bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of TET2 Mutation in Patients with Myeloproliferative Neoplasms and Thrombosis in Unusual Sites (Splanchnic Thrombosis and Cerebral Thrombosis)
Authors: Morsia Erika , Ranalli Paola , Baldoni Stefano , Lame Dorela , More' Sonia , La Barba Gaetano , Saladino Fabiola , Poloni Antonella , Olivieri Attilio , Rupoli Serena , Di Ianni Mauro , Kordasti Shahram 
Published: December 2024

Introduction:
Myeloproliferative neoplasms (MPNs) associated with unusual site thrombosis (UST) exhibit a distinct clinical profile, particularly in cases of splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT), requiring meticulous interdisciplinary collaboration. This study aims to characterize the molecular features of MPN-UST using next-generation sequencing (NGS), with a particular emphasis on the TET2 mutation.
Methods:
We reviewed clinical and morphological data and analyzed mutational profiles via NGS in 44 consecutive MPN patients (PV [n = 11], ET [n = 12], PMF [n = 14], and MPN-U [n = 7]) admitted to the Hematology Units at AOU delle Marche and Pescara between July 1992 and November 2020, who developed SVT or CVT either at diagnosis or during follow-up.
Results:
A total of 44 patients were included in the study, with CVT accounting for 13.6% of all thromboses (n = 6) and SVT representing 86.4% (n = 38). Half of the patients presented with thrombosis at the time of MPN diagnosis. A higher proportion of patients with MPN-U was observed among those with SVT, aligning with literature findings. Molecularly, 86.4% of patients had the JAK2 V617F mutation as the driver mutation, with a median JAK2 V617F VAF of 16.7% (range, 1.89-91.0). JAK2 was the sole mutation detected by NGS in 51.35% of cases. Conversely, in JAK2 non-mutated patients, the driver mutation was the only genetic lesion found in 16.67% of cases. The primary findings in NGS included mutations in TET2 (22.7%), followed by KIT (18.2%), ASXL1 (9.1%), SETBP1 (9.1%), RUNX1 (6.8%), and GATA2 (6.8%). In 34.1% of cases, three or more mutations were present.
No differences were observed between MPN-SVT and MPN-CVT patients in terms of sex, type of MPN, or symptoms. However, a higher percentage of MPN-CVT patients had a TET2 mutation (66.6% vs. 15.7%; p = 0.0057).
With a median follow-up of 8.7 years, 9 patients died. In our cohort, age at diagnosis (HR 1.03, 95% CI 1.02-1.05, p = 0.00813) and the presence of a TET2 mutation (HR 1.25, 95% CI 1.18-1.52, p = 0.0458) were associated with poorer survival in multivariable analysis.
Discussion:
This study highlights the significant role of TET2 mutations in patients with MPN associated with UST. Our findings indicate that TET2 mutations are notably more prevalent in patients with CVT compared to those with SVT. Moreover, the presence of a TET2 mutation is associated with poorer survival, underscoring its potential as a prognostic marker. These insights emphasize the importance of molecular profiling in MPN-UST patients for better risk stratification and tailored therapeutic approaches.
Efficacy and Prognosis of Blinatumomab As a Bridge Therapy for Hematopoietic Stem Cell Transplantation for B-ALL
Authors: Lin Ting , Li Nainong 
Published: December 2024

Objective:
Patients with B-ALL were included in the study. MRD of the target genes was quantified using a multiparameter Flow cytometry, and the bridged Hematopoietic stem cell transplantation was performed after 7 days of 28 UG of Blinatumoma treatment, it uses dexamethasone to prevent CRS, Levetiracetam to prevent ICAN, and trimetazidine to nourish the myocardium.
Methods:
Forty-four patients (22 female, 22 male) , with a median age of 36.5(13-60 years) . In 19 patients with Ph positive, MRD remained negative before and after transplantation in 14 patients and MRD clearance was achieved in 5 patients, while in 25 patients with Ph negative, MRD remained negative before and after transplantation in 21 patients and MRD clearance was achieved in 4 patients. During treatment with Emil Adolf von Behring, 16 patients (36.4%) developed grade 1 CRS, 1 patient developed Grade 2 CRS, and 1 patient developed grade 3 CRS. Two patients developed ICAN and one patient developed severe arrhythmia, so Emil Adolf von Behring was discontinued. All the 41 patients achieved deep remission after treatment with belintoin. On Blinatumomab, allogeneic Hematopoietic stem cell transplants were performed after a median interval of 0 days (0-40 days) , with 17 patients receiving single cord blood transplants, fifteen patients were treated with HID-HSCT in combination with cord blood transplantation, and 9 patients were treated with MSD-HSCT in combination with cord blood transplantation. With a median follow-up of 11 months, 41 patients had 1-year OS and PFS of 77.9% and 76.9% , respectively, and 10 MRD positive patients had 1-year OS and PFS of 66.4% and 65.6% , respectively, the 1-year OS and PFS of 31 MRD negative patients were 82.4% and 82% , respectively. Nine patients died after transplantation, including 9 from severe infection, 2 from GVHD and 3 from relapse.
