Bone Marrow Transplant Patients Research Articles

IMPACTO DA MUCOSITE ORAL EM PACIENTES TRANSPLANTADOS DE MEDULA ÓSSEA AUTÓLOGO E O PAPEL DO CIRURGIÃO DENTISTA

The Haematopoietic Stem Cell Transplantation (HSCT) is a form of treatment used for some types of hematological cancers in which the patient is both a donor and recipient. The most relevant side effect of this therapy for dentistry is oral mucositis, which in addition to causing mucosal irritation, delay and interruption of the chemotherapy cycle, can be a gateway to opportunistic infections and lead to a death outcome. As a dental surgeon increasingly active in the multidisciplinary team, the importance of dental care in the trans-HSCT phase has been widely reported in the literature. Thus, the general objective of the present work was to carry out a literature review on the impacts of oral mucositis in autologous bone marrow transplant patients, as well as the specific objective of highlighting the importance of the dental surgeon in the care of these patients. Thus, for the design of the research, the descriptors Stomatitis, Hospital Dental Team, Hematopoietic Stem Cell Transplantation, Autologous Transplantation, through DeSC; PubMed, Scielo and Lilacs databases and the Boolean operators AND, OR and NOT were used as a search strategy in the time period from 2004 to 2022. Concluding that the impacts of oral mucositis in patients undergoing auto-HSCT are pathophysiological, of morbidity, mortality and financial loss. However, the presence of the dental surgeon in the multidisciplinary team brought clinical relevance to reduce the impacts caused by oral mucositis, acting, even in a preventive way, with qualitative and quantitative reduction of the condition.

Opportunistic Identification of Coronary Artery Calcium and Valve/Vascular Calcifications on Chest X-Ray: Improvements With Single-Exposure Dual-Energy Imaging.

Purpose: To evaluate whether single-exposure, dual-energy chest X-ray (DEX) improves visualization of coronary artery calcium (CAC) and valve/vascular calcifications compared to conventional X-ray. Materials and Methods: Sixty-one bone-marrow transplant patients (22- 79 years; median 61; IQR 15; w/m, 24/37), underwent single-exposure dual-energy X-ray (Reveal 35C, KA imaging) in pa and lateral projection, followed by a standard-of-care chest CT. Two DEX pairs (pa/lateral) were calculated: a composite image (COMP) and a bone image with soft-tissue subtraction (BI). The COMP pair was reviewed by 2 chest radiologists, assessing the presence/absence of CAC and valve/vascular calcifications on a confidence scale from -2 (confidently not present) to 2 (confidently present). Subsequently, the BI pair was revealed, and readers reevaluated both pairs (COMP and BI) jointly using the identical scale. CTCAC scores were categorized according to the CAC-DRS (0-3) and served as standard of reference, valve/vascular calcifications were categorized on CT as present or absent. Results: For detecting CAC on DEX in any CAC-DRS category (1-3), in category 2-3, in category 3, and for valve/vascular calcifications, the ROC-AUC (combined for both readers) for COMP images was 0.74 (CI: 0.64-0.84), 0.81 (CI: 0.68-0.94), 0.84 (CI: 0.69-0.98), and 0.90 (CI: 0.83-0.99), and for the BI images 0.91 (CI: 0.83-0.98), 0.94 (CI: 0.86- 1.00), 0.89 (CI: 0.77-1.00), and 0.98 (CI: 0.96-1.00), with P = .0003, P = .044, P = .42, and P = .55, respectively. The Intraclass-Correlation-Coefficient (ICC) for CAC on COMP/BI was 0.973/0.954, and for valve/vascular calcifications 0.971/0.965. Conclusion: Single-exposure, dual-energy acquisition improves diagnostic confidence for coronary artery calcium and valve/vascular calcification identification on chest X-rays.

