Bone Marrow Transplant Patients Research Articles

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. Therefore, cfDNA concentration measurements are increasingly used in radiation oncology clinics to predict side effect risk. 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.

Association of Thrombocytopenia and C-reactive protein in COVID-19 Patients Attending a Tertiary Care Hospital

OBJECTIVE: This study evaluates the frequency and relationship between Thrombocytopenia and CRP levels in Covid-19 patients. METHODOLOGY: The cross-sectional retrospective study was conducted at Dr. Ishrat ul Ebad Khan's Institute of Blood Diseases from October 2021 to September 2022. Data was collected from existing data from the blood bank and hematology laboratory. C reactive protein (CRP) and complete blood count (CBC) levels were observed in Covid-19 patients. Both genders, all age groups, COVID-19 patients and patients having Thrombocytopenia and raised levels of CRP were included in this study. At the same time, other bone marrow transplant patients and other infectious diseases such as Hepatitis B, Hepatitis C, Dengue, and Malaria were excluded from this study. Statistical analysis was done by using the SPSS 20.0 version. RESULTS: Out of 844 patients, the mean age was 50 years, and the male proportion was high at 70% (n=590). Most patients, 95% (n=803) had grade 1 thrombocytopenia. The mean age was found to be higher (&gt;50 years) in Grades 1 and 2 as compared to Grades 3 and 4, where we found (&lt;40 years). A significant (p=0.002) mean age difference among grades was found. No significant (p=0.749) median difference in CRP among Grades were found. CONCLUSION: The current study shows that COVID-19 significantly increases C-reactive protein levels. While treating and managing the patients of COVID-19, it is essential to detect the biomarkers that can predict the severity and prognosis of this disease. KEYWORDS: Thrombocytopenia, Bleeding, C-reactive Protein, COVID-19

Oncology Care at Home: A Patient-Centered Approach to Managing Care for Bone Marrow Transplant and CAR-T Cell Therapy Patients

Introduction. More than half of patients with cancer who receive cytotoxic chemotherapy and/or immunotherapies experience deleterious side effects such as febrile neutropenia, infection, neurotoxicity, and cytokine release syndrome. Early intervention and treatment for these side effects can help avoid complications and improve outcomes, but delays in treatment administration are common as most outpatient management approaches depend on patient self-assessment and patient-initiated pursuit of follow-up care. Remote patient monitoring through digital health technologies offers the opportunity to bridge this gap without imposing undue burden on either patients or healthcare providers. This feasibility study assessed the results of a technology-assisted in-home oncology care program to remotely monitor bone marrow transplant and CAR T-cell therapy patients and provide early intervention for symptomatic episodes needing clinical management. The program also offered support for patients to obtain routine lab draws, hydration, antiemetics, intravenous antibiotics, and a provider assessment at home. Technical and operational feasibility were evaluated together with perceived user experience among patients, caregivers, and providers. Methods. Ten patients between 18-89 years old participated in the study for up to 90 days following allogeneic bone marrow transplant and up to 30 days following CAR T-cell therapy or autologous bone marrow transplant. Patients used continuous-wear biometric sensors for passive vital sign monitoring around the clock seven days per week and engaged with a chatbot by SMS text for health status checks and symptom reporting. Scheduled home care was administered by licensed home health providers. Virtual care center personnel evaluated patient status based on wearable data and patient messaging and followed up directly with patients or engaged patients' treating clinicians for notification and management of urgent issues as needed. Patients and caregivers were asked to complete surveys about their experience with and perceptions of the program at midpoint and study completion, while providers were asked to complete end-of-study surveys to capture their perspectives across all patients. Patients were also asked to participate in brief interviews at study midpoint and at the end of the study. Interim Results. Eighty percent of patients participated in the program as intended through wearing devices and responding to engagement prompts. Wearable sensors detected a total of 184 outpatient alerts from patients between April and July 2023, of which 57 led to follow up with patients, 12 required further follow up with the clinical care team, and 5 required follow up care in a clinical setting due to elevated temperature or respiratory rate. Sixty percent of patients responded more than 50% of the time to requested health assessment surveys. Patient engagement with the chatbot and symptom reporting system led to 48 events needing virtual care team follow up, of which 20 were to answer patient questions and 28 were in response to reports of concerning symptoms. A total of 11 events were further referred by the virtual care team to the clinical care team, of which 5 required follow up care in a clinical setting. Study data collection will complete in August 2023. Initial Conclusions. Technology-assisted remote patient monitoring is feasible for use with bone marrow transplant and CAR T-cell therapy patients at home. Successful integration with clinical practice settings requires tailoring to existing workflows. Further assessment of patient acceptance for short-term versus long-term monitoring is recommended.

