bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Human Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Immune Thrombocytopenia: A Prospective, Single Centre, Single Arm, Phase I Trial
Authors: Chen Yunfei , Yanmei Xu , Gao Yuchen , Chi Ying , Sun Ting , Dou Xueqing , Han Zhibo , Xue Feng , Li Huiyuan , Liu Wei , Liu Xiaofan , Dong Huan , Fu Rongfeng , Ju Mankai , Dai Xinyue , Wang Wentian , Ma Yueshen , Song Zhen , Gu Jundong , Gong Wei , Yang Renchi , Zhang Lei 
Published: December 2023

Background Patients with refractory immune thrombocytopenia (ITP) often suffer severe bleeding events and have poor responses to various treatments. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been used to treat multiple autoimmune diseases due to their low immunogenicity and strong immunomodulatory potential. To explore the safety and efficacy of UC-MSCs in treating refractory ITP, we conducted this phase Ⅰ clinical trial.
Methods Patients diagnosed with refractory ITP were screened for the study. The major inclusion criteria included age 18 to 60 years, ITP duration lasting for more than six months, platelet count &lt; 30 × 10 9/L and concomitant bleeding manifestations at enrolment. The study consisted of two parts: a dose-escalation phase for exploring the safety and efficacy of three different dosage groups according to the traditional 3+3 protocol and a dose-expansion phase for further verifying the optimal UC-MSC dosage. UC-MSCs were administered at doses of 0.5×10 6 cells/kg, 1.0×10 6 cells/kg, and 2.0×10 6 cells/kg per week four times in the dose-escalation phase and 2.0×10 6 cells/kg per week four times in the dose-expansion phase. The adverse events, platelet counts, and bleeding symptoms were evaluated and recorded during the administration and follow-up period. The study protocol was approved by the Ethics Committees of the Institute of Hematology and Blood Diseases Hospital, and informed consent was obtained from each participant according to the Declaration of Helsinki (ClinicalTrials.gov ID: NCT04014166).
Results Between November 2019 and August 2022, 18 refractory ITP patients hospitalized in our centre were successfully screened and enrolled in the study. Twelve patients were enrolled in the dose-escalation phase (three additional patients were added in the 2.0×10 6 cells/kg group due to the dose-limiting toxicity), and six patients were included in the dose-expansion phase. Thirteen patients (13/18, 72.2%) had one or more TEAEs. SAEs occurred in four patients (4/18, 22.2%), including gastrointestinal haemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). There were 0.0% (0/3), 66.7% (2/3), and 50.0% (6/12) patients in the 0.5×10 6, 1.0×10 6 and 2.0×10 6 cells/kg cohorts who achieved a response after treatment, respectively. The overall response rate was 44.4% (8/18) in all patients who received UC-MSCs.
Conclusion UC-MSC infusion achieved a 44.4% overall response rate in patients with refractory ITP and mild adverse events.
Long Term Disease Free Survival and Survival of Patients with Relapsed Hodgkin's Lymphoma Treated with Autologous Stem Cell Transplantation
Authors: Abedrabo Sabree , Rodriguez Tulio E. , Klein Leonard M. , Bitran Jacob 
Published: December 2023

CONCLUSION
Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin's Lymphoma (HL). We wish to report long term (&gt;10 year) outcomes for patient's with HL treated with ABMT at our institution. We treated 35 patients over a 30 year time period (1992-2022) Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalan (CEM,1992-2005) and BCNU, etoposide, cytarabine, and melphalan (BEAM, 2006 to present). Brentuximab was added was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem cell collections with high dose filgrastim and since 2008 filgrastim and plexiform. The required stem cell product was at a minimum 2 million CD34+ cells per kilogram of body weight.
Fifteen patients received CEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher's exact test). The median time to hematologic recovery was 12 days (range 8-21). Treatment related complications included: S. Epidermis sepsis (3 patients), E. coli sepsis (3 patients) and esophageal perforation that lead to death (1 patient). With a median follow up of 13 years (range 1-23 years).The actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), liposarcoma (1patient).
Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT. The most frequent long term complication is cardiomyopathy.
Number Needed to Treat Analyses of Zanubrutinib in Relapsed/Refractory Chronic Lymphocytic Leukaemia
Authors: Chanan-Khan Asher Alban , Hanna Kirollos S. , Xue Mei , Massoudi Marjan , Balk Mark , ZivariPiran Hossein , Duan Cecilia , Yang Keri 
Published: December 2023

