Objective primary mediastinal B-cell lymphoma (PMBCL) is a distinct, aggressive lymphoma predominantly affecting young adults. While dose-intensive regimens are often recommended, their associated long-term toxicities and the necessity of consolidative radiotherapy remain major concerns. Given that PMBCL was explicitly excluded from the landmark POLARIX trial, we sought to evaluate the real-world efficacy and safety of first-line Pola-R-CHP in this specific population. Methods this single-center study analyzed 16 consecutive patients with newly diagnosed PMBCL treated with six cycles of Pola-R-CHP between September 2023 and June 2025. Efficacy was assessed via PET/CT (Lugano 2014 criteria) and safety via NCI-CTCAE v5.0. Results the median age was 30 years, with a female predominance (62.5

BACKGROUND:Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or are refractory to first-line treatment. This study aimed to determine the effectiveness and tolerability of the combination of Polatuzumab vedotin and Zanubrutinib plus Rituximab (Pola-ZR) or Obinutuzumab (Pola-ZG) in patients with relapsed/refractory (R/R) DLBCL. METHODS:We conducted a prospective observational study as part of our registered cohort study (NCT06203652). Patients were planned to receive six 21-day cycles of Pola-ZR/G, followed by Zanubrutinib monotherapy. The primary endpoint was to evaluate the best overall response rate (BOR), while secondary endpoints included the median progression-free survival (mPFS), safety, and complete response rate (CRR). We collected data from 73 R/R DLBCL patients who received traditional salvage therapies (TST). After propensity score matching, they were paired 1:1 with the Pola-ZR/G arm to compare the effectiveness and survival outcomes. RESULTS:Twenty-two patients were enrolled (median age 68 years) in the Pola-ZR/G group. After a median follow-up of 16.1 months, the investigators assessed BOR; it was 70% (77.77% for Pola-ZR and 63.6% for Pola-ZG cohort), and CRR was 45% in 20 evaluable R/R patients. The mPFS was 8.3 months and was higher compared to the TST cohort. The median overall survival (OS) of the Pola-ZR/G cohort had not been reached at the time of analysis. The most common grade 3 to 4 adverse events were infections of all types and hematological toxicity. CONCLUSION:In our study, patients derived clinical benefit after receiving Pola-ZR/G compared to TST; the regimens had a tolerable safety profile in patients with R/R DLBCL.

Background Primary immune thrombocytopenia (ITP) is the most common bleeding disorder in hematological diseases, characterized by platelet count decrease in peripheral blood and higher risk of bleeding. Thrombopoietin receptor agonist (TPO-RA) is widely used as preferred second-line agent for patients with ITP. However, to date there are no predictors for its efficacy evaluation, combination therapy necessities, or tapering off opportunities.Methods The study enrolled 27 ITP patients, 27 normal controls and 15 chemotherapy-induced thrombocytopenia patients to examine the prognostic role of mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR) in TPO-RA treatment.Results The results revealed that MPV increased in ITP patients prior to the TPO-RA treatment and decreased in patients with good response after the treatment. NLR was higher in ITP patients both before and after TPO-RA treatment.Conclusion In patients with TPO-RA maintenance, MPV combined with NLR could predict the platelet count improvement of ITP patients.

