietic stem cell transplant (allo HCT) population. The acute leukemia (AL) chemotherapy population includes patients receiving intensive chemotherapy but do not all go on to have an allo HCT. The impact of EID on outcomes including mortality in the AL chemotherapy population is unknown. Microbiota composition from weekly stool samples was analyzed by 16S ribosomal RNA gene sequencing. Patients were analyzed in 2 cohorts: AL chemotherapy cohort and allo HCT cohort. Alpha-diversity and richness were calculated. Kaplan Meier Analysis was used to analyze mortality. 929 stool samples were collected from 139 patients. Both allo HCT and AL cohorts had a decline in α-diversity and richness over the course of treatment that tends not to return to baseline months later. EID was observed in at least one sample in 36% of allo HCT patients and 49% of AL patients. Patients with observed EID had lower alpha-diversity over time. Similar to the HCT cohort, AL patients with EID had reduced overall survival. We identified 4 other genera that were commonly found in ≥30% relative abundance within the microbiota, but none were associated with mortality. In fact, in allo HCT, Bacteroides abundance ≥30% was associated with improved survival. EID is associated with increased all-cause mortality in HCT and AL cohorts. UnlikeEID, relative abundance ≥30% by other genera is not associated with increased all-cause mortality.