This multicenter, randomized, controlled study was conducted to explore the safety and efficacy of low-dose baricitinib plus danazol for ITP patients who had failed corticosteroids and at least one recommended subsequent treatment. Participants were randomly assigned to receive baricitinib plus danazol (n = 108) or danazol alone (n = 108) by a central, interactive web-based system. Patients and caregivers were not blinded to group assignment. Efficacy assessments were performed in the intention-to-treat population by investigators blinded to group assignment. The primary endpoint was 6-month durable response. Forty-nine (45.4%) patients in the combination arm and 22 (20.4%) patients in the monotherapy arm achieved 6-month durable response (P < 0.001). The safety analysis set included patients who received at least one dose of study medication (n = 108 in the combination arm and n = 105 in the monotherapy arm). Fifty-two (48.1%) patients receiving baricitinib plus danazol and 47 (44.7%) patients receiving danazol alone reported at least one adverse event. Each arm reported two patients who developed an adverse event causing study discontinuation and one patient who developed a grade 3 or more severe adverse event. Low-dose baricitinib plus danazol might be a novel option for difficult-to-treat ITP. Funding: National Key Research and Development Program of China (No. 2023YFC2507800), National Natural Science Foundation of China (No. 82230004, No. 82430006, No. 82400157), Capital Health Development and Research of Special (No. 2022-1-4082), and Beijing Natural Science Foundation (No. 7242154 and No. 7232188). ClinicalTrials.gov identifier: NCT05852847.

BACKGROUND:Primary intestinal (PI) diffuse large B-cell lymphoma (DLBCL) represents a biologically and clinically heterogeneous subtype of extranodal lymphoma. The international prognostic index (IPI) was originally developed for predominantly nodal DLBCL (N-DLBCL) and inadequately reflected site-specific risk within the intestine. Prompted by colorectal carcinoma where primary tumor laterality (left vs right of the splenic flexure) is prognostically relevant, we raised the question of whether analogous intestinal laterality might influence survival in PI-DLBCL. AIM:To investigate whether intestinal laterality influences survival in PI-DLBCL and construct a location-integrated prognostic nomogram. METHODS:We retrospectively analyzed 3832 PI-DLBCL patients (SEER 2002-2021) and externally validated in 107 patients (Sun Yat-sen University Cancer Center 2014-2024). A prognostic nomogram integrating age, Ann Arbor stage, chemotherapy, surgery, and tumor sidedness (left vs right of the splenic flexure) was constructed. To mitigate treatment-selection bias, we additionally performed propensity score matching (PSM) for left- vs right-sided PI-DLBCL. RESULTS:Left-sided PI-DLBCL was independently associated with inferior overall survival (OS) (hazard ratio = 1.15, P = 0.035) and the association persisted after PSM. When compared with intra-abdominal N-DLBCL, right-sided PI-DLBCL showed superior OS, whereas left-sided PI-DLBCL had worse OS. The nomogram achieved superior discrimination vs the IPI (C-index: 0.749 vs 0.710) and higher time-dependent area under the curves (1-year: 0.865 vs 0.753; 2-year: 0.792 vs 0.731; 3-year: 0.786 vs 0.727) in the external validation cohort. The nomogram stratified patients into low-, median-, and high-risk groups with clear OS separation in both the training and external cohorts. CONCLUSION:Intestinal laterality is an independent, clinically actionable determinant of survival in PI-DLBCL. The proposed nomogram provides individualized survival prediction and risk stratification and showed higher discrimination than the IPI, supporting the incorporation of tumor anatomical location into prognostic assessment and risk-adapted management.

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is rare in immunocompetent individuals but is associated with an extremely high mortality rate. Here, we report a case of disseminated histoplasmosis (DHP) in an immunocompetent patient. The pathogen was confirmed by bone marrow smear microscopy and metagenomic next-generation sequencing (mNGS). The patient experienced rapid clinical deterioration and was subsequently diagnosed with HLH secondary to DHP. Following targeted antimicrobial therapy with amphotericin B and immunomodulatory treatment involving etoposide and ruxolitinib, the patient's clinical condition improved. Early clinical manifestations of DHP are often atypical, while conventional diagnostic methods frequently yield negative results in the early stage. This case indicates that bone marrow examination combined with mNGS facilitates early definitive diagnosis. Furthermore, this report rarely describes the sequential morphological changes of Histoplasma capsulatum in bone marrow tissue.

