Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

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.

Docosahexaenoic acid inhibits the invasion and migration of colorectal cancer by reversing EMT through the TGF-ß1/Smad signaling pathway.

The primary cause of mortality in colorectal cancer (CRC) patients is tumor metastasis. The epithelial-mesenchymal transition (EMT) stands out as a crucial factor promoting the metastasis of CRC. Previous findings suggest a potential inhibitory effect of docosahexaenoic acid (DHA) on CRC metastasis, but the precise mechanism remains unknown, this study aims to explore this issue. We assessed metastasis and recurrence, all-cause mortality, and cancer-related mortality rates according to DHA intake in independent CRC cohorts (n = 367) by survival analysis. The ability of DHA to block CRC cell migration and invasion was tested using transwell and wound-healing assays. The regulation of EMT marker genes in CRC by DHA was detected by quantitative real-time PCR (qPCR) and immunoblotting, and the effect of DHA on the TGF-ß1/Smad signaling pathway was further investigated. These cellular findings were validated using a subcutaneous CRC mouse model. Survival analyses showed that lower DHA intake was associated with a higher risk of CRC metastasis and a poorer prognosis. In vitro experiments showed that DHA inhibits the TGF-ß1/Smad signaling pathway and regulates downstream transcription factors, thereby reversing the EMT and inhibiting invasion and migration. In the mouse model, dietary DHA supplementation effectively increased blood DHA concentrations and inhibited CRC metastasis. Our study demonstrated that DHA inhibits CRC invasion and metastasis by inhibiting the TGF-ß1/Smad signaling pathway. Increased intake of DHA among CRC patients may provide additional benefits to the prognosis of colorectal cancer.

Dual-Lumen Extracorporeal Membrane Oxygenation Cannulation Technique Using Only Transthoracic Echocardiography - A Case Series.

BACKGROUND: Bicaval dual lumen cannula (DLC) is gaining popularity in veno-venous extracorporeal membrane oxygenation (V-V ECMO) for having less recirculation and facilitating mobilization. It is usually inserted under fluoroscopic or transesophageal echocardiographic guidance to prevent potentially fatal complications. Thus, their utilization was limited during the COVID-19 outbreak due to stringent quarantine policy and manpower shortage, especially when emergency insertion was required. PURPOSE: To describe our experience on DLC insertion using transthoracic echocardiography alone during the pandemic, with a focus on safety considerations by using detail step-by-step procedural guide. OUTCOME: Four patients were performed V-V ECMO using the transthoracic echocardiographic-guided DLC cannulation technique during the fifth wave of the COVID-19 outbreak, with no cannulation-related complications. CONCLUSION: Transthoracic echocardiographic guidance for DLC insertion is feasible and probably safe with a detailed guide, which can be adopted as a supplementary tool during future endemic outbreaks.

O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/ß, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or its O-GlcNAcylation re-sensitizes resistant cells to palbociclib. Moreover, clinical studies confirm the activation of MITF in tumors from patients who are palbociclib-resistant or undergoing palbociclib treatment. Collectively, our studies shed light on the mechanism regulating palbociclib resistance and present clinical evidence for developing therapeutic approaches to treat CDK4/6i-resistant breast cancer patients.

Mechanistic and kinetic insights into transcription factor biology via acute protein depletion.

Genetic downregulation of the BCL11A transcription factor (TF) reverses the switch from fetal to adult hemoglobin and is effective in treating ß-hemoglobinopathies. Genetic ablation results in a gradual reduction in protein abundance and does not lend itself to the analysis of the immediate consequences of protein loss or the determination of the direct interactors/targets of the protein of interest. We achieved acute degradation of the largely disordered and 'undruggable' BCL11A protein by fusing it with a conditional degradation (degron) tag, FKBP12F36V, called degradable tags (dTAG). Small molecules then depleted the BCL11A-dTAG through endogenous proteolytic pathways. By integrating acute depletion with nascent transcriptomics and cell cycle separation techniques, we demonstrate the necessity of BCL11A occupancy at the target chromatin for sustained transcriptional repression in erythroid cells. We advocate for expanding the exploration of TF function to include acute depletion, which holds the potential to unveil unprecedented kinetic insights into TF mechanisms of action.