Result:
Bridging transplantation after 7 days of continuous use of Blinatumoma has been shown to improve remission rates and long-term survival in patients with B-ALL, particularly in MRD-negative patients.
Quantitative Detection of the Expressions of BCL-2, BCL-Xl and MCL-1 in Bone Marrow Tissues with Immunofluorescence Might Predict the Efficacy of Venetoclax-Based Therapies in Acute Myeloid Leukemia
Authors: Nie Xiaqi , Yin Zhao , Yao Zurong , Chen Dandan , Liu Qifa , Yu Guopan 
Published: December 2024

The expressions of anti-apoptotic proteins might be associated with the response of venetoclax (VEN)-based therapies in acute myeloid leukemia (AML). Yet, there is not a fast, easy and accurate method to quantitatively detect the expressions of different anti-apoptotic proteins. In this study we combined immunohistochemical staining with immunofluorescence technique to develop a new method of immunofluorescence, and quantitatively detected the expressions of BCL-2, BCL-xL and MCL-1 in bone marrow tissues, and then analyzed the co-relationship between the efficacy of VEN-based therapies and the expressions of the three anti-apoptotic proteins in AML. Bone marrow tissues were obtained from 21 patients with relapsed/refractory (RR)-AML and 16 with newly diagnosed (ND)-AML at diagnosis, remission and relapse, who were treated with VEN-based regimens. First, we confirmed the accuracy and the repeatability of the immunofluorescence method by comparing the consistency of the results being detected by the immunofluorescence and western blotting method, and multi vision detection of the immunofluorescence, respectively. After being confirmed, the detection showed that the median expressions of the three anti-apoptotic proteins in the patients with RR-AML were all higher than that in the ND-AML patients, and the difference in MCL-1 was significant (P=0.004). Also, the median expressions of the three proteins were all higher in the patients without acquiring complete remission (CR) (n=15) compared to those with CR (n=22), and the difference in MCL-1 tended to be significant (P=0.051). In the patients with RR-AML, those with high expressions of BCL-2 had significantly lower CR rate than those with low expressions (P=0.030). Meanwhile, high expressions of MCL-1 tended to be associated with lower CR rate in the patients with either ND-AML (P=0.067) or RR-AML (P=0.063). Furthermore, patients with high expressions of ≥2 anti-apoptotic proteins experienced lower CR rate than those with ≤1 high expression of anti-apoptotic protein. Based on the same patients, the expressions of the three proteins increased if leukemia relapsed or did not acquire response, while they significantly decreased if patients acquired CR. In the patients with ND-AML, the expression of the three proteins presented not obviously impact on the survival, while in the patients with RR-AML, those with high expressions of the three proteins tended to have poorer survival than those with lower expressions. In conclusion, quantitative detection of the expressions of BCL-2, BCL-xL and MCL-1 in bone marrow tissues with the immunofluorescence might predict the efficacy of venetoclax-based therapies in AML.
Key words immunofluorescence, anti-apoptotic protein, venetoclax, acute myeloid leukemia, efficacy
Enhancing Compliance to Massive Hemorrhage Protocol through Clinical Decision Support Tool for Thromboelastography Interpretation
Authors: Imhoff Santiago , Bag Angila , Janosky Maxwell D. , Kaufman Margit , De St Paer Brendt 
Published: December 2024

Background
Englewood Health (EH) has adopted innovative approaches to Patient Blood Management (PBM) over the past 25 years, prioritizing Patient Blood Management techniques to enhance patient outcomes [1]. Implementing a massive hemorrhage protocol (MHP) based on thromboelastography (TEG) to tailor treatment of coagulopathy allows goal-directed blood product transfusion. TEG-assisted transfusion, widely used in liver transplantation, cardiac surgery, and trauma, has demonstrated a reduction in blood product use by up to 50% [2]. However, its application outside the operating room (OR) has been limited. Challenges in hospital guideline compliance due to unfamiliarity and difficulty with TEG interpretation have led to underutilization of viscoelastic tests. Simplifying viscoelastic interpretation through a decision support tool can aid physicians in treatment strategies. Tools like AvoMD, a clinical decision support (CDS) tool, help enhance compliance by providing structured guidance on TEG interpretation.
