Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi最新文献

Objective: To evaluate the efficacy and safety of Bruton tyrosine kinase inhibitor (BTKi) combined with R-CHOP regimen in newly diagnosed double-expressor diffuse large B-cell lymphoma (DE-DLBCL) . Methods: A retrospective analysis was conducted on 95 patients with DLBCL meeting DE criteria by immunohistochemistry (MYC protein expression ≥ 40% , BCL-2 protein expression ≥ 50% ) treated at the First Affiliated Hospital of Nanjing Medical University between June 2021 and June 2024. Among them, 35 patients received BTKi (zanubrutinib, orelabrutinib, acalabrutinib) combined with R-CHOP (BTKi + R-CHOP group) , and 60 received R-CHOP regimen alone (R-CHOP group) . Outcomes included objective response rate (ORR) , complete response (CR) rate, progression-free survival (PFS) , overall survival (OS) , and safety. Results: The median age of the BTKi+R-CHOP group was 61 (range, 29-73) years. At the end of induction therapy, the BTKi+R-CHOP group had a higher ORR (94.3% vs 71.7% , P=0.008) and CR rate (91.4% vs 65.0% , P=0.006) than the R-CHOP group. After a median follow-up of 30 (range, 6-47) months, the 1- and 2-year PFS rates in the BTKi+R-CHOP group were 88.5% (95% CI: 78.5% -99.8% ) and 85.1% (95% CI: 73.8% -98.1% ) , respectively, and the 1- and 2-year OS rate was 94.3% (95% CI: 86.9% -100% ) . In the R-CHOP group, the 1-year and 2-year progression-free survival (PFS) rates were 61.7% (95% CI: 50.5% -75.3% ) and 48.8% (95% CI: 37.4% -63.6% ) , respectively; the 1-year and 2-year overall survival (OS) rates were 80.0% (95% CI: 70.5% -90.8% ) and 65.1% (95% CI: 53.7% -78.8% ) , respectively. Between-group differences were significant for both PFS (P=0.002) and OS (P=0.010) . Subgroup analyses showed high ORRs across clinical subgroups in the BTKi+R-CHOP group (all ORR>85% ) . Grade ≥ 3 adverse events primarily included neutropenia (28.6% ) and pulmonary infection (14.3% ) ; no fatal bleeding or cardiovascular events occurred. Conclusion: BTKi combined with R-CHOP significantly improved response rates and survival in patients with DE-DLBCL, with manageable safety.

Romiplostim N01 (QL0911) is a novel thrombopoietin receptor agonist (TPO-RA) ; however, clinical data regarding its efficacy and safety in patients with refractory aplastic anemia (AA) who have failed multiple prior lines of therapy are limited. This retrospective single center study analyzed the clinical outcomes of 32 patients with refractory AA who received romiplostim N01 at Peking Union Medical College Hospital between May 2024 and December 2024. All patients had previously failed to respond to full dose cyclosporine and at least two oral TPO-RA administered for adequate treatment durations and had been treated with romiplostim N01 for ≥3 months and followed for ≥6 months. The median age of the cohort was 62 years (range, 24-79 years) , and 11 patients (34.4% ) were male. Thirty patients had transfusion-dependent non-severe AA (TD-NSAA) , and 2 had severe AA (SAA) . The median duration of romiplostim N01 treatment was 5 months (range, 3-10 months) , and the median follow-up time was 6 months (range, 6-10 months) . The overall response rates (ORR) at 3 months, 6 months, and the last follow-up were 71.9% , 75.0% , and 75.0% , respectively, and the complete response rates (CRR) were 28.1% , 28.1% , and 31.2% , respectively. The median time to hematologic response was 1 month (range, 1-4 months) , and the median time to complete response was 3 months (range, 1-4 months) , indicating a rapid onset of action even in this refractory population. A total of 14 patients (43.8% ) experienced adverse events, all of which were grade 1 and improved with symptomatic management; no dose reductions or treatment discontinuations were required, and no treatment related liver dysfunction, thrombotic events, or deaths were observed. During follow-up, relapse occurred in 3 patients who had previously responded (3/26, 11.5% ) , and newly detected myelodysplastic syndrome (MDS) -related gene mutations were identified in 2 patients (6.3% ) . No new or expanding paroxysmal nocturnal hemoglobinuria (PNH) clones were detected. These findings suggest that romiplostim N01 can induce rapid and high hematologic response rates with a favorable safety profile in patients with refractory AA who have failed full-dose cyclosporine A and multiple oral TPO-RA; no obvious short-term signals of clonal evolution were observed.

