bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-Low Dose Radiotherapy Combined with Orelabrutinib Improves the Complete Response Rate of Treatment for Localized Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma
Authors: Yang Shaoxin , Zhao Chong , Zhou Yixiong , Shi Jun 
Published: December 2024

Background: Extranodal marginal zone B-cell lymphoma (EMZL) is the most common lymphoma of the ocular adnexa (OA). Although radiotherapy is still the first-line treatment for localized OA-EMZL (stage I/II), the toxic effects of standard dose radiotherapy cannot be ignored. While reduced doses of radiotherapy can lessen these toxic effects, they also lower the complete response (CR) rate. We aim to use prospective trials to improve this CR rate while reducing the toxic effects of radiotherapy.
Methods: This is a single-arm, open clinical trial. Nine patients were diagnosed with OA-EMZL through surgery. These patients had Ann Arbor stage I/II with residual lesions. They received an ultra-low dose of radiation therapy, with each dose of 2 Gy administered twice, for a total of 4 Gy. Concurrently, the patients received oral orelabrutinib, 150 mg daily, every 4 weeks as a course of treatment, and the efficacy and adverse reactions were evaluated. During the treatment process, the patients continued to take oral orelabrutinib for four courses.
Results: One patient had involvement of both eyes, while the remaining eight had monocular involvement. Eight patients had lesions located in the orbit, and one had lesions in the orbit and lacrimal gland. Currently, five of the patients have completed treatment and all achieved CR, while the remaining four cases are still under treatment. Three patients achieved CR after three courses, and two patients achieved CR after four courses. Additionally, the lesions in the patients still undergoing treatment have shrunk compared to before treatment. During treatment with orelabrutinib, one patient experienced mild leukopenia and one patient experienced mild thrombocytopenia. There were no early toxic effects, such as dermatitis, xerophthalmia, conjunctivitis, watering eyes in eight patients. Moreover, dry eye was not aggravated in one patient due to lacrimal gland resection.
Conclusion: The combination of ultra-low dose radiotherapy and orelabrutinib in the treatment of OA-EMZL not only improves the effectiveness of treatment but also significantly reduces the toxic effects of radiotherapy, providing a new approach for the treatment of localized OA-EMZL.
First Interim Results of the Real-Life Study Evaluating the Efficacy and Safety of Belinostat in Patients with R/R PTCL in Brazil (BELBRA)
Authors: De Moura Ricardo Pereira , Abdo Andre N.R. , Chiattone Carlos , Canutti Valnei , Fischer Thais , O'Connor Owen A. 
Published: December 2024

Introduction: Belinostat (BEL) is a Pan-Histone Deacetylase Inhibitors (HDACi) that increases histone acetylation leading with anti-angiogenic and antitumor properties indicated in the treatment of in refractory or relapsed (R/R) Peripheral T-Cell Lymphoma (PTCL). BELBRA is the real-life observatory study initiated in Brazil with the participation of 90 lymphoma reference centers, with 97 patients to date.
Methods and Aims: To date, 97 R/R PTCL patients treated with Belinostat in Brazil have been identified. In this interim analysis, the demographic characteristics of the patients were analyzed. Furthermore, more detailed analyzes of 20 patients were carried out. Data collection and statistical analyzes continue to be conducted.
Results: The interim results of the BELBRA study, focus on the efficacy and safety of Belinostat (BEL) in treating R/R PTCL. The cohort demonstrated a diverse range of PTCL subtypes, with a majority being lymphoma NOS. Treatment primarily included CHOP or similar therapies, with Belinostat administered in later lines. The study reports a 45% overall response rate, stable disease in 10%, and disease progression in 45% of the detailed cohort, with treatments being well tolerated across an average of 5 cycles. No other AE´s than the Belief Study was observed.
Conclusion: These findings highlight Belinostat's potential as a favorable option for PTCL patients resistant to previous treatments, contributing as valuable real-world evidence to these challenging patients.
Therapeutic Potential of Roxadustat in Immune Thrombocytopenia: A Mendelian Randomization Analysis
Authors: Ma Jingyao , Wu Runhui 
Published: December 2024