Outcome of autologous bone marrow transplant in patients with relapsed and refractory diffuse large B-cell lymphoma in relation with prognostic factor: A single-center experience

Abstract: BACKGROUND Currently, about 50% of diffuse large B-cell lymphoma patients are relapsed following their complete response to first-line therapy. The treatment strategy for fit patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) has been done with salvage therapy with non-cross resistant combination chemo-immunotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). OBJECTIVES: The aim of study was to evaluate the outcome of ASCT for R/R DLBCL in relation to certain prognostic parameters. PATIENTS, MATERIALS AND METHODS: This is retrospective study, conducted from May 2014 to December 2022, at Hematology and BMT Center of Medical City Complex in Baghdad. Thirty-six patients with R/R DLBCL were investigated pre- and post-ASCT; the recorded data included patient disease status pre-transplant, early mortality rate, and type of response at day 100 post-transplant and, survival rate, relapsed rate, and mortality at the end of the study were documented accordingly. RESULTS: The mean age of DLBCL patients in this study was 41.3 (14–65) years, post-ASCT at day 100; there were 33 (91.6%), 2 (5.5%), and 1 (2.7%) patients in complete remission, relapsed progressive disease, and death, respectively, At 3-year posttransplant, the overall survival (OS) was 71%, whereas the event-free survival (EFS) was 59%. According to disease status pre-ASCT, the OS was 62%, 80%, and 66% with P = 0.7, whereas the EFS was 66%, 60%, and 50% with P = 0.5 for CR, UCR, and PR, respectively. CONCLUSION: Iraqi bone marrow transplant center data showed acceptable OS and EFS results in the treatment of R/R DLBCL patients in areas where there is no more option in terms of better OS and EFS but with insignificant relation to the available prognostic factor.

A study of pulmonary infectious and non-infectious complications in a pediatric hematopoietic stem cell transplantation (HSCT) center in Iran

Background: Pulmonary complications are important enough to notice in hematopoietic stem cell transplantation (HSCT). The patients undergoing HSCT might have infectious and non-infectious problems associated with morbidity and mortality. The pulmonary complications of HSCT are well-recognized in adults; however, studies on children are limited, especially in Iran. This study was done to evaluate the infectious and non-infectious pulmonary complications and the corresponding factors in children who underwent HSCT. Materials and Methods: This retrospective cohort study included the patients who underwent HSCT in Mofid Children’s Hospital in Tehran, Iran, during the years 2015 -2021. Overall, 144 medical files were evaluated, out of which 128 had undergone HSCT. The extracted data were about underlying diseases, age at transplant, sex, type of HSCT, donor type, cell source, conditioning regimen, graft versus host disease (GVHD) prophylaxis, infectious and non-infectious pulmonary complications, and associated factors. The data analysis was done by the SPSS software version 26. Chi-square, Fisher exact test and regression were also used for the analysis. Results: Infectious and non-infectious pulmonary complications were reported in 26 people (20.3%) and 11 people (8.6%), respectively. Positive coronavirus disease 2019 (COVID-19) PCR was detected only in two patients. Infectious complications were significantly lower in patients with neuroblastoma compared to other underlying diseases (2.7% vs. 27.5%, P = 0.002). These complications were significantly more frequent among those with other HSCT complications compared to those without such complications (34.6% vs. 16.7%, P=0.042). Non-infectious pulmonary complications were significantly higher in boys (13.5%) than in girls (1.9%) (P = 0.024). Conclusion: Due to the high rate of pulmonary infections in bone marrow transplant patients, clear differential diagnosis and diagnostic work are essential.

Respiratory viral infections in bone marrow transplant patients: insights from a tertiary care hospital in Rawalpindi, Pakistan.

