BACKGROUND:The combination of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) has dramatically improved the cure rate of acute promyelocytic leukemia (APL). However, differentiation syndrome (DS) remains a significant cause of early mortality in APL patients. This severe complication typically occurs during induction therapy with ATRA and/or ATO. Early prediction and timely intervention are crucial to reducing DS-related mortality. This study aimed to identify risk factors for DS and develop a predictive model tailored to children with non-high-risk (NHR) APL. METHODS:We conducted a multicenter retrospective analysis of 166 pediatric NHR-APL patients treated between 2011 and 2024. Clinical characteristics were compared between DS and non-DS groups. Logistic regression was used to identify independent predictors, and a nomogram was developed based on these variables. The model was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). RESULTS:Seventeen patients (10.2%) developed DS during induction. Multivariate analysis identified five independent risk factors: female sex, non-chemotherapy group, BCR subtype 3, elevated peripheral promyelocyte proportion (≥ 44%), and platelet count (≥ 20 × 109/L). The predictive nomogram achieved an AUC of 0.89 in the training set and 0.75 in the validation set. DCA demonstrated favorable clinical utility of the model. CONCLUSIONS:We developed and validated the first nomogram for predicting DS in pediatric NHR-APL. This tool enables early risk stratification and may guide clinical decision-making to reduce early mortality.

Objective To investigate risk factors for pediatric intensive care unit(PICU)admission among children with acute lymphoblastic leukemia(ALL)and risk factors for receipt of life-sustaining therapy(LST)in the PICU.Methods Clinical data of ALL patients treated at the Children's Medical Center of the Second Xiangya Hospital from June 2016 to June 2021 were retrospectively reviewed.Patients were categorized into PICU and non-PICU groups according to PICU admission.Multivariable logistic regression was applied to identify risk factors for PICU admission.The cumulative probability of PICU admission was estimated using Kaplan-Meier curves.PICU patients were further stratified into LST and non-LST groups according to whether LST was received,and multivariable logistic regression was used to identify risk factors for receiving LST.Results A total of 200 children with ALL were included;42(21.0%)were admitted to the PICU at least once,with 48 total admissions.Multivariable logistic regression analysis showed that hyperleukocytosis at diagnosis and lactate dehydrogenase(LDH)>500 U/L were independent risk factors for PICU admission(both P<0.05).Kaplan-Meier curves demonstrated that T-cell ALL and hyperleukocytosis were associated with higher cumulative PICU admission rates.Univariate analysis showed that C-reactive protein,albumin,and respiratory failure were significantly associated with the receipt of LST(all P<0.05).Further multivariable logistic regression analysis revealed that respiratory failure was significantly associated with an increased risk of receiving LST(OR=13.254,P=0.027).Conclusions Children with ALL who have hyperleukocytosis at diagnosis and LDH>500 U/L have a higher risk of PICU admission;respiratory failure is an independent risk factor for receipt of LST among PICU-admitted ALL patients.

Background:This study aimed to develop an efficient survival model for predicting event-free survival (EFS) in patients with Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL). Methods:Data related to Ph-like ALL were collected from the South China Children's Leukemia Group (SCCLG) multicenter study conducted from October 2016 to July 2021. A model for predicting the survival of patients with Ph-like ALL was built using Cox proportional hazards regression, random forest, extreme gradient boosting, and gradient boosting machine techniques. By integrating indicators including the concordance index (C-index), 1-, 3-, and 5-year area-under-the-receiver operating characteristics curve (AUROC), Brier score, and decision curve analysis, the predictive capabilities of each model were compared. Results:The random forest algorithm demonstrated the most robust predictive performance. In the test set, the C-index of the random forest model was 0.797 (95% CI: 0.736-0.821; P < 0.001). The AUROCs for 1, 3, and 5 years were 0.787 (95% CI: 0.62-0.953; P < 0.001), 0.797 (95% CI: 0.589-1; P < 0.001), and 0.861 (95% CI: 0.606-1; P < 0.001), respectively. The Brier scores for 1, 3, and 5 years were 0.102 (95% CI: 0.032-0.173; P < 0.001), 0.126 (95% CI: 0.063-0.19; P < 0.001), and 0.121 (95% CI: 0.051-0.19; P < 0.001), respectively. Conclusion:The random forest model effectively predicted the survival outcomes of patients with Ph-like ALL, which can aid clinicians to conduct personalized prognosis assessments in advance. Based on a web-based calculator, using random forest prediction models to calculate the prognosis of Ph-like ALL (https://songxiaodan03.shinyapps.io/RFpredictionmodelforPHlikeALL/) could facilitate healthcare professionals in carrying out clinical evaluation.