Comparison of Sonazoid-Contrast­Enhanced Ultrasound and Gd­EOB­DTPA­Enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVE: This study aims to evaluate and compare the predictive accuracy of Sonazoid-contrast-enhanced ultrasound (CEUS) and Gd-EOB-DTPA-enhanced MRI for detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: In this single-center prospective study, we included 64 patients with histopathologically confirmed single HCC lesions. Based on post-operative pathologic data, patients were categorized into two groups: those with MVI (n = 21) and those without MVI (n = 43). The diagnostic efficacy of CEUS was compared with that of MRI in predicting MVI. RESULTS: Multifactorial analysis revealed that US features (tumor size > 4.35 cm, peritumoral enhancement, post-vascular ring enhancement, peak energy in the arterial phase of the difference between the margin area of HCC and distal liver parenchyma <-1.0 × 106 a.u), MRI features (rim enhancement, irregular tumor margin, and the halo sign) were all independent predictors of MVI (p < 0.05). The sensitivity and specificity of CEUS features in predicting MVI ranged from 61.9% to 86.4% and from 42.9% to 71.4%, respectively. For MRI features, the sensitivity and specificity ranged from 33.3% to 76.3% and from 54.7% to 90.5%, respectively. No statistically significant differences were observed in the area under the curve between CEUS and MRI (p > 0.05). Notably, peak energy of the difference showed the highest sensitivity at 86.4%, while the halo sign in MRI exhibited the highest specificity at 90.5%. CONCLUSION: Sonazoid-CEUS and Gd-EOB-DTPA-enhanced MRI demonstrate potential in predicting MVI in HCC lesions. Notably, CEUS showed higher sensitivity, whereas MRI displayed greater specificity in predicting MVI.

CAR-T Therapy Followed by Hematopoietic Stem Cell Transplantation Can Improve Survival in Children Relapsed/Refractory Philadelphia Chromosome-positive B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Philadelphia chromosome (Ph)-positive B-cell acute lymphoblastic leukemia (ALL) has a high complete remission (CR) rate, but relapse and prolonged measurable residual disease remain serious problems. We sought to describe the CR rate measurable residual disease negative rate and address the results and safety of pediatric patients who underwent after receiving chimeric antigen receptor (CAR) specific for CD19 (CAR-19) followed by hematopoietic stem cell transplantation (HSCT) for the treatment of Ph-positive ALL. METHODS: A descriptive study was conducted at Peking University People's Hospital from September 2013 to January 2021. 13 patients with relapsed/refractory Ph-positive B-ALL who received CAR-T therapy followed by allo-HSCT were included. We concentrated on the overall patient survival and CR rate. RESULTS: The median time between CAR-T therapy and allo-HSCT was 58 days. Among all the patients, the CR rate was 100%, the flow cytometry negativity rate was 84.62%, and the BCR-ABL negativity rate was 53.85% at 1 month after CAR-T infusion. All the patients achieved a major molecular response in 6 months after HSCT. After a median follow-up of 45 months, the 3-year OS rate was 66.7%, and the 3-year DFS rate was 61.5%. The 3-year OS rate of patients with BCR-ABL-positive pre-HSCT was significantly lower than that in the BCR-ABL-negative group (40.0% vs. 85.7%, P =0.042). Also, the same trend was observed for the 3-year DFS rate but did not differ significantly (40.0% vs. 75.0%, P =0.233). CONCLUSIONS: CAR-T therapy followed by allo-HSCT can be a safe and effective treatment for Ph-positive B-ALL pediatric patients.

The effects of repeated freezing and thawing on bovine sperm morphometry and function.