Background: Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired megakaryocyte maturation. Hypoxia-inducible factor-1 alpha (HIF-1α), pivotal in the development of megakaryocytes and immune regulation, is downregulated in ITP, suggesting its role in disease pathogenesis. Given this relationship, roxadustat as an HIF-1α stabilizer, is a potential therapeutic agent in the treatment of ITP by augmenting HIF-1α mediated megakaryocyte development and immune system modulation.
Objectives: This study evaluates the safety profile of roxadustat and its therapeutic efficacy for ITP treatment using Mendelian randomization (MR) analysis.
Methods: We used expression Quantitative Trait Loci (eQTLseQTLs) data for roxadustat's target genes (EGLN1, EGLN2, EGLN3) and genetic associations with ITP, and adverse outcomes from the IEU OpenGWAS project. MR analysis included IVW, MR-Egger regression, weighted median, and MR-PRESSO methods to evaluate pleiotropy. Heterogeneity was assessed using Cochran's Q statistic and I² measure, with sensitivity analyses. A meta-analysis was performed to integrate effect sizes from multiple literature sources.
Results: MR analysis revealed a significant association between roxadustat and reduced ITP risk (OR 0.79, 95% CI 0.66-0.95, P=0.01) with no evidence of horizontal pleiotropy. Meta-analysis confirmed the protective effect of roxadustat on ITP risk. Utilizing eQTLs of roxadustat's target gene EGLN1 as instrumental variables, an MR analysis of 39 potential adverse reactions revealed no significant increase in risk, indicating a favorable safety profile for roxadustat.
Conclusion: Roxadustat demonstrates a potential protective effect against ITP without increasing the risk of adverse outcomes, suggesting its promise as a therapeutic option for ITP and warranting further investigation.
Comparisons between Haploidentical Hematopoietic Stem Cell Transplantation and Eltrombopag Adding to Standard Immunosuppression in Patients with Severe Aplastic Anemia
Authors: Fu Andie , Li Mengyuan , Peng Yizhou , Xu Bin , Li Li , Jia Jin-song , Yang Yan , Lin Shengyun , Wei Jia , Meng Fankai , Zhang Donghua , He Guangsheng 
Published: December 2024

Background:
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) becomes an alternative choice for patients in the absence of a matched donor1. The use of eltrombopag (EPAG) combined with intensive immunosuppressive therapy (IST) as a front-line treatment has been shown to enhance both the rate and rapidity of hematologic response in SAA patients2. However, no studies have compared the outcomes of IST + EPAG and haplo-HSCT for the treatment of SAA.
Methods:
The study was performed among 111 patients with SAA from 5 medical centers, including 51 patients in the IST+EPAG group and 60 patients in the haplo-HSCT group. The overall survival (OS), failure-free survival (FFS), GVHD-free FFS (GFFS)/ survival with CR status (CROS), overall response rate (ORR) as well as complications were compared between the two groups.
Results:
At 6 months post treatment, 91.67% patients in the haplo-HSCT group and 19.67% patients in the IST+EPAG group achieved normal blood routine (P=0.000). It turned out that the OS was comparable (92.16% vs 91.67%, P=0.775), while the FFS and GFFS/CROS in the haplo-HSCT group was superior to that in the IST+EPAG group (88.33% vs 72.55%, P=0.045 and 78.33% vs 25.49%, P=0.000). Being diagnosed with non-VSAA was a favorable factor for FFS, and the choice of haplo-HSCT was a favorable factor for GFFS/CROS in multivariate analysis. None of the evaluated factors was recognized as an independent favorable factor of OS. Multivariate analysis showed that being diagnosed with non-VSAA, patients aged &lt;40years, and receiving hematopoietic stem cell transplantation were significantly associated with good therapeutic outcomes. Using propensity score matching (PSM), a comparative analysis was conducted to assess the treatment outcomes between patients treated with haplo-HSCT (n=28) and patients who underwent IST+EPAG therapy (n=28). In the PSM cohort, OS and FFS who underwent haplo-HSCT were comparable to those of the IST+EPAG group (89.29% vs 96.43%, P=0.278 and 85.71% vs 82.14%, P=0.785); However, there was still a signiﬁcant difference between the 2 groups regarding GFFS/CROS (75.00 % vs 39.29%, P=0.024). The multivariate analysis showed that choosing haplo-HSCT was a favorable factor for GFFS/CROS, but did not affect FFS and OS in the PSM cohort。
Conclusions:
These results suggest that for the management of SAA patients, haplo-HSCT showed similar comparable long-term prognosis compared with IST+EPAG, whereas patients treated with haplo-HSCT could achieve faster hematopoietic reconstruction and higher CR rates.
Efficacy and Safety Study of Chimeric Antigen Receptor-T Cell Therapy for People with Relapsed/Refractory Follicular Lymphoma
Authors: Xu Ting , Zeng Liangyu , Wu Depei , Li Caixia 
Published: December 2024