BACKGROUND:Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML-CP) remain limited. METHODS:This prospective multicenter real-world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML-CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m2 twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event-free survival (EFS), and safety. RESULTS:Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2-year EFS was 93.3% (84.4%-100%). Nilotinib trough concentrations (Ctrough) correlated negatively with BCR::ABL1 transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5-fold higher risk of hyperbilirubinemia. CONCLUSIONS:Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML-CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.

Background: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood. Objectives: To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status. Design: A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020. Methods: We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the “surv_cutpoint” function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels. Results: Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, p = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations ( R = −0.666, p = 0.005) and peak concentrations ( R = −0.499, p = 0.049) on day 7. Conclusion: Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL. Trial registration: www.clinicaltrials.gov (NCT02200978).

BACKGROUND:Prednisone response (PR) remains a key early treatment indicator in pediatric acute lymphoblastic leukemia (ALL). However, its independent prognostic significance has waned with the advent of minimal residual disease (MRD)-guided risk assessment. Evaluating the enduring biological and clinical significance of PR, especially in high-risk subtypes, could enhance the precision of therapeutic approaches. METHODS:This retrospective study analyzed clinical data from 2,979 pediatric patients primarily diagnosed with acute lymphoblastic leukemia (ALL) and enrolled in the South China Children's Leukemia Group (SCCLG-ALL)-2016 Collaborative Group between October 2016 and June 2023. Patients were categorized into "good prednisone response" (GPR) and "poor prednisone response" (PPR) groups based on their response to prednisone. Clinical characteristics were compared between groups using the chi-square test. Logistic regression was employed to analyze the correlation between prednisone response and early minimal residual disease (MRD). Survival analysis was performed using Kaplan-Meier curves, and prognostic factors were evaluated using Cox regression models. RESULTS:Among the 2,979 patients, 2,649 were categorized as GPR and 330 as PPR. Children in the PPR group exhibited multiple high-risk clinical features and had a poorer prognosis than those in the GPR group. However, multivariate Cox regression analysis revealed that days 15 and 33 MRD had a stronger predictive value than prednisone response. Notably, PR showed strong predictive value for MRD positivity on both Day 15 and Day 33. CONCLUSIONS:In this large real-world Chinese cohort, PR was not an independent prognostic marker but was strongly associated with early MRD burden. These findings support the contextual use of PR as a practical surrogate for MRD in resource-limited settings, and highlight the need to reconsider its role in modern risk-adapted treatment strategies.

The clinical-genetic characteristics of ETV6-RUNX1-like acute lymphoblastic leukemia (ALL) is still unclear in pediatrics. Therefore, we conducted Fluorescent In Situ Hybridization (FISH), Polymerase Chain Reaction(PCR) and Whole Transcriptome Sequencing (WTS) on 2171 B-lineage ALL cases and identified 49 (2.3%) ETV6-RUNX1-like and 406 (18.7%) ETV6-RUNX1 cases. We found that: i) ETV6-RUNX1-like patients were characterized by ETV6 abnormalities and enrich for PAX5, KRAS, CDKN2A/2B, CRLF2, IKZF1, PTTN11, NRAS, FLT3. ii) Genes affecting of transcription factor regulation, RAS signal pathway, cell cycle regulation, JAK/STAT signal pathway and epigenetic modification were significantly frequent in ETV6-RUNX1-like ALL. iii) Four hub genes, ETV6, CDKN2A, ABL1 and MYC, were identified among ETV6-RUNX1-like ALL. The clinical characteristics highlighted that: i) ETV6-RUNX1-like patients had higher minimal residual disease (MRD) persistence at day 15 (D15 MRD) than ETV6-RUNX1 patients (P = 0.023). ii) 5-year event-free survival (EFS) and overall survival (OS) of ETV6-RUNX1-like patients were both significantly worse than ETV6-RUNX1 patients (65.8 ± 15.4% vs. 95.7 ± 1.0%, P < 0.001 and 91.3 ± 4.2% vs 98.2 ± 0.7%, P = 0.006). iii) ETV6-RUNX1-like positive was the risk factor for EFS (HR 3.25 (95% CI, 1.23–8.61); P = 0.018). Therefore, it is important to discern ETV6-RUNX1-like patients early and opt for more intensive chemotherapy for these patients.

