Mixed phenotype acute leukemia (MPAL) represents an uncommon but heterogenous disease, often posing both a diagnostic and therapeutic challenge. The purpose of this retrospective study was to analyze the overall survival, event-free survival, and severity of associated complications after allo-HSCT in children with MPAL, and provide feasible recommendations for the treatment of MPAL patients.

We retrospectively analyzed a total of 14 pediatric patients with MPAL who received allo-HSCT at our center between January 2010 and June 2024.

In terms of immunophenotype, coexpression of myeloid and B-lymphoid antigens was observed in 10 patients (71.4%), and myeloid and T-lymphoid antigens in 4 (28.6%). Chromosomal abnormalities were found in 8 patients (57.1%) and BCR/ABL(+) was the most common fusion gene (3/14; 21.4%). All 14 patients underwent allo-HSCT after achieving the CR1 (78.6% with MRD-negative status pretransplantation). Among the 14 transplanted children, the OS rate was 92.9% and the EFS rate was 85.7%. No significant difference in OS, EFS, and CIR rates between children with Haplo-HSCT and those with MSD-HSCT (P>0.05). The rate of acute GVHD was 57.1% (8/14), and the rate of chronic GVHD was 71.4%, of which 90% were assessed as mild cGVHD, with the skin being the most common organ involved in cGVHD. Only one patient developed TA-TMA and died from transplant-related complications.

The children with MPAL who received allo-HSCT after MRD-negative CR often had a favorable disease control. Compared with patients receiving conventional chemotherapy, pediatric patients who received allo-HSCT showed a significant improvement in OS, EFS, and CIR rates. Although the incidence of cGVHD was relatively high, most of them were assessed as mild with no significant impact on daily activities.

Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) have a poor prognosis. In Ph+ALL04, allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) was indicated for all patients, and was performed in those who remained in CR at the scheduled time of transplantation, with 4-year event-free survival (EFS) and overall survival (OS) rates of 54% (95% confidence interval [CI]: 38%-68%) and 78% (95% CI: 62%-88%), respectively.

The Japan Children's Cancer Group conducted ALL-Ph13, a multicenter single-arm Phase 2 clinical trial, to improve outcomes and reduce HSCTs by using chemotherapy with tyrosine kinase inhibitors (TKIs) guided by minimal residual disease (MRD). The primary endpoint was the 3-year EFS rate.

Between 2013 and 2017, 41 of 43 enrolled patients with Ph⁺ ALL aged 1-19 years were eligible. Imatinib was started on Day 15 of induction and switched to dasatinib if MRD-positive after consolidation IB. TKIs were administered until the end of maintenance treatment (Week 104), with temporary discontinuation due to the severity of nonhematological adverse events and resumption at 80% of the original dose. When MRD was positive after the three HR blocks, HSCT was performed. Following four sepsis-related deaths, the protocol was amended in 2016, after which no such deaths occurred. Six patients (15%) underwent HSCT in the first CR, one per protocol indication and five without. The 3-year EFS and OS rates were 65% (95% CI: 48%-78%) and 85% (95% CI: 70%-93%), respectively. As several relapses occurred beyond 3 years, the 5-year EFS and OS rates were also calculated: 48% (95% CI: 30%-64%) and 85% (95% CI: 70%-93%), respectively.

Compared with Ph+ALL04, HSCT was substantially reduced in ALL-Ph13 while maintaining comparable outcomes. Further optimization of treatment, particularly the duration of TKI administration, is needed to maintain long-term EFS.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The pro-drug 6-mercaptopurine (6-MP), essential during maintenance, is converted into active 6-thioguanine (6-TGN) and toxic 6-methylmercaptopurine (6-MMP) metabolites, resulting in marked variability in efficacy and toxicity. 6-MP therapy is further limited by poor adherence, variable absorption, and complex metabolism. Allopurinol is sometimes used to correct skewed metabolism, though its precise clinical role remains unclear.

This study aimed to develop population pharmacokinetic (popPK)-based strategies to optimize 6-MP dosing in children and improve therapeutic outcomes. A popPK model was developed using 6-MMP and 6-TGN concentrations from the pediatric oncology cohort. Model-based simulations in 1000 virtual patients were performed to explore optimized dosing strategies, with and without allopurinol, aiming to reach the therapeutic target (6-MMP <5700 pmol/8 × 10⁸ RBC and 6-TGN between 230 and 450 pmol/8 × 10⁸ RBC).