Although follicular lymphoma (FL) is an indolent lymphoma, it is prone to multiple recurrences and has a poor prognosis for progression of disease within 24 months (POD24) patients. To improve outcomes for patients with relapsed/refractory follicular lymphoma (R/R FL), we evaluated the efficacy and safety of Chimeric Antigen Receptor-T (CAR-T) cell therapy in these patients.
This retrospective study included 12 patients with R/R FL receiving CAR-T cell therapy from January 2017 to December 2023 in the First Affiliated Hospital of Soochow University who have consented to be included in our two clinical trials of CAR-T therapy. These two trials were registered at ClinicalTrials.gov, NCT03196830, NCT04539444.
The median age of the 12 patients was 46 (range, 28-59) years. Eight (66.7%) patients were male and four (33.3%) were female. FLIPI≥3 was present in 6 (50%) patients, and there were 7 (58.3%) patients with POD24. All patients received at least two lines of prior therapy. Eight (66.7%) patients received CD19 single-targeted CAR-T cell infusion and four (33.3%) patients received CD19/CD22 dual-targeted CAR-T cell infusion.
At 1 month after CAR-T cell infusion, the overall response (OR) and complete response (CR) rates for R/R FL patients were 12/12 (100.0%) and 9/12 (75.0%), respectively. By the cut-off date on March 7, 2024, the median follow-up time was 21.9 (range, 6.6-59.8) months. No deaths occurred. 10 (83.3%) patients continued their responses. 2 (16.7%) patients had progressive disease after 9 and 5 months. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 82.5% and 100.0%, respectively. In a subgroup analysis, the CR rate of patients in the POD24 group did not show a significant difference from that of the non-POD24 group (71.4% vs. 80.0%, p=0.735), and the estimated 2-year PFS rate of patients in the POD24 and non-POD24 groups did not show a significant difference (82.5% vs. 83.3%, p=0.964).
Only 2 (16.7%) patients had grade 3 cytokine release syndrome (CRS), which was resolved by glucocorticoid. No immune cellular-associated neurologic syndrome (ICANS) or treatment-related death occurred.
In conclusion, patients with R/R FL treated with CAR-T cell achieved durable response with favorable safety profile. The long-term efficacy and safety need to be confirmed in larger clinical trials and longer follow-up period.
Keywords: chimeric antigen receptor-T cell therapy, relapsed/refractory follicular lymphoma, outcome, progression of disease within 24 months
Patient Journey Mapping Enhances Nursing Care in Patients with Hematologic Diseases
Authors: Kuang Zhexiang , Yu Xiao , Wang Anni , Xu Jing , Zhao Jingyu , Li Xinli , Wu Guibin , Yuan Weiping , Shi Jun , Xu Li , Xie Wenjun 
Published: December 2024

