Hematopoietic Stem Cell Research Articles

Single-cell RNA-seq analysis revealed the stemness of a specific cluster of B cells in acute lymphoblastic leukemia progression.

Childhood acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The heterogeneous characterization of B cells in ALL progression poses new challenges to researchers. We used single-cell sequencing to explore the critical role of B cells in regulating the ALL immune microenvironment. We collected the single cell (sc) RNA-seq data of ALL and health sample from the gene expression omnibus (GEO) database, the "Seurat" and "harmony" R package was used for quality control and scRNA-seq analysis, in which the CellMarker2.0 database was used for cell type annotation. Subsequently, the FindAllMarkers function was used to identify the differentially expressed genes (DEGs) among various cell types and the DAVID database was applied for the biological process of DEGs. Then, the "inferCNV" package was used for copy number variation, regulons and cell communication were performed by SCENIC tool and CellChat package. The role of the target gene in regulating ALL progression was assessed using RT-qPCR, Transwell and scratch healing assays. We identified nine mainly cell clusters after scRNA-seq analysis, in which the B cells had higher infiltration proportion in the ALL samples and were sub-clustered into five cell sub-groups. The B cells 1 is closely associated with cell proliferation and stemness (TNFAIP3 and KDM5B), and the significant CNV of amplification occurred on chr6 and chr21 that supported stemness of B cells1. RXRB is a key transcription factor mediated the proliferation of B cells 1, which in turn suppressed hematopoietic stem cells (HSCs) proliferation and promoted cytotoxic NK/T cells activation through diverse cell communication ways. One of the key regulators of B cells is MYC, which promotes the migration and invasive ability of cell line leukemia cell lines. This study reveals the stemness characteristics of B cells and their critical role in ALL progression, a finding that provides new potential directions for the development of targeted therapies against ALL.

Maternal NO2 exposure and fetal growth restriction: Hypoxia transmission and lncRNAs-proinflammation-mediated abnormal hematopoiesis

Epidemiological studies show a strong correlation between air pollution and fetal growth restriction (FGR), but existing results are controversial due to inherent limitations, such as causality of specific pollutants, developmental origin, and maternal-fetal transmission. To address this controversy, we first conducted a retrospective analysis of 28,796 newborns and revealed that maternal nitrogen dioxide (NO2) exposure during the second trimester was positively associated with FGR, with an adjusted odds ratio of 1.075 (95% confidence interval: 1.020-1.133) per 10 μg/m3 NO2 increase for small for gestational age. Then, by establishing an animal model of prenatal NO2 exposure, we confirmed its adverse effects on embryonic growth and hematopoiesis in the yolk sac and fetal liver, primarily affecting the differentiation of hematopoietic stem and progenitor cells and erythroid maturation. By applying internal exposure analyses coupled with 15N isotope tracing, we found that maternal NO2 inhalation induced acquired methemoglobinemia through its byproducts and placental hypoxia in pregnant mice. Importantly, by combining transcriptional profiling, bioinformatics analysis, and RNA binding protein immunoprecipitation (RIP)/chromatin immunoprecipitation (CHIP), we clarified that placental-fetal hypoxia transmission activated hypoxia-inducible factors, disturbed hematopoiesis through the hypoxia-inducible factor 1β-long noncoding RNAs-CCAAT/enhancer binding protein alpha-proinflammatory signaling pathway, ultimately contributing to FGR progression. These findings provide insights for risk prevention and clinical intervention to promote child well-being in NO2-polluted areas.

Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis

ObjectivesB-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify...

Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset.

Acute graft-versus-host disease (aGVHD) represents the rejection of the recipient's skin, gut, and liver tissues of an allogeneic hematopoietic stem cell transplantation (HSCT) by the donor T-cells. The onset of aGVHD is often rapid and its evolution is unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected before aGVHD clinical onset in three patients and from one patient afterward. We used four HSCT recipients who remained free of aGVHD as controls. This analysis unveiled the presence of particular subpopulations of circulating monocytes and cytotoxic T cells (CTLs) in pre-aGVHD samples up to 18 days before clinical disease. These pre-aGVHD monocytes were characterized by an upregulation of the M2 polarity marker CD163 and the transmembrane protein SIGLEC1/CD169. At the same time, their CTL counterparts stood out for the upregulation of the CXCL10 receptor CXCR3 and the antigenic stimulation marker CD70. The occurrence of CD163/SIGLEC1 co-expressing monocytes upstream of aGVHD onset was validated using transcriptomic data from an independent cohort and by flow cytometry in additional blood samples. These findings point to potential early diagnostic tools and preventive therapeutic strategies for aGVHD.

