Primary central nervous system lymphoma (PCNSL) is a rare, aggressive malignancy presenting significant therapeutic challenges. Optimal maintenance therapy following initial remission remained debated. We conducted a multicentre, real-world study comparing BTK inhibitors (BTKi, n = 23) versus lenalidomide (n = 48) as maintenance in 71 newly diagnosed PCNSL patients in remission. With a median follow-up of 41.2 months, median overall survival (OS) and progression-free survival (PFS) remained unachieved for the total cohort. BTKi maintenance was associated with significantly superior PFS compared with lenalidomide (not achieved vs. 61.0 months; p = 0.016), with a substantially higher 6-year PFS rate (91.3

Waldenström macroglobulinemia (WM) is a low-grade non-Hodgkin lymphoplasmacytic lymphoma of the bone marrow, characterized by production of monoclonal immunoglobulin M (IgM) protein. Smoldering Waldenström macroglobulinemia (SWM) is asymptomatic and exhibits an increased risk of progression to WM. Myelodysplastic syndrome (MDS) arises from blood cancer in the hematopoietic stem cell compartment, featuring dysplastic changes in bone marrow and blood cells, along with cytopenias, including anemia, neutropenia, or thrombocytopenia. Their coexistence is extremely rare. We report a 74-year-old woman with IgM monoclonal gammopathy, anemia, and bone marrow dysplasia. Initially treated as WM, persistent cytopenias prompted reevaluation, leading to a revised diagnosis of SWM with MDS-IB-1 MDS with increased blasts-1. After six cycles of azacitidine, she achieved remission of MDS but rapidly progressed to AML and ultimately died. This case provides a key clinical lesson: persistent cytopenias during ibrutinib therapy were attributable to MDS progression rather than SWM, underscoring the importance of re-evaluation. Furthermore, it completely documents clonal evolution from 2.5% blasts (MDS with low blasts) to 6% blasts (MDS with increased blasts-1) and ultimately to AML (66% blasts), and it introduces the emergence of an FLT3-ITD mutation that rapidly drove the disease into AML even after the patient had achieved MDS remission. We also review the rare coexistence of WM and MDS/AML, and MGUS with MDS.

Background The increasing diversity of therapeutic modalities has raised new demands for undergraduate medical education. Undergraduate medical students are expected to integrate pharmacologic and non-pharmacologic treatments in clinical decision-making, yet therapeutics teaching is frequently fragmented and concentrated in early pharmacology courses. We developed a structured Clinical Therapeutics course positioned between preclinical teaching and clerkships to present systematic approaches to treatment decision-making. Methods A two-cohort pre–post educational study was conducted among honours-track medical students. The course included modality-based teaching, case discussions, and student presentations requiring multimodal treatment planning. Outcomes were assessed using pre- and post-course questionnaires on interest and perceived learning outcomes, and a performance-based presentation assessment scored independently by three faculty raters using an analytic rubric. Questionnaire responses and presentation scores were summarized descriptively. Results Before the course, students reported limited familiarity with several therapeutic domains, particularly non-pharmacological treatments. After completion, most students rated the modules as helpful and reported improvements in interdisciplinary analysis (57.1%), treatment-planning ability (38.1%), and conceptual understanding (47.6%). Interest in clinical therapeutics was maintained or increased. Students demonstrated therapeutic reasoning in structured presentations, with a mean score of 92.0 ± 3.2. Conclusions A structured Clinical Therapeutics course delivered prior to clerkships may serve as a bridge curriculum that supports early development of therapeutic reasoning. Introducing systematic approaches to treatment decision-making before clinical immersion may help link preclinical knowledge with clinical application and improve preparedness for clinical learning. Further studies should examine long-term effects on clinical performance.

