bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous hematopoietic stem cell transplantation may overcome the adverse impact of IKZF1 on the prognosis of B-ALL in CR1 with no detectable minimal residual disease
Authors: Wang Jiali , Ma Xiaoxiao , Zhang Rongli , Jiang Erlie 
Published: December 2024

Purpose: Ikaros family zinc finger 1 (IKZF1) mutation may serve as a poor prognostic factor in B-cell acute lymphoblastic leukemia (B-ALL). This study explored the impact of autologous hematopoietic stem cell transplantation (auto-HSCT) on the outcome of B-ALL patients with IKZF1 alterations.
Methods: we detected the IKZF1 mutation at diagnosis in the bone marrow of adult patients with B-ALL, and analyzed the clinical data of these patients retrospectively.
Results: A total of 44 B-ALL patients in CR1 were enrolled in the study, including 12 recipients of auto-HSCT and 32 of allo-HSCT. Auto-HSCT demonstrated comparable 2-year overall survival (OS) (60% vs. 83.3%, p = 0.88) and leukemia-free survival rates (60% vs. 81.1%, p = 0.96) compared to allo-HSCT for patients with negative MRD. Additionally, there was no significant difference in the 2-year cumulative incidence of relapse (CIR) between auto-HSCT and allo-HSCT groups (38.9% vs. 19.5%, p=0.65), and non-relapse mortality (NRM) rates were lower in the auto-HSCT group at 0% compared to 13.2% in the allo-HSCT group (p=0.22). The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after 1 or 2-3 chemotherapy cycles. The results revealed that after 1 cycle of chemotherapy, auto-HSCT showed promising 2-year OS(100% vs. 85.7% , p=0.35)and LFS rates(100% vs. 85% , p=0.35) , with no significant difference compared to allo-HSCT. Additionally, it displayed lower CIR and NRM(0% vs. 14.3%,p=0.35), indicating potential advantages. For MRD-negative patients after 2-3 cycles of chemotherapy, allo-HSCT may be more beneficial, as shown by the favorable 2-year OS(50% vs. 100%, p=0.018) and LFS rates(50% vs. 100%, p=0.0082), despite similar CIR(33.3% vs. 14.3%,p=0.11).
Conclusion: Auto-HSCT may be an attractive treatment for B-ALL patients of IKZF1 mutation with negative MRD after three chemotherapy cycles,especially after 1 cycle of chemotherapy. These findings provide valuable insights into the treatment efficacy of auto-HSCT and allo-HSCT in different MRD-negative patient subgroups, offering important implications for therapeutic strategies in this specific patient population.
Keywords: acute lymphoblastic leukemia, IKZF1, Allo-HSCT, Auto-HSCT,MRD
Homoharringtonine Combining with Azacitidine and Venetoclax (HAV) As First-Line Induction Therapy for Newly Diagnosed Adult Acute Myeloid Leukemia Patients
Authors: Lu Wenyi , Chen Xiangli , Zang Yuzhu , Zhu Zunmin , Zhang Wenhui , Bai Yanliang , Chen Yuqing , Jiang Li , Xing Yanyan , Liu Yuanbo , Shi Jie , Gao Zhenxing 
Published: December 2024

The targeted therapy regimen of venetoclax combined with demethylating agents has demonstrated a complete remission (CR) rate of approximately 70% in elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML). However, its efficacy in newly diagnosed fit AML patients has been unsatisfactory, leading to a lack of recommendation for this cohort. Recent reports suggest that combining venetoclax with homoharringtonine enhances its anti-leukemic effects, with promising results observed in refractory/relapsed AML cases. This study aims to evaluate the safety and efficacy of the homoharringtonine, azacitidine, and venetoclax (HAV) regimen in treating newly diagnosed adult AML.
This retrospective study analyzed newly diagnosed AML patients who received induction therapy with the HAV regimen at Henan Provincial People's Hospital from January 2021 to December 2023. The HAV regimen comprised homoharringtonine (2 mg/d, days 1-7), azacitidine (75 mg/m²/d, days 1-7), and venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3-14). The primary endpoint was the composite complete remission rate (cCR) after one cycle of induction therapy (CR+CRi). Secondary endpoints included event-free survival (EFS), overall survival (OS), and adverse effects.
A total of 24 newly diagnosed adult AML patients were included, with a median age of 62 years (range: 28-82 years). According to the 2022 ELN risk stratification, 3 patients were classified as favorable, 11 as intermediate, and 10 as adverse-risk. After one cycle of induction with the HAV regimen, the cCR rate was 95.8%, and the MRD-negative CR rate was 62.5%. Safety analysis revealed that grade ≥3 adverse reactions included neutropenia in 23 patients (95.8%), thrombocytopenia in 22 patients (91.7%), anemia in 11 patients (45.8%), febrile neutropenia in 23 patients (95.8%), and pneumonia in 7 patients (29.2%). No treatment-related deaths occurred. The median follow-up time was 221 days, with a 1-year OS rate of 90% (95% CI: 76.9%-100%) and a 1-year EFS rate of 72.4% (95% CI: 51.6%-93.2%).
In conclusion, the HAV regimen is an effective and safe induction therapy for newly diagnosed AML patients, achieving a high complete remission rate. This regimen offers a promising treatment strategy for adult patients with newly diagnosed AML.
RNA-Lnp-Mediated CAR-T Cell Manufacturing: A Paradigm Shift in Precision Immunotherapy
Authors: Sun Xiulian , Zhao Sheng , Wang Wei 
Published: December 2024