Refreezing the remaining genetic resources after in vitro fertilization (IVF) can conserve genetic materials. However, the precise damage inflicted by repeated freezing and thawing on bovine sperm and its underlying mechanism remain largely unexplored. Thus, this study investigates the impact of repeated freeze-thaw cycles on sperm. Our findings indicate that such cycles significantly reduce sperm viability and motility. Furthermore, the integrity of the sperm plasma membrane and acrosome is compromised during this process, exacerbating the advanced apoptosis triggered by oxidative stress. Additionally, transmission electron microscopy exposed severe damage to the plasma membranes of both the sperm head and tail. Notably, the "9 + 2" structure of the tail was disrupted, along with a significant decrease in the level of the axonemal protein DNAH10, leading to reduced sperm motility. IVF outcomes revealed that repeated freeze-thaw cycles considerably impair sperm fertilization capability, ultimately reducing the blastocyst rate. In summary, our research demonstrates that repeated freeze-thaw cycles lead to a decline in sperm viability and motility, attributed to oxidative stress-induced apoptosis and DNAH10-related dynamic deficiency. As a result, the utility of semen is compromised after repeated freezing.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

CEUS in prediction of early recurrence of hepatocellular carcinoma after curative resection and to stratify the risk of early recurrence: a retrospective observational study.

PURPOSE: Early recurrence (ER) after surgery is related to early death in patients with hepatocellular carcinoma (HCC) after radical resection. To explore the role of preoperative contrast-enhanced ultrasound (CEUS) in predicting ER of HCC after curative resection and to stratify the risk of ER. MATERIALS AND METHODS: This study evaluated consecutive 556 patients with HCC who were examined by CEUS during the 2 weeks before curative resection between January 2011 and December 2018. ER was defined as intrahepatic and/or extrahepatic recurrence within 2 year after resection of HCC. Univariate and logistic regression analyses were performed to identify independent risk factors for ER after surgical resection of HCC. Recurrence-free time (RFS) rates were analyzed and compared by log-rank test. RESULTS: ER occurred in 307 (55.2%) of the 556 patients. Univariate and multivariate analyses revealed that a tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL(deep learning) radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level were significantly associated with ER (P < .05). Based on the number of predictors present, patients with CEUS LR-5 HCC were stratified into three risk subgroups: risk group 3 (high-risk patients, 4 predictors), risk group 2 (medium-risk patients, 2-3 predictors), and risk group 1 (low-risk patients, 0-1 predictor). The 2-year RFS rate was 19.4% in risk group 3, 40.9% in risk group 2, and 48.1% in risk group 1; the corresponding mean RFS times were 14.0 ± 2.9 months, 43.7 ± 6.6 months, and 55.5 ± 2.8 months, respectively (P < .001). CONCLUSIONS: Tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level can predict ER of HCC.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

The in vitro replication phenotype of hepatitis B virus (HBV) splice variants Sp3 and Sp9 and their impact on wild-type HBV replication.

Prior to nuclear export, the hepatitis B virus (HBV) pregenomic RNA may be spliced by the host cell spliceosome to form shorter RNA sequences known as splice variants. Due to deletions in the open reading frames, splice variants may encode novel fusion proteins. Although not essential for HBV replication, the role of splice variants and their novel fusion proteins largely remains unknown. Some splice variants and their encoded novel fusion proteins have been shown to impair or promote wild-type HBV replication in vitro, and although splice variants Sp3 and Sp9 are two of the most common splice variants identified to date, their in vitro replication phenotype and their impact on wild-type HBV replication are unclear. Here, we utilize greater than genome-length Sp3 and Sp9 constructs to investigate their replication phenotype in vitro, and their impact on wild-type HBV replication. We show that Sp3 and Sp9 were incapable of autonomous replication, which was rescued by providing the polymerase and core proteins in trans. Furthermore, we showed that Sp3 had no impact on wild-type HBV replication, whereas Sp9 strongly reduced wild-type HBV replication in co-transfection experiments. Knocking out Sp9 novel precore-surface and core-surface fusion protein partially restored replication, suggesting that these proteins contributed to suppression of wild-type HBV replication, providing further insights into factors regulating HBV replication in vitro. IMPORTANCE: The role of hepatitis B virus (HBV) splice variants in HBV replication and pathogenesis currently remains largely unknown. However, HBV splice variants have been associated with the development of hepatocellular carcinoma, suggesting a role in HBV pathogenesis. Several in vitro co-transfection studies have shown that different splice variants have varying impacts on wild-type HBV replication, perhaps contributing to viral persistence. Furthermore, all splice variants are predicted to produce novel fusion proteins. Sp1 hepatitis B splice protein contributes to liver disease progression and apoptosis; however, the function of other HBV splice variant novel fusion proteins remains largely unknown. We show that Sp9 markedly impairs HBV replication in a cell culture co-transfection model, mediated by expression of Sp9 novel fusion proteins. In contrast, Sp3 had no effect on wild-type HBV replication. Together, these studies provide further insights into viral factors contributing to regulation of HBV replication.

Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions.

Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes in chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate the direct role of the abundant nuclear complex protein Matrin3 (Matr3) in chromatin architecture and development in the context of myogenesis. Using an acute targeted protein degradation platform (dTAG-Matr3), we reveal the dynamics of development-related chromatin reorganization. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial chromatin loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected, accompanied by the emergence of novel YY1-mediated enhancer-promoter loops, which occurred concurrently with changes in histone modifications and chromatin-level binding patterns. Changes in chromatin occupancy by Matr3 also correlated with these alterations. Overall, our results suggest that Matr3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and highlight a conserved and direct role for Matr3 in maintenance of chromosomal architecture.

Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis.

This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1mut ) and 144 AML patients with wild-type RUNX1(AML-RUNX1wt ) were selected using the case-pair method(1:4). Compared to AML-RUNX1wt , AML-RUNX1mut showed higher frequency of ASXL1 (p < 0.001), SRSF2 (p < 0.001), BCORL1 (p < 0.001), RAS (p = 0.010) mutations, and absent NPM1 mutations (p = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1mut and AML-RUNX1wt were 73.1% versus 68.0% (p = 0.64) and 80.7% versus 71.6% (p = 0.37), respectively. AML-RUNX1mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; p = 0.006). Multivariate analysis showed that EZH2 mutation (p = 0.003), white blood cell (WBC) ≥30 × 109 /L (p = 0.036) and age ≥60 years (p = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1mut ; WBC ≥30 × 109 /L (p = 0.013) and DNMT3A mutation (p = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1mut . In conclusion, AML-RUNX1mut showed unique clinical characteristics, but the survival between AML-RUNX1mut and AML-RUNX1wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .

Corrigendum: Corpus of Mandarin Child Language: a preliminary study on the acquisition of semantic content categories in Mandarin-speaking preschoolers.

[This corrects the article DOI: 10.3389/fpsyg.2023.1234525.].

Outcome and prognostic factors of haploidentical allogeneic hematopoietic stem cell transplantation in pediatric relapsed or refractory ETV6/RUNX1-positive acute lymphoblastic leukemia.

INTRODUCTION: the role of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients with relapsed or refractory (R/R) ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of ETV6/RUNX1-positive ALL. METHODS: we analyzed the clinical characteristics and treatment outcomes of 20 pediatric patients who were diagnosed with ETV6/RUNX1-positive ALL and received chemotherapy/chimeric antigen receptor T-cell bridged to haplo-HSCT between 2016 and 2021 at our institution. RESULTS: with a median follow-up time of 47 months, the 3-year cumulative incidence of relapse, disease-free survival, and overall survival were 35.9% (95% confidence interval (CI): 15.3-57.1%), 59.1% (95% CI: 37.2-81.0%), and 75.0% (95% CI: 56.0-94.0%), respectively. Multivariate analysis revealed that pre-HSCT measurable residual disease (MRD) positivity (hazard ratio, 13.275; 95% CI: 2.406-73.243; P = 0.003) had a significant negative impact on relapse. A total of 7 patients experienced positive ETV6/RUNX1 gene expression at a median of 7.2 months after haplo-HSCT, 5 of them experienced relapse at a median time of 12.1 months after haplo-HSCT. ROC curve analysis was performed to analyze the significance of pre-HSCT and post-HSCT ETV6/RUNX1 transcripts for predicting relapse; the AUC were 0.798 (95% CI: 0.567-1.0, P=0.035) and 0.875 (95% CI: 0.690-1.0, P=0.008), respectively. The optimal cut-off points to predict an inevitable relapse were 0.011% and 0.0019%, respectively. CONCLUSION: patients with R/R ETV6/RUNX1-positive ALL may benefit from haplo-HSCT. Deeply eliminating pre-HSCT MRD and preemptive treatment for post-HSCT MRD may be crucial to further improving the prognosis.