BACKGROUND:IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS:A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS:The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS:Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

Background: Realgar-Indigo naturalis formula (RIF) containing A S as a major ingredient is an oral arsenic available in China. The efficacy of RIF on pediatric acute promyelocytic leukemia (APL) is comparable to arsenic trioxide (ATO). However, it remains to be explored that the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorder which are the two main life-threatening events in children with APL. Procedure: We analyzed 68 consecutive children with newly diagnosed APL involved in SCCLG-APL study (NCT02200978). Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO (0.16 mg/kg·d) or RIF (135 mg/kg·d) was administrated on day 5 after mitoxantrone on day 3 (non-high-risk group, NHR) or day 2-4 (high-risk group, HR). Results: The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) groups ( p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis, respectively ( p = 0.04). The dynamic changes of WBC between the ATO and RIF groups were not statistically different. However, patients with high WBC counts or percentage of promyelocytes in peripheral blood tended to develop differentiation-related hyperleukocytosis. The improvement of coagulation indexes in the ATO and RIF groups had no statistical difference. Fibrinogen and prothrombin time had the quickest recovery rate. Conclusions: This study provides evidences that the incidence of DS and recovery of coagulopathy are similar whenever treating with RIF or ATO in children with APL.

Background: Maintenance therapy is an important part of childhood acute lymphoblastic leukemia (ALL). However, the optimal chemotherapy regimen for maintenance therapy is still controversial. We aimed to evaluate the benefits of the continuous use of 6-mercaptopurine(6-MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX) in maintenance therapy for pediatric ALL.Methods: A total of 3,008 pediatric patients with ALL were enrolled in South China (2008-2022) and assigned to one of three maintenance regimens. Randomly selected subjects (n=2406;80%) and the remaining subjects comprised the development and validation groups, respectively. The overall survival (OS) probability was calculated using a predictor-based nomogram to evaluate maintenance regimens impact on OS in relation to baseline characteristics. Nomogram performance was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve with 500 bootstrap resample validations. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the nomogram. Then interaction between predicted OS probability and actual overall mortality in different maintenance regimens was tested.Findings: According to the minimum criteria of non-zero coefficients of Lasso and logistic regression screening, elder age, high risk group, T-cell, higher white blood count cell(WBC), lower platelet(PLT), day-15 minimal residual disease(MRD) and d-33 MRD positive were independently associated with a lower OS. A nomogram model for OS was established based on these predictors. The AUC (C statistic) of the nomogram was 0.788 (95% CI: 0.72–0.856) in the development group and 0.746 (95% CI:0.692-0.846) in the validation group. The calibration curves after 1000 bootstraps displayed a good fit between the actual and predicted probabilities in both the development and validation groups. DCA showed that the model in the development and validation groups had a net benefit when the risk thresholds were 0–0.2 and 0–0.25, respectively. This model was used to predict the 5-year OS probability in different maintenance regimens. When the predicted 5-year OS probability between 75% and 95%, the benefit of continuous use of 6-MP and MTX with pulses of VCR and DEX on OM decreased progressively as predicted OS decreased(P<0.05).Interpretation: We have developed a predictive model that can be used to identify pediatric patients with ALL who benefit from continuous use of 6-MP and MTX with pulses of VCR and DEX in terms of OS. Specifically, patients with worse baseline characteristics appear to benefit the most.Trial Registration: The trial is registered at http://www.clinicaltrials.gov with the identifier NCT00846703, and is registered with the Chinese Clinical Trial Registry (Chi-CTR; https://www.chictr.org.cn/;number ChiCTR2000030357).Funding: This work was supported by the Guangzhou Science and Technology Program key projects (No.201803010032), Bethune Medical Scientific Research Fund Project (No.SCE111DS), Guangdong Medical Scientific Research Foundation(A2024057), Guangzhou Basic and Applied Basic Research Foundation (2024A04J4686), Yat-sen Excellent Young Scientists Fund (2024A03J1185) and Sun Yat-sen Pilot Scientific Research Fund (YXQH202205).Declaration of Interest: The authors declare that they have no competing interests.Ethical Approval: Written informed consent with or without assent was obtained from each participant and parent/legal guardian, in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, and by ethics committee of other cooperation centers

