allo-HSCT Recipients Research Articles

Role of letermovir therapeutic drug monitoring for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplantation recipients: a prospective study.

The role of therapeutic drug monitoring (TDM) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receiving letermovir has not yet been clarified. This study is to explore letermovir trough concentration (Cmin) correlation with its clinical efficacy and adverse events, and factors affecting its plasma concentrations. A prospective, non-interventional study was performed in allo-HSCT recipients receiving letermovir prophylaxis. Plasma concentrations were determined using high-performance liquid chromatography-tandem mass spectrometry. Data analysis was performed using logistic regression, linear regression, and classification and regression tree (CART) models. 701 trough concentrations from 71 recipients were included, uncovering pronounced intra- and inter-individual variability in letermovir Cmin. During 24-week follow-up, CMV infection incidence was 16.4%. A significant correlation was identified between letermovir Cmin and its clinical efficacy, and the CART model showed an increased risk of CMV infection when Cmin ≤ 2731 ng/mL. However, no clear correlation was found between Cmin and adverse events. Gastrointestinal graft-versus-host disease, cyclosporine Cmin, gender, and concomitant medications, including mycophenolate mofetil, ondansetron, caspofungin, and methylprednisolone, may impact letermovir Cmin. Additionally, coadministration with cyclosporine injection significantly decreased median letermovir Cmin compared with cyclosporine capsules (2311 vs. 3386 ng/mL). Moreover, with the extension of time post-transplant, trough concentrations of both cyclosporine and letermovir significantly decreased. TDM for letermovir may be beneficial in allo-HSCT recipients considering the variability in letermovir Cmin and its correlation with clinical efficacy. Moreover, drug interactions and the effects of changes in cyclosporine dosage forms or concentrations require careful monitoring for their effect on letermovir Cmin.

Narrative Review: Advancing Dysbiosis Treatment in Onco-Hematology with Microbiome-Based Therapeutic Approach

This review explores the complex relationship between gut dysbiosis and hematological malignancies, focusing on graft-versus-host disease (GvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We discuss how alterations in microbial diversity and composition can influence disease development, progression, and treatment outcomes in blood cancers. The mechanisms by which the gut microbiota impacts these conditions are examined, including modulation of immune responses, production of metabolites, and effects on intestinal barrier function. Recent advances in microbiome-based therapies for treating and preventing GvHD are highlighted, with emphasis on full ecosystem standardized donor-derived products. Overall, this review underscores the growing importance of microbiome research in hematology–oncology and its potential to complement existing treatments and improve outcomes for thousands of patients worldwide.

Biological markers of bronchiolitis obliterans syndrome in recipients of allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) or lung transplantation. Early diagnosis of BOS requires new approaches including the search for biological markers of pulmonary damage after allo-HSCT. The aim of this work is to review literary data on biological markers of BOS. Conclusion. Literary data on biomarkers of BOS in allo-HSCT recipients are limited. Further research is needed.

Immunogenicity of Comirnaty Omicron XBB.1.5 booster COVID-19 mRNA vaccine in long-term survivors after allogeneic hematopoietic stem cell transplantation

Primary mRNA vaccination against COVID-19 typically involves three doses for immunocompromised individuals, including hematopoietic stem cell transplantation (allo-HSCT) recipients. However, optimal subsequent boosting strategies remain unclear. This study aimed to assess the immunogenicity of a booster dose using the most recently updated vaccine (Comirnaty Omicron XBB.1.5) among long-term allo-HSCT survivors having previously received multiple mRNA vaccine doses, in median 4 (2–6). Thirty-four allo-HSCT recipients were enrolled at Sahlgrenska University Hospital, and peripheral blood samples were collected immediately before and four weeks after booster. Antibodies against the receptor-binding domain (anti-RBD) of spike 1 (S1) and nucleocapsid, as well as S1-specific ex vivo T-cell responses, were evaluated. Adverse events were monitored. Despite a median of 13 months since the prior vaccine dose, both humoral and T-cell responses against S1 were present in the pre-booster samples in all but two participants, who suffered from severe chronic Graft-versus-host disease. Notably, 62% of participants had a previously confirmed COVID-19 infection. Significantly higher pre-booster antibody levels were observed in women than men (p = 0.003). Booster dosing strengthened specific antibody and T cell responses and equalized pre-booster gender differences, although responses remained significantly lower among those receiving immunosuppressive treatment (p = 0.041). In a population of long-term allo-HSCT survivors, the majority of whom had a prior confirmed COVID-19 infection, both pre- and post-booster immune responses were robust. However, patients undergoing immunosuppressive treatment for GvHD exhibited significantly weaker responses.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells.