To determine the incidence of respiratory viral infections in bone marrow transplant patients. The prospective, descriptive, cross-sectional study was conducted at a tertiary care hospital in Rawalpindi, Pakistan, from September 2019 to August 2020, and comprised respiratory specimens from recipients of haematopoietic stem cell transplant. The specimens were collected in viral transport medium, and were then taken to the Department of Virology. Multiplex polymerase chain reaction was performed on the specimens to ascertain the incidence and prevalence of respiratory viruses. Data was analysed using SPSS 24. Of the 85 subjects, 53(62.35%) were males and 32(37.65%) were females. The overall median age was 20.0 years (interquartile range: 11.0-32.0 years). Respiratory viral infections were detected in 31(36.4%) specimens. Among them, human rhinovirus was detected in 12(38.7%) cases, respiratory syncytial virus in 5(16.1%), influenza A/H3 in 4(13%), human parainfluenza virus-1 in 3(9.7%), adenovirus in 2(6.4%), human parainfluenza virus-3 in 1(3.2%), human parainfluenza virus-4 in 1(3.2%) and human metapneumovirus in 1(3.2%) case. There were 2(6.4%) cases of co-infection. More than one-third recipients of haematopoietic stem cell transplant were found to have respiratory viral infections, highlighting the importance of employing multiplex respiratory polymerase chain reaction in early diagnosis and treatment of such infections.

Oral And Dental Evaluation Of Bone Marrow Transplant Patients: A Retrospective Observational Study

This retrospective observational study aims to evaluate the oral and dental conditions of 100 bone marrow transplant (BMT) patients. The study assessed oral pathologies, including root canal treatments, extractions, squamous cell carcinoma cases, oral prophylaxis procedures, and restorations. The findings provide valuable insights into the oral health challenges faced by BMT patients, emphasizing the need for specialized dental care and preventive measures in this vulnerable population

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

RSL3 enhances ROS-mediated cell apoptosis of myelodysplastic syndrome cells through MYB/Bcl-2 signaling pathway

Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies and seriously threaten people’s health. Current therapies include bone marrow transplantation and several hypomethylating agents. However, many elderly patients cannot benefit from bone marrow transplantation and many patients develop drug resistance to hypomethylating agents, making it urgent to explore novel therapy. RSL3 can effectively induce ferroptosis in various tumors and combination of RSL3 and hypomethylating agents is promising to treat many tumors. However, its effect in MDS was unknown. In this study, we found that RSL3 inhibited MDS cell proliferation through inducing ROS-dependent apoptosis. RSL3 inhibited Bcl-2 expression and increased caspase 3 and PARP cleavage. RNA-seq analysis revealed that MYB may be a potential target of RSL3. Rescue experiments showed that overexpression of MYB can rescue MDS cell proliferation inhibition caused by RSL3. Cellular thermal shift assay showed that RSL3 binds to MYB to exert its function. Furthermore, RSL3 inhibited tumor growth and decreased MYB and Bcl-2 expression in vivo. More importantly, RSL3 decreased the viability of bone marrow mononuclear cells (BMMCs) isolated from MDS patients, and RSL3 had a synergistic effect with DAC in MDS cells. Our studies have uncovered RSL3 as a promising compound and MYB/Bcl-2 signaling pathway as a potential target for MDS treatment.

Radiation Biological Toximetry Using Circulating Cell-Free DNA (cfDNA) for Rapid Radiation/Nuclear Triage.

Optimal triage biodosimetry would include risk stratification within minutes, and it would provide useful triage despite heterogeneous dosimetry, cytokine therapy, mixed radiation quality, race, and age. For regulatory approval, the U.S. Food and Drug Administration (FDA) Biodosimetry Guidance requires suitability for purpose and a validated species-independent mechanism. Circulating cell-free DNA (cfDNA) concentration assays may provide such triage information. To test this hypothesis, cfDNA concentrations were measured in unprocessed monkey plasma using a branched DNA (bDNA) technique with a laboratory developed test. The cfDNA levels, along with hematopoietic parameters, were measured over a 7-day period in Rhesus macaques receiving total body radiation doses ranging from 1 to 6.5 Gy. Low-dose irradiation (0-2 Gy) was easily distinguished from high-dose whole-body exposures (5.5 and 6.5 Gy). Fold changes in cfDNA in the monkey model were comparable to those measured in a bone marrow transplant patient receiving a supralethal radiation dose, suggesting that the lethal threshold of cfDNA concentrations may be similar across species. Average cfDNA levels were 50 ± 40 ng/mL [±1 standard deviation (SD)] pre-irradiation, 120 ± 13 ng/mL at 1 Gy; 242 ± 71 ng/mL at 2 Gy; 607 ± 54 at 5.5 Gy; and 1585 ± 351 at 6.5 Gy (±1 SD). There was an exponential increase in cfDNA concentration with radiation dose. Comparison of the monkey model with the mouse model and the Guskova model, developed using Chernobyl responder data, further demonstrated correlation across species, supporting a similar mechanism of action. The test is available commercially in a Clinical Laboratory Improvement Amendments (CLIA) ready form in the U.S. and the European Union. The remaining challenges include developing methods for further simplification of specimen processing and assay evaluation, as well as more accurate calibration of the triage category with cfDNA concentration cutoffs.

