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To date, the predictive role of laboratory indicators for the phenomenon of no flow is unclear. Hence, our objective was to conduct a meta‐analysis to investigate the association between laboratory parameters and the risk of the no‐reflow phenomenon in patients with ST‐elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). This, in turn, aims to offer valuable insights for early clinical prediction of no‐reflow. We searched Pubmed, Embase, and Cochrane Library from the establishment of the database to October 2023. We included case‐control or cohort study that patients with STEMI following primary PCI. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results indicated that elevated white blood cell (WBC) count (odds ratio [OR] = 1.061, 95% confidence interval [CI]: 1.013–1.112), neutrophil count (OR = 1.324, 95% CI: 1.128–1.553), platelet (PLT) (OR = 1.002, 95% CI: 1.000–1.005), blood glucose (OR = 1.005, 95% CI: 1.002–1.009), creatinine (OR = 1.290, 95% CI: 1.070–1.555), total cholesterol (TC) (OR = 1.022, 95% CI: 1.012–1.032), d‐dimer (OR = 1.002, 95% CI: 1.001–1.004), and fibrinogen (OR = 1.010, 95% CI: 1.005–1.015) were significantly associated with increased risk of no‐reflow. However, elevated hemoglobin was significantly associated with decreased risk of no‐reflow. In conclusion, our comprehensive analysis highlights the predictive potential of various parameters in assessing the risk of no‐reflow among STEMI patients undergoing PCI. Specifically, WBC count, neutrophil count, PLT, blood glucose, hemoglobin, creatinine, TC, d‐dimer, and fibrinogen emerged as significant predictors. This refined risk prediction may guide clinical decision‐making, allowing for more targeted and effective preventive measures to mitigate the occurrence of no‐reflow in this patient population. [ABSTRACT FROM AUTHOR]

Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft‐versus‐tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8+ T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty‐one patients were enrolled in this study. It was found that the high post‐DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA‐1 headpiece opening. When blocking the integrin‐ligand interaction between LFA‐1 and ICAM‐1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA‐1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies. [ABSTRACT FROM AUTHOR]

Acute graft‐versus‐host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T‐cell‐replete haploidentical hematopoietic cell transplantation (haplo‐HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo‐HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1‐year cumulative incidence of 19.0% (95% CI: 14.5–24.6). Grade III–IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD‐related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse‐free survival (HR: 1.9, p = 0.020) and cGVHD relapse‐free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently. [ABSTRACT FROM AUTHOR]

BACKGROUND: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) has been reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)–based myeloablative allo‐HCT. METHODS: A total of 603 fecal specimens from 100 consecutive patients receiving allo‐HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next‐generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes. RESULTS: The diversity decreased to the lowest level at approximately day 12 after allo‐HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low‐ and high‐diversity groups. Two‐year overall survival in the high‐diversity group was significantly longer than that in the low‐diversity group (83.7% vs 60.6%, P =.026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P =.046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo‐HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased. CONCLUSIONS: This study indicates that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival. LAY SUMMARY: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) is reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens.It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)–based T‐cell repletion myeloablative allo‐HCT.Our study indicated that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival. Gut dysbiosis in platforms of antithymocyte globulin–based myeloablative allogeneic hematopoietic stem cell transplantation featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival. [ABSTRACT FROM AUTHOR]

Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations. [ABSTRACT FROM AUTHOR]

MicroRNA-9-1( miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines. [ABSTRACT FROM AUTHOR]

The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in acute myeloid leukemia ( AML), and it gives rise to acute myeloid gene 1 ( AML1) -myeloid transforming gene 8 ( ETO)-positive AML, which has a relatively favorable prognosis. However, the molecular mechanism related to a favorable prognosis in AML1- ETO-positive AML is still not fully understood. Our results show that the AML1-ETO fusion protein triggered activation of early growth response gene l ( EGR1) by binding at AML1-binding sites on the EGR1 promoter and, subsequently, recruiting acetyltransferase P300, which is known to acetylate histones. However, AML1- ETO could not recruit DNA methyltransferases and histone deacetylases; therefore, EGR1 expression was affected by histone acetylation but not by DNA methylation. Both transcription and translation of EGR1 were higher in AML1- ETO-positive AML cell lines than in AML1- ETO-negative AML cell lines, owing to acetylation. Furthermore, when AML1- ETO-positive AML cell lines were treated with C646 (P300 inhibitor) and trichostatin A (histone deacetylase inhibitor), EGR1 expression was significantly decreased and increased, respectively. In addition, treatment with 5-azacytidine (methyltransferase inhibitor) did not cause any significant change in EGR1 expression. Overexpression of EGR1 inhibited cell proliferation and promoted apoptosis, and EGR1 knockout promoted cell proliferation. Thus, EGR1 could be a novel prognostic factor for a favorable outcome in AML1- ETO-positive AML. The results of our study may explain the molecular mechanisms underlying the favorable prognosis in AML1- ETO-positive AML. [ABSTRACT FROM AUTHOR]

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high-risk hematologic patients due to the absence of HLA-matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies. STUDY DESIGN AND METHODS: Patients who underwent unmanipulated HLA-mismatched/haploidentical PBSCT from July 2007 to March 2010 with high-risk hematologic malignancies were enrolled for retrospective analysis. RESULTS: Twenty-one patients with high-risk hematologic malignancies underwent unmanipulated HLA-mismatched/haploidentical PBSCT with myeloablative conditioning. The numbers of CD34+ cells infused at transplantation were 4.81 (range, 2.61-11.47) × 106/kg. Patients achieved myeloid and platelet engraftment at a median of 16.5 and 20 days, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) on Day 100 was 52.7 ± 10.7%, and the 2-year cumulative incidence of chronic GVHD was 39.5 ± 10.6%. The cumulative incidences of cytomegalovirus antigenemia and hemorrhagic cystitis within 100 days after PBSCT were 59.5 ± 16.7 and 34.8 ± 13.3%, respectively. One hundred-day transplantation-related mortality (TRM) rate and the 2-year cumulative TRM rate were 14.3 and 20.5 ± 7.8%, respectively. The 2-year cumulative overall survival was 62.1 ± 11.4% and the probability of disease-free survival at 2 years was 55.6 ± 10.7% with a 16-month median follow-up. CONCLUSION: Unmanipulated PBSCT is a promising protocol in HLA-mismatched/haploidentical transplant settings. [ABSTRACT FROM AUTHOR]