BACKGROUND:Eltrombopag is an effective second-line therapy for immune thrombocytopenia (ITP), but its long-term efficacy is limited. All-trans retinoic acid (ATRA) has immunomodulatory effects targeting ITP pathophysiology. We investigated whether combining ATRA with eltrombopag improves long-term outcomes for glucocorticoid-resistant or relapsed ITP. METHODS:We conducted a multicenter, randomized, open-label trial in adults with glucocorticoid-resistant or relapsed ITP (platelets <30×109/l). Patients were randomly assigned 1:1 to ATRA (12 weeks) plus eltrombopag or eltrombopag monotherapy. The primary outcome was an 18-month sustained response (platelet count ≥30×109/l without clinically significant bleeding or rescue therapy). RESULTS:Ninety-six patients were randomly assigned, 48 per group. At 18 months, 60% (29/48) in the ATRA-plus-eltrombopag group achieved a sustained response, versus 35% (17/48) in the monotherapy group (odds ratio: 2.78; 95% confidence interval [CI]: 1.22-6.37; P=0.014). The combination was associated with a higher complete response rate (79% vs. 58%; 95% CI for difference, 2 to 39 percentage points) and longer median response duration (75 vs. 37 weeks; hazard ratio for relapse, 0.45; 95% CI, 0.23-0.86). Adverse events were comparable between groups, with no grade 3-4 events or treatment-related deaths. However, clinically significant bleeding of World Health Organization grades 2 or 3 was 21% in the combination group at baseline compared with 10% in the monotherapy group. CONCLUSIONS:In patients with glucocorticoid-resistant or relapsed ITP, a 12-week ATRA course with eltrombopag significantly enhanced the 18-month sustained response rate compared to eltrombopag alone. (Funded by Capital Health Research and Development of Special Fund and others; ClinicalTrials.gov number, NCT05438875.).

Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with poor prognosis that requires intensive systemic therapy, highlighting the potential impact of psychosocial factors on disease management and clinical outcomes. In this population-based study using SEER data from 2013 to 2022, we identified 5,919 patients newly diagnosed with PTCL. Propensity score matching (PSM) was applied to control for baseline differences, and survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Unmarried patients were more likely to be female, younger, and of non-White race. Survival analysis demonstrated that unmarried patients had significantly lower 5-year overall survival (OS: 40.7

Familial hemophagocytic lymphohistiocytosis (FHL) is the prototypical genetic form of hemophagocytic lymphohistiocytosis (HLH), a potentially fatal hyperinflammatory condition. Limited awareness of HLH with isolated central nervous system (CNS) involvement often leads to underdiagnosis or diagnostic delay. Here, we report a 13-year-old girl with FHL type 3 (FHL3) presenting with isolated CNS involvement who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT). This case expands the clinical spectrum of FHL3 and highlights that isolated neurological symptoms may be the initial or sole manifestation of FHL, even without systemic signs. Allogeneic HSCT remains the only definitive therapy for FHL. The patient received a conditioning regimen comprising thiotepa, etoposide, busulfan, cyclophosphamide, and antithymocyte globulin (TT/VP16/BU/CY/ATG). The graft consisted of 20.4 × 10⁸/kg mononuclear cells and 4.71 × 10⁶/kg CD34 + cells. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX). Neutrophil engraftment (absolute neutrophil count ≥ 0.5 × 10⁹/L) occurred on day + 13, and platelet engraftment (≥ 20 × 10⁹/L) on day + 19. The patient did not develop GVHD and achieved full, stable donor chimerism with successful engraftment and minimal toxicity. Neurological remission was observed following transplantation. At the last follow-up on day 679, the patient remained alive without neurological relapse or systemic HLH. In conclusion, this patient achieved long-term CNS remission and correction of the underlying molecular defect following allogeneic HSCT with a TT/VP16/BU/CY/ATG conditioning regimen.