Introduction: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) following at least one prior line of therapy, either as monotherapy or in combination with gemcitabine and oxaliplatin (GemOx). However, real-world data on glofitamab-based regimens are lacking. To provide evidence outside of clinical trials, we retrospectively analyzed patients treated with glofitamab-based regimens to evaluate clinical outcomes in r/r aggressive B-cell lymphoma. Methods: This investigator-initiated, retrospective study enrolled consecutive patients with r/r aggressive B-cell lymphoma who received glofitamab-based regimens as salvage at Zhongshan Hospital, Fudan University, between March 2024 and August 2025. Efficacy was assessed by whole-body 18F-FDG PET/CT or contrast-enhanced CT scans. Responses were evaluated using the 2014 Lugano criteria, and adverse events (AEs) were graded per NCI-CTCAE 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome were graded according to consensus criteria from the American Society for Transplantation and Cellular Therapy. Study endpoints included best complete response (CR) rate, best overall response rate (ORR), safety profiles, progression-free survival (PFS), and overall survival (OS). Subgroup analyses were performed to identify potential predictors of efficacy. Results: A total of 35 consecutive patients were enrolled in this study. The median age was 68 years old (range: 43-94), with 24 patients (68.5%) aged over 60 years old. Three patients (8.5%) had Burkitt lymphoma, and 32 patients (91.4%) had DLBCL. Thirty-four patients (97.1%) were staged Ann-Arbor Ⅲ to Ⅳ, and 24 patients (68.6%) were classified as high-risk by International Prognostic Index score. Other high risk prognostic factors were prevalent in this cohort: 26 patients (74.3%) had elevated lactate dehydrogenase, 34 patients (97.1%) presented with extra-nodal involvement, and 13 patients (37.1%) had bulky diseases. For subtype and biological markers in DLBCL patients, 18 patients were classified as non-germinal center B-cell subtype, 11 patients were diagnosed with double-expressor lymphoma, and 17 patients showed high P53 expression. The median prior lines of treatment exposure were 2 lines (range: 1-6). Specifically, 6 patients (17.1%) had a history of bendamustine exposure, and 4 patients (11.4%) had undergone both autologous stem cell transplantation and chimeric antigen receptor T-cell therapy. As of now, the median number of glofitamab-based regimen cycles administered was 3 (range: 1-12). Among them, the regimens included glofitamab monotherapy (28, 80.0%), glofitamab combination with bruton tyrosine kinase inhibitors (3, 8.6%), GemOx (2, 5.7%), polatuzumab vedotin (1, 2.9%) or dose-reduced ifosfamide, carboplatin and etoposide (1, 2.9%). Twenty-six patients were evaluable for efficacy, and the best CR rate was 26.9% and best ORR was 50.0%. Subgroup analysis showed that similar response rates were observed across various subgroups including age, cell of origin, bulky disease. However, population with normal LDH at baseline tended to benefit more (best CR rate of normal vs elevated LDH: 57.1% vs. 15.8%) from glofitamab-based regimens. Compared to those who did not achieve CR, patients in best CR subgroup had a significant higher CD4-positive T-cell count (CR vs non-CR: 418 [138] vs 251 [144], mean [SD], p=0.03). The most common AEs were anemia (85.7%), leukocytopenia (54.3%), neutropenia (54.3%), and CRS (28.6%), most of which were grade 1-2. With a median follow-up of 5.5 months (95% CI: 1.4-not applicable), the median PFS was 2.6 months (95% CI: 2.17-not applicable), and the median OS was not reached. Conclusions: Our findings characterize disease features of heavily treated r/r aggressive B-cell lymphoma and real-world outcomes with glofitamab-based salvage. Even in the subgroups with adverse prognosis factors, glofitamab-based regimens still demonstrated efficacy and manageable toxicities.

Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) improved progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) in Polarix study. But little evidence has been provided for patients with lower international prognostic index (IPI) scores or ineligible for clinical trials. We retrospectively enrolled 117 consecutive DLBCL patients aged over 18 years old who received Pola-R-CHP as first-line therapy to investigate efficacy and safety from April 1, 2023, to October 31, 2024. Polatuzumab vedotin was administered 1.8 mg/KG, rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 or epirubicin 70 mg/m2, all intravenously on Day 1. Prednisone was given 100 mg orally once daily from Day 1 to Day 5. The primary end point was the complete response (CR) rate after 6 cycles. The median age was 56 years old (range: 18-76). Twenty-four (20.5%) patients had an IPI of 0 to 1. Fifty-seven (48.7%) patients were ineligible for Polarix trial. Forty-seven (40.2%) patients received epirubicin instead of doxorubicin. After a median follow-up of 7.1 months (95% CI: 5.967-8.800), CR rate after 6 cycles was 80.6% in all 72 patients who have reached the primary end point, 91.7% in IPI 0-1 subgroup, and 73.5% in Polarix-ineligible subgroup. Lung infection, neutropenia, and leukopenia were the most common grade 3 to 5 adverse events, accounting for 20.5%, 17.9%, and 12.8%. Dose modification of polatuzumab vedotin occurred in 4 patients in Polarix-ineligible group, and 1 in Polarix-eligible group. Pola-R-CHP performed well in first-line Polarix trial-ineligible and IPI 0-1 DLBCL patients with manageable safety.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is most diagnosed among patients aged over 65 years old, however, the 5-year overall survival was merely 55.8%. First-line regimen incorporating efficacy with fewer toxicities is needed for this population. Following the approval of polatuzumab vedotin in April 2023 in China, we introduced a combination of polatuzumab vedotin, zanubrutinib and rituximab (Pola-ZR) in untreated elderly and frail DLBCL patients that the complete response (CR) rate reached 83% in the retrospective study (Yuhong Ren et al., Ann Hematol, 2025). To further elucidate the efficacy and safety of Pola-ZR, we initiated a prospective phase 2 clinical trial (NCT05940064) with revised prophylaxis for infections. We reported the preliminary efficacy results at European Hematology Association 2025 Congress (PF943). Here we update the molecular features and latest follow-up outcomes. Methods: Untreated DLBCL patients aged over 70 years old or aged between 60 to 69 years old with a performance status score of 2 to 4 were enrolled in this study. Central nervous system involvement was excluded. The treatment and follow-up procedures remained consistent with our previous reports. The primary endpoint was CR rate after 6 cycles of Pola-ZR. The secondary endpoints were safety, overall response rate, and 24-month progression-free survival (PFS). Peripheral blood was tested for circulating tumor DNA (ctDNA) at baseline, cycle 4, cycle 7, and end-of-treatment by KAPA Hyper Prep Kit. Fresh tissue specimens were obtained at baseline and examined by whole-exome sequencing (WES) and RNA sequencing to explore the molecular features. Sequencing was performed using an Illumina Novaseq 6000 following Illumina-provided protocols for 2×150 paired-end sequencing. Results: Thirty-two DLBCL patients were screened from December 20, 2023, to January 3, 2025, and thirty patients were enrolled. The median age was 72 years old (range: 67-83). Twenty-four (80.0%) patients were aged over 70 years old. Fourteen (46.7%) patients were female. Twenty-two (73.3%) patients had an international prognostic index score of 3 to 5. Eleven (36.7%) patients were GCB subtype, and nineteen (63.3%) patients were non-GCB. At the cut-off date August 4, 2025, the median cycle of treatment was 10.5 (range: 3-12). Twenty-eight patients were evaluable for the primary endpoint. Th preliminary results showed a CR rate of 71.4% after 6 cycles of Pola-ZR. After a median follow-up of 11.6 months (95% Confidence Interval: 10.637-12.563), the median PFS was 18.5 months (95% Confidence Interval: 6.579-30.421) and the median overall survival was not reached. Grade 3 to 4 lung infection remained 10.0% as previously reported under mandatory prophylaxis for pneumocystis jirovecii pneumonia (PJP). Treatment-related leukopenia remained 26.7% and was all in grade 1 to 2. Dose de-escalation or discontinuation of polatuzumab vedotin was still not observed. A total of 22 samples were validated for WES analysis, of which 21 were successfully genotyped, including 6 cases of A53 subtype, 5 cases of MCD subtype, 3 cases of N1 subtype, 4 cases of ST2 subtype, 2 cases of BN2 subtype and 1 case of EZB subtype. A total of 20 samples were validated for RNA sequencing, of which 8 cases were GCB subtype, 10 cases were ABC subtype, and 2 cases were unclassified. Conclusions: Pola-ZR showed sustained efficacy in untreated elderly and frail DLBCL patients in this prospective clinical trial. Safety profiles were manageable, as lung infection was brought under control by mandatory prophylaxis for PJP. Preliminary WES and RNA sequencing results showed consistency with our clinical findings. Ongoing treatment, follow-up, and molecular mechanism analysis will be further updated.