Objective: To analyze the clinical characteristics and genetic mutations in two families with combined antithrombin (AT) and protein C (PC) deficiency, and to explore the relationship between combined SERPINC1 and PROC gene mutations and disease development. Methods: The AT activity (AT∶A) , AT antigen (AT∶Ag) , PC activity (PC∶A) , PC antigen (PC∶Ag) , and protein S activity (PS∶A) of the probands and their family members were measured. Next-generation sequencing (NGS) and CNVplex technology were used to detect point mutations, small deletions or insertions, and CNVs in the coding and regulatory regions of the selected genes, with mutation sites verified by Sanger sequencing. The conservation of mutation sites was analyzed using ClustalX-2.1-win software; the pathogenicity of these mutations was predicted using online bioinformatics tools; thrombin generation was assessed using the CAT method. Results: In proband 1, a c.400+5G>A splice site mutation was found in exon 5 of the PROC gene, along with a c.883G>A (p.Val295Met) heterozygous missense mutation in exon 5 of the SERPINC1 gene; in proband 2, a c.811C>T (p.Arg271Trp) heterozygous missense mutation in exon 9 of the PROC gene and a c.880C>T (p.Arg294Cys) heterozygous missense mutation in exon 5 of the SERPINC1 gene were identified. The mutation sites were inherited from the patient's father and mother, respectively. Bioinformatics analysis revealed that most of the mutation sites were conserved, and the majority of these gene mutations were predicted to be "disease-causing and harmful." These mutations may lead to abnormal levels or functions of AT and PC by altering protein structure and destabilizing protein stability. Thrombin generation tests showed that all four mutation carriers exhibited varying degrees of increased endogenous thrombin potential, indicating a hypercoagulable state. In the presence of soluble thrombomodulin (sTM) , the anticoagulant function of the PC pathway was significantly impaired. Conclusion: Two families were found to harbor mutations in AT and PC genes, respectively, which may contribute to recurrent venous thromboembolism in the affected patients. Notably, individuals carrying combined mutations in the SERPINC1 and PROC genes have a significantly higher risk of venous thrombosis.

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. The efficacy of standard first-line glucocorticoid treatment is limited; more than 40% of patients develop steroid-refractory aGVHD with an extremely poor prognosis. In recent years, mesenchymal stromal cell (MSC) as a second-line treatment for steroid-refractory aGVHD has been widely studied worldwide. In 2025, the first domestic MSC product was conditional approved by the National Medical Products Administration for steroid-refractory aGVHD in patients aged 14 years and above in China. In light of this, this article reviews the clinical research progress of MSC in the treatment of steroid-refractory aGVHD, focusing on mechanisms and efficacy evaluation, aiming to deepen the understanding of the clinical potential and existing challenges of MSC.

Chronic myelomonocytic leukemia (CMML) is one of myeloid neoplasms originating from hematopoietic stem/progenitor cells, featuring both myelodysplastic and myeloproliferative characteristics. Significant revisions have been made to the diagnostic and classification criteria for CMML in the 5th edition WHO classification (WHO 2022) and the International Consensus Classification (ICC) . Furthermore, besides the previously proposed CMML-specific prognostic scoring system (CPSS) , newer prognostic models such as CPSS-Mol, BLAST, and BLAST-Mol have recently been introduced, incorporating cytogenetic and molecular data. Treatment decisions for CMML patients should be comprehensively determined based on prognostic stratification, considering the patient's symptoms, disease burden (manifested as cytopenias or proliferative features) , evidence of disease progression, as well as individual patient status and preferences. This article provides an overview of diagnostic considerations, prognostic assessment and therapeutic options.

Myelodysplastic neoplasms (MDS) are a group of highly heterogeneous myeloid malignancies characterized by cytopenia, dysplasia, and a high risk of leukemic transformation. Next-generation sequencing (NGS) technology enables efficient detection of gene mutations and has been incorporated into the diagnostic classification, prognostic assessment, and treatment decision-making systems for MDS. To further standardize the clinical application of NGS technology in MDS, Leukemia & Lymphoma Group, Chinese Society of Hematology, Chinese Medical Association have developed this expert consensus by integrating the latest advances in MDS diagnosis and treatment, relevant domestic and international guidelines/consensus recommendations, and expert opinions from China. The aim is to promote the rational use of NGS in the diagnosis and treatment of MDS in China.