ABSTRACT:Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) typically have a poor prognosis. In preclinical studies, lenalidomide and a Bruton tyrosine kinase (BTK) inhibitor demonstrated synergistic antitumor effects. Zanubrutinib, a next-generation BTK inhibitor, has greater selectivity to minimize off-target binding. BGB-3111-110 was a phase 1 multicenter dose-escalation/-expansion study. Patients with R/R DLBCL received zanubrutinib 160 mg twice daily plus lenalidomide (15, 20, or 25 mg once daily) until progression or unacceptable toxicity. Primary end points were safety, recommended phase 2 dose (RP2D), and overall response rate (ORR; Lugano 2014 criteria). Sixty-six patients were enrolled and treated. Patients had a median of 2 previous therapies, 83% had stage III/IV disease, and ∼67% had non-geminal center B-cell-like or activated B-cell-like DLBCL. No dose-limiting toxicities occurred; the lenalidomide RP2D was 25 mg once daily when combined with zanubrutinib 160 mg twice daily. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 74%; the most common (>20%) grade ≥3 TEAEs were decreased neutrophil count (58%) and decreased white blood cell count (29%). TEAEs led to 7 treatment discontinuations (11%) and 2 deaths (3%). At the RP2D, ORR and complete response rate were 58% and 42%, respectively; median time to response was 2.8 months. Median duration of response was 14.9 months. Median progression-free survival was 5.5 months (95% confidence interval [CI], 2.9-11.1); the 12-month event-free rate was 34% (95% CI, 21-48). Zanubrutinib plus lenalidomide demonstrated acceptable tolerability and antitumor activity in patients with R/R DLBCL. This trial was registered at www.clinicaltrials.gov as NCT04436107.

ABSTRACT Background Secondary primary solid malignancies (SPSMs) significantly impact long‐term outcomes in lymphoma patients. However, subtype‐specific differences remain unclear, such as diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods This study collected 1,377 DLBCL and 489 FL patients, identifying 50 DLBCL and 31 FL cases with SPSMs. Clinical characteristics, SPSM types, and survival were compared in these 81 patients. Demographic, clinical, treatment‐related variables (including radiotherapy for primary lymphoma, recorded as yes/no), and survival outcomes were collected. Overall survival (OS) was analyzed using Kaplan–Meier estimates and Cox proportional hazards models. The cumulative incidence of SPSMs was evaluated with competing risk analysis (death as a competing event), and group comparisons were performed with Gray's test. Prognostic factors identified in univariable analysis (p < 0.05) were included in a multivariable Cox model. A nomogram was developed, with discriminative ability assessed by the area under the receiver operating characteristic curve (ROC). Statistical significance was set at p < 0.05. Results SPSMs were observed more frequently in FL (6.34%) than DLBCL (3.63%). Thyroid cancer predominated (22.2%, 18/81). DLBCL patients developed SPSMs earlier than FL patients (median 28.47 vs. 41.77 months, p = 0.031), though cumulative incidence accounting for competing risks did not differ significantly (Gray's test p = 0.34). DLBCL patients with SPSMs had inferior OS compared to FL patients (p = 0.04). Non‐GCB DLBCL showed greater SPSM diversity and survival disadvantage. Multivariable analysis identified FL (vs. DLBCL) subtype (HR = 0.328, p = 0.018), bone marrow infiltration (HR = 2.815, p = 0.014), initial radiotherapy before SPSM diagnosis (HR = 3.475, p = 0.005), and shorter time to SPSM development (HR = 0.973 per month, p = 0.021) as independent prognostic factors for worse OS. The nomogram model showed acceptable discrimination, with an AUC of 0.761 in the time‐dependent ROC analysis. Conclusion This study provides novel insights into SPSM characteristics and prognostic differences in DLBCL and FL patients within a Chinese cohort. SPSMs in FL patients were observed more frequently, while DLBCL patients, particularly those with non‐GCB subtypes, experience earlier SPSM onset and poorer survival. The validated nomogram, incorporating lymphoma‐related factors, enables personalized risk stratification. However, the single‐center design, small sample size (n = 81), and lack of SPSM‐specific data limit generalizability, necessitating multi‐center studies with comprehensive SPSM characterization for validation.