Background Chimeric antigen receptor T-cell (CAR T-cell) therapy is an innovative immunotherapy that has demonstrated impressive clinical efficacy in relapsed/refractory (R/R) B-cell lymphomas and multiple myeloma (MM). Despite its substantial clinical benefits, suboptimal responses and disease recurrence are frequently observed in clinical practice. CAR T-cell therapy combined with autologous stem cell transplantation (ASCT) has been hypothesized to improve long-term disease control. However, comparative data on the efficacy and safety of CAR T-cell therapy versus CAR T-cell therapy combined with ASCT remain limited. We therefore performed this meta-analysis to systematically evaluate the clinical efficacy and safety of the combination regimen versus CAR T-cell therapy alone.Methods We conducted a systematic search of electronic databases, including PubMed and EMBASE, through June 1, 2026. Outcomes of interest included overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infections, and hematologic toxicities.Results Nine comparative studies encompassing 854 patients were analyzed. In R/R B-cell lymphoma, CAR T-cell therapy combined with ASCT yielded a superior ORR (OR 3.96; 95% CI, 2.20–7.13), CRR (OR 4.34; 95% CI, 2.48–7.59), PFS (HR 0.35; 95% CI, 0.20–0.61), and OS (HR 0.32; 95% CI, 0.16–0.60) compared with CAR T-cell therapy alone. In R/R MM, the combination strategy significantly increased the CRR (OR 27.00; 95% CI, 1.45–501.49) and prolonged survival (PFS HR, 0.20; OS HR, 0.13), despite comparable overall response rates (OR 1.59) between the two treatment strategies. Subgroup analyses within the R/R B-cell lymphoma cohort demonstrated superior clinical outcomes with CAR T-cell therapy combined with ASCT versus CAR T-cell therapy alone in high-risk subgroups. Specifically, among high-risk patients harboring TP53 alterations, CAR T-cell therapy combined with ASCT achieved higher CRR and prolonged survival (PFS HR = 0.35; OS HR = 0.23) relative to CAR T-cell therapy alone, despite comparable ORR between the two treatment strategies. Compared with CAR T-cell therapy alone, superior clinical benefits of CAR T-cell therapy combined with ASCT were also observed in patients with central nervous system involvement or ≥3 prior lines of therapy. Furthermore, CAR T-cell therapy combined with ASCT exhibited sustained clinical superiority over CAR T-cell therapy alone across single-targeted and dual-targeted CAR T-cell products. In terms of safety profiles, although CAR T-cell therapy combined with ASCT demonstrated higher risks of any-grade CRS (OR 4.42) and ICANS (OR 1.67) versus CAR T-cell therapy alone, the incidence of grade ≥3 CRS and ICANS showed no significant difference between the two treatment strategies. Notably, grade ≥3 neutropenia (OR 11.29) and thrombocytopenia (OR 34.84) were more common in the combination therapy versus CAR T-cell therapy. Conclusion The combination therapy outperformed CAR T-cell therapy alone in achieving deeper remission and conferring more durable disease control, albeit with an increase in severe hematologic adverse events.

BACKGROUND:Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS:We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS:A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION:For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Patients with high-grade B-cell lymphoma (HGBCL), who are in early relapse or primary refractory, always have poor outcomes. Even intensive chemotherapy or CAR-T cell therapy is not always the best solution. Here is a case of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), who achieved complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction and followed by autologous stem cell transplantation (ASCT) consolidation. The patient has achieved a sustained CMR and a progression-free survival (PFS) of 25 months (ongoing) from progression. Hepatitis B virus (HBV) seroconversion occurred during ASCT before stem cell engraftment, and was effectively suppressed with entecavir. Immune function was monitored in our case by flow cytometry. Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with fully activated immune function, which may explain why the patient responded rapidly and maintained durable efficacy. Immune analysis also exhibited B cell subset exhaustion and a disrupted naïve/memory T cell ratio which suggested an immunosenescence phenotype. It is speculated that an over activation of immune function promotes immunosenescence following bispecific antibody therapy, this needs attention. This case highlights the potential of glofitamab induction followed by ASCT consolidation to achieve durable remission in aggressive triple-hit HGBCL. The immune function after bispecific antibody treatment should be monitored and needs further investigation.

Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive extranodal non-Hodgkin lymphoma, mostly diffuse large B-cell type. Despite high initial remission rates, many patients have poor outcomes, emphasizing the need for early risk stratification. 18F-FDG PET aids in staging and extranodal assessment, while MRI remains the standard for intracranial lesions. Baseline PET parameters-SUVmax, TMTV, and TLG-may have prognostic value, but evidence is inconsistent. Methods: A systematic search identified studies up to February 2026 assessing associations between baseline PET parameters and progression-free survival (PFS) or overall survival (OS). Meta-analysis was performed using Review Manager (RevMan) version 5.4. Results: Six studies with 345 patients were included. Baseline PET parameters were not significantly associated with PFS. Higher SUVmax showed a modest but significant association with poorer OS (HR 1.05, 95% CI 1.00-1.09, p=0.03), whereas SUVmean, TMTV, and TLG were not. Substantial heterogeneity was observed for TMTV and TLG. Subgroup analyses suggested SUVmax prognostic value was more evident in retrospective and smaller studies, while heterogeneity for volumetric parameters persisted. Conclusion: Baseline 18F-FDG PET may provide prognostic insight in PCNSL, with SUVmax modestly predicting OS. Volumetric measures (TMTV, TLG) show potential but are limited by heterogeneity and small sample sizes. Larger, standardized studies are needed to validate PET-derived metrics for routine clinical use.

Central nervous system involvement by chronic lymphocyte leukemia (CNS-CLL) without Richter transformation is a rare and hard-to-diagnose condition. Nonspecific symptoms and the need for a brain biopsy complicate diagnosis. We report a 58-year-old male with Rai stage 0 CLL who had severe neurological signs. His initial MRI suggested autoimmune-related demyelinating disease. However, high-dose steroids and intravenous immunoglobulin (IVIG) did not help. His neurological status continued to worsen. A multidisciplinary team used advanced imaging (PET-CT showing a hypermetabolic lesion with SUVmax 8.2) and stereotactic brain biopsy. Immunoglobulin heavy chain (IGH) gene clonal rearrangement showed identical clones (IGHV3-64*01/02/07) in both cerebral tissue and bone marrow. This confirmed CNS-CLL. Treatment with ibrutinib stabilized the disease and led to partial cognitive recovery. The patient survived five years without progression. This case and a literature review show that CNS-CLL can have atypical imaging and occur even in early-stage disease. Under targeted therapy, this rare condition may have a better prognosis than previously reported. The report highlights the importance of molecular studies for diagnosis and recommends a multidisciplinary diagnostic approach.

BackgroundAplastic anemia (AA) is a bone marrow failure syndrome. Whether the combination of TPO-RAs and IST is superior to IST alone is an ongoing debate. This meta-analysis compares the efficacy of EPAG+IST versus IST alone, and assesses the initiation timing and treatment duration of eltrombopag (EPAG) across different age groups of AA patients.MethodsThe literature was retrieved from Chinese and English databases up to October 1, 2025. The analysis was conducted using RevMan 5.4 software, employing a fixed-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the outcomes. The I² statistic was used to assess heterogeneity among included studies.Results21 studies involving 2,239 patients were included. The overall response rate in the EPAG+IST group was higher at 3 months (OR = 2.13, 95% CI 1.65 – 2.74, P < 0.00001) and 6 months (OR = 2.13, 95% CI 1.73 – 2.61, P < 0.00001). There was no significant difference between the two groups at 12 months (OR = 1.14, 95% CI 0.86 – 1.51, P = 0.36, I² = 35%).ConclusionThe addition of EPAG to IST may improve early hematological responses at 3 and 6 months in patients with AA, with no significant difference at 12 months. Concurrent initiation (within 7 days) was associated with earlier responses in adults.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024604778