Methods
In 2023, EH decided to expand TEG for institution-wide viscoelastic testing. EH collaborated with AvoMD to integrate its customized MHP into a TEG interpretation interface, allowing clinicians to input key metrics and receive real-time treatment recommendations. Retrospective analysis compared the annual number of rotational thromboelastometry (ROTEM), previously used at EH prior to AvoMD implementation, with the number of TEG tests ordered after.
Results
Since implementation of AvoMD, the number of viscoelastic tests ordered surged by 168%. From 2020 to 2022, an average of 83 tests were ordered annually, increasing to 223 tests per year from 2023 to 2024 following AvoMD integration.
Conclusion
Recommendations for treatment of ongoing bleeding are to provide goal-directed therapy to treat the underlying issue. TEG allows physicians to assess coagulation in real time and tailor blood product administration, decreasing costs and improving patient outcomes [3,4,5]; however, viscoelastic testing use outside the cardiac OR was minimal due to clinician unfamiliarity and infrequent use.
CDS systems integrate patient information with a knowledge base to improve guideline adherence and ultimately, patient safety [6, 9]. AvoMD is a platform designed to streamline clinical decision-making by simplifying evidence-based guidelines. The TEG interpretation interface not only increased the number of viscoelastic tests ordered but also empowered physicians by providing evidence-based recommendations at point of care.
The integration of EH's PBM protocols into workflow through the AvoMD platform represents a significant advancement in the quality of patient care. This project highlights the potential of emerging technology, such as the integration of CDS platforms into electronic medical records, to enhance protocol compliance and improve patient safety [7,8].
Dose-Adjusted EPOCH-R Is Superior to R-CHOP in Frontline Treatment of Mediastinal Large B-Cell Lymphoma
Authors: Ma'koseh Mohammad , Yaseen Abeer , Abu Abed Nebras , Shahin Omar Ahmad , Abufara Alaa , Halahleh Khalid , Al-Rwashdeh Mohammad , Abdel Rahman Zaid , Al-Rabi Kamal , Abdel-Razeq Hikmat 
Published: December 2024

Introduction : Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive B-cell non-Hodgkin lymphoma. Dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R), and rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone (RCHOP), are used as front-line treatments. Our study aims to compare the efficacy of these two regimens in newly diagnosed PMLBCL.
Methods: We retrospectively reviewed the medical records of adults (≥18 years) diagnosed with PMLBCL and treated in our center from 2010 to 2023. Baseline characteristics were compared using chi- square and Mann-Whitney U tests, as appropriate. Survival outcomes, including overall survival (OS), progression free survival (PFS) and relapse free survival (RFS) were plotted using the Kaplan-Meier method and compared using the log-rank test. OS and PFS were calculated from the date of initiation of chemotherapy to death and/or disease progression, respectively. Relapse free survival (RFS) was calculated from the date of documentation of complete response (CR) to relapse or death.
Results: Eighty-seven patients were included in the study, with a median age of 30 years (range: 18-55). The majority (86.5%) presented with bulky mediastinal disease (&gt;7.5 cm) and 29 (32.6%) had an advanced-stage disease (stage III or IV). An International Prognostic Index (IPI) of &gt;1 was observed in 28 (31.5%). Of the 87 patients, 48 (55.2%) were given R-CHOP, and 39 (44.8%) were given DA-EPOCH-R. Baseline characteristics were comparable between the 2 groups. The median number of chemotherapy cycles was 6 in both groups. Radiotherapy was more frequently administered to the R-CHOP group (66.7% vs 15.4%, P&lt;0.001).
Following completion of first-line therapy (chemotherapy with or without radiotherapy), the complete response (CR) rate was significantly higher in patients treated with DA-EPOCH-R (92.3% vs 66.7%, P=0.004). After a median follow-up of 46.7 months (58.2 months for R-CHOP group and 26.8 months for DA-EPOCH-R), patients treated with DA-EPOCH-R had superior OS with 2-year OS rates of 94.4% compared to 72.1% for RCHOP (P=0.014), as well as PFS rates of 86.5% vs 62.2% (P=0.017). However, relapse-free survival (RFS) was similar in both treatment groups (2-year RFS 93.5% vs 93.3%, respectively, P=0.93). No therapy-related deaths occurred in either group.