Introduction: Chronic lymphocytic leukaemia (CLL) is the most common leukaemia type. In 2020, there were an estimated 207,463 people living with CLL, with an annual incidence of approximately 4.9 per 100,000 in the United States (US). Zanubrutinib is a Bruton tyrosine kinase inhibitor that is FDA-approved and an NCCN preferred and recommended treatment of CLL. In the phase 3 ALPINE trial (NCT03734016), zanubrutinib elicited a significantly higher overall response rate and significantly longer progression-free survival (PFS) than ibrutinib. This study aimed to compare zanubrutinib versus ibrutinib in Relapsed/Refractory (R/R) CLL by calculating the number needed to treat (NNT) to avoid one progression or death and associated incremental costs.
Methods:A health-economic model was developed to evaluate the number of R/R CLL patients needed to be treated to avoid a progression or death from the US payer perspective. Payer blend was assumed with 40% Commercial and 60% Medicare payer mix. Clinical efficacy data were extracted from the ALPINE trial. Final analysis result of 24-month PFS (79.5% for zanubrutinib and 67.3% for ibrutinib) was used for the base-case analysis in the model. Treatment, adverse event management, other medical resource use, and subsequent treatment costs were considered in the model. The NNT, incremental cost per treated patient, and incremental cost per additional patient with progression or death were captured. Deterministic sensitivity analyses were conducted to assess parameter uncertainties and explore key model drivers. Scenario analyses were conducted to test the impact of different PFS estimates.
Results: The base-case results fromthe NNT model showed that for every 8 patients treated with zanubrutinib, 1 event of progression or death would be avoided compared to using ibrutinib. The total costs per patient treated with zanubrutinib and ibrutinib are $370,558 and $430,150, respectively, with a cost savings of $59,593 associated with using zanubrutinib (Table). Drug costs and PFS have the greatest impact on the incremental cost per patient. Varying the PFS scenarios, including adjustment with drug interruption, COVID death, or treatment discontinuation, change the NNT from 8 to 12, and are associated with cost savings of $58,179 to $67,153 per zanubrutinib-treated patient in a 24-month time frame. Applying the model result to a hypothetical scenario of a clinical practice of 100 patients treated with zanubrutinib versus ibrutinib suggest that approximately 13 patients will avoid disease progression events or death.
Conclusions: The NNT model suggests thatusing zanubrutinib to treat R/R CLL patients, compared to ibrutinib, will result in more favorable clinical and economic outcomes in the US.
Systematic Literature Review to Identify Influencing Factors of Efficacy and Safety Outcomes of Chimeric Antigen Receptor T-Cell Therapies in Large B-Cell Lymphoma
Authors: Heger Jan-Michel , Jost Jonas , Riou Sybille , Walzer Stefan , Mahlich Joerg , Borchmann Peter 
Published: December 2023