Multidisciplinary Management of Morbidities Associated with Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor. While the mainstay of treatment has remained systemic immunosuppression with glucocorticoids, progress has been made within the last few years with approvals of three oral agents to treat steroid-refractory cGVHD: ibrutinib, ruxolitinib, and belumosudil. Iatrogenesis contributes a significant portion of the morbidity experienced by patients with cGVHD, primarily from glucocorticoids. This review highlights the myriad impacts of cGVHD, including and beyond the traditional organ systems captured by the National Institutes of Health Consensus Criteria, including iatrogenic complications of long-term immunosuppression. It presents the implications of cGVHD and its treatment on cardiovascular and metabolic health, bone density, endocrine function, sexual health, and ocular and pulmonary disease and outlines a framework around the comprehensive multidisciplinary approach for its evaluation and management.

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.

MG4101, an allogeneic natural killer cell, in patients with relapsed or refractory acute myeloid leukemia: a pilot study

We evaluated the safety and efficacy of allogeneic, ex-vivo expanded, NK cells, MG4101, in patients with refractory or relapsed AML. The relationship between immunological characteristics and clinical responses was analyzed. Between April 2018 and February 2020, 11 patients (male:female = 5:6) were treated with MG4101. Of eight evaluable patients, two (25.0%) showed partial response and two (25.0%) showed stable disease. The median overall survival was 3.4 months (95% confidence interval [95% CI], 2.5–4.3 months), and the allogeneic hematopoietic stem cell transplantation (HSCT) censored duration of response was 2.9 months (95% CI, 1.5–4.4 months). Two patients underwent HSCT after MG4101 treatment. Except for one grade 3 infusion-related reaction, no serious adverse events were observed. The sum of activating KIRs in responders tended to be higher than that in non-responders. Analyses of NKRL and KIR highlighted the importance of immunological mechanisms in treating myeloid neoplasms.

Clinical features and long-term prognostic analysis of relapsed pediatric acute lymphoblastic leukemia

Objective: To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse (HR=3.91, 95%CI 1.96-7.79; HR=4.15, 95%CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (HR=6.50, 95%CI 2.58-16.34; HR=5.19, 95%CI 1.78-15.16), with ETV6::RUNX1 (HR=0.23, 95%CI 0.07-0.74) and HSCT after relapse (HR=0.24, 95%CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions: Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

Hyperbaric oxygen therapy in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Introduction: Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by inflammation and bleeding of the bladder. Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of radiation-induced HC. However, the optimal treatment for HC after allogeneic HSCT has not yet been established. Furthermore, limited research has been conducted on the use of HBOT in this setting. This study aimed to evaluate the effectiveness and safety of HBOT in patients with late-onset HC after allogeneic HSCT. Methods: Twenty-five-year (1998–2022) retrospective analysis performed in all consecutive patients with confirmed late-onset HC after allogeneic HSCT treated with HBOT at two centers in Portugal. Medical records were reviewed for clinical and laboratory features, primary indications for allogeneic HSCT, conditioning regimen, and treatment strategies for HC. Patients received 100% oxygen at 2.1–2.5 atmosphere absolute pressure (ATA) for 70–90-minute periods, once daily, five times per week. Complete clinical response was defined as the absence of macroscopic hematuria sustained for at least 2 weeks, and partial response was described as a downgrading in the severity of HC. Statistical significance was considered for values of p < 0.05. Results: The sample included 61 patients with a mean age of 28.0 (SD 14.2) years, 33 males. Complete response was achieved in 72.1% (n = 44) of patients and partial response in 14.8% (n = 9). Concerning patients with a complete response, the median number of HBOT sessions was 15.5 sessions (IQR 10.0-26.8). Patients treated with 10 or more sessions of HBOT had a higher rate of complete or partial response (OR 12.5, 95%CI 1.9–83.2, p-value < 0.05). There was no response in 8 (13.1%) patients, and 6 interrupted the treatments early. Only 2 patients suspended the HBOT due to a lack of clinical benefit. Conclusion: Our study supports using of HBOT as an adjunctive treatment for late-onset HC after allogeneic HSCT. Furthermore, 10 or more HBOT sessions delivered seem to impact the rate of HC resolution. Prospective, randomized, and well-controlled trials are needed to establish HBOT’s definitive efficacy and safety.

