bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the Unexpected: Tongue Bleeding As the First Sign of Extranodal NK-T Cell Lymphoma
Authors: Shah Nagma , Hajiabbasi Maryam , Haylock Alberto Busmail , Bhatt Navin , Feliciano Erin Garbes , Shah Vaibhav , Guevara Elizabeth 
Published: December 2024

Abstract: Natural Killer/T-cell lymphoma (NKTCL) is a rare and aggressive form of non-Hodgkin lymphoma involving natural killer (NK) cells or T lymphocytes, commonly affecting the nasal cavity and upper aerodigestive tract. However, it can also present in extranasal locations like the skin, lungs, and gastrointestinal tract. Here, we describe a rare case of primary extranodal NK/T-cell lymphoma, nasal type (ENKTCL), with an unusual extranasal presentation in the tongue. This led to significant buccal bleeding and hemorrhagic shock due to a lingual artery pseudoaneurysm, an unprecedented complication of ENKTCL.
Case Presentation: A 25-year-old male from Guatemala, residing in the United States, presented with a week-long history of tongue pain, swelling, and a muffled voice following an accidental tongue bite. Examination revealed a large, foul-smelling puncture wound on the tongue with fibrinous exudate, and initial labs showed anemia with a hemoglobin level of 8.8 g/dl. Flexible laryngoscopy revealed erythematous nasal mucosa without masses, and a CT scan of the head and neck showed submandibular lymphadenopathy. Despite treatment with antibiotics and steroids, the tongue lesion did not improve. A biopsy revealed extranodal NK/T-cell lymphoma, nasal type, with necrosis, confirmed by immunostaining positive for CD2, CD7, CD25, TIA-1, granzyme B, and other markers. Before planned radiation therapy, the patient returned to the emergency department with severe tongue bleeding, initially managed with silver nitrate. However, a subsequent episode of profuse bleeding caused hemorrhagic shock. CT angiography identified a lingual artery pseudoaneurysm, necessitating emergent embolization to achieve hemostasis. Further biopsies confirmed NK/T-cell lymphoma with extensive necrosis, and a liver biopsy revealed chronic hepatitis with mild lobular activity and portal fibrosis. The patient was started on chemotherapy with etoposide, steroid, high dose ara-C and cisplatin (ESHAP), however developed further complications and passed away within the following two months.
Conclusion: This case highlights a rare and aggressive presentation of ENKTCL, nasal type, manifesting unusually in the tongue and complicated by a lingual artery pseudoaneurysm. Prompt recognition and management of such atypical presentations are crucial for improving patient outcomes. This case underscores the importance of considering ENKTCL in the differential diagnosis of unusual oral lesions, especially when significant bleeding complications arise.
Treatment Landscape for TP53 Wild-Type CLL: Venetoclax-Obinutuzumab or Second-Generation Bruton Tyrosine Kinase Inhibitors (BTKi)? a Trinetx Review
Authors: Desai Devashish , Sampat Parth , Goodman Alexandra , Madhira Bhaskara Reddy 
Published: December 2024