Background:
The interpretation of clinical data involving chimeric antigen receptor T-cell therapies (CAR-T's) in Large B-Cell Lymphoma (LBCL) requires a thorough understanding of factors that influence efficacy and safety outcomes.
Materials & Methods:
To identify relevant influencing factors of efficacy and safety outcomes, we conducted a systematic literature review for CAR-T cell therapies. Articles were searched on PubMed from 06.2018 till 06.2023. Data for progression free survival (PFS), overall survival (OS), complete response (CR), objective response rate (ORR), duration of response (DOR), and safety (i.e. Immune Effector Cell-Associated Neurotoxicity Syndrome [ICANS], and Cytokine Release Syndrome [CRS]) were extracted in accordance with the PRISMA guidelines.
Results:
A total of 236 articles were identified and narrowed to 44 publications for full text screening. 13 articles were included in the final analysis. The main reasons for exclusion were other indications, missing data, and lack of significance.
Factors affecting OS that were identified in more than one publication were Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) ≥ 2, presence of bulky disease, and high lactate dehydrogenase (LDH) values. For PFS it was presence of bridging therapy before CAR-T infusion, and LDH values as well. Table 1 presents the full list of identified variables. For DOR no influencing factor was observed.
Influencing factors for safety outcomes are summarized in table 2. Evidence is less compelling here because all identified variables were supported by one publication only.
Conclusion:
This review provides a set of factors that influences efficacy and safety outcomes of CAR-T therapies in LBCL. It can be used to assess comparability of different treatment arms in randomized controlled studies or to make careful adjustments when performing indirect treatment comparisons in order to better understand the true value of innovative treatments.
A Phase I/II Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of Glofitamab As Monotherapy and in Combination with R-ICE Chemoimmunotherapy in Children and Young Adults with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (iMATRIX-GLO)
Authors: Burkhardt Birgit , Rossato Gianluca , Dixon Mark , Carlile David John , Dmytrasz Steven , Wulff Jade , Negricea Raluca , Wulff Beate 
Published: December 2023

Background: Although rare,relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) in children, adolescents, and young adults is an area of high unmet need, with 1-year overall survival rates of &lt;30% and complete remission (CR) rates of 27% after treatment with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemoimmunotherapy (Burke et al. Leukemia 2020). New treatment regimens are urgently needed (Woessmann et al. Blood 2020; Burkhardt et al. Cancers (Basel) 2021). T-cell engagers have been identified as medicinal products with the greatest probability of being beneficial for the pediatric population (Pearson et al. Eur J Cancer 2019).
Glofitamab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells and is currently under investigation as monotherapy and in combination with chemoimmunotherapy for the treatment of adults with R/R B-NHL, with encouraging clinical activity and a manageable safety profile. Known risks associated with glofitamab are cytokine release syndrome (CRS), febrile neutropenia, tumor flare, tumor lysis syndrome, pyrexia, and infections. The safety profile of glofitamab in children is expected to be similar to that seen in adults.
Study Design and Methods: iMATRIX-GLO (NCT05533775) is a Phase I/II, open-label, single-arm, two-part trial to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of glofitamab as monotherapy in children 6 months to &lt;18 years of age with second and higher R/R B-NHL (i.e. relapse after 2 or more lines of treatment), or in combination with R-ICE in children and young adults ≤30 years of age with first R/R disease (i.e. relapse after the first line of treatment). Patients with a histologically confirmed diagnosis of CD20-positive R/R B-NHL are eligible. Study treatment is administered with a single dose of obinutuzumab pretreatment followed by glofitamab step doses and repeated glofitamab full doses every 21 days as monotherapy or in combination with R-ICE.
Primary objectives and endpoints are the achievement of CR after up to three cycles of combination therapy (glofitamab plus R-ICE) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants, evaluation of glofitamab safety (CRS by ASTCT 2019 criteria, otherwise by NCI CTCAE v5.0 criteria), tolerability, and PK as monotherapy and as combination therapy. The first patient was enrolled in November 2022 and the study is ongoing. The study is planned at 23 sites in 9 countries (Europe, Australia, North America, South Korea, and China).
Provisional Prognostic Score for Mast Cell Leukemia
Authors: Haddad Philip A , Chennapragada Suma Sri 
Published: December 2023