Aspergillus calidoustus and Talaromyces columbinus infections in chronic graft-versus-host disease.

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents.

Efficacy of Letermovir for Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant

In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs. Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26 - 75 years) and 55.5 years (range: 20 - 73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5 - 23.9%] vs 55.6% [95% CI: 41.2 - 67.8%], p < 0.0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the two groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6 - 24.9%] vs. 36.5% [95% CI: 23.6 - 49.5%], p=0.0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.

Clinical characteristics and risk stratification for late-onset herpes zoster following allogeneic hematopoietic stem cell transplantation

The incidence of herpes zoster (HZ) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is significantly higher than that of the general public. Although routine antiviral prophylaxis is recommended, late-onset HZ has been highlighted, yet limited information is known about its clinical features and predictors. Here, we conducted a retrospective nested case-control study to identify patients with late-onset HZ, defined as a diagnosis of HZ after 1 year of transplantation, among allo-HSCT recipients between 2012 and 2017 at Peking University People's Hospital. Three controls were matched for each patient. A total of 201 patients developed late-onset HZ. Age over 20 years, absence of neutrophil engraftment by 14 days, mental disorders, immunosuppressant use at 1 year, and a peripheral CD4+/CD8+ ratio ≥0.5 at 1 year were independent risk factors, among which the CD4+/CD8+ ratio demonstrated good discriminative power for predicting late-onset HZ. For patients with a CD4+/CD8+ ratio <0.5, patient age, neutrophil engraftment time, mental disorders, and immunosuppressant use were potential risk factors. A stratification algorithm was accordingly established, classifying the transplant recipients into three risk groups. Whether the algorithm could facilitate the administration of posttransplant antiviral prophylaxis merits further validation.

Risk factors for in-hospital mortality in recipients of allogeneic hematopoietic stem cell transplantation with acute respiratory distress syndrome: a retrospective study based on the 2023 new definition of acute respiratory distress syndrome

IntroductionARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively.MethodsFrom Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported.ResultsUnder the new definition, SOFA score (OR = 1.351, 95% CI: 1.146–1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972–0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164–3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961–0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313–40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072–1.265, P < 0.01) were independently associated with in-hospital mortality.ConclusionThese prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.

Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infections after Allogeneic Hematopoietic Stem Cell Transplantation

Early and accurate identification of pathogens in pulmonary infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critically important. The clinical usefulness of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary infections after allo-HSCT remains under discussion. This multicenter retrospective study was conducted to compare mNGS and conventional microbiological tests (CMTs) in identifying the pathogens of pulmonary infections in allo-HSCT recipients. One hundred forty allo-HSCT recipients with suspected pulmonary infections who underwent bronchoscopy were included. mNGS and CMTs performed on bronchoalveolar lavage fluid specimens showed 71.4% positivity on mNGS compared to 55.0% positivity on CMTs. mNGS identified 182 pathogens, including bacteria (n = 88), fungi (n = 35) and viruses (n = 59), compared to 106 pathogens detected by CMTs (bacteria, n = 31; fungi, n = 24; viruses, n = 51). Pulmonary infection was finally diagnosed in 98 patients, including 22 bacterial, 7 fungal, 18 viral, and 48 mixed infections and 3 infections with an unknown pathogen. Mixed infections were identified in 50.5% of the patients with pulmonary infection. The sensitivity of mNGS and CMTs for diagnosing pulmonary infections was 88.8% and 69.4%, respectively (P = .001), and the specificity were 81.0% and 85.7%, respectively (P = .688). Our findings suggest that mNGS may be a promising technology for diagnosing pulmonary infections in allo-HSCT recipients.