Objective To assess nursing care using Patient Journey Mapping (PJM) approach in patients with hematological diseases.
Methods This study enrolled 268 patients with hematological diseases admitted to a grade-A tertiary hematological specialty hospital in Tianjin from January to December 2023. Nursing care based on PJM was integrated into standard healthcare, involving interventions across five stages: encounter, diagnosis, treatment, recovery, and outpatient follow-up, with a period of four weeks. At the time of patients' first admission and as they prepare for readmission, we evaluated their nutritional status, psychological well-being including anxiety and depression, sleep quality, and self-management abilities using Nutritional Risk Screening (NRS) 2002, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and Self-Care Ability Scale (ESCA).
Results A total of 260 patients completed this study. There was a statistically significant difference in the NRS2002 scores pre and post intervention (P=0.008), with mean scores of (2.07±0.48) and (2.04±0.46), respectively. We observed statistically significant differences in psychological well-being, sleep quality and self-management abilities before and after intervention (P&lt;0.001). Specifically, the HAMA scores were (8.30±4.43) and (7.78±3.67), the HAMD scores were (11.01±5.30) and (10.17±4.26), the PSQI scores were (8.47±2.47) and (6.97±2.05), the ESCA scores were (55.28±15.33) and (114.21±20.04), respectively.
Conclusion PJM can enhance the nutritional status, sleep quality and self-care abilities of patients, while also alleviating their negative emotions,thus effectively improving their overall healthcare experience.
Pharmacological and Pharmacokinetic Evaluation of AST-202, CD25-Targeted Aptamer Conjugated with Anti-Mitotic MMAE Warhead for the Treatment of Hematological Malignancies
Authors: Lee Daekyun , Kang Ju-Hyung , Song Inu 
Published: December 2024

CD25 is an alpha subunit of IL-2 receptor that is overexpressed in various hematological malignant conditions. Evidences for meta-analysis and literatures indicate that the abnormal expression of CD25 is closely associated with poorer outcome and prognosis in lymphoma and leukemia patients. AST-202 is the novel micellar aptamer-drug conjugate (ApDC) composed of CD25-targeting aptamer precisely conjugated with 3 anti-mitotic MMAE warhead which is delivered to eliminate CD25-expressing leukemic/lymphoblastic cells.
Strong amphiphilic nature due to add 3 hydrophobic drugs at the end of an aptamer led AST-202 to self-assemble into a spherical micellar structure with hydrodynamic radius ~180nm (hydrophobic drug core and hydrophilic aptamer surface).
Interestingly, when the in vitro plasma stability of aptamer-MMAE linkage was monitored by measuring the released MMAE over a 4-day period, the amount of MMAE released was only less than 1% in AST-202 while the aptamer with a single MMAE lost 50~60% of its payload within 4 days, suggesting the significant improvement of the metabolic stability of AST-202. ). This improvement of stability was found to translate to improved PK profile relative to AST-202(1), resulting in the dramatic increase of AUC and half-life as well as the decreased CL.
Cytotoxicity evaluation against a panel of human lymphoma and leukemia cell lines with different CD25-expression level revealed the correlation of the expression level of the target and CD25-negative Daudi and H929 cells (derived from B-cell lymphoma and multiple myeloma, respectively) were not affected in the range of treatment up to 1uM.
Comparative in vivo study with subcutaneous xenografts of AST-202 and single MMAE-conjugated aptamer demonstrated CD25-specific tumor targeting and the superior anti-tumor efficacy of AST202 relative to ApDC with a single payload. The following study with a disseminated tumor model showed dramatic extensions of survival in all treatment groups compared with vehicle and non-binding ApDC controls and survival difference between AST-202(1) and AST-202(3) was not observed at the tested dose range.
Consequently, based on the improved in vitro stability, PK profile, and efficacy, AST-202(3) which is a novel micellar aptamer-drug conjugate could be a potential candidate for further preclinical development as a therapeutic candidate against hematological malignancies.
The Dark Horse: Introducing a Comparative Hematology Course into the Post-Clerkship Phase of Medical School
Authors: Kometas Marisa L. , Raman Ganesh , Adkins Brian , Rambally Siayareh , Hofmann Sandra L. , Aird William C. , Bavli Natalie 
Published: December 2024