Background
Mast cell leukemia (MstCL) is a rare but aggressive variant of systemic mastocytosis (SM), defined by the presence of &gt;20% atypical mast cells in the bone marrow. It is further classified into leukemic and aleukemic variants based on the presence or absence of &gt;10% atypical mast cells in the peripheral blood, respectively. There is a wide variation in treatment regimens used to treat MstCL. Despite this, prognosis remains poor. While MstCL often follows an aggressive course, its outcomes vary considerably. We conducted this study to develop a provisional MstCL prognostic score (MCLPS) for this rare disease.
Methods
We used our constructed MstCL database, which contains retrospective data on 144 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 144 cases, only 104 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios.
Results
The median OS of the cohort was 9 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: Age&lt;55 (6 vs. 15 months), Hgb&lt;10g/dl (3 vs. 29 months), Platelets&lt;100K (3 vs. 23 months), leukemic phase (7 vs. 18 months), and complex cytogenetics (2.3 vs. 23 months). A prognostic model was devised using these variables to identify different levels of risk. Each variable was assigned a score of 1 when present for a maximum score of 5. In this exploratory cohort, low risk was assigned a score of 0, intermediate risk a score of 1-2, and high risk a score of 3-5. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of 29, 8, and 2.4 months, respectively (p=0.0006).
Conclusion
This MCLPS is a promising new tool for risk-stratifying patients with MstCL. However, it still requires prospective validation.
PET Radiomics Score Generated By Cross-Combination Approach for Treatment Response and Prognosis Prediction in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma Patients
Authors: Zhao Jincheng , Rong Jian , Teng Yue , Chen Man , Chen Bing , Jiang Chong , Chen Jianxin , Xu Jingyan 
Published: December 2023

Background: Current risk stratification for primary gastrointestinal diffuse large B-cell lymphoma（PGI-DLBCL） relies on mainly on clinical factors. Radiomics score (RadScore) associated with survival outcomes have been developed for other cancer types, however few studies have thus far examined the role of radiomics in PGI-DLBCL.
Objective: In this study, we investigated the value of PET RadScore constructed using a machine learning cross-combination approach in predicting the early treatment response and prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) treated with the R-CHOP-like regimen.
Methods: A retrospective analysis was conducted on 108 PGI-DLBCL patients diagnosed through histopathological examination at two independent medical centers from March 2011 to March 2023, with 86 patients in the training cohort and 22 patients in the validation cohort. Seven different machine learning models were used to generate 49 feature selection-classification candidates, and the optimal candidate was selected based on the area under curve of ROC to establish RadScore. Risk factors were identified through logistic regression, and a radiomics nomogram was constructed by combining RadScore with the selected risk factors. The model was evaluated through calibration curves and decision curve analysis (DCA) using the training cohort and validation cohort.
Results：A total of 111 radiomics features were extracted, and 19 features with strong predictive performance were selected to generate RadScore. The results suggest that RadScore can stratify patient prognosis.The logistic regression analysis results in the training cohort showed that elevated lactate dehydrogenase (LDH) level (OR=3.53, 95%CI: 1.21-10.31, p=0.021), intestinal involvement (OR=3.04, 95%CI: 1.04-8.88, p=0.042), and total lesion glycolysis (TLG) (OR=6.73, 95%CI: 2.23-20.29, p＜0.001) were independent risk factors for predicting early treatment response. A multi-parameter model incorporating clinical risk factors, metabolic factors, and RadScore was constructed (training cohort AUC: 0.834; validation cohort AUC: 0.902), and the performance of the model was evaluated.
Conclusion：The RadScore, constructed based on a cross-combination approach using machine learning, can predict the survival of PGI-DLBCL patients. When RadScore is combined with clinical risk factors and metabolic factors, it forms a combinatorial model suitable for predicting early treatment response to R-CHOP-like chemotherapy regimens. Larger studies will be needed to validate these results.
Keywords ： Primary gastrointestinal diffuse large B-cell lymphoma · [18F]FDG PET/CT · Early treatment response · Prognosis · Machine learning
Efficacy and Safety of Chidamide Combined with BEAM Conditioning Regimen in Autologous Transplantation for T-Cell Lymphoma
Authors: Shen Yige , Zheng Zhong , Ji Mengmeng , Tang Wei , Zhao Wei Li 
Published: December 2023