Effect of pretransplantation serum activin A on outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is the preferred treatment for a number of life-threatening diseases, including acute leukemia and aplastic anemia. However, HSCT is frequently complicated by syndromes characterized by endothelial dysfunction, such as graft-versus-host disease (GVHD) or veno-occlusive disease. The transforming growth factor beta (TGF-beta) superfamily protein activin A is required for endothelial integrity and tissue repair. TGF is a tumor suppressor that induces apoptosis or autophagy, inhibits the cell cycle, and regulates cytokine and chemokine expression. Many mutations in genes encoding receptors and decreased expression of TGF pathway components have been observed in carcinoma. Activin A has been shown to play dual roles in cancer progression, depending on genetic and cellular context as well as tumor stage, exerting early tumor-suppressive and late prometastatic effects. Aims The goal of this study was to measure activin A levels before and after allogeneic HSCT and to correlate serum activin A with posttransplantation GVHD. Patients and methods Serum activin A was measured using an enzyme-linked immunosorbent assay in 30 preallogenic bone marrow transplant patients in comparison with 10 healthy controls recruited from the bone marrow transplantation unit at Ain Shams University Hospitals. Result The serum activin A level was higher in allogenic transplantation patients than in controls, with a statistically significant difference between patients and controls (P=0.001). Activin A was found to be associated with chronic GVHD (P=0.004 and 0.002, respectively). Conclusion Activin A levels are useful biomarkers for detecting GVHD from allogeneic bone marrow transplantation.

Genetic sex validation for sample tracking in next-generation sequencing clinical testing

ObjectiveData from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.ResultsPrecise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined.

Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (-0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

A dyadic analysis of financial toxicity and health-related quality of life among bone marrow transplant patients and their caregivers.

Relatively few dyad-based studies have evaluated the shared psychosocial and financial toxicity (FT) experiences of hematologic patients and their caregivers, especially those undergoing bone marrow transplantations (BMTs). This study evaluated the association of FT with health-related quality of life (QOL) among BMT patient-caregiver dyads. Survey and electronic health record data were collected between April 2021 and January 2022 from BMT patients and their caregivers pre- (T1) and post-intervention (T2). Thirty-four patient-caregiver dyads completed surveys; all dyads included a patient experiencing elevated T1 FT. The effect of the total FT score (i.e., the combination of psychological response, coping behaviors, and material conditions domain scores) on physical health, mental health, anxiety, depression and distress scores was evaluated using Actor-Partner Interdependence Modeling (APIM). Patients and caregivers who reported lower total FT scores had better physical and mental health, and lower anxiety, depressive symptoms, distress (APIM actor effects). None of the partner effects were significant in the APIM models. Other model findings indicated that compared with caregivers, patients had lower reported physical health; mental health scores were higher, on average, for all participants at the T2 compared with T1; and members of dyads whose caregiver took time off work reported better physical health and lower depressive symptoms and distress than those whose caregiver did not. Our study addresses a significant gap in dyad-based cancer FT studies; the findings underscore the need for additional research to help develop tailored dyad-level FT interventions for improving health-related QOL among BMT patients.

Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.