Conclusions: In PMLBCL, front-line treatment with DA-EPOCH-R is associated with higher CR rates and superior PFS and OS than R-CHOP. However, RFS was similar between groups. Longer follow-up is required to evaluate long-term toxicities and potential late effects.
A Phase 1, Multicenter, Open-Label Study of UB-VV111 in Combination with Rapamycin in Relapsed/Refractory CD19+ B-Cell Malignancies
Authors: Garcia Jacob , Dehner Christine , Teoh Jeffrey , Wallis Wayne 
Published: December 2024

Background and Significance:
Autologous, ex vivo-manufactured chimeric antigen receptor (CAR) T cells directed against CD19 have demonstrated clinical activity. These products have gained approvals in the relapsed/ refractory (R/R) setting in multiple B-cell malignancies (BCMs), including large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, challenges in product availability due to limited manufacturing capacity, the need for apheresis and lymphodepletion, failure to prior ex vivo CAR T therapy, and the level of patient fitness needed to wait for and receive ex vivo autologous CAR T therapy all pose significant challenges to the field, presenting significant unmet clinical need.
UB-VV111 is a third-generation, self-inactivating, replication-incompetent lentiviral vector (LVV) investigational drug product comprising an envelope with cocal virus fusion glycoprotein (cocal) and surface engineered with a membrane-bound multidomain fusion (MDF) protein. The MDF protein contains CD58, CD80, and anti-CD3 single-chain variable fragment (scFv) components that provide both T-cell tropism and activation signals thought to be critical for effective CAR T-cell generation. UB-VV111 is designed to generate CD19-directed CAR T cells in a patient, thus addressing the delivery limitations that exist for currently available autologous CD19-directed CAR T cell therapies. UB-VV111 is to be administered by either the intranodal (IN) or intravenous (IV) route of administration (ROA). Administration of UB-VV111 by either the IN or IV ROA is expected to transduce T cells to generate CAR T cells designed to bind to CD19 antigen to mediate cell killing and express the rapamycin-activated cytokine receptor (RACR) system which, in the presence of rapamycin, is designed to enhance specific expansion of transduced cells.
Study Design and Methods:
Study UB-VV111-01 (INVICTA-1, NCT06528301) is a first-in-human, global, multicenter, dose-finding study of UB-VV111 administered IN or IV +/- rapamycin in CAR-naïve and CAR-exposed subjects with R/R LBCL and CLL/SLL. Dose escalation will proceed independently for each ROA using a Bayesian optimal interval (BOIN) design. Confirmation of CD19 expression will be required for all subjects with prior CD19-directed therapy. Major eligibility criteria include adults with R/R LBCL/CLL/SLL following at least 2 lines of prior therapy who have standard organ function, measurable disease according to Lugano 2014 (LBCL) or iwCLL 2018 (CLL/SLL), ECOG 0 or 1, and no prior allogeneic transplant. Primary objectives include determining the safety profile, maximum tolerated/administered dose, and recommended Phase 2 dose of UB-VV111 +/- rapamycin. Secondary/exploratory objectives include measuring preliminary antitumor activity (magnitude and durability), as well as translational correlates of safety/efficacy.
The Impact of the after-Hours Carechart Program in Assessing and Triaging after-Hours Patients with Malignancies Inquiries and an Analysis of the Changes to Service Access over the Course of the Covid-19 Pandemic
Authors: Bansal Saumya , Ali Amer Al Maqrashi Zainab , Youssef Cynthia , Ellis Peter 
Published: December 2024

Background
Oncology patients with hematological or solid organ malignancies have limited access to their clinical team after hours, leading to increased use of emergency services and avoidable hospitalizations. A pilot project, CAREchart, employing a nurse-led after-hours telephone service, reduced emergency department (ED) visits and was subsequently implemented across Ontario, including at the Juravinski Cancer Centre (JCC) in Hamilton, Canada.
Methods
In this retrospective cohort study, data were abstracted from electronic records, including patient and disease characteristics, reason for calling, and outcomes of the call between Oct 2019 and April 2021. Patients included were aged 18 or older receiving systematic/radiation therapy at JCC. The primary outcome was the proportion of patients accessing CAREChart who were referred to the ED and admitted to the hospital. Secondary outcomes covered the impact of the COVID-19 pandemic wave 1 and 2 on the primary outcome.
