Hongmei Jing

Introduction: Mantle cell lymphoma (MCL) constitutes an aggressive subtype of B-cell lymphoma and demonstrates significant clinical and biological heterogeneity. B symptoms are important clinical indicators in tumors. In the present study, we investigated the frequency and prognostic significance of B symptoms among different primary sites of MCL. Method: We conducted an observational study of 2,025 MCL patients from the SEER database. We analyzed the frequency of B symptoms at different primary sites and evaluated their impact on prognosis. Results: The highest incidence of B symptoms was observed in the small intestine (35.29%), and the lowest in the nasopharynx (6.67%). Among patients with primary lymph node involvement, the intrathoracic and abdominal lymph nodes showed the highest proportion of B symptoms (both 40%), while the head, face, and neck lymph nodes showed the lowest (9.3%). In patients with primary site involvement of lymph nodes or nasopharynx, those with B symptoms had a worse prognosis than those without B symptoms (P < 0.05). Similarly, patients with primary lesions involving multiple regional lymph nodes, lymph node not otherwise specified (NOS), or inguinal/leg lymph nodes exhibited worse prognosis when B symptoms were present (P < 0.05). Conclusion: In summary, our study highlights the heterogeneity in both the frequency and prognostic significance of B symptoms across different primary sites in MCL patients.

Sequential allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR‐T) therapy for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). The long‐term survival rates following allo‐HSCT after CAR‐T cell therapy remain controversial. We previously reported the results of 122 patients with R/R B‐ALL who achieved minimal residual disease negative (MRD−) complete remission (CR) after anti‐CD19 CAR‐T, including 67 patients without subsequent transplantation (non‐transplant group) and 55 patients with subsequent haplo‐HSCT (transplant group). Here, we present the extended follow‐up of this cohort, with a median of 72.9 months. Compared with the non‐transplant group, transplantation recipients had a higher 5‐year LFS (50.5% vs. 25.7%; p < 0.001) and OS (53.5% vs. 25.6%; p < 0.001). Multivariable analysis identified MRD positivity at transplantation as an independent factor associated with worse LFS, OS, and a higher cumulative incidence rate of relapse (CIR). MRD‐negative patients before transplant (MRD− group) had a lower 5‐year CIR compared to MRD‐positive patients (MRD+ group) (20.8% vs. 50.0%; p = 0.014). The 5‐year LFS rates in the MRD+ and MRD− groups were 26.7% and 59.4%, respectively ( p = 0.003). The 5‐year OS of the MRD− group was higher than that of the MRD+ group (62.0% vs. 30.5%; p = 0.006). For patients who achieve CR after CAR‐T therapy, haplo‐HSCT with pre‐transplant MRD negativity was associated with better long‐term survival. However, infections emerged as a significant complication that may reduce the long‐term survival benefits. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1900023957.

Chimeric Antigen Receptor T‐cell Immunotherapy represents a breakthrough in treating relapsed/refractory hematologic malignancies, yet immune‐related adverse events, particularly hemophagocytic lymphohistiocytosis (HLH), also known as immune effector cell‐associated HLH‐like syndrome (IEC‐HS), are rapid‐progressing and life‐threatening. This systematic review and meta‐analysis searched PubMed, Embase, and Cochrane CENTRAL up to August 20, 2025. Nineteen studies were analyzed using a random‐effects model, covering 2780 patients, 47 HLH cases, and 20 HLH‐related deaths. The pooled incidence of HLH was 1.6% at a median follow‐up of 12.9 months, with an associated HLH mortality of 0.7%. The incidence of HLH differed markedly by disease entity ( p = 0.0008), highest in B‐cell acute lymphoblastic leukemia (B‐ALL: 6.9%). CAR T‐cell product was also a significant determinant ( p = 0.0036), with tisagenlecleucel (Tisa‐cel) showing the highest incidence (4.3%). Subgroup analyses confirmed that Tisa‐cel had a significantly higher HLH incidence than axicabtagene ciloleucel (Axi‐cel) in large B‐cell lymphoma (2.4% vs. 0.6%, p = 0.038), and ciltacabtagene autoleucel (Cilta‐cel) had a higher incidence than idecabtagene vicleucel (Ide‐cel) in multiple myeloma (2.6% vs. 0.7%, p = 0.022). Higher‐grade cytokine release syndrome (CRS) was positively correlated with HLH incidence, particularly in MM. Overall HLH incidence was significantly positively correlated with mortality. In conclusion, HLH risk after CAR T‐cell therapy is primarily driven by underlying disease type and specific CAR T‐cell product, with additional contribution from severe CRS. Enhanced surveillance and early intervention are strongly recommended for high‐risk groups, particularly B‐ALL patients and recipients of Tisa‐cel or Cilta‐cel.