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

ObjectivesThe prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children’s Leukemia Group (SCCLG).MethodsA total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction.ResultsThe frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (P = 0.002) and poorer treatment response (P <0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (P = 0.030) and a higher risk of 3-year cumulative incidence of relapse (P = 0.008), while no impact was observed on 3-year overall survival (P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016).ConclusionCNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 × 10 5 hUCMSCs, 25 µg/ml hUCMSC-EVs, 50 µg/ml hUCMSC-EVs were co-cultured with 2 × 10 6 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4 + T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4 + T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-β1) ( P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 ( P > 0.05); only hUCMSCs inhibited CD19 + B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 ( P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multisystemic and multi-organ involvement, recurrent relapses and remissions, and the presence of large amounts of autoantibodies in the body as the main clinical features. The mechanisms involved in this disease are complex and remain poorly understood; however, they are generally believed to be related to genetic susceptibility factors, external stimulation of the body’s immune dysfunction, and impaired immune regulation. The main immune disorders include the imbalance of T lymphocyte subsets, hyperfunction of B cells, production of large amounts of autoantibodies, and further deposition of immune complexes, which result in tissue damage. Among these, B cells play a major role as antibody-producing cells and have been studied extensively. B1 cells are a group of important innate-like immune cells, which participate in various innate and autoimmune processes. Yet the role of B1 cells in SLE remains unclear. In this review, we focus on the mechanism of B1 cells in SLE to provide new directions to explore the pathogenesis and treatment modalities of SLE.

Objective:To analyze the efficacy, safety, and economy of RIF compared with intravenous arsenic trioxide (ATO) for the induction and consolidation therapy of pediatric APL.Materials and Methods:In this randomized control clinical trial (NCT02200978), children with newly diagnosed APL from June 2013 to December 2017 were randomly divided into RIF and ATO groups. The groups were treated with RIF or ATO in combination with all-trans retinoic acid (ARTA) and conventional chemotherapeutic drugs during induction and consolidation therapy.Results:Ninteen patients were enrolled, including eight in the RIF group and 11 in the ATO group. After induction therapy, the bone marrow morphologic complete remission (CR) rate, the median time to CR, and molecular remission (promyelocytic leukemia protein (PML)/retinoic acid receptor α (RARα) conversion) rates showed no significant differences between patients in the RIF versus ATO groups (100% vs. 100%, p=1.000; 22 vs. 24 days, p=0.395; 28.5% vs. 54.5%, p=0.367, resp.). After consolidation therapy, the molecular remission rate was 100% in both groups. At the end of more than two years of follow-up, the disease-free survival (DFS) rate was 100% in both groups.Conclusion:Oral RIF can achieve similar efficacy to intravenous ATO for APL in children with good safety, less toxicity, fewer side effects, and fewer inpatient days. Therefore, oral RIF can be used as an alternative to intravenous ATO for the treatment of APL in children.

Objective Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children’s leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan–Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.