Abstract Introduction Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) that predominantly occurs in young adults and presents with bulky mediastinal mass. In the rituximab era, dose-dense regimens are recommended for newly-diagnosed PMBCL, with concerns regarding long-term toxicities. Single agent of polatuzumab vedotin (Pola) was proved to significantly induce cytotoxicity against PMBCL in vitro, while this population was excluded in the POLARIX trial, the landmark study which changes the frontline DLBCL treatment landscape. ObjectiveTo determine the safety and efficacy of first-line Pola-R-CHP regimen in patients with newly-diagnosed PMBCL. MethodsFrom September 2023 to December 2024, patients with previously untreated PMBCL that received Pola-R-CHP regimen were enrolled in this study, adhering to the same dosage and schedule as outlined in the POLARIX trial. Positron emission tomography/computed tomography (PET/CT) scans were conducted at baseline, following three cycles (Interim) and six cycles (End of Treatment, EoT) of therapy. Treatment response was assessed utilizing the 2014 Lugano response criteria. Adverse events (AEs) were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. ResultsA total of 14 PMBCL patients received Pola-R-CHP as initial treatment. The median age was 32 years (range, 17-51) and there was a female predominance (64.3%). 64.3% of patients exhibited bulky diseases, 50% presented with B symptoms, and 71.4% had elevated LDH. Most patients had limited-stage disease (Ann Arbor I–II, 92.9%), good performance status (ECOG 0-1, 92.9%), and low-risk aaIPI scores (0–1, 85.7%). Pleural and pericardial effusions were detected in 28.6% and 42.9% of patients, respectively. Over a median follow-up of 13.1 months (range, 6.0-21.5), all patients completed 6 cycles of Pola-R-CHP, achieving an objective response rate (ORR) of 100%. Interim PET/CT showed a partial metabolic response (PMR) in 64.3% and complete metabolic response (CMR) in 35.7% of patients. Upon completion of the Pola-R-CHP treatment, CMR rate increased to 92.9%. 8 patients with PMR at interim improved to CMR at EoT, with only 1 patient remaining in PMR. Throughout the follow-up period, no progression or deaths occurred. The safety profile was favorable and manageable. Treatment was well-tolerated with no discontinuations due to AEs. The most common grade 3–4 AEs were neutropenia (42.9%, resolved with G-CSF) and vomiting (14.3%). ConclusionsOur research fills the evidence gap in the POLARIX trial by providing real-world experience for the use of Pola-R-CHP as an upfront treatment in PMBCL, which demonstrates promising trends towards sustained response with acceptable safety profile. These findings necessitate further validation in future trials.

First-line treatment balancing efficacy and safety is urgently needed for frail and elderly diffuse large B-cell lymphoma (DLBCL) patients. We designed a triplet chemo-light regimen, Pola-ZR, in previously untreated frail and elderly DLBCL patients to assess the efficacy and safety in a prospective DLBCL cohort (NCT06203652). Polatuzumab vedotin was given 1.8 mg/KG intravenously on day 1, zanubrutinib 160 mg twice a day orally from day 1 to day 21, and rituximab 375 mg/m2 intravenously on day 1. Twenty-one days were a cycle. If assessed complete response (CR) after 6 cycles, patients would receive zanubrutinib alone for another 6 cycles. PET/CT or contrast-enhanced CT scan was scheduled every 3 cycles. The primary end point was overall response rate (ORR) after 6 cycles. Twenty-four patients were enrolled from 01 Apr 2023 to 20 Dec 2023. Median age was 73. Sixteen (66.7