Introduction: Developing a deep understanding of pathophysiology is integral to training competent physicians. Although the basic sciences are taught primarily in preclinical curriculum, revisiting these concepts during the fourth year of medical school promotes integration into clinical medicine (Spencer et. al, 2008). Immersive comparative physiology courses increase trainee appreciation of physiology and its incorporation into patient care (Herzig et al, 2012). We introduced comparative physiology curriculum during a fourth-year medical student course at University of Texas Southwestern (UTSW) Medical School. Our course aimed to deepen students' understanding of human pathophysiology and its clinical applications by highlighting evolutionarily conserved and adaptive changes among diverse species.
Methods: We developed a one-week comparative physiology curriculum to present to fourth-year medical students in April 2024. The curriculum utilized the four stages of Kolb's Experiential Learning Theory through multimodal methodologies, including introductory lectures, case-based learning, laboratory experiments on human and animal blood with integrated case studies and group projects, and evolutionary biology group presentations at the Fort Worth Zoo. The UTSW Institutional Review Board approved the dissemination of pre- and post-course surveys. The surveys incorporated a 7-point Likert scale (1= strongly disagree, 2= disagree, 3= somewhat disagree, 4= neither agree nor disagree, 5= somewhat agree, 6= agree, 7= strongly agree). Anonymous six-digit identifiers tracked changes in individual perceptions. Scores were calculated by summing responses to series of questions evaluating perceptions of construct and knowledge. Paired samples t-tests through Microsoft Excel assessed the significance of differences between pre- and post-course mean perception of construct and confidence in knowledge scores.
Results: Fifteen fourth-year medical students enrolled, and 93% completed both surveys. Self-assessed confidence in knowledge significantly increased (p =1.02x10-5) in multiple concepts, including interpretation of the peripheral blood smear and of the complete blood count. In the post-course survey, 79% of respondents agreed or strongly agreed that comparative physiology models should be incorporated into medical education, 79% agreed or strongly agreed that the course increased their interest in hematology, and 100% strongly agreed to recommend the course.
Conclusion: Incorporating immersive comparative physiology curriculum into the post-clerkship phase of medical school can enhance understanding of core hematologic physiology principles and promote interest in hematology.
The Surface-Exposed Nuclear Speckle Protein SRRM2 Confers a Novel Target Molecule for the Immunotherapy of Acute Myeloid Leukemia
Authors: Zhang Wanqiu , Gao Zhimai , Gärtner Kathrin , Wang Huiping , Wu Fan , Guo Jinjing , Li Yingwei , Li Zijian , Li Lietao , Li Cong , Liang Xue , Xiao Hao , Zhai Zhimin 
Published: December 2024

Acute myeloid leukemia (AML) is a serious, life-threatening and hardly curable hematological malignancy with a 5-year survival rate of only about 30%. CAR T-cell therapy has emerged as a highly effective option for the treatment of B-cell malignancies. Serine/arginine repetitive matrix 2 (SRRM2) is a nuclear speckle protein involved in RNA splicing that may contribute to survival of blast cells and drug resistance in AML. Interestingly, we recently identified SRRM2 on the surface of malignant cells, including AML blasts. Here, we investigated the specific level and characteristics of SRRM2 protein expression in AML patients and whether the protein can serve as a target antigen for AML treatment.
In this study, we detected and analyzed the expression and cellular localization of SRRM2 in AML cell lines and patients newly diagnosed/relapsed with AML using a proprietary SRRM2-specific antibody (EX02). Subsequently, a second-generation CAR-T cell targeting SRRM2 was constructed, and the efficacy and safety of SRRM2 CAR-T cells were assessed in vitro and in vivo using a NSG mouse model of AML.
Our results show that SRRM2 is exposed at the surface of most blast cells from various types of AML cell lines and patients with AML, and that the level of surface SRRM2 directly correlates to high risk, relapse and poor prognosis. Even more important, in normal hematopoietic stem cells and differentiated mature blood cells, as well as in normal tissues from lung etc., SRRM2 was only found to be located in the nucleus. Finally, SRRM2 CAR-T cells exhibited significantly elevated secretion of IFN-γ and TNF-α and enhanced cytotoxicity against AML cell lines. In the AML mouse model, SRRM2 CAR-T cells displayed significant suppression on AML and extended survival.
Collectively, we demonstrated that the ectopic exposure of the SRRM2 protein on the surface of AML cells constitutes an attractive target molecule for the development of targeted therapies against AML, like SRRM2-specific CAR-T cells.
The use of human material for these investigations was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University (NO. YJ-YX2019-015).