The landscape of cancer treatment is being revolutionized by the advent of chimeric antigen receptor T (CAR-T) cell therapies, which harness the power of the immune system to target and eliminate cancer cells. Despite their remarkable therapeutic potential, the production of CAR-T cells remains a complex and personalized process, fraught with challenges such as genetic modification risks, manufacturing inefficiencies, and the need for scalable solutions. This study introduces a novel RNA-lipid nanoparticle (RNA-LNP) technology for the efficient and safe delivery of therapeutic RNAs, including messenger RNA (mRNA), circular RNA (circRNA), and self-amplifying RNA (saRNA), into T cells, thereby enhancing the manufacturing process of CAR-T cells.
Our methodology involves the generation of RNA-LNPs through a precisely controlled process, ensuring uniform particle size and RNA encapsulation efficiency. The RNA-LNPs are then complexed with the therapeutic RNAs and administered to T cells. The RNA-LNP technology offers several advantages over traditional CAR-T cell manufacturing methods, including the avoidance of genomic integration, reduced immunogenicity, and the flexibility to modulate the expression levels of therapeutic proteins. The RNA-LNP system is designed to encapsulate and protect the fragile RNA molecules, facilitating their delivery into T cells with high efficiency. The encapsulated mRNA enables rapid and transient expression of the CAR protein, circumventing the need for permanent genetic alteration. This approach significantly reduces the risk of off-target effects and potential genotoxicity associated with viral vector-based gene therapies. Furthermore, the inclusion of circRNA in the RNA-LNP formulation provides a stable and enduring source of CAR transcripts with reduced immunogenicity, potentially extending the therapeutic window and safety of the treatment. To augment the functionality of the engineered CAR-T cells, saRNA is employed to further expand the existence period of CAR transcripts and therapeutic window by its self-amplifying capability. In this study, we compared the CAR expression and functional CAR-T cells among different types of RNA.
The RNA-LNP-mediated delivery of therapeutic RNAs represents a paradigm shift in the field of CAR-T cell therapy. It simplifies the manufacturing process, enhances the safety profile of the treatment, and provides a versatile platform for the development of next-generation cell-based immunotherapies. Our findings pave the way for a more accessible, efficient, and personalized approach to cancer treatment, offering renewed hope to patients and clinicians alike.
Triple-Drug Regimen for Naïve MDS and AML Patients: Efficacy and Safety of Chidamide, Azacitidine, and Venetoclax in a Prospective Multicenter Study
Authors: Zhang Min , Zhao Miaomiao , Ge Renying , Cao Xie-Na , Xue Mei , He Jing , Zhong Zhaodong , Fu Xin 
Published: December 2024