Incidence, clinical classification and risk factors of cyclosporin A-induced liver injury in allogeneic haematopoietic stem cell transplant recipients.

There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI. Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included. Patient information was collected to assess suspicious CILI by the Roussel Uclaf causality assessment method (RUCAM) scale. We evaluated the pattern and severity of CILI. The independent risk factors of CILI were identified by multivariable logistic regression. A total of 216 allogeneic HSCT (allo-HSCT) recipients were included in this study. The incidence of CILI was 15.3% (95% confidence interval [CI]: 10.4%-20.1%). Among these cases, 84.8% displayed a hepatocellular pattern, and 90.9% of CILI was of mild severity. Baseline alanine aminotransferase (ALT) level (OR = 1.030, 95% CI: 1.008-1.053, P = .008) and trough concentration level of CsA (OR = 1.007, 95% CI: 1.002-1.012, P = .009) were identified as independent risk factors for CILI. The incidence of CILI in allo-HSCT recipients is notably high. Recipients with elevated baseline ALT levels and higher exposure to CsA are more susceptible to developing CILI.

CD34 Chimerism Directed Donor Lymphocyte Infusion With or Without Azacitidine Results in Reduced Relapse and Superior Overall Survival When Full Donor Chimerism is Achieved in Allogeneic Stem Cell Transplant Recipients With Acute Myeloid Leukaemia/Myelodysplastic Syndrome

BackgroundRegular monitoring of CD34 donor chimerism (DC) is a highly sensitive method of predicting relapse in allogeneic stem cell transplant (alloHSCT) recipients with AML/MDS. A fall of CD34 DC below 80% is an indicator of ensuing relapse. There are limited studies assessing the efficacy of donor lymphocyte infusion (DLI) triggered by mixed CD34 DC (MDC), in addressing falling chimerism. Patients and methodsWe performed a retrospective analysis of consecutive alloHSCT patients between 2012 to 2023 who received DLI (with or without azacitidine) for CD34 MDC without morphologic relapse at the time of infusion. ResultsOf the 21 patients with follow up CD34 DC available, 14 (66.7%) achieved CD34 full donor chimerism (FDC) following DLI with or without azacitidine (dli-FDC), while 7 (33.3%) did not (dli-MDC). The 2-year cumulative incidence of relapse (CIR) was significantly lower in dli-FDC compared to dli-MDC (21.4% vs. 85.7%, P < 0.001), correlating with superior overall survival (OS; median years not reached vs. 0.67 years [95% CI, 0.58-ND], P < .001). Rates of grade II-IV acute GVHD post-DLI were 14.9%, and moderate-severe cGVHD was 42.8% in the dli-FDC group. The 5-year nonrelapse mortality (NRM) of the dli-FDC group was 7.1% following DLI. ConclusionOur study shows the restoration of CD34 FDC post-DLI is associated with reduced relapse and improved overall survival, with low NRM.

The impact of the donors' COVID-19 status on the outcomes of allogeneic hematopoietic stem cell transplantation: a multi-center retrospective study.