Hemophagocytic lymphohistiocytosis (HLH) has been described as a threshold disease depending on triggering factors and the residual cytotoxic capacity of NK cells. This study aimed to investigate the clinical characteristics of Epstein–Barr virus (EBV)-triggered primary HLH and the prognostic value of EBV-DNA load in EBV-triggered primary HLH cases. We retrospectively analyzed the clinical data of 95 patients with primary HLH treated between January 2013 and January 2024. Based on the peripheral blood EBV status at initial diagnosis, 57 patients were categorized into the EBV-triggered primary HLH group and 38 patients into the non-EBV-triggered primary HLH group. Clinical and functional characteristics, response to treatment, and prognosis were compared between the two groups. Among patients with EBV-triggered primary HLH, the proportion of patients with familial HLH type 2 (FHL2) was significantly lower (P = 0.011), whereas the proportion of patients with X-linked lymphoproliferative disorder (XLP) was higher (P = 0.037). Functional assays showed that in primary HLH patients with gene defects in cytotoxic degranulation, the proportion of EBV-triggered primary HLH patients with reduced NK cell activity and degranulation function was significantly higher (P = 0.026 and P = 0.030). Importantly, multivariate Cox regression analysis identified EBV-DNA > 10,000 copies/mL as an independent risk factor affecting the prognosis of patients with EBV-triggered primary HLH, particularly in non-FHL cases (P = 0.045). EBV-triggered primary HLH is more prevalent in patients with XLP but less frequent in FHL2 patients. High EBV-DNA load is an adverse prognostic factor in EBV-triggered primary HLH patients.

Introduction: An accurate and reliable prognostic model for Nasal Extranodal Natural Killer/T-cell Lymphoma (ENKTL) is critical for survival outcomes and personalized therapy. Currently, there is no Magnetic Resonance Imaging (MRI)- based radiomics analysis in the prognosis model for nasal ENKTL patients. Objective: We aim to explore the value of MRI-based radiomics signature in the prognosis of patients with nasal ENKTL. Methods: A total of 159 nasal ENKTL patients were enrolled and divided into a training cohort (n=81) and a validation cohort (n=78) randomly. Radiomics features from pretreatment MRI examination were extracted, respectively. Then two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to select the radiomics signatures and establish the Rad-score. Univariate and multivariate Cox proportional hazards regression models were used to investigate the prognostic value of baseline clinical features and establish clinical models. A radiomics nomogram based on the Rad-score and clinical features was constructed to predict Overall Survival (OS). The predictive efficacy of the three models was evaluated in two cohorts. Results: A total of 1,345 features were extracted from T2-weighted (T2-w) and Contrast-enhanced T1-weighted (CET1-w) images, respectively, and 1,037 features with Intraclass Correlation Coefficient (ICC) >0.7 were selected. Ultimately, 20 features were chosen to construct the Rad-score, which showed a significant association with OS. The C-indexes of the Rad-score were 0.733 (95% confidence interval [CI]: 0.645 to 0.816) and 0.824 (95% CI: 0.766-0.882), respectively, in training and validation cohorts. Through the univariate and multivariate analyses, three independent risk factors for OS were identified: Rad-score (HR: 10.962, 95% CI: 3.417-35.167, P <0.001), lactate dehydrogenase (LDH) level (HR: 3.009, 95% CI: 1.128-8.510, P = 0.028) and distant lymph-node involvement (HR: 2.966, 95% CI: 1.015-8.664, P = 0.047). Patients with distal lymph node involvement and LDH level before treatment were included in the clinical model, which achieved a C-index of 0.707 (95% CI: 0.600–0.814) in the training cohort and 0.635 (95% CI: 0.527–0.743) in the validation cohort. We integrated the Rad-score and clinical variables to establish a radiomics nomogram, which exhibited a satisfactory prediction performance with the C-indexes of 0.849(95% CI: 0.781-0.917) and 0.931(95% CI: 0.882-0.980) in two cohorts, respectively. The radiomics nomogram was more accurate in predicting OS in patients with nasal ENKTL than the other two models. Based on the radiomics nomogram, patients were categorized into low-risk and high-risk groups in two cohorts (P all < 0.05). The high-risk group defined by this nomogram exhibited a shorter OS. Conclusion: The Rad-score was significantly correlated with OS for nasal ENKTL patients. Moreover, the MRI-based radiomics nomogram could be used for risk stratification and might guide individual treatment decisions.