Systemic sclerosis-associated interstitial lung disease: How to manage in 2024?

Systemic sclerosis (SSc) or scleroderma is an autoimmune disease characterized by immune dysregulation which leads to progressive fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is present in approximately 65% of patients with SSc and it accounts for approximately 40% of all SSc deaths. Risk factors associated with the development of systemic sclerosis related interstitial lung disease (SSc-ILD) include male sex, African heritage, high modified Rodnan skin score (mRSS), presence of anti-Scl-70/Topoisomerase I antibodies, and nucleolar pattern on antinuclear antibody (ANA). The primary tool to diagnose ILD in patients with SSc is high-resolution computed tomography (HRCT). Full pulmonary function tests (PFTs) with diffusing capacity of the lungs for carbon monoxide (DLco) and ambulatory desaturation testing should be obtained following the diagnosis of SSc-ILD for disease monitoring. The purpose of this review is to provide an updated guide for the management of SSc-ILD. Our proposed first line treatment for SSc-ILD is immunosuppressive therapy such as mycophenolate mofetil, tocilizumab, and rituximab which are discussed in depth, and we present the evidence-based data that has justified the use of these pharmacotherapies. Other immunosuppressive treatments are also reviewed, and we discuss the role of antifibrotic therapy. Finally, we dive into other avenues of treatments such as chimeric antigen receptor (CAR)-T cell therapy and hematopoietic stem cell transplant.

Scientometrics Analysis of Global Researches on Anemia

Background: Anemia is a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal. This study aims to show the intellectual structure of knowledge regarding anemia and gives a comprehensive and up-to-date image of research in this area. Materials and Methods: This is a descriptive-analytical study with a scientometric approach. The PubMed database was searched for research publications indexed under "anemia" including 8484 records between 2011 and 2020. Data were analyzed using Co-word analysis, clustering methods, and strategic diagrams with the help of SPSS and Ucinet 6 software. Results: The keyword “Anemia Sickle Cell” and two pairs of frequently used keywords, namely “Anemia, Iron *Iron” were the most frequent in the research area. The results shaped the concepts of anemia in 9 clusters. The clusters "Hydroxyurea and sickle cell anemia", "Fetus transfusion", "Management of Thalassemia Major", "Hemolytic Uremic Syndrome", "Management and Control of Anemia", "Chronic Kidney Failure and Anemia", "Hematopoietic Stem Cell Transplantation" are topics that may be emerging or disappearing. The “Thalassemia and blood transfusion" are immature clusters. Conclusion: This study uses co-word networks that indicate important links between keywords of the research areas. Most research approaches are in the therapeutic aspects. Despite the importance of the effect of anemia on all levels of society, including economics, education, and other types of anemia, as well as its impact on learning and mental disorders, these subjects have not been given sufficient consideration.

Microbial metabolomics in acute myeloid leukemia: From pathogenesis to treatment.

Acute myeloid leukemia (AML), the most common leukemia in adults, is a biologically heterogeneous disease arising from clonally proliferating hematopoietic stem cells. Increased appreciation of novel genetic methods has improved the understanding of AML biology. Recently, the emerging field of metabolomics has indicated qualitative and quantitative alterations in metabolic profiles in AML pathogenesis, progression and treatment. Multiple metabolic and molecular pathways regulate human metabolism and host-microbiome interactions may significantly affect this biochemical machinery. Microbiota have been found to play a significant role in hematopoietic function, metabolism and immunity, contributing to AML occurrence. A large number of studies have highlighted the importance of the composition and diversity of the gut microbiota (GM) in response to treatment and prognosis in AML. Moreover, strong evidence emphasizes the detrimental link between dysbiosis and infectious complications, a leading cause of morbidity and mortality for patients with AML. Several microbiota-related mechanisms have been linked to particular changes in host physiology so far, and microbial-derived metabolites belong to one of the most important. Circulating in the body, they modulate human conditions both locally and systemically. The extensive and diverse repertoire of bacterial metabolic functions plays a critical role in numerous processes, including leukemogenesis. Integrative analysis of microbiome and metabolome data is a promising avenue for better understanding the complex relationship between the microbiota, biochemical alterations and AML pathogenesis to effectively prevent, treat and mitigate its outcomes. This review concentrates on the pathologic roles and therapeutic implications of microbe-derived metabolites in AML settings.