The popPK model revealed a linear correlation between 6-MP dose and metabolite concentrations. Allopurinol co-administration substantially shifted metabolites' distribution from 80% 6-MMP/20% 6-TGN to 21% 6-MMP/79% 6-TGN. Simulations identified optimal 6-MP doses of 40-75 mg/m² without allopurinol, and only 10-15 mg/m² when co-administered.

Allopurinol co-treatment reduces toxicity while maintaining therapeutic efficacy at lower 6-MP doses. The proposed model warrants prospective evaluation for clinical relevance confirmation.

Pulmonary fiducial markers (FMs) allow real-time tracking for stereotactic body radiotherapy (SBRT) by CyberKnife, which is an alternative to surgery in early-stage inoperable non-small-cell lung cancer (NSCLC) or intrathoracic oligometastatic disease. We conducted a systematic review and meta-analysis to compare the clinical performance and safety of 3 available approaches for FMs insertion for peripheral pulmonary lesions (PPL): transthoracic, endovascular, and endobronchial accesses.

A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all articles on FM implantation before SBRT. Outcomes included clinical performance (inaccurate FM location and tracking rate) and per-procedural complications (pneumothorax and hemoptysis). We included 27 studies for a total of 2065 patients (627 with endobronchial access, 993 with transthoracic access, and 445 with endovascular access) and 4149 FMs insertions.

The lowest inaccurate FM location rate was found with nonlinear FM inserted by endobronchial access (0.030, 95% CI: 0.004-0.074). Tracking rate was high and similar with endobronchial (0.975, 95% CI: 0.949-0.994), endovascular (0.999, 95% CI: 0.941-1.000), and transthoracic approaches (0.985, 95% CI: 0.963-0.998). The highest rates of pneumothorax (0.342, 95% CI: 0.261-0.427) and hemoptysis (0.035, 95% CI: 0.015-0.060) occurred with the transthoracic access.

While nonlinear FM insertion through endobronchial access achieved the lowest rate of inaccurate FM location, all 3 implantation approaches demonstrated high tracking feasibility for SBRT delivered using the CyberKnife system.

Liver transplantation (LT) is the only curative option for patients with unrespectable hepatocellular carcinoma (HCC). In the United States. current organ allocation policies grant the same priority to patients with tumors within the Milan criteria. This uniform approach leads to higher waitlist dropout among candidated with more advanced tumors of with more aggressive tumor biology. A model to stratify HCC candidates into different risk groups could optimize organ allocation by providing priority to patients within transplantable criteria but at increased risk of dropout.

Data from 30,565 adult HCC LT candidates within the Scientific Registry of Transplant Recipients (SRTR) (2002-2022) were used. Inclusion criteria were age ≥18 years and tumors within Milan criteria. Recipients of previous transplants, multi-visceral grafts, and those with missing exception applications for HCC were excluded. The population was randomly divided into development (n = 15,282) and validation (n = 15,283) cohorts. The primary outcome was 5-year LT survival benefit, defined as the difference in survival with and without LT.

C-MELD 3.0, serum AFP, and tumor burden score (TBS) were the strongest predictors of LT survival benefit. The HCC-Liver Transplant Survival Benefit model was defined as HCC-LTSB = 0.65 × (C-MELD 145 3.0 - 6) + 1.99 × (TBS - 2.25) + 0.68 × log2(AFP). Validation demonstrated strong performance (Pearson's r = 0.93; 95% CI: 0.93-0.94; R² = 0.87; C-index = 0.91).

The HCC-LTSB model accurately predicted the survival benefit provided by LT in candidates listed with unresectable HCC within UNOS criteria.

Evidence to guide treatment after progression on immunotherapy remains limited in advanced non-small cell lung cancer (NSCLC). We descriptively report real-world outcomes of two PD-1 rechallenge strategies (PD-1 plus chemotherapy and PD-1 plus anlotinib) using a contemporaneous docetaxel cohort as contextual reference.

Patients with advanced NSCLC who failed prior immunotherapy were screened retrospectively, 33 patients received PD-1 blockade plus chemotherapy, 31 received PD-1 blockade plus anlotinib and 63 patients treated with docetaxel monotherapy were served as a contextual reference cohort. Outcomes including objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were summarized by cohort. Survival outcomes were estimated using Kaplan-Meier methods.