This Phase I/II clinical trial (NCT04471064) evaluated the preliminary efficacy, safety, and pharmacokinetics of XY0206, a novel oral FMS‐like tyrosine kinase 3 (FLT3) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (R/R AML). From September 2020 to December 2022, this open‐label, multicenter study enrolled patients aged ≥ 18 years with R/R AML. The trial included dose‐escalation and dose‐expansion phases, with six cohorts receiving XY0206 at doses ranging from 12.5 to 62.5 mg once daily or 25 mg twice daily. Of the 61 enrolled participants, 37 had FLT3 mutation‐positive (FLT3 ^mut+ ) AML. The overall response rate (ORR) was 34.4% in the entire cohort and 48.6% in FLT3 ^mut+ patients. Among FLT3 ^mut+ patients, the composite complete remission rate (CRc) was 45.9%, including a complete remission (CR) rate of 5.4% and a CR with partial hematologic recovery (CRh) rate of 13.5% and a CR with incomplete hematologic recovery (CRi) rate of 27.0%. In patients with FLT3 internal tandem duplication (FLT3‐ITD) mutations, the ORR was 56.7%, with a CRc of 53.3% (CR: 6.7%; CRh: 16.7% ; CRi: 30.0%). The 37.5 mg dose cohort, identified as the target dose, was expanded exclusively for FLT3 ^mut+ patients. XY0206 exhibited a favorable safety profile and demonstrated potent antileukemic activity, particularly in FLT3 ^mut+ R/R AML patients, supporting its further clinical development. Trial Registration: CTR20201214 (CDE); ClinicalTrials.gov ID: NCT04471064

Cell division cycle 20 homolog (CDC20), a critical substrate-recruiting subunit of the anaphase-promoting complex/cyclosome (APC/C), binds to APC/C to form the active APC/C-CDC20 complex, which regulates the degradation of key cell cycle substrates to ensure accurate and timely mitotic progression. Accumulating evidence demonstrates that CDC20 functions as an oncogenic factor, with its overexpression observed in various malignancies. Its dysregulation is closely associated with tumor initiation, progression, drug resistance, and poor clinical outcomes, underscoring its potential as a therapeutic target in anti-cancer strategies. In this review, we describe the biological functions of CDC20 in cancers, discuss its role and underlying mechanisms in solid tumors and hematological malignancies, and elucidate currently reported CDC20-targeted inhibitors along with their clinical benefits and challenges. By emphasizing the oncogenic significance of CDC20, we propose that the development of specific, safe, and potent CDC20 inhibitors could provide a promising therapeutic approach for cancer patients exhibiting CDC20 overexpression.

Although targeting the ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) has shown promise in treating a number of diseases, its function in mantle cell lymphoma (MCL) and its regulatory connection to SOX11 are yet unknown. Our study showed that UHRF1 is markedly upregulated in MCL, and this overexpression is associated with a poorer overall survival rate in MCL patients. Furthermore, in clinical MCL specimens, UHRF1 showed a positive correlation with the expression of SOX11 and Ki-67. In vitro, UHRF1 knockdown induced apoptosis and caused G2/M-phase arrest while functionally suppressing MCL cell motility, invasion, and proliferation. In MCL xenograft models, UHRF1 silence significantly delayed tumor development, and pharmacological targeting UHRF1 with CM272 effectively inhibited MCL progression with a tolerable safety profile. Mechanistically, SOX11 drives the transcriptional activation of UHRF1 by directly binding to its promoter region. Our results reveal that the SOX11-UHRF1 regulatory axis is a critical modulator of tumor cell growth and proliferation and identify UHRF1 as a key oncogenic driver in MCL. Additionally, CM272's antitumor effect was validated in preclinical MCL animal models while exhibiting an acceptable safety profile.