BackgroundThe global epidemiological trends of chronic lymphocytic leukemia (CLL) provide a crucial macrolevel foundation for guiding precision medicine. However, translating broad risk factors and burden disparities into actionable clinical strategies requires a bridge to molecular pathogenesis. This study analyzes the global CLL burden to not only delineate its public health landscape but also inform the development of biomarker-based prevention and early detection frameworks.MethodsLeveraging data from the Global Burden of Disease Study 2021, we evaluated primary pre-pandemic trends in CLL incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019 using estimated annual percentage change (EAPC), joinpoint regression, and decomposition analysis to identify key drivers of trends and inequalities. Predictive modeling (ARIMA) was employed to project future burden. Critically, the epidemiological insights-particularly regarding identified risk factors (e.g., smoking, high BMI) and high-burden populations-were framed as a strategic map to prioritize hypotheses for subsequent biomarker discovery research in CLL etiology and progression. We additionally analyzed three independent Gene Expression Omnibus (GEO) transcriptomic cohorts including CLL patients and nonleukemic controls. Differential expression analysis across cohorts identified 67 overlapping CLL-related genes, which underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Using least absolute shrinkage and selection operator (LASSO)-regularized logistic regression in a training cohort, we derived a 14-gene predictive signature and validated its discriminative performance in independent datasets.ResultsThe analysis revealed a mild decline in global age-standardized incidence but significant declines in mortality (31.3%) and DALYs (32.9%), alongside marked socioeconomic disparities. Decomposition analysis quantified the dominant role of population aging in driving DALY increases in Western Europe (+11403.53%) and epidemiological factors in Central Asia (+633.72%). Smoking and high body mass index were reaffirmed as modifiable risk factors. Projections indicate declining incidence and mortality but rising prevalence through 2040. These findings pinpoint specific demographics and risk exposures as high-priority targets for biomarker investigation and stratified screening. At the molecular level, differential expression analyses across three GEO cohorts identified 67 overlapping CLL-related genes, which were significantly enriched in immune cell differentiation, leukocyte adhesion, T/B cell receptor signaling, and cytokine/growth factor pathways. A LASSO-based model further distilled these into a 14-gene signature that effectively discriminated CLL from non-CLL samples in the training cohort and retained stable predictive performance in independent validation sets.ConclusionThis study synthesizes the global epidemiology of CLL into a framework that informs clinical and translational research. By combining global burden analysis with a complementary transcriptomic investigation, it provides epidemiological context and candidate molecular features for future biomarker-based risk stratification and early identification strategies in CLL.

Interferon-gamma (IFN-γ) is a central mediator of immune-driven bone marrow failure (BMF) in acquired aplastic anemia (AA). Persistent IFN-γ signaling alters the bone marrow microenvironment by activating the JAK-STAT1 pathway, which results in immunological imbalance, inflammatory amplification, and depletion of hematopoietic stem and progenitor cells (HSPCs). IFN-γ disturbs HSPC quiescence and self-renewal, interferes with thrombopoietin (TPO)-c-Mpl communication, and stimulates cytotoxic T-cell-dominant immunological responses. Simultaneously, IFN-γ destabilizes local immunological homeostasis by disrupting immune crosstalk through the IDO1 axis and regulatory T-cell (Treg) malfunction. In addition to discussing new therapeutic methods, such as Treg-based therapies and JAK inhibition, as prospective precision approaches for AA, this review incorporates current mechanistic insights into IFN-γ-driven cellular interactions inside the bone marrow niche.

ABSTRACT Background The pathogenesis of HSPCs impairment in aplastic anemia (AA) remains unclear. We focused on CD8+ T cells and investigated platelets, CD4+ T cells, macrophages, and mitochondrial energy metabolism, aiming to elucidate the cellular atlas changes associated with bone marrow failure (BMF). Methods We have successfully established a mouse model of bone marrow failure and analyzed the immune response at the single‐cell level. Results Platelets regulate CD4+/CD8+ T cells and macrophages by releasing PF4. CXCR3/CXCR5 bind to PF4, activating mitochondrial signaling pathways. The decrease of Treg weakens immunosuppression. Additionally, there is a significant increase in CD8+ effector T cells. Increased energy metabolism was observed in CD8+ stress T cells. It should be noted that platelet reduction itself in AA weakens energy metabolism, subsequently impairing the hemostatic and thrombotic functions. However, platelets' regulatory function in immune cells remains significant. An imbalance in M1 and M2 macrophage polarization is observed. While a phenotype macrophage and CD8+ naive T cells are important cell phenotypes in marrow aging, they do not contribute to pathology failure. Conclusion The possible mechanisms of BMF in AA: based on PF4, platelet‐T cell/macrophage crosstalk leads to immune overactivation and the release of cytokines such as IFN‐γ and TNF‐α, which attack the marrow. Therefore, transforming imbalanced CD8+ effector T cells, stress T cells, Treg cells, and M1/M2 macrophages into CD8+ naive T cells and a phenotype of macrophages via inhibiting platelet immune regulatory function may provide a promising strategy to reverse BMF.