CONCLUSION Hepatic light chain amyloidosis is caused by malignant plasma cells that abnormally secrete immunoglobulin light chains, which undergo a conformational change to a β-pleated sheet configuration and are deposited in the liver. The amyloid fibrils are deposited mainly in the hepatic sinusoids, the space of Disse and the walls of blood vessels. Previous autopsy studies have shown that the proportion of systemic light chain amyloidosis with liver involvement is extremely high; however, there are fewer systematic analyses of the clinical features in the Chinese population. Therefore, this study retrospectively analysed the clinical data of patients with hepatic lightchain amyloidosis in our center to further explore the clinical characteristics of this disease. A total of 40 patients with hepatic light chain amyloidosis were included in the analysis from 2007 to 2022. Inclusion criteria were positive liver tissue biopsy or positive biopsy of other organs with alkaline phosphatase (AKP) greater than 1.5 times the upper limit of normal or total liver span >15 cm in the absence of heart failure. The median age of these patients was 58±10 years and 80% were male. Of these 40 patients, 66% had light-chain amyloidosis secondary to myeloma and the remainder had primary amyloidosis. The proportion of patients with symptoms related to liver injury as the initial clinical presentation was 33%. Symptoms included malaise, abdominal distention, or jaundice. 40% of patients with symptoms related to abnormal heart function, such as chest tightness, severe shortness of breath, and dizziness. 25% of the patients were first seen for symptoms related to impaired renal function, such as proteinuria with lower limb edema or hypourocrinia. κ-type was found in 28% of the patients and λ-type in 73%. All patients had other sites of involvement, 95% with cardiac involvement (72.9%, Mayo 2004 stage III) and 48% with renal involvement. AKP was elevated in 100% of patients, r-GT in 95%, liver enzymes in 33%, total bilirubin in 44%, and the maximum anteroposterior diameter of the right lobe of the liver was 16.6±1.7 cm (upper limit of normal was 10 cm). In this cohort of patients, 80% received a 2- to 3-drug combination regimen based on proteasome inhibitors and 5% received a 2-drug combination regimen based on melphalan, with a median survival time of 6.5±31.3 months, and patients with a normal total bilirubin level had an overall survival time 2.4 times longer than those with an elevated level (p< 0.05,Figure 1). Contrary to previous reports of hepatic light chain amyloidosis, λ light chain amyloidosis was predominant in our center; elevated total bilirubin was an independent risk factor for survival.

Background Primary immune thrombocytopenia (ITP) is characterized for the skewed Th differentiation towards Th1 and Th17 cells as well as the impaired number and function of regulatory T cells (Tregs). Tregs are capable of co-expressing effector Th markers in different inflammatory milieu, which probably indicates Treg dysfunction and incompetence to counter over-activated immune responses. Methods Ninety-two primary ITP patients from March 2013 to December 2018 were included, and proinflammatory plasticity in different Treg compartments, age groups, and TGFBR2 variant carrier status were investigated. Results Patients were categorized into elderly (n = 44) and younger (n = 48) groups according to an age of 50 years at disease onset. The overall remission rate was 82.6% after first-line regimens, including 47.8% complete remission. TGFBR2 variants were found in 7 (7.6%) patients with three V216I and four T340M heterozygote carriers. ITP patients demonstrated elevated co-expression of IL-17 and decreased co-expression of both IFN-γ and IL-13 than health control (all p < 0.01). The elderly group demonstrated elevated prevalence of TGFBR2 variants ( p = 0.037) and elevated co-expression of IL-17 ( p = 0.017) in Tregs, while female predominance was found in the younger group ( p = 0.037). In the elderly group, TGFBR2 variant carriers demonstrated further elevated co-expression of IL-17 ( p = 0.023) and decreased co-expression of both IFN-γ ( p = 0.039) and IL-13 ( p = 0.046) in the aTreg compartment. Conclusions Our findings revealed additional aberrations of Treg proinflammatory plasticity in elderly primary ITP patients, and highlighted the potential role of Treg dysfunction and senescence in the pathogenesis and management among these patients.