Results
A total of 636 calls were made to the CAREChart program from October 2019 to April 2021. Among these, 199 (31.3 %) of calls were directed to ED, 154 (24.4%) visited ED, out of which 93 (14.6%) required admission. This finding was consistent across different time periods: pre-COVID-19, COVID-19 Wave 1, and COVID-19 Wave 2, with 30.8%, 30.8%, and 31.7% of patients directed to the ED, respectively. Similarly, 10.8%, 15.4%, and 15.6% of patients required admission during the pre-COVID-19 period, COVID-19 Wave 1, and COVID-19 Wave 2, respectively. Forty patients (6.3%) visited the ED, and 27 required admission (4.2%) when they were not initially advised to go to the ED through CAREChart.
Conclusions
The CAREChart program provides a unique avenue for JCC cancer patients to access care after hours. The program was successful in avoiding &gt;65% of potential ED visits thus reducing hospitalizations in these patients.
Et Tu, Bruton? Head-to-Head Comparison of the Mortality Rates and Side Effects of 3 Bruton Tyrosine Kinase Inhibitors in Treatment of Chronic Lymphocytic Leukemia
Authors: Rizwan Umer , Fletcher Reece , Meng Ryan , Cheshire Michael 
Published: December 2024

Background
Bruton tyrosine kinase inhibitors (BTKi's), first FDA approved in 2013, specifically target Bruton tyrosine kinase, allowing treatment of B-cell cancers, such as chronic lymphocytic leukemia (CLL). Side effects of BTKis vary due to each drug's affinity for Burton tyrosine kinase and other kinases. This study uses an aggregate of data to compare efficacies and side effect profiles of three first-line BTKi's in treating of CLL: acalabrutinib, ibrutinib, and zanubrutinib.
Methods
Data on patients with CLL treated with acalabrutinib, ibrutinib and zanubrutinib was collected from a large federated multi-national network database and compared with a focus on mortality rate and side effect profile. All cohorts used were matched by age, sex assigned at birth and comorbidities including hypertension, heart failure, and diabetes mellitus.
Results
In a cohort of 3,410 patients with CLL where 1705 were treated with acalabrutinib and 1705 were treated with ibrutinib, there were 181 deaths (10.616%) with acalabrutinib compared to 174 deaths (10.205%) with ibrutinib. The risk ratio was 1.04 (95% CI: 0.854,1.267) with a hazard ratio of 1.146 (95% CI:0.93, 1.411, p&lt;0.2925). Acalabrutinib had a statistically significant increased risk of diarrhea (3.695%, p&lt;0.0004) and headache (2.698%, p&lt;0.0009) in headache compared to ibrutinib.
In a cohort of 1,622 patients with CLL where 811 were treated with ibrutinib and 811 were treated with zanubrutinib, there were 74 deaths (9.125%) with ibrutinib compared to 56 deaths (6.905%) with Zanubrutinib. The risk ratio was 1.321 (95%CI = 0.947,1.844) with a hazard ratio of 0.943 (95%CI = 0.662,1.342, p&lt;0.8162). Ibrutinib had a statistically significant decreased risk of neutropenia (-2.959%, p&lt;0.0116) and thrombocytopenia (-4.562%, p&gt;0.0275), and an increased risk of joint pain (3.699%, p&gt;0.0290).
In a cohort of 1,502 patients with CLL where 751 were treated with acalabrutinib and 751 were treated with zanubrutinib, there were 84 deaths (11.185%) with acalabrutinib compared to 52 deaths (6.924%) with zanubrutinib. The risk ratio was 1.615 (95%CI=1.16, 2.249) with a hazard ratio of 1.248 (95%CI=0.88,1.77, p&lt;0.7093). Acalabrutinib had a statistically significant increased risk of diarrhea (6.125%, p&lt;0.0001), joint pain (7.19%, p&lt;0.0001) and headache (2.663%, p&lt;0.0247) compared to zanubrutinib.
Conclusion
No statistically significant difference in mortality risk was found between the three BTKi's. However, Acalabrutinib is associated with higher risks of diarrhea, joint pain, and headache compared to both Zanubrutinib and Ibrutinib. Ibrutinib is associated with lower risks of neutropenia and thrombocytopenia compared to Zanubrutinib, but higher risk of joint pain compared to Zanubrutinib. These statistically significant differences in side effects warrant clinical judgment in selecting appropriate treatment for patients with CLL.