Platelets are increasingly recognized as immune modulators that influence T-cell activation and metabolism through direct interactions and mediator release. This review focuses on platelet–T-cell crosstalk in aplastic anemia (AA) and hematological disorders. Platelet factor 4/C-X-C motif chemokine ligand 4 (CXCL4) and transforming growth factor-beta (TGF-β) serve as central mediators. PF4 binds T-cell CXCR3 to activate the Akt-PGC1α-TFAM axis, reprogramming mitochondrial metabolism and promoting T Helper 1 (Th1) polarization while restraining T Helper 17 (Th17) responses. TGF-β exerts context-dependent effects – inducing regulatory T-cells (Tregs) under homeostasis but driving Th17 differentiation in inflammatory conditions like AA. In hematological malignancies, this crosstalk extends to tumor metabolic reprogramming and immunosuppression via microparticles. Emerging evidence also implicates platelet–T-cell interactions in neurological disorders, including myasthenia gravis and ischemic stroke. Understanding this axis offers therapeutic opportunities, including thrombopoietin receptor agonists (e.g., eltrombopag) that modulate platelet production and immunity, and strategies targeting PF4/CXCR3 or TGF-β signaling to restore immune homeostasis.

BACKGROUND:Central nervous system lymphoma (CNSL) is aggressive, and treatment with Bruton tyrosine kinase (BTK) inhibitors (BTKis) plays a key role. For this systematic review and meta-analysis, the authors evaluated BTKis for the treatment of primary CNSL (PCNSL) and secondary CNSL (SCNSL). METHODS:By May 1, 2025, the authors conducted a systematic search of databases, including PubMed, EMBASE, etc. Included studies were those that investigated BTKi-treated CNSL and analyzed the overall response rate (ORR) as well as the complete response (CR) and partial response (PR) rates using systematic review and meta-analysis software. RESULTS:Forty studies (935 patients) were included in the meta-analysis. The pooled ORR and CR and PR rates were 73%, 49%, and 28%, respectively. The pooled ORR and CR rates for BTKi monotherapy were 60% and 34%, respectively; whereas the rates for BTKi plus chemotherapy or immunochemotherapy were 79% and 55%, respectively. For PCNSL, the pooled ORR and PR rates were 73% and 49%, respectively. For SCNSL, the pooled ORR and CR rates reached 75% and 53%, respectively. Among patients with PCNSL, zanubrutinib achieved pooled ORR and CR rates of 85% and 54%, respectively. Ibrutinib had pooled ORR and CR rates of 67% and 46%, respectively; whereas orelabrutinib demonstrated pooled ORR and CR rates of 70% and 59%, respectively. For SCNSL, zanubrutinib achieved pooled ORR and CR rates of 77% and 62%, respectively; whereas ibrutinib achieved rates of 72% and 54%, respectively. Hematologic toxicities and transaminase increases were grade 3-5 toxicities according to common toxicity criteria. CONCLUSIONS:The combination of BTKis with traditional chemotherapy or immunochemotherapy offers superior response rates compared with BTKis alone, and the safety profile is acceptable. Efficacy varies by BTKi type and should be selected based on patient condition. Specifically, for PCNSL, the response rates of zanubrutinib and obinutuzumab are better; for SCNSL, there is a minimal difference in efficacy among the various BTKis; and, overall, regardless of whether it is PCNSL or SCNSL, the off-target effects and side effects of covalent BTKis (zanubrutinib, obinutuzumab), except for ibrutinib, have improved.