ORR and DCR were 30.3% (95% CI: 15.6%-48.7%) and 84.8% (95% CI: 68.1%-94.9%) in PD-1 plus chemotherapy cohort, 22.6% (95% CI: 9.6%-41.1%) and 80.6% (95% CI: 62.5%-92.5%) in PD-1 plus anlotinib cohort, 15.9% (95% CI: 7.9%-27.3%) and 54.0% (95% CI: 40.9%-66.6%) in docetaxel cohort. Median DoR among responders was 6.9 months (95% CI: 0.7-13.1), 7.1 months (95% CI: 5.0-9.2), and 3.1 months (95% CI: 1.9-4.3), respectively. Median PFS was 7.0 months (95% CI: 0.7-13.3), 6.5 months (95% CI: 2.2-10.8), and 3.3 months (95% CI: 2.2-4.4), and median OS was 17.8 months (95% CI: 8.0-27.6), 16.8 months (95% CI: 13.9-19.7), and 9.5 months (95% CI: 4.8-14.2), respectively. Any-grade TRAEs occurred in 84.8%, 80.6%, and 81.0%, and grade ≥3 TRAEs were 42.4%, 41.9%, and 34.9%, respectively. No treatment-related deaths were observed.

PD-1 rechallenge strategies showed measurable antitumor activity and manageable safety profile in a subset of previously immunotherapy-treated advanced NSCLC. Limitations existed in this study and the findings were descriptive and hypothesis-generating and should be interpreted cautiously because treatment selection was non-random and important confounders might be incompletely captured.

With HPV vaccines for males recently approved in China (2025), this study assessed awareness of HPV and HPV vaccine among junior high school boys in Eastern China, a population underrepresented in research.

A cross-sectional study was conducted in Zhejiang Province in 2023 using multistage cluster sampling. Three cities were purposively selected; within each city, one urban district and one rural county were randomly chosen. A total of six junior high schools (one from each selected district/county) participated in the study, with students randomly sampled from each grade level. Participants completed an anonymous online questionnaire. Univariate and multivariate logistic regression analyses were performed to identify factors associated with awareness of HPV and the HPV vaccine among male junior high school students.

Among 1,786 male participants, awareness rates for HPV and the HPV vaccine were 24.7 and 30.7%, respectively. Multivariate analysis revealed factors significantly associated with HPV awareness: urban residence (aOR = 2.20, 95% CI: 1.57-3.08), knowing someone affected by cancer (aOR = 1.40, 95% CI: 1.02-1.92), cervical cancer awareness (aOR = 5.04, 95% CI: 3.48-7.28), HPV vaccine awareness (aOR = 21.31, 95% CI: 15.35-29.60), and concern for partner's cervical cancer risk (aOR = 1.75, 95% CI: 1.23-2.49). Factors significantly associated with HPV vaccine awareness included: knowing someone affected by cancer (aOR = 1.58, 95% CI: 1.18-2.13), cervical cancer awareness (aOR = 2.43, 95% CI: 1.78-3.33), HPV awareness (aOR = 19.84, 95% CI: 14.39-27.36), concern for partner's cervical cancer risk (aOR = 1.47, 95% CI: 1.47-2.91), perceiving being less likely to be infected with HPV (aOR = 1.48, 95% CI: 1.06-2.06), and having received school-based health education on HPV/vaccine (aOR = 2.27, 95% CI: 1.67-3.08).

Awareness of HPV and HPV vaccine among junior high school boys in Zhejiang province is low. Targeted interventions, particularly school health programs emphasizing HPV and vaccine knowledge, male HPV risks, the benefits of vaccination, and partner protection, are crucial to improve vaccine uptake in this population.

Treatment failure in glioblastoma (GBM) is primarily attributed to the convergence of multiple barriers, including an immunosuppressive tumor microenvironment (TME), intratumoral heterogeneity, and the blood-brain barrier. Chimeric antigen receptor macrophages (CAR-M) therapy presents a promising new avenue for GBM treatment, leveraging its inherent tumor-homing capacity, TME reprogramming function, and potential to bridge innate and adaptive immunity. However, despite promising preclinical data, clinical efficacy in GBM remains unproven. This review critically analyzes the translational gap. We first outline the theoretical rationale and inherent advantages of CAR-M therapy in overcoming the core barriers of GBM. We then critically assess the limitations of current preclinical evidence and the uncertainties associated with its extrapolation to the clinical setting. We then focus on bottlenecks such as target selection strategies, engineering design, and TME-driven issues like phenotypic inactivation and antigen escape, discussing corresponding optimization approaches like armoring modifications, logic-gated designs, and convection-enhanced delivery. Finally, we propose a pragmatic clinical translation pathway prioritizing mechanistic validation. This pathway emphasizes integrating CAR-M therapy with combinatorial approaches and smart technologies in early-phase clinical trials, supported by biomarker analyzes, to address fundamental biological questions regarding the homing, survival, and function of these cells in patients. This review aims to provide a systematic and critical reference to guide the translation of CAR-M therapy from concept to clinical application, a path characterized by both opportunities and challenges.