Stem cell research and improving cancer treatments

Stem cell research has emerged as a pivotal area in oncology, offering innovative approaches to cancer treatment. This research explores the potential of stem cells to enhance therapeutic outcomes in various cancer types. To evaluate the role of stem cells in cancer treatment, focusing on their ability to differentiate into specialized cell types, promote tissue regeneration, and deliver targeted therapies. A comprehensive review of current literature was conducted, analyzing studies that investigate the application of stem cells in hematological malignancies and solid tumors. Key methodologies included in vitro experiments, animal models, and clinical trials assessing stem cell therapies, including hematopoietic stem cell transplantation and mesenchymal stem cell-based therapies. Findings indicate that stem cells can improve treatment efficacy by facilitating tumor regression, enhancing immune responses, and reducing treatment-related toxicity. Notably, mesenchymal stem cells have shown promise in delivering therapeutic agents directly to tumors and modulating the tumor microenvironment. Stem cell research holds significant potential to revolutionize cancer treatment strategies. Continued exploration of stem cell applications may lead to more effective, personalized therapies, ultimately improving patient outcomes in various cancer types. Further clinical trials are necessary to establish standardized protocols and assess long term effects.

Maintenance therapy promotes profound organ and haematologic response in light-chain amyloidosis patients not undergoing autologous stem cell transplantation

Background Evidence on maintenance therapy following frontline induction is sparse in primary light-chain amyloidosis (AL), especially for those who do not undergo autologous haematopoietic stem cell transplantation (ASCT). Methods We enrolled primary AL patients who achieved at least haematologic very good partial response (VGPR) by the 4th month at the frontline from December 2008 to June 2023 at Zhongshan Hospital, Fudan University. Those who followed maintenance therapy were identified as the maintenance group (n = 44), whereas those entering the observational phase were classified as the observational group (n = 24). Results After 7.2(interquartile range, 4.7–18.6) months of maintenance therapy, 9(20.5%), 14(31.8%) and 5 (11.4%) patients achieved improvement in haematologic, cardiac and renal response respectively. Five (11.4%) patients had minimal residual disease (MRD) response conversion from positive to negative based on maintenance therapy. In the observation group, none of the patients had haematologic response improvement, with 3(12.5%) and 1(4.2%) patient showing cardiac and renal response improvement during follow-up. Conclusion This study identified the clinical benefits of maintenance therapy in patients with AL who did not undergo ASCT in real-world practice.

Therapy-Related Myeloid Neoplasms: Complex Interactions among Cytotoxic Therapies, Genetic Factors, and Aberrant Microenvironment.

Therapy-related myeloid neoplasm (t-MN), characterized by its association with prior exposure to cytotoxic therapy, remains poorly understood and is a major impediment to long-term survival even in the era of novel targeted therapies due to its aggressive nature and treatment resistance. Previously, cytotoxic therapy-induced genomic changes in hematopoietic stem cells were considered sine qua non in pathogenesis; however, recent research demonstrates a complex interaction between acquired and hereditary genetic predispositions, along with a profoundly senescent bone marrow (BM) microenvironment. We review emerging data on t-MN risk factors and explore the intricate interplay among clonal hematopoiesis, genetic predisposition, and the abnormal BM microenvironment. Significance: t-MN represents a poorly understood blood cancer with extremely poor survival and no effective therapies. We provide a comprehensive review of recent preclinical research highlighting complex interaction among emerging therapies, hereditary and acquired genetic factors, and BM microenvironment. Understanding the risk factors associated with t-MN is crucial for clinicians, molecular pathologists, and cancer biologists to anticipate and potentially reduce its incidence in the future. Moreover, better understanding of the molecular pathogenesis of t-MN may enable preemptive screening and even intervention in high-risk patients.

The CHIP-clinic as the catalyst of preventive medicine

Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD) and is a precursor stage to the BCR-ABL negative chronic myeloproliferative neoplasms (MPNs). These diseases are acquired stem cell neoplasms, arising due to mutations in the hematopoietic stem cell. The most prevalent is the JAK2V617F (JAK2) mutation, which potently generates reactive oxygen species (ROS), and accordingly contributes greatly to the chronic inflammatory state and the increased risk of thrombosis in MPNs. The MPNs are largely underdiagnosed blood cancers with a long pre-diagnostic phase of several years, when the elevated blood cell counts are considered reactive to smoking, blood clots, infections or chronic inflammatory diseases. Since the JAK2 mutation as CHIP-JAK2 associates with an increased risk of CVD and an increased risk of hematological and non-hematological cancers there is an urgent need to explore and validate the JAK2 mutation as a novel risk factor for CVD and to establish CHIP-clinics, which in an interdisciplinary collaboration between experts from several disciplines, and ensure timely diagnosis of the undiagnosed MPN patient and associated comorbidities. We envisage studies of the JAK2 mutation in large CVD cohorts to deliver the “Proof of Concept” for the JAK2 mutation to be implemented as a novel, highly important risk factor for CVD. These novel preventive strategies are considered to have the potential of reducing morbidity and mortality in a large population of citizens and patients, carrying the thrombosis- and CVD-promoting JAK2 mutation.