Background:
T cell lymphoma (TCL) is a group of highly heterogeneous aggressive non-Hodgkin lymphomas with different pathogenesis and clinical prognosis. Despite the survival benefits of anthracycline-based chemotherapy bridging autologous stem cell transplantation (ASCT), 40% to 50% of TCL patients fail to respond to treatment and relapse or die within a short period of time. Chidamide is an oral selective histone deacetylase inhibitor (HDACi), interferes with epigenetic regulation by deacetylating nuclear transcription factors, affects proliferation and differentiation of tumor cells, and regulates cytokines in the tumor microenvironment. Chidamide combined with chemotherapy has promising clinical applications in ASCT.
Aims:
This prospective Phase II trial aims to evaluate the efficacy and safety of chidamide in combination with carmustine, etoposide, cytarabine, and melphalan (Chi-BEAM) conditioning regimen in ASCT of TCL patients received CR/PR to first-line chemotherapy.
Method:
In this study, eligible patients with TCL (except IPI 0-1 ALK+ anaplastic large cell lymphoma) aged 18-65 years were enrolled. All patients received Chi-BEAM conditioning regimen before ASCT. 30mg of chidamide was administered twice a week for at least 2 years after ASCT.The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end points were 2-year overall survival (OS) rate and safety evaluation.
Results:
At the time of data cut off, a total of 18 patients were enrolled, with a median age of 48 (15-65) years. The 1-year PFS rate and OS rate after ASCT were 90.0% and 100.0%, respectively. The median implantation time of neutrophils was 10 days (9-13 days), and the median implantation time of platelets was 17 days (11-25 days). Most of the adverse reactions (AEs) were tolerable, including controlled grain deficiency with fever, electrolyte disturbance, and abnormal liver function.
Conclusion:
Chidamide combined with BEAM as a conditioning regimen for ASCT can significantly improve PFS and OS in TCL patients, and the AEs are controllable. The study is ongoing and further results will be continuously released.
Orelabrutinib Plus R-CHOP Regimen in Treatment-Naïve Patients with TP53-Mutated Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Xiao Yi , Wu Jiaying , Zhou Mi , Shang Zhen , Zhu Ming 
Published: December 2023

Background: TP53-mutated DLBCL may be refractory to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The A53 subtype was reported to be sensitive to Bruton's tyrosine kinase inhibitors (BTKi). Orelabrutinib (O), a novel BTKi with high selectivity for B-cell lymphomas, combined with R could produce higher anti-tumor effects. O plus R-CHOP-like regimens have shown an encouraging efficacy and acceptable safety in the first-line therapy of DLBCL.
Methods: This study retrospectively collected data on the efficacy and safety of patients (pts) with TP53-mutated DLBCL who received OR-CHOP-based regimens as the first-line therapy between Mar 2021 and Mar 2023. The primary endpoint was complete response (CR) rate at the end of treatment (EOT).
Results: Seven pts (4 males; median age, 56.0 years) were included. Key baseline characteristics included 71.4% IPI score 2-5, 57.1% Ann Arbor stage III-IV, 57.1% non-GCB, 28.6% ECOG PS 2-3, 42.9% MYD88&CD79B co-mutations, 57.1% extranodal lesions, 14.3% HBV and 0% EBV. Two pts had transformed DLBCL from follicular lymphoma. Of 7 pts, 5 pts received OR-CHOP, 2 OR-CHOP plus lenalidomide. With a median follow-up of 9.1 months (range, 3.5-11.8 months), 4 pts completed first-line therapy and 1 died due to progressive disease after 2.5-month discontinuation of medication for economic reasons. Of these 5 pts, 4 (80.0%) achieved a CR at the EOT. During the whole therapy, 4 of 7 (57.1%) pts had a CR as best response; 2 (28.6%) pts with a PR remained on treatment (Table 1 and Figure 1). As cut-off date (March 26, 2023), median progression-free survival and overall survival were not reached, with 12-month PFS rate of 80.0% and 12-month OS rate of 75.0%. Most common adverse events (AEs) of any grade were erythropenia (6 [85.7%]), infection (5 [71.4%]), fever (4 [57.1%]), and anemia (4 [57.1%]), with 71.4% grades 3-4. AEs associated with BTKi off-target activities such as atrial fibrillation, hypertension, and hemorrhage were not reported.
Conclusions: These data supported that OR-CHOP-based regimens had favorable anti-tumor activity and manageable safety profile in pts with TP53-mutated DLBCL. BTKi related off-target AEs were rarely observed. More prospective studies are warranted to validate our findings.