Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

Effects of cell-free DNA on kidney disease and intervention strategies.

Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.

The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-ß1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-ß1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation.

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.

Immunophenotypic clustering in paediatric acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations. Cox regression analysis unveiled key antigens influencing the prognosis of AML patients. In terms of underlying genotypes, we observed that the antigenic profiles and outcomes of one specific group, primarily composed of CBFA2T3::GLIS2 and FUS::ERG, were analogous to the reported RAM phenotype. Overall, our data highlight the significance of immunophenotype to tailor treatment for paediatric AML.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

A noise robust sparse time-frequency representation method for measuring underwater gas leakage rate.

Passive acoustic monitors analyze sound signals emitted by seafloor gas bubbles to measure leakage rates. In scenarios with low-flux gas leaks, individual bubble sounds are typically non-overlapping. Measurement methods for these bubble streams aim to estimate the frequency peak of each bubble sound, which correlates with the bubble's size. However, the presence of ocean ambient noise poses challenges to accurately estimating these frequency peaks, thereby affecting the measurement of gas leakage rates in shallow sea environments using passive acoustic monitors. To address this issue, we propose a robust measurement method that includes a noise-robust sparse time-frequency representation algorithm and an adaptive thresholding approach for detecting bubble frequencies. We demonstrate the effectiveness of our proposed method using experimental data augmented with ocean ambient noise and ship-transit noise recorded from a bay area.

High-dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study.

This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high-dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady-state MTX concentrations (<56 µmol/L) and poorer outcomes in intermediate-/high-risk (IR/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with MLL rearrangements. In contrast, such an association did not emerge within the low-risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation-based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200 mg/kg dosage for infants under 1 year. The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower-risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady-state concentrations within the optimal range.

Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia.

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.

Systemic Immune-Inflammation Index Was Significantly Associated with All-Cause and Cardiovascular-Specific Mortalities in Patients Receiving Peritoneal Dialysis.

Purpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD. Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan-Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities. Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088-1.327, P<0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126-1.456, P<0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066-1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185-2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only. Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.

Prediction and potential risk factors for electronic cigarette use behaviors among adolescents: a pilot study in Chiayi, Taiwan.

Introduction: Electronic cigarette (e-cigarette) use among adolescents has become increasingly common; therefore, effectively reducing adolescent e-cigarette use is an urgent issue. We aimed to predict and identify potential factors related to adolescent e-cigarette use behaviors. Methods: This cross-sectional study was conducted using anonymous questionnaires given to Taiwanese high school students in 2020. Approximately 1,289 adolescent students completed questions on e-cigarette use, personal characteristics, family environment, and substances used. We performed multivariate logistic regression analyses to assess the model's predictive performance in terms of the area under the receiver operating characteristic curve. Results: We found that 9.3% of adolescent students used e-cigarettes. Tobacco smoking, close friends' reactions to e-cigarette use, and the use of other substances were independent risk factors for adolescent e-cigarette use. Furthermore, relative to tobacco nonuse, tobacco use and tobacco smoking dependence had odds ratios of 76.49 and 113.81, respectively. The predictive accuracy of adolescent e-cigarette use from personal characteristics, family environment, and substance use status was 73.13, 75.91, and 93.80%, respectively. Conclusion: The present study highlights the need for early prevention of e-cigarette use among adolescents, particularly those with a history of using tobacco and other substances and those who have close friends with positive attitudes towards e-cigarette use.

Polyglycerol-Amine Covered Nanosheets Target Cell-Free DNA to Attenuate Acute Kidney Injury.

Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA-associated diseases, but a nanomaterial-based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol-amine (PGA)-covered MoS2 nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models. The nanosheets exhibit higher cfDNA binding capacity than polymer PGA and PGA-based nanospheres owing to the flexibility and crimpability of their 2D backbone. Moreover, with low cytotoxicity and mild protein adsorption, the nanosheets effectively reduced serum cfDNA levels and predominantly accumulated in the kidneys to inhibit the formation of neutrophil extracellular traps and renal inflammation, thereby alleviating both lipopolysaccharide and ischemia-reperfusion induced AKI in mice. Further, they decreased the serum cfDNA levels in samples from AKI patients. Thus, PGA-covered MoS2 nanosheets can serve as a potent cfDNA scavenger for treating AKI and other cfDNA-associated diseases. In addition, this work demonstrates the pivotal feature of a 2D sheet-like structure in the development of the cfDNA scavenger, which can provide a new insight into the future design of nanoplatforms for modulating inflammation.