Interleukin-1β modulates lymphoid differentiation of Flt3-positive multipotent progenitors after transplantation

Myeloablative pre-conditioning facilitates the differentiation of transplanted hematopoietic stem and progenitor cells (HSPCs). However, the factors in the stress environment that regulate HSPC behavior remain elusive. Here, we investigated the mechanisms that shaped the cell fates of transplanted murine multipotent progenitors (MPPs) expressing the Fms-related receptor tyrosine kinase 3 gene (Flt3). Using lineage tracing, clonal analysis, and single-cell RNA sequencing (RNA-seq), we showed that the myeloablative environment increased lymphoid priming of Flt3+ MPPs and that their efficient B cell output required intact interleukin 1 (IL-1) signaling. The Flt3+ MPPs with short-term exposure to IL-1β underwent a myeloid-biased to lymphoid-biased cell fate switch and produced more lymphoid-biased progeny with a strongerB lymphopoiesis capacity invitro. Correspondingly, a brief exposure to IL-1β facilitated the B cell output of transplanted Flt3+ MPPs invivo. Together, our study demonstrated an unrecognized function of IL-1β in promoting B lymphopoiesis and highlighted a latent effect of IL-1β in regulating MPP cell fate dynamics.

Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders.

Incidence of bacterial blood stream infections in patients with acute GVHD.

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients (n = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%). Patients with grade III/IV AGVHD had the highest BSI risk (HR 2.45; 95% CI 1.99-3.0; p < 0.0001). Lower GI involvement increased BSI risk (HR 1.54; 95% CI 1.17-2.02; p = 0.0019). BSI post-engraftment through day 100 was associated with worse survival (HR 1.64, 95% CI 1.43-1.87; p < 0.001) and higher non-relapse mortality (NRM), (HR 2.22; 95% CI 1.91-2.59; p < 0.001). Those with stage III/IV GI involvement are at highest risk for BSI. Future studies evaluating novel methods for preventing BSI in these high risk populations are needed to reduce mortality associated with AGVHD.

Hematopoietic stem cell transplantation therapy for refractory' Crohn disease: A systematic review and meta-analysis.

Despite the availability of numerous treatments for Crohn disease, there are patients who do not respond to any therapy, thereby diminishing their quality of life. The aim of this review is to analyze the efficacy and safety of autologous hematopoietic stem cell transplantation therapy for refractory Crohn disease. This work is a systematic review with meta-analysis conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Electronic databases such as PubMed, Scopus, Web of Science, and ClinicalTrials were consulted. The searches were carried out in August 2024. To evaluate the efficacy of autologous hematopoietic stem cell transplantation in inducing remission, the mean and standard deviation of the Crohn's Disease Activity Index pre- and post- treatment were used, and a fixed-effects meta-analysis was conducted. Additionally, to assess the efficacy in perianal fistulas, a random-effects meta-analysis was performed, collecting data on the number of subjects with fistulas at the beginning and end of the intervention. All 95% confidence intervals were calculated, and the I2 statistic was used to assess the heterogeneity of the outcome variables. A total of 609 records were identified from databases, with 12 studies selected for inclusion in the review. Immediate intervention proved effective in inducing a decrease in the Crohn Disease Activity Index compared to late intervention with conventional therapies. Moreover, the meta-analysis demonstrated efficacy for Crohn disease and associated fistulas with a mean decrease in the CDAI of -217.53 ± 14.3. When evaluating the efficacy of the procedure in perianal fistulas, a risk ratio of 0.47 with a 95% CI of [0.26, 0.86] was obtained. However, the procedure showed adverse effects, such as infections, acute renal failure or deaths. Systemic autologous hematopoietic stem cell transplantation has shown efficacy in patients who fail to achieve remission of their Crohn disease with conventional therapies. This procedure has also demonstrated efficacy in treating perianal fistulas. However, it is essential to carefully evaluate de implementation of this procedure due to the associated risks.