Monogenic causes of inflammatory bowel diseases (IBD) are increasingly being discovered. To date, much attention has been placed in those resulting from inborn errors of immunity. Therapeutic efforts have been largely focused on offering personalized immune modulation or curative bone marrow transplant for patients with IBD and underlying immune disorders. To date, less emphasis has been placed on monogenic causes of IBD that pertain to impairment of the intestinal epithelial barrier. Here, we provide a comprehensive review of monogenic causes of IBD that result in impaired intestinal epithelial barrier that are categorized into 6 important functions: (1) epithelial cell organization, (2) epithelial cell intrinsic functions, (3) epithelial cell apoptosis and necroptosis, (4) complement activation, (5) epithelial cell signaling, and (6) control of RNA degradation products. We illustrate how impairment of any of these categories can result in IBD. This work reviews the current understanding of the genes involved in maintaining the intestinal barrier, the inheritance patterns that result in dysfunction, features of IBD resulting from these disorders, and pertinent translational work in this field.

Multi-Parametric Whole Body MRI before and after Bone Marrow Transplantation in Patients with Multiple Myeloma

Multi-Parametric Whole Body MRI before and after Bone Marrow Transplantation in Patients with Multiple Myeloma

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

Analysis of Hospitalization Outcomes in Bone Marrow Transplant Patients with Graft-Versus-Host Disease: A Nationwide Study

Background: Graft-versus-host disease (GVHD) is a well-known complication in patients with bone marrow transplantation. There is a need for additional data on the in-patient outcomes of GVHD in patients who have undergone bone marrow transplantation. Our analysis aims to evaluate the outcomes of GVHD in hospitalized patients with bone marrow transplantation. Method: In this retrospective study, we utilized data from the National Inpatient Sample (NIS) database from 2016 to 2019. Using ICD-10 codes, we identified hospitalizations involving bone marrow transplantation and categorized them into two groups: those with GVHD and those without GVHD. To account for potential confounding variables, we considered a comprehensive set of factors, including age, sex, race, zip code-based income quartile, hospital region, hospital teaching status, hospital division, hospital bed size, insurance status, and the Charlson comorbidity index score. We performed univariable logistic regression analysis to calculate unadjusted odds ratios. Subsequently, we conducted a multivariable logistic regression analysis to account for potential confounding effects and calculated adjusted odds ratios.(see Figure), where the model included only variables that were found to be associated with the outcome of interest in the univariable regression analysis at a significance level of P &amp;lt; 0.2. Proportions were compared using the Fisher exact test for categorical variables, and continuous variables were compared using the Student t-test. All P-values were two-sided, and the significance level was set at P &amp;lt; 0.05, indicating statistical significance. Results: From 2016 to 2019, data were collected from 13,999 hospitalizations involving bone marrow transplants. Among these cases, 836 hospitalizations were linked to GVHD patients. A comparison of patient characteristics showed that individuals with GVHD had a mean age of 51.61 years, while those without GVHD had a slightly higher mean age of 55.55 years. There were slight variations in gender and race distributions between the two groups, with a higher percentage of males and whites observed in the GVHD group compared to the group without GVHD. The analysis of outcomes between the two groups revealed significant differences. Patients with GVHD experienced notably longer mean lengths of stay (41.40 days vs. 21.31 days, P = 0.000) and incurred higher mean total hospital charges ($824,058 vs. $335,765, P = 0.000). Furthermore, after adjusting for confounding factors, GVHD posed a substantial risk to patients undergoing bone marrow transplantation. The adjusted odds ratio (aOR) for mortality in those with GVHD was 7.20 (95% CI: 5.54 to 9.36, P = 0.000) compared to those without GVHD, indicating a considerably higher risk of death. The coefficient for the length of stay was 19.36 days (95% CI: 17.29 to 21.42), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889) in patients with GVHD compared to those without GVHD hospitalizations. Moreover, the presence of GVHD in patients was associated with elevated risks of various medical conditions. The adjusted odds ratios (aORs) for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in patients with GVHD were 2.79 (95% CI: 2.28 to 3.41, P = 0.000), 3.30 (95% CI: 2.57 to 4.24, P = 0.000), 5.10 (95% CI: 4.01 to 6.49, P = 0.000), 4.88 (95% CI: 3.75 to 6.34, P = 0.000), 1.45 (95% CI: 1.13 to 1.86, P = 0.003), and 3.57 (95% CI: 2.97 to 4.29, P = 0.000), respectively (see Figure). Conclusion: Patients with GVHD in patients with bone marrow transplantation experience higher mortality rates, extended hospital stays, and increased hospital charges. Additionally, they are at a significantly higher risk of developing severe medical conditions, including sepsis, pneumonia, acute respiratory failure, Clostridium difficile infection, and acute kidney injury (AKI). These findings highlight the importance of closely monitoring and effectively managing GVHD to enhance patient outcomes and alleviate the burden of complications associated with bone marrow transplantation. Nevertheless, further prospective studies are necessary to gain a deeper understanding and more comprehensive evaluation of the outcomes in these hospitalized patients.