To explore the impact of donors' COVID-19 status on allogeneic stem cell transplantation (allo-HSCT), we compared the transplant outcomes of 74 participants. This multi-center retrospective study included nine participants receiving grafts from COVID-19 positive donors (CPD), 45 from COVID-19 experienced donors (CED), and 20 from COVID-19 naive donors (CND). We evaluated engraftment, complications, and survival rates among the three groups. All apheresis procedures were successful with no significant differences in CD34+ cells or lymphocytes in grafts among the three groups. All patients achieved engraftment by day 30 post-HSCT. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 55.6%, 20%, and 10% in the CPD, CED, and CND groups, respectively (p = 0.024). Multivariate analysis indicated that COVID-19 positivity in donors at the time of apheresis was an independent risk factor for II-IV aGVHD (p = 0.020, OR = 12.159, 95% CI 1.783 -135.760). No differences were observed among the groups in terms of chronic GVHD, viral infection, or sinusoidal obstruction syndrome. The 6-month overall survival and disease-free survival rates were also similar among the three groups. Our results suggest that the COVID-19-positive status of donors might not impact graft collection, engraftment, or short-term survival of allo-HSCT recipients but might increase the risk of aGVHD. Further research is needed to explore the influence of donors' COVID-19 status on long-term complications and survival in allo-HSCT recipients.

Fludarabine-induced bradycardia in allogeneic hematopoietic stem cell transplantation: A retrospective study.

Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.

Reactivation of cytomegalovirus and bloodstream infection and its impact on early survival after allogeneic haematopoietic stem cell transplantation: a multicentre retrospective study.

Cytomegalovirus reactivation (CMVr) and bloodstream infections (BSI) are the most common infectious complications in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Both are associated with great high morbidity whilst the BSI is the leading cause of mortality. This retrospective study evaluated the incidence of CMVr and BSI, identified associated risk factors, assessed their impact on survival in allo-HSCT recipients during the first 100 days after transplantation. The study comprised 500 allo-HSCT recipients who were CMV DNA-negative and CMV IgG-positive before allo-HSCT. Amongst them, 400 developed CMVr and 75 experienced BSI within 100 days after allo-HSCT. Multivariate regression revealed that graft failure and acute graft-versus-host disease were significant risk factors for poor prognosis, whereas CMVr or BSI alone were not. Amongst all 500 patients, 56 (14%) developed both CMVr and BSI in the 100 days after HSCT, showing significantly reduced 6-month overall survival (p = 0.003) and long-term survival (p = 0.002). Specifically, in the initial post-transplant phase (within 60 days), BSI significantly elevate mortality risk, However, patients who survive BSI during this critical period subsequently experience a lower mortality risk. Nevertheless, the presence of CMVr in patients with BSI considerably diminishes their long-term survival prospects. This study provides real-world data on the impact of CMVr and BSI following transplantation on survival, particularly in regions such as China, where the prevalence of CMV IgG-positivity is high. The findings underscore the necessity for devising and executing focused prevention and early management strategies for CMVr and BSI to enhance outcomes for allo-HSCT recipients.

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

Identifying risk factors for severe omicron infection in allogeneic hematopoietic stem cell transplant recipients with hematologic malignancies.

In December 2022, a large-scale epidemic occurred in China due to Omicron variant of SARS-CoV-2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS-CoV-2 Omicron infection among recipients of allo-HSCT. This single-center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1-65 years), with the male-to-female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non-Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p < .0001), cGVHD (p = .0195), concurrent bacterial infection (p < .0001), low absolute lymphocyte count (p = .026), low CD4/CD8 ratio (p = .0091), high CRP (p < .0001), high serum ferritin (p = .0023), high D-dimer (p < .0001), low CD4 absolute count (p = .0057), and low B-cell absolute count (p = .0154). A moderate to high HCT-CI score tended to be associated with moderate to severe infection (p = .0596). This study indicates that risk factors for severe Omicron infection include certain clinical characteristics, such as age, cGVHD, and inflammatory response.