Efficacy of Sinopharm Vaccine Among Stem Cell Transplant Recipients During Two Peaks of Delta and Omicron variants of COVID-19.

Considering the dearth of research on the complications of Sinopharm coronavirus disease 2019 (COVID-19) vaccine in immunocompromised individuals and the lack of available data on COVID-19 vaccination from Iran. This study aimed to investigate the efficacy of vaccine of Sinopharm COVID-19 vaccine and its complications in bone marrow transplant (BMT) recipients. This was a retrospective cross-sectional study conducted on 250 patients with BMT who were referred to Montaserieh Hospital, Mashhad, Iran. Among them, 53 cases who received at least two doses of Sinopharm COVID-19 vaccine from March to January 2021 were entered in this study. The data were extracted from a student dissertation (Code:4000370). Sinopharm vaccine side effects were reported only in 7.7% of the patients, and shingles was the only serious side effect of the Sinopharm vaccine, which was observed only in one case. The results also revealed that Sinopharm COVID-19 vaccine side effects were not related to age or gender. Infection with the Delta variant of COVID-19 was reported in 7.5% (n=4) and no mortality was reported among them. Vaccine failure was reported in 39.6% of the cases; however, no mortality was reported among patients infected with the Omicron variant of COVID-19. In summary, it seems that Sinopharm COVID-19 vaccine adverse effects were not serious among stem cell transplant recipients. However, it may lead to some severe complications in the population. Vaccine failure against the Delta and Omicron variants of COVID-19 has been reported among more than one-third of BMT patients; however, no mortality was observed among BMT patients infected with the new variants of COVID-19.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005–2013)

Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

Cytokine release syndrome after bronchoalveolar lavage

BackgroundImmunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population.Case presentationWe report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient’s clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient.ConclusionThe patient’s clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.

Assignment of the antibacterial potential of Ag2O/ZnO nanocomposite against MDR bacteria Proteus mirabilis and Salmonella typhi isolated from bone marrow transplant patients

The rate of infectious diseases started to be one of the major mortality agents in the healthcare sector. Exposed to increased bacterial infection by antibiotic-resistant bacteria became one of the complications that occurred for bone marrow transplant patients. Nanotechnology may provide clinicians and patients with the key to overcoming multidrug-resistant bacteria. Therefore, this study was conducted to clarify the prevalence of MDR bacteria in bone marrow transplant recipients and the use of Ag2O/ZnO nanocomposites to treat participants of diarrhea brought on by MDR bacteria following bone marrow transplantation (BMT). Present results show that pathogenic bacteria were present in 100 of 195 stool samples from individuals who had diarrhea. Phenotypic, biochemical, and molecular analysis clarify that Proteus mirabilis and Salmonella typhi were detected in 21 and 25 samples, respectively. Successful synthesis of Ag2O/ZnO nanocomposites with a particle enables to inhibition of both pathogens. The maximum inhibitory impact was seen on Salmonella typhi. At low doses (10−5 g/l), it prevented the growth by 53.4%, while at higher concentrations (10−1 g/l), Salmonella typhi was inhibited by 95.5%. Regarding Proteus mirabilis, at (10−5 g/l) Ag2O/ZnO, it was inhabited by 78.7%, but at higher concentrations (10−1 g/l), it was inhibited the growth by 94.6%. Ag2O/ZnO nanocomposite was therefore found to be the most effective therapy for MDR-isolated bacteria and offered promise for the treatment of MDR bacterial infections that cause diarrhea.