BACKGROUND:To investigate the value of pretreatment nasopharyngeal and neck magnetic resonance imaging (NN-MRI) combined with positron emission tomography (PET)/CT-guided therapy for improving survival in upper aerodigestive tract NK/T-cell lymphoma (UADT-NKTL) patients. METHODS:We performed a prospective cohort study including 171 untreated patients histologically diagnosed with UADT-NKTL, of whom 71 patients received PET/CT combined with NN-MRI and the other 100 patients received PET/CT alone. The clinical stage of every patient was classified according to the Ann Arbor and TNM staging systems. Clinical stage, target volume delineation, and survival were evaluated and compared for PET/CT with and without NN-MRI. RESULTS:By detecting additional local lesions, NN-MRI upgraded the clinical stages on the basis of the Ann Arbor staging system and TNM staging system compared to the results of PET/CT (9/71, p = 0.011; 11/71, p = 0.019, respectively), which revised the target volume delineation of radiotherapy (9/71) in the PET/CT-MRI group. Compared with those in the PET/CT group, 3-year local recurrence-free survival was prolonged in the PET/CT-MRI group (100% vs. 74.9%; p < 0.001), and 3-year overall survival and progression-free survival were better in the PET/CT-MRI group (84.5% vs. 76.3%, p = 0.04 and 78.3% vs. 67.3%, p = 0.03, respectively). CONCLUSION:NN-MRI and PET/CT-guided therapy could complementarily assist in optimizing the determination of clinical stage and target delineation, which could improve the prognosis of UADT-NKTL patients.

Objective:To investigate the risk factors,clinical characteristics,and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease,so as to provide a reference for infection control.Methods:The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected.The clinical characteristics,susceptibility factors,and antibiotic resistance of the children were retrospectively analyzed.Results:Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children(≤14 years old)with hematological diseases was the highest(19.91％)and significantly higher than other bacteria,accounting for 38.64％of Gram-positive cocci,and presented as an increasing trend year by year.A total of 427 children tested positive blood cultures,including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever.Most children experienced a recurrent high fever in the early and middle stages(≤6 d)of neutropenia and persistent fever for more than 3 days.After adjusting the antibiotics according to the preliminary drug susceptibility results,the body temperature of most children(63.5％)returned to normal within 4 days.The 85 children were mainly diagnosed with acute myeloid leukemia(AML),accounting for 84.7％.The proportion of children in the neutropenia stage was 97.7％.The incidence of oral mucosal damage,lung infection,and gastrointestinal injury symptoms was 40％,31.8％,and 27.1％,respectively.The ratio of elevated C-reactive protein(CRP)and procalcitonin was 65.9％and 9.4％,respectively.All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid,and the resistance rate to penicillin,cefotaxime,levofloxacin,and quinupristin-dalfopristin was 10.6％,8.2％,9.4％,and 14.1％,respectively.None of children died due to bloodstream infection caused by Streptococcus mitis.Conclusion:The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases,especially in children with AML.Among them,neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors.The common clinical symptoms include persistent high fever,oral mucosal damage,and elevated CRP.Penicillin and cephalosporins have good sensitivity.Linezolid,as a highly sensitive antibiotic,can effectively control infection and shorten the course of disease.