Daily diary engagement among caregivers of patients undergoing hematopoietic stem cell transplant.

e23064 Background: Caregivers of allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients bear significant responsibilities involving commitment to be available 24/7 up to at least 100 days post-transplant to provide emotional and physical support to their patients. Caregiving for such an extended duration is associated with reduced quality of life, compromised psychological well-being, and dysregulated metabolic and immunological functioning. Ecological momentary assessment (EMA) may allow a better understanding of the dynamic day-to-day experiences of this unique population. However, no prior research on EMA exists in this population. This study reports on the feasibility of delivering EMAs in the form of a daily diary (DD) and how completion of the DD relates to the patient’s course of treatment and caregiver’s demographics among the caregivers of allo-HSCT caregivers. Results are part of an ongoing 3-arm randomized controlled trial (71% enrolled to date) of those individuals randomized to the usual care condition. Methods: Caregivers (n = 46) received DD prompts for 6 weeks during their patient’s active treatment phase: before transplant (week 1), transplant through discharge (weeks 2 and 3), after discharge (weeks 3 through 6). The DD included six affect items from the Positive and Negative Affect Schedule (stressed, overwhelmed, frustrated, drained, guilty, and hopeful), three state mindfulness items (attention, non-judgement, and decentering), and one item related to caregiver’s self-efficacy in patient care. Results: Among 46 caregivers (mean age = 55.8 [SD = 15.7], 74% female, 32% retired), the overall completion rate (CR = total number of prompts completed/total number of prompts received) was 65.5%, with 72% of participants completing &gt; 50% and 22% of participants completing &gt; 85% of the prompts. For the duration before transplant, the overall CR was 63.2%, with 66.7% of participants completing &gt; 50%, and 33.3% completing &gt; 85% of the prompts. For the duration between transplant through discharge, the overall CR was 65.57%, with 76% of participants completing &gt; 50%, and 26% completing &gt; 85% of the prompts. Similarly, for the duration after discharge, the overall CR was 65.14%, with 66.7% completing &gt; 50%, and 28.9% completing &gt; 85% of the prompts. DD completion was not related to the caregiver’s age, sex, or employment status ( ps &gt; 0.1). Conclusions: The completion rate for the DD was very similar across the patient’s course of treatment, suggesting EMA completion is not excessively burdensome for caregivers potentially experiencing dynamic distress. Furthermore, EMA completion was not associated with age, sex, or employment status, indicating that all caregivers, regardless of demographics, were amenable to completing EMAs. Our findings suggest that delivering EMAs is feasible in this population. Clinical trial information: NCT05078229 .

Alteration of Gut Microbiota Composition and Diversity in Acute and/or Chronic Graft-versus-Host Disease Following Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.

Changes in gut microbiome composition have been implicated in the pathogenesis of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our objective was to explore the microbial abundance in patients with GvHD after allo-HSCT. We conducted a single-center, prospective study in patients who underwent allo-HSCT and developed grade II or higher acute GvHD and/or moderate or severe chronic GvHD, to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected fecal specimens at -2 to +2 (T1), +11 to +17 (T2), +25 to +30 (T3), +90 (T4), and +180 (T5) days to assess changes in gut microbiota, with day 0 being the day of allo-HSCT. We included 20 allo-HSCT recipients in the study. Compared with timepoint T1, at timepoint T4 we found a significant decrease in the abundance of Proteobacteria phylum (14.22% at T1 vs. 4.07% at T4, p = 0.01) and Enterobacteriaceae family (13.3% at T1 vs. <0.05% at T4, p < 0.05), as well as a significant increase in Enterococcus species (0.1% at T1 vs. 12.8% at T4, p < 0.05) in patients who developed acute GvHD. Regarding patients who developed chronic GvHD after allo-HSCT, there was a significant reduction in the abundance of Eurobactereaceae family (1.32% at T1 vs. 0.53% at T4, p < 0.05) and Roseruria genus (3.97% at T1 vs. 0.09% at T4, p < 0.05) at T4 compared with T1. Alpha and beta diversity analyses did not reveal a difference in the abundance of bacteria at the genus level in GvHD patients at T4 compared with T1. Our study reinforces results from previous studies regarding changes in gut microbiota in patients with acute GvHD and provides new data regarding the gut microbiome changes in chronic GvHD. Future studies will need to incorporate clinical parameters in their analyses to establish their association with specific changes in gut microbiota in patients with GvHD after allo-HSCT.