Background: Aplastic anemia (AA) is a bone marrow failure syndrome. How to achieve better efficacy of Eltrombopag (EPAG) and IST in the treatment of AA is still unclear. This meta-analysis compares the efficacy of EPAG+IST verses IST alone, and assesses the optimal timing and duration for starting EPAG in different ages of AA patients. Methods: The literature was retrieved from Chinese and English databases up to July 1, 2025. The analysis was conducted using RevMan 5.4 software, employing a fixed effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the outcomes. The I² statistic was used to assess heterogeneity among included studies. Results: 21 studies involving 2,239 patients were included. The overall response rate in the EPAG+IST group was higher at 3 months (OR = 2.13, 95% CI 1.65–2.74, p < 0.00001) and 6 months (OR = 2.13, 95% CI 1.73–2.61, p < 0.00001). There was no significant difference between two groups at 12 months (OR = 1.14, 95% CI 0.86–1.51, p = 0.36, I² = 35%). For adults, it is recommended the concurrent therapy of EPAG and IST, and continue for a period of 3 months to achieve significant hematological improvement (HI). If EPAG was added after 7 days, patients will achieve HI for about 6 months. For children, regardless of the concurrent or nonconcurrent therapy, it is recommended to continue for about 6 months to achieve better HI. Conclusion: Eltrombopag should be used as early as possible, as it shows a better HI compared with simply IST treatment within 3-6 months, with no significant difference in risk. Concurrent therapy of EPAG should be performed and extending EPAG treatment beyond 12 months may not yield significantly enhanced benefits. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024604778

Aplastic anemia (AA) is a bone marrow failure syndrome. Whether the combination of TPO-RAs and IST is superior to IST alone is ongoing debate. This meta-analysis compares the efficacy of Eltrombopag (EPAG)+IST verses IST alone, and assesses the optimal timing and duration for starting EPAG in different ages of AA patients. The literature was retrieved from Chinese and English databases up to May 1, 2025. The analysis was conducted using RevMan 5.4 software, employing a fixed effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the outcomes. The I² statistic was used to assess heterogeneity among included studies. 21 studies involving 2,239 patients were included. The overall response rate in the EPAG+IST group was higher at 3 months (OR = 2.13, 95% CI 1.65–2.74, p < 0.00001) and 6 months (OR = 2.13, 95% CI 1.73–2.61, p < 0.00001). There was no significant difference between two groups at 12 months (OR = 1.14, 95% CI 0.86–1.51, p = 0.36, I² = 35%). For subgroup analysis, 1) For adults, it is recommended the concurrent therapy of EPAG and IST (EPAG was added within 7 days of the start of IST treatment), and continue for a period of 3 months to achieve significant HI. If EPAG was added after 7 days, patients will achieve HI for about 6 months. 2) For children, regardless of the concurrent or nonconcurrent therapy, there was no significant difference compared with IST alone in 3 months. It is recommended to continue for about 6 months to achieve better HI. 3) For all AA patients, the HIs of additional Eltrombopag for more than 12 months were not significantly different from those of simply IST. Our study indicates that Eltrombopag should be used as early as possible, as it shows a better hematological improvements (HIs) compared with simply IST treatment within 3-6 months, with no significant difference in risk. Concurrent therapy of EPAG should be performed and extending EPAG treatment beyond 12 months may not yield significantly enhanced benefits. https://www.crd.york.ac.uk/prospero/, identifier CRD42024604778 Aplastic anemia (AA), Bone marrow failure (BMF), Eltrombopag(EPAG), Immunosuppressive therapy (IST), Thrombopoietin receptor agonists (TPO-RA)