Background: Marginal zone lymphoma (MZL) collectively is the third most common type of B-cell non-Hodgkin's lymphoma (NHL) worldwide, with an increased trend in incidence during the last two decades (Rossi D E et al., N Engl J Med. 2022). The lack of predominant first-line systemic therapy and toxicities associated with current rituximab-based therapies have inspired the exploration of more optimal treatment strategies (Becnel MR et al., Br J Haematol, 2019). Given the crucial role of bruton tyrosine kinase (BTK) in the B-cell receptor signaling pathway, BTK inhibitor has been proven to yield robust outcomes with improved tolerability in the development of NHL (Dhillon S et al., Drugs, 2021; Xu W et al., Blood, 2019; Song Y et al., Blood, 2019). Orelabrutinib is a novel BTK inhibitor with high selectivity and has been approved in China for relapsed/refractory MZL recently (Dhillon S et al., Drugs, 2021). Meanwhile, several clinical studies reported that orelabrutinib in combination with rituximab in NHL could preserve natural killer cell-mediated antibody-dependent cellular cytotoxicity induced by rituximab and enhance the clinical efficacy (Yu H et al., Mol Ther Oncolytics, 2021; Qu C et al., Blood, 2023). However, orelabrutinib plus rituximab as the first-line treatment for MZL remains largely understudied, thus, we conducted a retrospective study to evaluate its effectiveness and safety. Methods: Between July 27, 2021 and March 18, 2023, 10 patients with MZL who received orelabrutinib (150 mg, qd, po) with rituximab (375 mg/m 2, iv, day 1 of each 28-day cycle) as first-line therapy were included in this retrospective study. After 6 cycles of treatment, patients underwent orelabrutinib monotherapy (150 mg, qd, po) as maintenance for a year. Dynamic dose adjustment was performed according to the patient's clinical status. Effectiveness was assessed by positron emission tomography/computed tomography-based 2014 Lugano criteria. The primary endpoint was the overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Ten patients (6 males; median age 63.5 years, range 45-76) were included in this study, 4 with extranodal MZL of mucosa-associated lymphoid tissue (40.0%), 2 with nodal MZL (20.0%), 1 with splenic MZL (10.0%), and 3 with unknown subtype (30%). Among a total of 10 patients, 3 (30%) achieved complete response (CR) and 6 (60%) attained partial response (PR) as their best response for an ORR of 90% ( Figure 1). After a median follow-up of 13.0 months (range 7.8-24.7), the median PFS was not reached and a 6-month PFS rate was 100% ( Table 1). OS could not be assessed due to there were no deaths occurred. As of the cut-off date (May 6, 2023), 8 patients received orelabrutinib maintenance treatment and the median duration of maintenance treatment was 9.6 months (range 3.0-17.8). The ORR was 75% (6/8) during maintenance treatment, while 1 patient had stable disease (SD) and 1 developed progressive disease (PD). In addition, abnormal hematology due to disease gradually recovered with the therapy within 4 months. No serious adverse events were observed. The off-target related AEs such as atrial fibrillation, diarrhea, and major hemorrhage were not reported. Conclusion: This retrospective data suggests that orelabrutinib with rituximab has an encouraging anti-tumor activity in MZL, with a favorable safety profile. These results provide a potential first-line treatment strategy in MZL. Further verification in prospective clinical trials of clinical outcomes of orelabrutinib in first-line MZL is warranted in the future.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder in which macrophages play a critical role. Mammalian sterile-20-like kinase 4 (MST4), a member of the germinal-center kinase STE20 family, has been demonstrated to be a regulator of inflammation. Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive. The expression and function of MST4 in macrophages of ITP patients and THP-1 cells, and of a macrophage-specific Mst4−/− (Mst4ΔM/ΔM) ITP mouse model were determined. Macrophage phagocytic assays, RNA sequencing (RNA-seq) analysis, immunofluorescence analysis, coimmunoprecipitation (co-IP), mass spectrometry (MS), bioinformatics analysis, and phosphoproteomics analysis were performed to reveal the underlying mechanisms. The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients, and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment. The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages. Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines, and impaired phagocytosis, which could be increased by overexpression of MST4. In a passive ITP mouse model, macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid, attenuated the expression of M1 cytokines, and promoted the predominance of FcγRIIb in splenic macrophages, which resulted in amelioration of thrombocytopenia. Downregulation of MST4 directly inhibited STAT1 phosphorylation, which is essential for M1 polarization of macrophages. Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.