Purpose:Treatment options for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients remain limited, underscoring the need for novel, more effective therapeutic strategies. This prospective, open-label study evaluated the efficacy and safety of a triple combination regimen comprising chidamide, azacitidine, and venetoclax (VAC regimen) in treatment-naïve patients with these hematologic malignancies.
Patients and Methods: Sixteen newly diagnosed patients (6 MDS, 10 AML) with an average age of 57.9 years were treated with the VAC regimen consisting of chidamide, azacitidine, and venetoclax. The primary endpoint was overall response rate (ORR). Secondary endpoints included complete remission (CR) rate, event-free survival (EFS), overall survival (OS), and safety/tolerability.
Results: The ORR was 93.8%, with a remarkable CR rate of 87.5% (CR in 12 patients, CRi in 2 patient). Rapid hematologic recovery was observed, with a median time to tri-lineage recovery of 15 days. The 6-month EFS and OS rates were 80.8% and 81.8%, respectively, demonstrating promising survival outcomes. Three MDS patients underwent allogeneic stem cell transplantation following remission.All participants experienced AEs, predominantly non-hematological in nature. The frequent non-hematological AEs included infections (notably pneumonia), nausea, fatigue, vomiting, hypokalemia, hypoalbuminemia, and febrile neutropenia, with most of these being mild or moderate (grade 1/2).Given the adverse event (AE) data, the VAC regimen demonstrated an acceptable safety profile.
Conclusions: The VAC regimen demonstrated exceptional efficacy and an encouraging safety signal in treatment-naïve MDS and AML patients. These promising results highlight the potential of this novel triple combination as a frontline therapeutic option warranting further investigation in larger randomized trials.
Real-World Study of Glofitamab for the Treatment of Relapse or Refractory Diffuse Large B-Cell Lymphoma in East China
Authors: Tong Jiefeng , Jiang Songfu , Luo Qian , Qian Shanhu , Ouyang Guifang , Lai Yanli , Jiang Huifang , Jiang Yuxia , Zeng Hui , Ye Baodong , Jiang Wei , Qian Wenbin 
Published: December 2024

Introduction: Glofitamab is a CD20×CD3 bispecific monoclonal antibody, with demonstrated efficacy and manageable safety for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in clinical studies. In November 2023, glofitamab was approved by the China National Medical Products Administration (NMPA) for the treatment of R/R DLBCL. This study aimed to evaluate the efficacy and safety of glofitamab in the Chinese population in a real-world setting.
Methods: We retrospectively enrolled R/R DLBCL patients who received at least 1 dose of glofitamab in 7 medical centers in east China from November 2023 to June 2024. We reported the objective response rate (ORR) and complete response (CR) rate based on Lugano criteria, and cytokine release syndrome (CRS) and immune effector cells-associated neurotoxicity syndrome (ICANS) based on ASTCT consensus 2019.
Results: A total of 28 patients were included. At baseline (initiation of obinutuzumab pretreatment), the median age of patients was 63 years (range, 35-83), with 18 patients (64.3%) aged 60 years or older. 17 (60.7%) patients were male. 26 (92.9%) patients were diagnosed with DLBCL, not otherwise specified (including 2 primary central nervous system lymphoma (PCNSL) patients), 1 with high-grade B-cell lymphoma, and 1 with transformed follicular lymphoma. 10 (35.7%) patients had an ECOG score of 2-4, and 24 patients with Ann-Arbor stages III-IV. The median number of previous therapies was 2.5 (range, 1-6) and 82.1% (n=23) patients received 2 or more lines of previous therapies. 4 (14.3%) patients underwent autologous stem cell transplantation and 6 (21.4%) patients received CAR-T cell therapy. 10 (35.7%) patients had relapsed disease, and 12 (42.9%) were refractory to any prior therapy.
Median follow up was 3 months. Patients received a median of 3 (1-12) cycles of glofitamab treatment and 16 patients were still under treatment atdata cutoff. Of the 24 patients evaluable for response, the ORR and CR rate was 62.5% and 25%, respectively. 2 PCNSL patients all responded. Median PFS and OS were not reached at data cutoff. The most common adverse event was CRS, which occurred in 39.3% of the patients with 2 patients having grade 3 events. No grade 4 CRS appeared. 1 patient developed grade 4 ICANS and was consequently deceased.
Conclusions: This real-word study demonstrated that glofitamab has a consistent efficacy in Chinese R/R DLBCL patients as in previous clinical studies, with a lower incidence of adverse events. The actual CR rate might be higher since most patients were still under treatment.
Clinical Analysis of 15 Cases of Extramedullary Relapse of Acute B-Lymphoblastic Leukemia Post-Transplant Treated with CART Combined with Radiotherapy
Authors: Zheng Ruyue , Yan Hong , Li Biyi , Lin Yuehui , Liu Shuangyou , An Lihong , Deng Biping , Zhang Jun , Tong Chunrong , Wu Tong , Zhao Defeng 
Published: December 2024