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disorder characterized by excessive cytokine release. More than 30% of HLH cases are refractory to frontline therapy. Unfortunately, there is no universally accepted second-line regimen, and about 30% of patients fail to respond to current salvage treatments. Moreover, evidence guiding alternative therapies and the optimal timing for switching to new treatments in refractory patients is limited. This study retrospectively analyzed the efficacy and safety of the RED regimen (ruxolitinib, emapalumab, and dexamethasone) in 15 refractory HLH patients who had failed at least two previous salvage therapies. Overall, eight (53.3%) patients achieved partial remission, and four of those eight proceeded to hematopoietic stem cell transplantation (HSCT). Notably, pre-RED levels of C-X-C motif chemokine 9 (CXCL9) and interleukin-18 (IL-18) were significantly higher in patients who later responded to RED, suggesting that these biomarkers may predict a better response. We also observed that, for eight partial-remission patients, hemoglobin, fibrinogen, aspartate aminotransferase, calcium, and CXCL9 levels tracked well with early therapeutic responses (one to two weeks). No grade 3 or higher adverse effects were linked to the RED regimen. This comprehensive investigation of the RED approach in HLH, although small in sample size, supports the possibility that RED can serve as an effective and relatively safe salvage therapy for refractory HLH.

CLL1-targeted chimeric antigen receptor T (CAR-T) cell therapy has shown clinically meaningful activity in relapsed/refractory acute myeloid leukemia (R/R AML). This updated phase I study enrolled 38 adults with R/R AML to evaluate the safety and efficacy of this treatment according to the prespecified protocol. Treatment-related adverse events included grade 3/4 cytokine release syndrome (CRS) in 17 patients (44.74 www.chictr.org.cn , TRN: ChiCTR2000041054, Registration date: 17 December 2020.

Secondary Hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening complication mostly occurs in adult patients with rheumatic disease, infection or lymphoma. To adequately steer treatment, clear discrimination of sHLH entities is essential. We aimed to discriminate serum biomarkers which can separate MAS from EBV associated HLH (EBV-HLH) and Lymphoma associated HLH (L-HLH) adequately. Samples from patients aged > 15 diagnosed with sHLH were analyzed using Luminex Multiple Assays (34-plex for pre-2022; 11-plex for post-2022). 209 patients were divided into three cohorts due to change of Luminex kits. Among 86 patients enrolled pre-2021, 45 patients enrolled in 2021–2022, and 78 patients enrolled post-2022. Clinical data and serum biomarkers were analyzed among MAS, EBV-HLH and L-HLH in three cohorts by Kruskal-Wallis Analysis (K-W). The Heatmap and Principal Component Analysis (PCA) were used to describe the distinctive expression of serum biomarkers in MAS, EBV-HLH and L-HLH. Other than the relationship between clinical data and biomarkers was exhibited in the Heatmap according to the Spearman’s Rank Co-efficient. Furthermore Network analysis recognized the prominent biomarker in MAS. The blooding cells disproportion declined in MAS patients relative to EBV-HLH and L-HLH. Other than the level of sCD25 increased higher in EBV-HLH and L-HLH patients than MAS patients. Progressive levels of MIP-1α and IL-10 were elevated in patients with EBV-HLH and L-HLH relative to MAS. PCA and the heatmap of serum biomarkers expressions did not discriminate MAS from EBV-HLH and L-HLH efficiently. Although there was no significant difference in the relationship between clinical data and serum biomarkers, we observed the further positive association between myeloid and lymphoid-derived serum biomarkers in MAS compared with EBV-HLH and L-HLH. Further analysis revealed that IL-17 was as a prominent biomarker in pathology in MAS by Network Analysis. (1) The relationship between myeloid and lymphoid-derived biomarkers was further relevant in MAS than EBV-HLH and L-HLH. (2) The IL-17 released mostly by Th-17 cells was grouped together closely with other inflammatory mediators and we infer that IL-17 may exert an important role in MAS. These findings could guidance the efficacy of drugs targeting key cell and biomarkers specifically associated with MAS.