Peripheral blood cell counts and cytokines can be used as predictors of multiple myeloma (MM) patients’ outcomes. 313 newly diagnosed MM patients treated with novel agents were divided into training and validation cohorts. We selected the common peripheral blood cell counts, including the lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and serum cytokines which contained tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) as related variables. The least absolute shrinkage and selection operator (LASSO) regression was conducted to sort the predictor variables in the training cohort, and then the developed nomogram was assessed in the training and validation cohort. Our study showed that SIRI, PLR, and IL-8 were independent prognostic factors for the survival of MM patients. Patients with lower SIRI (≤ 0.87) had superior survival than patients with higher SIRI (> 0.87). Further, according to the LASSO regression, a nomogram embracing LMR (> 3.78), SIRI (> 0.87), PLR (≤ 106.44), and IL-8 was established. The nomogram demonstrated a better correlation with the outcomes of MM patients in the training cohort than International Staging System (ISS) and Revised-International Staging System (R-ISS). The same results were verified in the validation cohort. The nomogram incorporating inflammatory cells and cytokines could be a helpful tool to stratify MM patients in the era of novel agents.

目的:评价含苯达莫司汀方案治疗蛋白酶体抑制剂和免疫调节剂双重难治性多发性骨髓瘤(DRMM)的有效性和安全性.方法:纳入本中心10例使用含苯达莫司汀方案治疗的DRMM患者,所有患者均对蛋白酶体抑制剂(硼替佐米或伊沙佐米)和免疫调节剂(来那度胺或泊马度胺)双重难治.治疗方案为苯达莫司汀联合其他药物(包括沙利度胺、泊马度胺、硼替佐米、伊沙佐米及地塞米松).苯达莫司汀剂量为60～90 mg/m2,第1、2天或第1、8天静脉滴注(每周期2剂),每28 d为1个周期.评估患者疗效、生存情况及安全性.结果:10例DRMM患者中位既往治疗线数为2.5(1-8),对硼替佐米、伊沙佐米、来那度胺、泊马度胺难治的患者分别为8、7、10、3例,所有患者均从末线治疗中进展.5例患者具有17p-或t(4;14),9例患者具有1q21扩增.患者接受苯达莫司汀的中位治疗周期为1.75(1～5),中位治疗剂数为3.5(2～10).9例患者疗效可评估,3例(33.3％)获得≥微小缓解,7例(77.8％)获得≥疾病稳定.中位无进展生存期及总生存期均为2.36个月.3～4级不良反应主要包括贫血(55.6％)、中性粒细胞减少(22.2％)、血小板减少(33.3％)、感染(22.2％).结论:含苯达莫司汀方案治疗DRMM安全性可控,在中国患者药物可及性相对少、经济负担较重的客观条件下,为DRMM患者可考虑的挽救性治疗方案.

目的:探索多学科团队(multidisciplinary team,MDT)诊疗模式对纵隔疾病的治疗策略.方法:回顾性分析在 2020 年 1-12 月复旦大学附属中山医院接受纵隔MDT讨论的纵隔疾病患者的临床资料,并与 2019 年未进行MDT讨论的胸腺肿瘤患者的临床资料进行对比.结果:共为 166 例患者进行 185 次MDT讨论,涉及的病种包括 112 例胸腺上皮肿瘤、12 例淋巴瘤、21 例生殖源性肿瘤、6 例后纵隔神经源性肿瘤,、12 例其他肿瘤、3 例非肿瘤性疾病.35 例首选手术治疗,35 例在放化疗后进行手术治疗.与既往未接受纵隔MDT讨论的胸腺肿瘤患者的临床资料进行比较,接受纵隔MDT讨论的胸腺肿瘤患者的中位诊断治疗间隔时间缩短(13 vs 7 d),接受手术治疗的比例提高(35.8％vs 45.7％),手术完全切除的比例提高(76.5％vs 79.1％),术后平均住院时间缩短(9 vs 7 d).结论:MDT讨论对于复杂纵隔疾病的治疗具有潜在优势,能够为患者制定安全合理的治疗策略.