Background:
Chimeric Antigen Receptor T-cell (CART) therapy has become an important approach for treating acute B-lymphoblastic leukemia (B-ALL) that relapses after hematopoietic stem cell transplantation (HSCT). Radiotherapy may aid in treating leukemia with extramedullary infiltration. Combining CART with radiotherapy might enhance the treatment of extramedullary relapse of B-ALL post-transplant.
Objective:
To investigate whether CART combined with radiotherapy can improve outcomes in treating extramedullary relapse of B-ALL post-transplant.
Methods:
This study included 15 cases of extramedullary relapse of B-ALL post-HSCT treated at Beijing Boren Hospital from August 2017 to October 2023. The median age was 31.5 years (range: 12-71 years), with 7 males (46.7%) and 8 females (53.3%). Nine patients (60%) had concurrent bone marrow relapse before treatment. All patients received CART combined with local radiotherapy targeting sites of extramedullary infiltration. The follow-up period ended on July 1, 2024, with a median follow-up duration of 413 days. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints.
Results:
Among the 15 patients treated with CART combined with local radiotherapy, 11 achieved complete remission in both bone marrow and extramedullary sites, yielding a remission rate of 73.3%. By the end of the follow-up period, 6 patients (54.5%) had relapsed, while 5 remained in continuous remission (45.5%). The median PFS of 1428 days. The 1-year PFS rate is 62.3%, and the 2-year PFS rate is 51.9%. The median OS not yet reached. The 1-year OS rate is 100.0%, and the 2-year OS rate is 83.3%.
Conclusions:
CART is an effective treatment method for post-transplant relapsed acute B-lymphoblastic leukemia.
Combining CART with radiotherapy may help improve the remission rates for post-transplant extramedullary relapsed acute B-lymphoblastic leukemia.
Integration of Gene Mutations in Risk Prognostication for Watch-and-Wait Follicular Lymphoma Patients Initiating First-Line Treatment
Authors: Xu Tianyuan , Wang Nan , Sun Rui , Li Ruichi , Fu Di , Zhao Yan , Xu Pengpeng , Cheng Shu , Wang Li , Tang Wei , Zheng Zhong , Zhao Weili 
Published: December 2024

Introduction
Follicular lymphoma (FL) patients with low tumor burden at diagnosis frequently undergo the watch-and-wait (W&W) strategy. The study aimed to facilitate risk assessment in predicting the time to lymphoma treatment (TLT) for W&W patients through an integrated analysis of clinical factors and genetic mutations.
Methods
A retrospective analysis was conducted on 214 FL patients managed with W&W between 2016 and 2023. Among all, 184 patients underwent targeted sequencing. The median follow-up was 30.4 months (IQR 21.4-41.9, range 6.4-95.8). A clinic-genetic model was developed using the multivariate Cox proportional hazards method.
Results
The clinic-genetic model incorporated two clinical factors (bone marrow involvement and elevated β2-MG) and three gene mutations (KMT2D, EP300, and TP53). Each factor was assigned one point based on its relative importance, as indicated by the z-Wald values from the Cox model. The total score for each patient was calculated as the sum of these points. Since this model includes two clinical factors overlapping with those in PRIMA-PI, along with three additional gene mutations, we termed it m3-PRIMA-PI. Patients were stratified into three risk groups based on their scores: low (score 0-1, n=127, 69.0%), intermediate (score 2, n=40, 21.7%), and high (score 3-5, n=17, 9.2%). The probabilities of treatment initiation at one year were 11.0% (95% CI, 5.2%-16.5%), 26.0% (95% CI, 10.7%-38.7%), and 54.3% (95% CI, 22.3%-73.1%); and at two years were 29.4% (95% CI, 20.2%-37.5%), 49.8% (95% CI, 31.1%-63.4%), and 93.5% (95% CI, 56.7%-99.0%), respectively. The predictive performance for TLT was superior with m3-PRIMA-PI, achieving a C-index of 0.66 (95% CI, 0.63-0.69), compared to established indexes like FLIPI (C-index 0.59, 95% CI 0.56-0.62) and FLIPI2 (C-index 0.59, 95% CI 0.55-0.61).
Conclusion
Integration of genetic mutations with clinical risk factors presents a promising tool for risk stratification in W&W FL patients.
UHRF1 Is a Promising Therapy Target in Aggressive Mantle Cell Lymphoma
Authors: Yang Yuan , Yang Ping , Zhang Weilong , Wang Jing , Chen Yingtong , Li Chunyuan , Jing Hongmei 
Published: December 2024