Objective: To validate the Response to Ruxolitinib After 6 Months (RR6) prognostic model in Chinese patients with myelofibrosis (MF) treated with ruxolitinib and assess its incremental prognostic value when integrated with high molecular risk mutations (HMR(mt)) and/or RAS pathway mutations (RASp(mt)) . Methods: Altogether, 153 patients with myeloproliferative neoplasm-associated MF treated with ruxolitinib at our hospital from May 2016 to February 2024 were retrospectively enrolled. The RR6 prognostic model was applied for prognostic stratification and OS analysis, and calibration curves were plotted to evaluate the model's calibration. The predictive efficacy and clinical benefit of the RR6 model and its integrated models were comprehensively assessed and compared using the concordance index (C-index), time-dependent area under the curve (AUC), net reclassification improvement (NRI), and decision curve analysis (DCA) . Results: Altogether, 153 patients were diagnosed with primary myelofibrosis (n=114), post-polycythemia vera (post-PV) MF (n=17), and post-essential thrombocythemia (post-ET) MF (n=22). Patients had a median follow-up time from the initiation of ruxolitinib treatment of 44.6 (IQR: 27.3-64.5) months; 106 (69.3%) patients survived, 47 (30.7%) died, and 94 (61.4%) were still receiving ruxolitinib as of the last follow-up. According to the RR6 model, 28 (18.3%), 92 (60.1%), and 33 (21.6%) patients were classified as having low, intermediate, and high risks, respectively, with the estimated median overall survival (mOS) not reached for both the low- and intermediate-risk groups and 32 (95% CI: 24.0-39.5) months for the high-risk group (P=0.012). The calibration curves indicated that the RR6 model demonstrated good calibration performance at 1, 2, and 3 years. Among 102 patients with next-generation sequencing data, the integrated RR6+HMR(mt)+RASp(mt) model demonstrated the best predictive efficacy, with the highest C-index (0.735) and AUC value. The NRI also confirmed that this model significantly improved risk reclassification at 1 and 2 years (P=0.016, P<0.001). Moreover, DCA showed significant net clinical benefit. Conclusion: The present study confirms that the RR6 prognostic model has favorable prognostic predictive ability in Chinese patients with MF and can be utilized for the early identification of high-risk patients. The integration of HMR(mt) and RASp(mt) may enhance the predictive power of the RR6 model.

Objective: To investigate the molecular mechanisms underlying compound heterozygous mutations in a patient with hereditary plasminogen (PLG) deficiency. Methods: The proband presented to the First Affiliated Hospital of Wenzhou Medical University with a 2-day history of left-sided limb weakness. Plasminogen activity (PLG∶A) and plasminogen antigen (PLG∶Ag) were measured by chromogenic substrate and enzyme-linked immunosorbent assays, respectively, in the proband and family members (eight individuals across three generations). Sanger sequencing was performed to identify the PLG mutation sites. Bioinformatic analyses were conducted to assess evolutionary conservation and to predict pathogenicity of the mutation sites. Mutant protein models were constructed to examine mutation-induced structural changes. Recombinant plasmid expression vectors were constructed, and in vitro expression of recombinant PLG protein was studied using quantitative real-time PCR (qRT-PCR), ELISA, and Western blot analysis. Results: The proband's PLG∶A was 27% (reference range, 80%-120%) and PLG∶Ag was 103% (reference range, 50%-150%), consistent with type Ⅱ plasminogen deficiency. Genetic analysis revealed compound heterozygous missense mutations in the proband: c.1702G>A (p. Gly568Arg) in exon 14 and c.1858G>A (p. Ala620Thr) in exon 15. The c.1702G>A site is highly conserved across seven species, and is predicted to be pathogenic by bioinformatic tools. Protein modeling showed that p. Gly568Arg introduces a longer side chain and forms a new hydrogen bond with Leu686. In vitro expression showed that neither mutation caused abnormalities in PLG transcript levels, protein expression, or secretion; however, the PLG∶A/PLG∶Ag ratios in the culture supernatants were significantly lower than wild-type for both variants (Ala620Thr: 0.598 ± 0.114 vs 1.000, P=0.013; Gly568Arg: 0.412 ± 0.079 vs 1.000, P=0.022) . Conclusion: The heterozygous missense mutations p.Gly568Arg and p. Ala620Thr are associated with decreased PLG∶A in the family proband and may cause functional impairment by altering protein conformation.

We retrospectively analyzed the clinical data and clonal architecture of two multiple myeloma (MM) patients harboring concurrent IGH::FGFR3 and IGH::CCND1 fusions, with a review of relevant literature. Fluorescence in situ hybridization (FISH) confirmed biallelic IGH translocations in both cases. Case 1, diagnosed with smoldering MM (SMM), exhibited co-positivity for both IGH translocations in 91% of bone marrow plasma cells. Case 2, with active MM, showed predominant IGH::FGFR3 positivity (93% of cells), with a minor subclone (5%) co-expressing IGH::CCND1. This study demonstrates that primary biallelic IGH translocations can lead to the coexistence of IGH::FGFR3 and IGH::CCND1, revealing a novel genetic mechanism driven by biallelic IGH translocations in the founding clone. Furthermore, it elucidates the clonal heterogeneity in biallelic IGH translocation events.