目的 分析Castleman病(Castleman disease,CD)的病理及临床特征,以及诊治方面的特点.方法 回顾性分析95例病理确诊为CD患者的基线临床资料、实验室指标、病理亚型、治疗方案及生存资料,分析患者病理、临床及诊治特点.结果 CD患者的病理亚型以透明血管型(HV)较多(56/95);单中心型(UCD)较多(69/95),21例患者为特发性多中心型Castleman病-非特指型(iMCD-NOS).UCD及MCD患者间病理亚型、病灶最大径、B组症状、脾大、浆膜腔积液发生率及多项实验室指标差异有统计学意义(P<0.05).39例(41.1％)患者存在淋巴细胞绝对值降低.UCD及无症状性MCD(aMCD)患者未行全身药物治疗;iMCD患者均接受激素、免疫调节剂、利妥昔单抗、化疗药物中的一种或多种全身治疗.CD患者的3年无进展生存率(PFS)为78.8％,预测3年总生存率(OS)为92.2％;MCD患者3年OS为78.2％,5年OS为70.2％.结论 CD患者合并脾大、浆膜腔积液等情况的比例较低,常合并淋巴细胞绝对值降低;MCD患者5年预测OS优于既往报道.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disorder. The existence of autoreactive T cells has long been proposed in ITP. Yet the identification of autoreactive T cells has not been achieved, which is an important step to elucidate the pathogenesis of ITP. Methods: ITP patients' peripheral blood was collected prior to the treatment and one month after initiating dexamethasone treatment per related therapeutic guideline. Serum cytokines were profiled to examine T cell subtypes imbalance using a protein chip. TCR Vβ analysis in CD8+T cells of ITP patients, and TCR CDR3 DNA sequencing of CD4+T and CD8+T cells were performed to determine the autoreactive T cells' clones. Results: Cytokine profiling revealed imbalanced distribution of T cells subtypes, which was confirmed by CD4+T and CD8+T cells' oligoclonal expansion of TCR Vβ analysis and TCR CDR3 DNA sequencing. VDJ segments were found to be more frequently presented in ITP patients, when compared with health controls. There was an individualized CD4+T cell or CD8+T cell CDR3 sequence in each ITP patient. Conclusions: The present study revealed that T cell clones expanded in ITP patients' peripheral blood, and each clone had an individualized TCR CDR3 sequence. The expanded T cell clones preferred to use some specific VDJ segment. Further studies are warranted to get access to individualized treatment such as Car-T in patients with ITP.

OBJECTIVES:We recently reported a high rate of nontherapeutic thymectomy. Mediastinal lymphomas (MLs) are the malignancies most likely to be confused with thymic epithelial tumours (TETs). This study aimed to establish a predictive model by evaluating clinical variables and positron emission tomography to distinguish those diseases. METHODS:From 2018 to 2021, consecutive patients who were pathologically diagnosed with TETs or MLs were retrospectively reviewed. Univariable and multivariable analyses were used to identify association factors. The Akaike information criterion was used to select variables. A nomogram was developed and validated to differentiate MLs from TETs. RESULTS:A total of 198 patients were included. Compared with TETs, patients with MLs were more likely to be younger with higher metabolic tumour volume (154.1 vs 74.6 cm3), total lesion glycolysis (1388.8 vs 315.2 g/ml cm3), SUVmean (9.2 vs 4.8), SUVpeak (12.9 vs 6.3) and SUVmax (14.8 vs 7.5). A nomogram was established based on the stepwise regression results and the final model containing age and SUVmax had minimal Akaike information criterion value of 72.28. Receiver operating characteristic analyses indicated that the area under the curve of predictive nomogram in differentiating MLs from TETs was 0.842 (95% CI: 0.754-0.907). The internal bootstrap resampling and calibration plots demonstrated good consistence between the prediction and the observation. CONCLUSIONS:Combination of age and SUVmax appears to be a useful tool to differentiate MLs from TETs. The novel predictive model prevents more patients from receiving nontherapeutic thymectomy.

BACKGROUND:Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by a decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease in which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP.METHODS:Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP), and 10 healthy controls.RESULTS:The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 were decreased significantly in ITP patients compared with SLE-TP patients, SLE-NTP patients, and healthy controls (P<0.05). While there was no significant difference in the serum level of IL-37 between ITP and SLE-TP patients, there was a positive correlation between the platelet count and IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33, and IL-37 could be considered biomarkers in the diagnosis of ITP.CONCLUSIONS:Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.