Backgrounds: Therapy resistance and recurrent relapses continue to be significant challenge in the management of mantle cell lymphoma (MCL), which cannot be explained by genetic alone. Discovering drugs that can successfully correct epigenetic changes is a promising strategy to address the inadequate therapeutic response in MCL. Epigenetic regulator ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is aberrantly expressed in many human diseases and correlated with disease progression, but its function in MCL remains unclear.
Methods: Through integrative analyses of the gene-expression profile and clinical parameters, UHRF1 was screened as a potential epigenetic therapy target in MCL patients. The pro-tumor function of UHRF1 was demonstrated by in vitro and in vivo experiment. The anti-tumor effect and safety of CM272, a functional inhibitor of UHRF1, was assessed in MCL xenograft animal model.
Results: UHRF1 was highly expressed and positively correlated with Ki67 expression in MCL tissues samples. UHRF1-high expression predicted poor prognosis in MCL patients. Knockdown of UHRF1 inhibited MCL cell proliferation, migration and invasion whereas induced MCL cell apoptosis and cell cycle arrest. Administration of mice with CM272 significantly inhibited MCL progression and no obvious treatment-related side effects in liver and renal.
Conclusion: Our study demonstrated that UHRF1 signaling involved in MCL tumorigenesis and progression, and provides a novel insight for therapeutic interventions in MCL by targeting UHRF1.
Association between Lipid Profile and Molecular Signature of Monocytes in Patients with Lower-Risk MDS
Authors: Kotsianidis Ioannis , Tasis Athanasios , Rimpa Christina Maria , Kymparidou Chrysa , Hatzikirou Haralampos , Mitroulis Ioannis 
Published: December 2024

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with accelerated atherosclerosis and a 40% increased risk of cardiovascular disease (CVD), linked to increased innate immune cell activation (Jaiswal et al., 2017). Monocytes are critical players in CVD, due to their infiltration in atherosclerotic plaques and their differentiation to foam cells, whereas dyslipidemia is linked to long-term inflammatory activity of monocytes (Mitroulis et al., 2023). Herein, we sought to investigate whether lipid profile is associated with the molecular signature of peripheral monocytes in patients with lower-risk MDS (LR-MDS; i.e., IPSS-R &lt;3.5).
To do so, peripheral blood samples were collected from 11 patients with LR-MDS (MDS with low blasts n=9, MDS with SF3B1 n=2). RNA sequencing performed in isolated monocytes. Differential expression analysis was performed utilizing the edgeR Bioconductor R package. Statistically significant differentially expressed genes (DEGs) were identified based on a FDR threshold of &lt;0.1 and a logFC threshold of &gt;0.58. Gene set enrichment analysis (GSEA) was performed, using well-annotated Hallmark gene sets from the Molecular Signatures Database (MSigDB) as input.
Principal Component Analysis (PCA) demonstrated a clear segregation of samples into two distinct subgroups (Subgroup_1 and _2). Differential expression analysis identified 483 DEGs upregulated in Subgroup_1 and 1035 DEGs upregulated in Subgroup_2. Pathway enrichment analysis revealed an enrichment of genes associated with oxidative phosphorylation (OXPHOS) and TNF-α signaling in Subgroup_1. Of note, Subgroup_1 exhibited an upregulation of the cholesterol homeostasis pathway, which was in line with the significant increase in total and non-HDL cholesterol and triglycerides in this group. Moreover, unsupervised clustering based on the expression levels of genes involved in inflammasome-related signatures (Basiorka et al., 2016), led to clear separation of the two groups, with Subgroup_1 displaying significantly higher expression levels of the inflammasome-related genes NRLP3 and PYCARD.
Herein, we show that lower lipid levels in LR-MDS patients is associated with a suppressed inflammatory signature in peripheral monocytes and a down-regulation in the expression of genes related to inflammasome. Considering the link between CVD and CHIP, our findings show that early administration of lipid-lowering regimens can be beneficial in patients with LR-MDS, suppressing the inflammatory potential of monocytes, a critical cell population in CVD.
Acknowledgements: Supported by the UAE-NIH Collaborative Research grant AJF-NIH-25-KU