1015. A multicenter evaluation of antimicrobial utilization in hospitalized bone marrow transplant (BMT) and T-cell therapy (CAR-T) patients, and the impact on rates of C. difficile infection (CDI)

Abstract Background Benchmarking antimicrobial utilization through the National Healthcare Safety Network (NHSN) will be a CMS requirement in 2024. NHSN benchmarking is available for some hospitalized populations, but there are currently no benchmarking capabilities for BMT units. Additionally, there are no published manuscripts describing antimicrobial utilization in BMT hospitals. Intra-Hospital BMT Antimicrobial Utilization Data from the Vizient Clinical Data Base used with permission of Vizient, Inc. All rights reserved. Methods This retrospective multicenter study was conducted by the Vizient Pharmacy Network AMS Committee. Antimicrobial utilization was evaluated for Vizient-member hospitals that treat at least 50 BMT patients per year. Vizient Clinical Database was used to identify patients via ICD10 codes for allogeneic transplant, autologous stem cell transplant and CAR-T therapy. Total antimicrobial days of therapy (DOTs) per 1,000 patient days was evaluated across all hospitals for each type of transplant, and for 9 different groups of antimicrobials (anti-pseudomonal beta-lactams, carbapenems, MDRO gram-negatives, fluoroquinolones, MRSA-active agents, antifungals, CMV-active agents, high-risk C. difficile agents, and C. difficile treatments). ANOVA was used to compare antimicrobial utilization across hospitals and across antimicrobial types. Results A total of 90 hospitals and 63,379 patient encounters were included in the analysis from 2018-2021. The median total antimicrobial utilization for allogeneic, autologous, and CAR-T patients were 2,562, 2,083, and 2,187 DOTs per 1,000 patient days, respectively. Figure 1 describes the variability in intra-hospital prescribing for 9 antimicrobial categories. Hospitals with higher antimicrobial utilization rates in allogenic transplant patients were associated with a higher incidence of CDI in this population (p=0.0368). Conclusion Significant variation in intra-hospital antimicrobial utilization exists for allogeneic transplant, autologous stem cell transplant, and CAR-T patients; and across 9 different categories of antimicrobials! Increasing rates of antimicrobial utilization were associated with increases in C. difficile infections in allogeneic transplants. Benchmarking antimicrobial utilization in BMT patients may help improve systematic approaches to minimize unnecessary antimicrobial exposure. Disclosures All Authors: No reported disclosures

Impact of a New Diagnostic Stewardship Team on Utilization and Interpretation of a Microbial Cell-Free DNA Detection Test