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive B-cell lymphoma. Due to the use of Rituximab, the prognosis for DLBCL has significantly improved. However, in patients with intermediate-high risk International Prognostic Index (IPI) scores (i.e., IPI ≥ 3) —a widely accepted tool for risk stratification—are prone to early relapse or disease progression, resulting in poor long-term outcomes. The therapeutic value of autologous hematopoietic stem cell transplantation (ASCT) as consolidation therapy compared to chemotherapy alone remains controversial in younger patients with high-risk DLBCL who achieve first-line remission. Aim We conducted a retrospective study to evaluate the prognostic impact of first-line ASCT versus chemotherapy alone in newly diagnosed DLBCL patients with high-risk IPI scores (≥3). Propensity score matching(PSM) was employed to balance baseline characteristics between treatment groups. Methods A retrospective analysis was conducted on newly diagnosed DLBCL patients with IPI scores ≥3 treated at Beijing 6 Medical Center between March 2014 and March 2023. Among 194 eligible patients, 104 received ASCT following first-line remission induction (transplant group), while 90 were treated with chemotherapy alone or combined with radiotherapy (non-transplant group). To minimize baseline imbalances, a 1:1 PSM was performed based on age. Results Among the 194 patients, 102 were male patients and 92 were female, yielding a male-to-female ratio of 1.11:1. The median age was 53（22-69）years. Among these patients, 116 patients had an IPI score of 3, while 78 had scores of 4-5. A total of 51 pairs of DLBCL patients were successfully matched for data analysis, and the baseline characteristics of the two groups well balanced consistent after matching. After PSM the 1-,3-,and 5-year progression-free survival(PFS) rates for the transplant group and non-transplant group were 95.7%、86.8%、80.2% vs 77.8%、68.0%、60.6%, respectively. The Log-rank test showed a statistically significant difference in the overall PFS between the two groups (P<0.05). The 1-,3-,and 5-year overall survival(OS)rates for the transplant group and non-transplant group were 97.8%、91.0%、84.5% vs 98.0%、77.6%、71.3%, respectively. The Log-rank test showed no statistically significant difference in the overall OS between the two groups (P>0.05) Based on 194 patients, univariate analysis identified auto-HSCT, old age, high-risk IPI score, and elevated LDH as significant predictors of PFS (P<0.05), with auto-HSCT acting as a protective factor. Conversely, old age, high-risk IPI, and elevated LDH were associated with prognostic factors. For OS, auto-HSCT, old age, IPI score 5, and elevated LDH showed significant associations (P<0.05), where auto-HSCT remained protective. After excluding variables with >30% missing data, variables with P<0.2 in univariate analysis were included in multivariate modeling. Auto-HSCT retained its independent protective effect on PFS (P<0.05), while elevated LDH remained an independent adverse prognostic indicator (P<0.05). Multivariate analysis confirmed age and elevated LDH as the sole independent predictors of OS (P<0.05). Post-PSM subgroup analysis demonstrated that auto-HSCT significantly improved PFS across all patient subgroups. Notably, patients with IPI score 3(HR = 0.12, 95% CI: 0.01–0.92, P = 0.041), non-GCB subtype(HR = 0.31, 95% CI: 0.11–0.89, P = 0.029), or elevated LDH(HR = 0.36, 95% CI: 0.14–0.95, P = 0.039) exhibited markedly enhanced PFS benefits from auto-HSCT compared to the non-transplant cohort. Trends toward improved PFS were observed in patients with CD5 positivity(HR = 0.18, 95% CI: 0.02–1.33, P = 0.093), double-expression(HR = 0.34, 95% CI: 0.09–1.27, P = 0.107), bone marrow involvement(HR = 0.32, 95% CI: 0.10–1.06, P = 0.063), or ≥1 extra-nodal sites(HR = 0.43, 95% CI: 0.17–1.07, P = 0.070). Additionally, auto-HSCT demonstrated a trend toward improved OS in patients with IPI score 3(HR = 0.16, 95% CI: 0.02–1.28, P = 0.084). Conclusion Thus, ASCT represents a promising consolidation strategy that significantly improves PFS in specific subgroups of DLBCL patients with intermediate-high or high risk. Its potential benefits in OS deserve further validation.

Introduction:Connective tissue diseases (CTDs), which include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), and so on, represent a group of autoimmune disorders that predominantly affect the body's connective tissues. Aim:This study aimed to investigate the clinical efficacy of sirolimus in patients with connective tissue disease complicated with refractory thrombocytopenia (CTD-RTP) and its effect on immune regulation. Material and methods:A retrospective study was conducted on 13 patients diagnosed with CTD-RTP who were treated with oral sirolimus for 6 months, starting with a daily dose of 1 mg. Changes in platelet counts, T cell lymphocyte subsets, regulatory T cells (Tregs), B cells, and cytokine levels were assessed from baseline to the end of the 6-month treatment. From November 2020 to December 2023, 13 patients with CTD-RTP were consecutively enrolled and monitored. Results:The treatment was well tolerated with no severe drug-related toxicities were reported. After 3 months of sirolimus treatment, 7 patients exhibited a positive response (PR), with 1 patient achieving complete response (CR), resulting in an overall response rate of 61.5%. Continued treatment for 6 months led to further improvements, with the total effective rate reaching 76.9%. Importantly, there was a significant increase in peripheral blood Tregs after treatment compared with the baseline level. Conclusions:Sirolimus is an effective and safe treatment option for CTD-RTP patients, and its effect may be related to its ability to increase the level of regulatory T cells in peripheral blood.