Treating refractory acetylcholine receptor-positive generalized myasthenia gravis (AChR+ gMG) remains challenging, especially for patients requiring long-term immunosuppressive therapy. Current treatments often lack specificity and pose significant long-term risks, underscoring the need for alternatives. Telitacicept, a novel dual inhibitor of B lymphocyte stimulator (BLyS) and proliferation-inducing ligand (APRIL), offers a promising targeted therapeutic approach. This study aimed to evaluate the efficacy and safety of telitacicept in the treatment of refractory AChR+ generalized myasthenia gravis.

This retrospective study included 42 patients with refractory AChR+ gMG who received telitacicept. The primary outcomes assessed were changes from baseline in Quantitative Myasthenia Gravis (QMG) scores, analyzed using mixed-effects models. Secondary outcomes comprised cumulative response rates, reductions in concomitant immunosuppressive medications, and safety events.

A total of 42 refractory MG patients with MGFA class II-IV were enrolled. Significant improvements were observed in the QMG total score (least-squares [LS] mean change at month 5: -2.24, 95% CI -3.34 to -1.15, p<0.001), with sustained benefits across ocular, limb, and bulbar areas. Cumulative response rates reached 69.9% for MGFA-PIS and 73.8% for QMG improvement (≥3-point reduction) by 6 months. Notable decreases in prednisone (LS mean -10.17 mg/day, p<0.001) and immunosuppressant use were also seen. The therapy demonstrated a promising safety profile.

Telitacicept demonstrated significant efficacy in refractory AChR+ gMG and may reduce dependence on traditional immunosuppressants. These real-world findings support its use as a valuable treatment choice for this challenging patient group.

Immunotherapy combined with chemotherapy has improved outcomes in advanced gastric cancer (GC), but reliable biomarkers to predict clinical benefit remain limited. Metabolomics provides a comprehensive assessment of systemic metabolic changes and may yield prognostic indicators to guide treatment selection.

We performed untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics on baseline plasma from 40 patients with advanced GC receiving first-line programmed cell death protein-1 (PD-1) inhibitor plus chemotherapy. Patients were stratified into long-term survivors (LTS) and short-term survivors (STS) based on median overall survival (OS). Differential metabolites were identified using multivariate statistics, followed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis to construct a metabolite-based risk score. Prognostic performance was evaluated using Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) curves, and multivariate Cox models. Comparisons with conventional clinical factors were conducted, and a prognostic nomogram was developed. Proportional-hazards assumptions were assessed with Schoenfeld residuals; discrimination was optimism-corrected using 1,000-bootstrap resampling; Harrell's concordance index (C-index), time-dependent area under the curve (AUC), and bootstrap-corrected calibration curves were reported. Twelve-month decision-curve analysis (DCA) quantified net clinical benefit compared with clinicopathologic baselines.

A total of 4,298 metabolites were detected, including 830 Level 1 and 1,321 Level 2 identifications. Principal component analysis and orthogonal partial least squares discriminant analysis showed clear separation between LTS and STS groups. Differential analysis revealed metabolites enriched in bile acid, amino acid, and retinol metabolism pathways. Cox and LASSO analyses identified six independent prognostic metabolites. The resulting metabolite-based risk score significantly stratified OS and progression-free survival (p < 0.01) and demonstrated stable predictive accuracy over 6-24 months. Compared with age, sex, tumor grade, and programmed death-ligand 1 combined positive score (PD-L1 CPS), the risk score showed superior discrimination. A nomogram integrating risk score, grade, and PD-L1 CPS yielded accurate OS predictions with strong calibration and higher net benefit in DCA. Internal validation supports the robustness of findings within this single-center, 40-patient cohort.

A plasma metabolite-based risk score derived from six biomarkers independently predicts survival in advanced GC treated with PD-1-based immunotherapy and offers a practical tool for individualized prognosis.