This national, multicenter, retrospective study analyzed 1070 patients with newly diagnosed systemic light-chain (AL) amyloidosis in China (2008-2025). Findings reveal increasing annual diagnoses and a marked shift in first-line therapy from proteasome inhibitor (PI)-based regimens to predominantly daratumumab-based regimens since 2024. Monthly kinetic assessments demonstrated that daratumumab-based induction produced deeper and faster hematologic responses than PI-based therapy [≥ very good hematologic partial response (HemVGPR): 80.3% vs. 70.8%, p = 0.012; median time to ≥ HemVGPR: 1.2 vs. 1.8 months, p = 0.001], with significantly superior cardiac overall response (63.1% vs. 53.3%, p = 0.030). Early mortality rates at 1, 3, and 6 months were 5.5%, 13.2%, and 16.2%, respectively, with daratumumab-based therapy identified as an independent protective factor for 6-month mortality. Median event-free survival (EFS) was 44.4 months, while median overall survival (OS) was not reached. Achievement of hematologic complete response (HemCR) conferred superior EFS and OS over HemVGPR (both p < 0.001), with minimal residual disease negativity further improving EFS in HemCR patients (p = 0.043). Concurrent hepatic and cardiac involvement defined a high-risk subgroup with poor outcomes (median EFS 12.8 months, OS 51.0 months). Multivariable analysis confirmed Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 2, liver involvement, and gain1q as adverse prognostic factors for EFS, whereas ≥ HemVGPR was protective. For OS, liver involvement, concomitant multiple myeloma, and ECOG PS > 2 were independent risk factors, while ≥ HemVGPR and cardiac response predicted improved survival. This study establishes a contemporary benchmark for AL amyloidosis management in China, confirming the superior real-world efficacy of daratumumab-based frontline therapy.

Subgroup analysis of the best ORR (CR + PR) in patients in the Trial A.

Clinical characteristics of Trial A and B after PSM.

Primary Sjögren’s syndrome-associated peripheral neuropathy (pSS-PN) represents a clinically heterogeneous complication linked to significant morbidity. This study aims to characterize its prevalence, clinical phenotypes, predictive factors, and prognosis. In this retrospective cohort study conducted at Shanghai Tongji Hospital, 553 consecutive pSS patients (2002 American–European Consensus Group criteria) were evaluated. After applying the exclusion criteria, 320 eligible patients completed the full assessment protocol and constituted the final analytical cohort. Based on the diagnostic criteria for peripheral neuropathy (PN), 59 patients were diagnosed with pSS-PN, while the remaining 261 were classified as pSS without PN (pSS-nPN). The prevalence of pSS-PN was 18.4

CRS, ICANS and cytopenias happened in Trial A and B.

Background:Cardiac amyloidosis (CA) has been recognized as a more frequent cause of heart failure with preserved ejection fraction (HFpEF). However, missed and delayed diagnosis in CA by cardiologists are common. The study aimed to develop a simple nomogram to identify high risk of CA in HFpEF patients, warranting a further systematic diagnostic algorithm of CA. Methods:A total of 337 consecutively hospitalized HFpEF patients [ejection fraction (EF) ≥40%] with increased wall thickness (IWT; ≥12 mm) who underwent a complete diagnostic evaluation for suspected CA from April 2015 to September 2024 were retrospectively included. The diagnosis of transthyretin CA (ATTR-CA) was mainly established by 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, whereas the diagnosis of immunoglobulin light chain CA (AL-CA) was predominantly confirmed by histological biopsy. Patients were randomly divided into training and validation cohorts at a ratio of 7:3. A simple nomogram was established to predict the risk of CA by multivariate logistic regression analysis in the training cohort (n=236) and then validated in the validation cohort (n=101). Results:A final diagnosis of CA was established in 152 patients, among whom 35 (23%) were identified as ATTR-CA and 117 (77%) as AL-CA, indicating that the prevalence of AL-CA was significantly higher than that of ATTR-CA in our cohort of Chinese HFpEF patients. More importantly, ATTR-CA and AL-CA exhibited comparable clinical and echocardiographic characteristics, thus we developed a simple and unified nomogram model incorporating the absence of hypertension, poor precordial R wave progression, relative wall thickness (RWT), early diastolic mitral peak flow velocity/late diastolic mitral peak flow velocity (E/A) ratio, and right ventricular (RV) wall thickening to identify high risk of CA in Chinese HFpEF patients. The area under the curve (AUC) for the training cohort was 0.881, and for the validation cohort was 0.854, indicating good discrimination. Meanwhile, the calibration curves comparing predicted frequency against observed frequency indicated excellent concordance. Decision curve analysis (DCA) further validated the utility of the nomogram in a clinical setting. Conclusions:The nomogram model based on 5 easily assessable variables aids identifying increased risk of CA in Chinese HFpEF patients. It provides a practical approach and facilitates clinical decision-making by cardiologists for further systematic diagnostic algorithm of CA.