Abstract Background After commercial metagenomic next-generation sequencing of plasma microbial cell-free DNA (NGS-mcfDNA) became available at Children’s Healthcare of Atlanta (CHOA) in 2018 with an institutional requirement for Infectious Disease (ID) consultation and approval, we observed an initial period of test utilization without consistent ID involvement. Subsequently we assembled a Diagnostic Stewardship Team (DST) composed of a clinical microbiologist and 3 ID clinicians with expertise in diagnosis and management of infections in immunocompromised children and antimicrobial stewardship, to improve test utilization by clinicians and to optimally impact patient care. Methods We performed a retrospective medical record review as an IRB-deemed Quality Improvement project. NGS-mcfDNA results and their clinical impacts prior to the formation of the DST were assessed, using previously published standardized criteria as an initial framework (Hogan 2021)1. We shared our findings with Bone Marrow Transplant (BMT), Pediatric Intensive Care Unit (PICU), and ID clinicians, providing education on the potential benefits and limitations of NGS-mcfDNA testing. Stakeholder acceptability and engagement with the DST was prioritized, with emphasis on highlighting the benefits to clinicians of expertise in patient selection for testing and with interpretation of results which can be discordant with conventional microbiological tests. DST approval became required for all NGS-mcfDNA tests, with approval decision and discussion documented in the medical record, followed by documentation of test results, interpretation, and communications with treating and consulting clinicians. After one year of DST engagement, which began on June 1, 2021, we repeated our analysis of NGS-mcfDNA utilization and clinical impacts to evaluate the results of DST involvement. We classified time periods into pre-DST, February 28, 2018 - April 12, 2021, and post-DST, June 1, 2021 – May 31, 2022. Results The majority of NGS-mcfDNA tests sent in both the pre- and post-DST periods resulted in no or indeterminate clinical impact (65% pre-DST vs. 73% post-DST), while post-DST the percentage of positive clinical impacts increased (18% pre-DST vs. 25% post-DST), and the percentage of negative clinical impacts decreased (16% pre-DST vs. 2% post-DST), likely due to DST engagement. The number of tests per year increased by three-fold, while fewer patients had multiple NGS-mcfDNA tests sent. Awareness of the requirement for DST consultation and test approval lead to more selective NGS-mcfDNA test requests on the part of BMT clinicians, and the majority of positive clinical impacts from NGS-mcfDNA testing in BMT patients resulted from collaboration between BMT and ID in de-escalation of antimicrobials. An increased awareness of the potential benefits of NGS-mcfDNA testing for pre-treated and diagnostically challenging patients led to an increase in NGS-mcfDNA test requests from ID clinicians. Conclusion Implementation of a DST resulted in universal ID engagement with clinicians requesting NGS-mcfDNA tests and ID involvement in test interpretation. Discussion with experienced diagnostic stewards at the time of NGS-mcfDNA test consideration, with attention to the rationale for test request and consideration of potential test limitations prior to return of results, in addition to rigorous interpretation of results, can increase the positive clinical impacts and decrease the negative clinical impacts of NGS-mcfDNA tests. Reference 1. Hogan CA, Yang S, Garner OB, Green DA, Gomez CA, Dien Bard J, Pinsky BA, Banaei N. Clinical Impact of Metagenomic Next-Generation Sequencing of Plasma Cell-Free DNA for the Diagnosis of Infectious Diseases: A Multicenter Retrospective Cohort Study. Clin Infect Dis. 2021 Jan 27;72(2):239-245. doi: 10.1093/cid/ciaa035. PMID: 31942944. Characteristics of NGS-mcfDNA tests sent from CHOA NGS-mcfDNA tests in BMT patients post-DST (n=19 tests)

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and Aims Optimizing treatment for heart failure early after initiation of chemotherapy may prevent myocardial dysfunction. We hypothesized that early initiation of treatment with sacubitril/valsartan (sac/val) or enalapril (ena) may prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with normal LV ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF). Results The 3 treatment groups had similar age, sex, risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (-19.8±2.8 vs -19.3±4.1%, p=0.403 for sac/val, -20.3±2.8 vs -20.0±3.6%, p=0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (-20.9±2.1% vs -18.5±2.2, p=0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p=0.826 for sac/val, 58.8±5.4 vs 60.7±7.1%, p=0.419, for ena), while a borderline deterioration was noticed after treatment with placebo (60.6±5.4 vs 57.7±6.7%, p=0.045). Moreover, in the sacubitril/valsartan group, we noticed a significant reduction of left ventricular end diastolic and end-systolic volume [(102.3±26.9 vs 93.9±21.5 ml, p=0.042 and 44.5±15.4 vs 38.6±9.6ml, p=0.012), respectively]. At 6 months, we did not observe any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril (p&amp;gt;0.05). Conversely, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GWW was reduced (111.5±75.7 vs 86.4±43.1 mmHg%, p=0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p=0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p=0.045), GWE was also reduced (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GCW did not change at 6 months. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved LV ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.