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation.

Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.

Childhood Leukemia Classification via Information Bottleneck Enhanced Hierarchical Multi-Instance Learning.

Leukemia classification relies on a detailed cytomorphological examination of Bone Marrow (BM) smear. However, applying existing deep-learning methods to it is facing two significant limitations. Firstly, these methods require large-scale datasets with expert annotations at the cell level for good results and typically suffer from poor generalization. Secondly, they simply treat the BM cytomorphological examination as a multi-class cell classification task, thus failing to exploit the correlation among leukemia subtypes over different hierarchies. Therefore, BM cytomorphological estimation as a time-consuming and repetitive process still needs to be done manually by experienced cytologists. Recently, Multi-Instance Learning (MIL) has achieved much progress in data-efficient medical image processing, which only requires patient-level labels (which can be extracted from the clinical reports). In this paper, we propose a hierarchical MIL framework and equip it with Information Bottleneck (IB) to tackle the above limitations. First, to handle the patient-level label, our hierarchical MIL framework uses attention-based learning to identify cells with high diagnostic values for leukemia classification in different hierarchies. Then, following the information bottleneck principle, we propose a hierarchical IB to constrain and refine the representations of different hierarchies for better accuracy and generalization. By applying our framework to a large-scale childhood acute leukemia dataset with corresponding BM smear images and clinical reports, we show that it can identify diagnostic-related cells without the need for cell-level annotations and outperforms other comparison methods. Furthermore, the evaluation conducted on an independent test cohort demonstrates the high generalizability of our framework.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Risk of motor vehicle collisions after methadone use: A systematic review and meta-analysis.

INTRODUCTION: Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk of motor vehicle collisions after methadone use have been conflicting. In the present study, we compiled the available evidence on the risk of motor vehicle collisions after methadone use. METHODS: We completed a systematic review and meta-analysis of studies identified on six databases. Two reviewers independently screened the identified epidemiological studies, extracted data, and used the Newcastle-Ottawa Scale to assess the quality of the studies. Risk ratios were retrieved for analysis, conducted using random-effects model. Sensitivity analyses, subgroup analyses, and tests for publication bias were conducted. RESULTS: Among 1446 identified relevant studies, a total of 7 epidemiological studies enrolling 33226142 participants met the inclusion criteria. Overall, study participants with methadone use had a higher risk of motor vehicle collisions than did those without methadone use (pooled relative risk 1.92, 95% CI 1.25-2.95; number needed to harm 11.3, 95% CI 5.3-41.6); the I2 statistic was 95.1%, indicating substantial heterogeneity. Subgroup analyses revealed that database type explained 95.36% of the between-study variance (p = 0.008). Egger's (p = 0.376) and Begg's (p = 0.293) tests revealed no evidence of publication bias. Sensitivity analyses indicated that the pooled results were robust. CONCLUSION: The present review revealed that methadone use is significantly associated with a nearly doubled risk of motor vehicle collisions. Therefore, clinicians should exercise caution in implementing methadone maintenance therapy for drivers.

Gas-Mediated Intestinal Microbiome Regulation Prompts the Methanol Extract of Schizonepetae Spica to Relieve Colitis.

Intestinal dysbiosis plays an important role in the pathogenesis of colitis (UC). Schizonepetae Herba can achieve anti-inflammatory effects as a medicine and food homologous vegetable. Luteolin, eriodictyol, fisetin, and kaempferol are the main anti-inflammatory active compounds obtained through mass spectrometry from the methanol extract of Schizonepetae Spica (JJSM). JJSM intervention resulted in attenuated weight loss, high disease-activity-index score, colon length shortening and colonic pathological damage in DSS-induced colitis mice. Interestingly, hydrogen sulfide (H2S) was inhibited remarkably, which is helpful to elucidate the relationship between active substance and intestinal flora. Furthermore, JJSM administration improved intestinal flora with down-regulating the abundance of harmful bacteria such as Clostridiales and Desulfovibrio and up-regulating the abundance of beneficial bacteria such as Muribaculaceae and Ligolactobacillus and enhanced the production of SCFAs. It is worth noticing that Desulfovibrio is related to the production of intestinal gas H2S. The elevated levels of Desulfovibrio and H2S will hasten the onset of colitis, which is a crucial risk factor for colitis. The results displayed that JJSM could considerably ameliorate colitis by rebuilding H2S-related intestinal flora, which provides a new therapeutic strategy for Schizonepetae Spica to be utilized as a functional food and considered as an emerging candidate for intestinal inflammation.