Abstract At present, human umbilical cord mesenchymal stem cells(hUCMSCs) have been used in the clinical treatment of systemic lupus erythematosus(SLE), However, the detailed mechanism of MSCs remains unclear. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE.We isolated splenic mononuclear cells from MRL/lpr mice , a classical animal model of SLE.PBS(Phosphate-buffered saline), 2×105 hUCMSCs, 25µg/ml hUCMSC-EVs, 50µg/ml hUCMSC-EVs were co-cultured with 2×106 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4+T cell subsets and the concentrations of cytokines were detected .Both hUCMSCs and hUCMSC-EVs inhibited CD4+T cells , increased the production of T helper(Th)17 cells , promoted the production of interleukin（IL）-17 and transforming growth factor beta 1(TGF-β1) (P＜0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg )cells and IL-10 (P＞0.05);only hUCMSCs inhibited CD19+ B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P＜0.05).hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, hUCMSC-EVs play novel and potential regulator roles in SLE.

This study investigated the management and clinical outcomes along with associated factors of posterior reversible encephalopathy syndrome (PRES) in childhood hematologic/oncologic diseases. We present data from children with hematologic/oncologic diseases who developed PRES after treatment of the primary disease with chemotherapy and hematopoietic stem cell transplantation (HSCT) at 3 medical centers in Changsha, China from 2015 to 2020, and review all previously reported cases with the aim of determining whether this neurologic manifestation affects the disease prognosis. In the clinical cohort of 58 PRES patients, hypertension [pooled odds ratio (OR) = 4.941, 95% confidence interval (CI): 1.390, 17.570; P = 0.001] and blood transfusion (OR = 14.259, 95% CI: 3.273, 62.131; P = 0.001) were significantly associated with PRES. Elevated platelet (OR = 0.988, 95% CI: 0.982, 0.995; P < 0.001), hemoglobin (OR = 0.924, 95% CI: 0.890, 0.995; P < 0.001), and blood sodium (OR = 0.905, 95% CI: 0.860, 0.953; P < 0.001), potassium (OR = 0.599, 95% CI: 0.360, 0.995; P = 0.048), and magnesium (OR = 0.093, 95% CI: 0.016, 0.539; P = 0.008) were protective factors against PRES. Data for 440 pediatric PRES patients with hematologic/oncologic diseases in 21 articles retrieved from PubMed, Web of Science, and Embase databases and the 20 PRES patients from our study were analyzed. The median age at presentation was 7.9 years. The most common primary diagnosis was leukemia (62.3%), followed by solid tumor (7.7%) and lymphoma (7.5%). Most patients (65.0%) received chemotherapy, including non-induction (55.2%) and induction (44.8%) regimens; and 86.5% used corticosteroids before the onset of PRES. Although 21.0% of patients died during follow-up, in most cases (93.2%) this was not attributable to PRES but to severe infection (27.3%), underlying disease (26.1%), graft-vs.-host disease (14.8%), multiple organ dysfunction syndrome (8.0%), and respiratory failure (3.4%). PRES was more common with HSCT compared to chemotherapy and had a nearly 2 times higher mortality rate in patients with oncologic/hematologic diseases than in those with other types of disease. Monitoring neurologic signs and symptoms in the former group is therefore critical for ensuring good clinical outcomes following treatment of the primary malignancy.

Mitochondria participate in immune regulation through various mechanisms, such as changes in the mitochondrial dynamics, as metabolic mediators of the tricarboxylic acid cycle, by the production of reactive oxygen species, and mitochondrial DNA damage, among others. In recent years, studies have shown that extracellular vesicles are widely involved in intercellular communication and exert important effects on immune regulation. Recently, the immunoregulatory effects of mitochondria from extracellular vesicles have gained increasing attention. In this article, we review the mechanisms by which mitochondria participate in immune regulation and exert immunoregulatory effects upon delivery by extracellular vesicles. We also focus on the influence of the immunoregulatory effects of mitochondria from extracellular vesicles to further shed light on the underlying mechanisms.