Background N6-methyladenosine (m6A) is the most common RNA modification and plays a key role in the initiation, progression, and relapse of multiple cancers, including hematologic malignancies. However, the role of m6A and m6A regulatory genes in myelodysplastic syndromes (MDS) remains unclear. This study aims to elucidate the function and molecular mechanism of methyltransferase METTL14 in MDS. Methods RT-qPCR was used to assess the expression of multiple m6A regulators, focusing on METTL14 in MDS patients and cell lines. METTL14 overexpressing and knockdown cell lines were established, and CCK-8, EdU, and flow cytometry assays were performed to explore the biological functions of METTL14.Dot blot, MeRIP-Seq, MeRIP-qPCR, RT-qPCR, and Western blot were employed to investigate the underlying molecular mechanism. Results Dysregulation of multiple m6A regulators was observed in MDS, among which METTL14 was upregulated. Elevated METTL14 expression increases MDS risk and adverse prognosis, emerging as a biomarker for poor prognosis. METTL14 promoted proliferation and cell-cycle progression of MDS cells while inhibiting apoptosis; corresponding changes were observed in cell cycle and apoptosis markers. METTL14 regulated cellular m6A levels. Downstream targets of METTL14 were enriched in cell cycle-related pathways, with CCNE1 identified as a critical target. Knockdown of METTL14, actinomycin D, or S-adenosylhomocysteine treatment reduced CCNE1 mRNA and protein levels. Furthermore, METTL14 activated MAPK-ERK and PI3K-AKT signaling via CCNE1 in an m6A-dependent manner, thereby promoting proliferative MDS cells' capacity. Conclusions This study delineates a METTL14/m6A/CCNE1 signaling axis in MDS progression and suggests that METTL14-mediated m6A modification may be a potential therapeutic target for MDS.

Multivariate analysis of prognostic factors for PFS after PSM and IPTW.

Cellular kinetics of CD19 and CD22 CAR transgenes in peripheral blood and B cell aplasia

Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.

Treatment of multiple myeloma (MM) has entered the era of deep remission-oriented therapy, where minimal residual disease (MRD) has become a key indicator for treatment response and long-term prognosis, surpassing conventional complete remission criteria. However, the optimal integration of MRD into clinical decision-making remains to be established. This expert consensus offers evidence-based guidance on redefining treatment goals in the era of CD38-based therapy, incorporating MRD status into therapeutic decisions, standardizing MRD detection, and integrating new technologies to address current challenges. The consensus supports including MRD assessment in treatment evaluation for almost all MM patients and recommends a comprehensive approach that combines bone marrow, imaging, and peripheral blood-based assessments. For patients receiving CD38-based therapy, achieving and sustaining MRD negativity is strongly linked to improved outcomes. The timing and frequency of MRD testing should be adapted to treatment phases, and CD38-based therapy may be used as part of active maintenance strategies, especially in high-risk populations. Dynamic MRD monitoring is emphasized as a critical part of disease management. Both next-generation flow and next-generation sequencing are considered interchangeable for prognostic assessment, while peripheral residual disease detection is a promising direction for future disease surveillance. This consensus provides a practical framework for integrating MRD assessment into MM clinical management. Dynamic, MRD-guided treatment strategies may enable more precise risk stratification and personalized therapy, ultimately improving long-term patient outcomes.

Protease nexin 1 (PN1) is an endogenous serine protease inhibitor (SERPIN), expressed at high levels in the prostate, and capable of inhibiting the proliferation of prostate cancer cells. We previously showed that PN1-uPA complexes inhibited Sonic Hedgehog (SHH) signalling through engagement of the LRP receptor. Here, we describe an alternative anti-proliferative mechanism through which PN1 expression leads to apoptosis. In prostate cancer cells, increased expression of PN1 led to substantial reduction of XIAP levels and apoptosis mediated through the uPAR, but not the LRP receptor. The alterations in XIAP were effected in two ways 1) via alteration in the NF-κB pathway, a pathway known to signal XIAP transcription and 2) by promoting XIAP instability. The AKT pathway is known to phosphorylate XIAP at serine 87 leading to protein stability and PN1 expression is shown to interfere with this process. As a result of both mechanisms, programmed cell death is substantially increased. Consistent with these observations, reduced PN1 protein correlated with elevated p65/XIAP expression and with higher Gleason scores in human prostate tissue arrays. Thus, PN1 expression appears to differentially down-regulate distinct oncogenic pathways depending upon the cell surface receptor engaged by its complexes and demonstrates a novel molecular mechanism by which the protein can promote tumor cell apoptosis.

This study reports an adult-onset case of NK cell–predominant chronic active Epstein-Barr virus infection (CAEBV) harboring multiple heterozygous germline variants affecting antiviral immunity. Functional assessments of NK cell cytotoxicity and degranulation in the patient and her family members revealed subclinical immune defects in several relatives, leading to the exclusion of related donors. The patient ultimately underwent a fully HLA-matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT), achieving early virologic remission and complete donor chimerism. However, the post-transplant course was complicated by severe immune-related adverse events, including acute and chronic graft-versus-host disease (GVHD), thrombotic microangiopathy, viral reactivations, and secondary hemophagocytic lymphohistiocytosis, ultimately resulting in death due to severe pulmonary infection and multi-organ failure. This case underscores the critical role of immunogenetic risk stratification in guiding transplant decisions. Matched unrelated donor transplantation, supported by comprehensive functional and genetic screening, offers curative potential while avoiding the use of immunologically compromised donors. Nevertheless, long-term outcomes in CAEBV depend not only on virologic remission but also on sustained immune reconstitution. In addition, this report reviews precision transplantation strategies that integrate host genetic background, immune function, and viral dynamics, providing a roadmap for the future management of CAEBV.

Subgroup analysis of the best ORR (CR + PR) in patients in all patients.

Survivals of patients with Trial A and Trial B after IPTW

Prognostic impact of risk factors in patients with R/R DLBCL.

Cytopenias occour in Trial A and B

Subgroup analysis of the best ORR (CR + PR) in patients in the Trial B.

The lymphocyte subsets of the peripheral blood of Trial A and B.

Representativeness of Study Participants