Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Severe combined immunodeficiency (SCID) represents a group of genetically heterogeneous disorders characterized by mutations that lead to profound defects in both humoral and cellular immunity. Transplacental maternal engraftment (TME) is a frequently observed complication in SCID. While most cases of SCID with TME exhibit no substantial impact on disease progression, a subset of patients may encounter diagnostic delays or therapeutic challenges due to TME interference. Furthermore, TME may predispose these individuals to graft-versus-host disease (GVHD) prior to hematopoietic stem cell transplantation, thereby increasing diagnostic complexity and treatment risks. This review systematically examines the etiology and clinical manifestations of SCID associated with TME, analyzes its implications for disease management, and evaluates current detection methodologies. The synthesized evidence provides a theoretical foundation for future research and offers potential insights into the clinical diagnosis and management of SCID associated with TME.
Humans ; Severe Combined Immunodeficiency/diagnosis* ; Pregnancy ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Maternal-Fetal Exchange/immunology* ; Graft vs Host Disease/etiology* ; Animals ; Placenta/immunology*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

Gut microbiota and its metabolites are associated with a variety of hematological malignancies, including acute myeloid leukemia (AML). AML patients commonly suffer from imbalances in intestinal homeostasis before and after chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). The diversity and abundance of gut microbiota, as well as the levels of metabolites, may be biomarkers for predicting the occurrence of infection and graft-versus-host disease (GVHD) in AML patients. In order to offer a theoretical foundation for optimizing treatment strategies for AML patients, this review summarized the latest research progress on gut microbiota and its metabolites in relation to the occurrence, development, treatment and prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation ; Graft vs Host Disease

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

OBJECTIVES: To investigate the clinical characteristics of cytokine release syndrome (CRS) in children with thalassemia major (TM) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and their prognosis. METHODS: A retrospective analysis was performed for the clinical data of 280 children with TM who underwent haplo-HSCT in the Department of Hematology and Oncology, Shenzhen Children's Hospital, from January 2019 to December 2021. According to the CRS criteria, they were divided into two groups: CRS grade <3 (260 children) and CRS grade ≥3 (20 children). The children with TM were analyzed in terms of clinical characteristics of CRS after haplo-HSCT and their prognosis. RESULTS: There were significant differences between the two groups in neutrophil engraftment time, clinical manifestations of CRS, and the rate of use of glucocorticoids within 4 days after haplo-HSCT (P=0.012, 0.040, and <0.001 respectively). For the CRS grade <3 group, the incidence rate of acute graft-versus-host disease (aGVHD) was 9.6% within 3 months after transplantation, while no aGVHD was observed in the CRS grade ≥3 group within 3 months after transplantation, but there was no significant difference in the incidence of aGVHD between the two groups within 3 months after transplantation (P=0.146). No transplantation-related death was observed in either group within 3 months after haplo-HSCT. CONCLUSIONS The children with CRS grade≥3 have an early neutrophil engraftment time, severe and diverse clinical manifestations of CRS, and a high rate of use of glucocorticoids within 4 days after haplo-HSCT. For these children, early use of low-dose glucocorticoids after transplantation may alleviate CRS response and reduce the incidence of aGVHD, thereby bringing more benefits to the children. CRS after haplo-HSCT has no significant impact on the prognosis of the children.
Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Retrospective Studies ; Child, Preschool ; Graft vs Host Disease/prevention & control* ; beta-Thalassemia/therapy* ; Adolescent ; Cytokine Release Syndrome/etiology* ; Transplantation, Haploidentical/adverse effects* ; Infant ; Prognosis ; Glucocorticoids/therapeutic use*

OBJECTIVE: To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology. METHODS: 20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×10⁷/mice, n=20) and spleen nucleated cells (5×10⁶/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5⁺ and Clu⁺ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings. RESULTS: The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5⁺ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu⁺ cells were observed in the 5% group. The Lgr5⁺ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu⁺ cells in the 20% group significantly increased. CONCLUSION The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.
Mice ; Female ; Animals ; Mice, Inbred C57BL ; Bone Marrow Transplantation ; Graft vs Host Disease ; Stem Cells ; Organoids