Risk of motorcycle collisions among patients with type 2 diabetes: a population-based cohort study with age and sex stratifications in Taiwan.

AIMS: To investigate the overall and sex-age-specific absolute and relative risks of motorcycle collisions at road traffic accidents among patients with type 2 diabetes. METHODS: A cohort study in Taiwan was conducted by following 989,495 patients with type 2 diabetes and the same number of matched controls recruited between 2010 and 2012 to the end of 2016. Collision events by motorcycle driver victims were identified from the Police-reported Traffic Accident Registry. Overall and sex-age-specific incidence rates of collision involving motorcycle driver victims were estimated under Poisson assumption. The Cox proportional hazard regression models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of collision in association with type 2 diabetes. RESULTS: Over an up to 7 years of follow-up, patients with type 2 diabetes had a higher incidence rate of motorcycle collision than controls at 1.16 and 0.89 per 100 person-years, respectively, which represented a significantly elevated HR of 1.28 (95% CI 1.27-1.30) after adjusting for potential confounders including various diabetic complications. The elevated HR was similarly seen in both men and women patients, and was significantly decreasing with increasing age regardless of sex. Little evidence supported the dose-response relationship between duration of type 2 diabetes and motorcycle collision risk. CONCLUSIONS: After adjustment for common diabetic complications and comorbidities that could impair driving performance, patients with type 2 diabetes still suffered from increased risk of motorcycle collisions, regardless of sex, but was more evident in younger than in older patients.

Schizophrenia, but not depression or bipolar affective disorder, adds additional risk of aspiration pneumonia among stroke survivors: A national cohort study in Taiwan.

OBJECTIVE: Few studies have assessed the sex-specific and age-specific risk of aspiration pneumonia (AP) in patients with stroke and evaluated whether mental disorders may increase this risk. In this population-based cohort study, we investigated the sex-specific and age-specific risk of AP in association with stroke and the joint effects of stroke and mental disorders on the risk of AP. METHODS: We included 23,288 patients with incident stroke admitted between 2005 and 2017 and 68,675 matched nonstroke controls. Information on mental disorders was obtained from medical claims data within the 3 years before the stroke incidence. Cox proportional hazards models considering death as a competing risk event were constructed to estimate the hazard ratio of AP incidence by the end of 2018 associated with stroke and selected mental disorders. RESULTS: After ≤14 years of follow-up, AP incidence was higher in the patients with stroke than in the controls (11.30/1000 vs. 1.51/1000 person-years), representing a covariate-adjusted subdistribution hazard ratio (sHR) of 3.64, with no significant sex difference. The sHR significantly decreased with increasing age in both sexes. Stratified analyses indicated schizophrenia but not depression or bipolar affective disorder increased the risk of AP in the patients with stroke. CONCLUSION: Compared with their corresponding counterparts, the patients with schizophrenia only, stroke only, and both stroke and schizophrenia had a significantly higher sHR of 4.01, 5.16, and 8.01, respectively. The risk of AP was higher in younger stroke patients than those older than 60 years. Moreover, schizophrenia was found to increase the risk of AP in patients with stroke.

Reduced Dose Intensity of Daunorubicin During Remission Induction for Low-Risk Patients With Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of the Chinese Children's Cancer Group.

It is urgently necessary to reduce the adverse effects of chemotherapy while maintaining their cure high rates for children with acute lymphoblastic leukemia (ALL). The present study aimed to determine whether the dose intensity of daunorubicin during the remission-induction phase could be reduced for low-risk patients with ALL. A total of 2396 eligible patients, who participated in CCCG-ALL-2015 study and were provisionally assigned to the low-risk group, were included and divided into single-dose group and double-dose group according to the dosage of daunorubicin during the remission-induction phase. For patients with ETV6-RUNX1 positive ALL or hyperdiploidy ALL, there were no significant differences in outcomes between the two groups. For other patients, the 5-year event-free survival rate was significantly better and the 5-year cumulative risk of any relapse was significantly lower in the double-dose group compared with the single-dose group. Both the 5-year overall survival rate and the risk of early deaths were not significantly different between the two groups. Our results suggested that only B-lineage ALL patients with ETV6-RUNX1 positivity or hyperdiploidy who achieved an early negative minimal residual disease status were suitable candidates for dosage reduction of daunorubicin during the remission-induction phase. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=10115, identifier ChiCTR-IPR-14005706.