Background:
Venetoclax plus obinutuzumab (V+Obi) as well as acalabrutinib and zanubrutinib (BTKi) are approved as first line treatment options for TP53 negative CLL. Here we have analyzed the real-world data on comparing these treatments.
Methods:
TrinetX, a global federated research network, provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients with CLL excluding ones with TP53 mutation or Li-Fraumeni syndrome. The population was further divided into two groups, those who received V+Obi and those who received the newer second generation BTKi. Further, propensity score matching (PSM) was carried out to match age, sex, and race. Descriptive analysis was used for demographic data and for overall survival. Kaplan Meier analysis using log-rank test, as well as Cox regression for hazard ratio (HR) was used.
Results:
3,849 CLL patients were identified to have no aberration in the TP53 gene and received some form of treatment (2,777 in BTKi group and 1,072 in V+Obi group). Patients who received BTKi were older (71.9±10.4 vs 66.7±10.6, p&lt;0.0001) compared to V+Obi recipients. Males were the predominant gender in both the groups, but more females received BTKi compared to V+Obi (35% vs 29%, p=0.0003). Caucasians were the predominant race in both groups, and was more statistically significant in the BTKi group (79% vs 70%, p&lt;0.0001). Patients with unknown race were significantly less in the BTKi group (12% vs 20%, p&lt;0.00001). Median follow up was 420 days and 544 days in the BTKi and the V+Obi group respectively. More deaths occurred in the BTKi group (328 (11.86%) vs 105 (9.83%), p=0.0732, OR = 1.236 (0.98-1.559). The Kaplan Meier curve was separated in favor of V+Obi, with log-rank test p = 0.0028, and HR = 1.397 (1.121-1.741). After PSM, both groups had about 1,000 patients, with no significant difference in deaths (105 (10.07%) vs 103 (9.86%), p=0.8723, OR = 1.024 (0.769-1.363)). The Kaplan Meier curves were not separated, with log-rank test showing p=0.3366 and HR = 1.143 (0.87-1.5).
Conclusion:
Our analysis shows that using V+Obi is non inferior to BTKi in impacting overall survival. With V+Obi's fixed duration, it is an excellent option for CLL patients, as compared to BTKi's indefinite treatment, especially for younger patients.
Low-Dose Venetoclax with Azacitidine in Adults with Acute Myeloid Leukemia: Impact of Phenotype on Outcomes
Authors: Ugarte Luis , Lopez-Garcia Yadith Karina , De La Garza Fernando , Rubio Francisco , Morcos Michelle , Gonzalez Alexia , Tejada Vasquez Ana Cristina , Vega Mateos Antonio , Garcia-Salas Gerardo , Colunga-Pedraza Perla R. , Gomez-Almaguer David , Gomez-De Leon Andres 
Published: December 2024

Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease that can express more than one phenotypically distinct clone at diagnosis and during its evolution. Venetoclax, a BCL-2 inhibitor, along with azacitidine has been proposed as a therapeutic option. There are reports suggesting that people with AML and monocytic phenotype may experience resistance to venetoclax, although this has not been confirmed in a population of patients who are candidates for intensive treatment.
Patients and methods: In this retrospective, single-center study, we evaluated responses with low-dose venetoclax with itraconazole and azacitidine (Aza-Ven) in adults with AML according to their immunophenotype and compared them to a historical cohort from the intensive chemotherapy era. The primary outcome was the response at the end of induction. Secondary outcomes were event-free survival and overall survival.
Results: 92 patients were included from January 2017 to April 2024, with a median age of 46 years. Thirty-six patients received first-line Aza-Ven, of whom 27.8% had a monocytic phenotype (n=10) and 72.2% other phenotypes (n=26). In patients who received Aza-Ven , the response at the end of induction was 30% vs. 53.8% in patients with monocytic phenotype vs. others, respectively (p=.18). Median OS for monocytic patients was 6.4 months vs. 10.9 months for other phenotypes (p=.171); median DFS was 2.4 months vs. 5.2 months, respectively (p=.075)
In the historical cohort of 46 patients who started intensive chemotherapy, 20 patients had monocytic phenotype. Complete response was observed in 61.9% of patients with this phenotype vs. 42.9% in other phenotypes (p=0.297). The mean OS for patients with monocytic phenotype was 7.1 vs 9.3 months in other phenotypes (p.803). The median DFS was 4.8 months vs. 2.6 months, respectively (p=.929). OS 9.2 months in patients with monocytic phenotype compared to 6.54 and 12.1 months in patients with other phenotypes.
In the Cox regression model, age for all patients was associated with an increased risk of the event (HR 1.02 95% CI 1-1.04), while use of Aza-Ven decreased the risk of the event (HR 0l.508 95% CI 0.276-0.936). When separated by treatment groups, only age was predictive of OS in the intensive QT group (HR 1.02 (95% CI 1-1.04), but not the phenotype.
Conclusion: Patients with monocytic phenotype experienced higher rates of refractoriness and worse outcomes, although no statistical significance was obtained in this small sample. It´s imperative to analyze prospective trials involving the use of venetoclax-based regimens in patients with this monocytic phenotype, in light of previous reports and the findings in this single-center study, seeking to optimize therapy in this population
Real-World Wutcome of Defibrotide for Treatment of Adult Patients Who Developed Severe Hepatic VOD/SOS after Allogeneic Hematopoietic Cell Transplantation
Authors: Yoon Jae-Ho , Kwag Daehun , Min Gi June , Park Sung-Soo , Park Silvia , Lee Sung-Eun , Cho Byung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Kim Hee-Je , Min Chang-Ki , Cho Seok-Goo , Lee Seok 
Published: December 2024

Background: Hepatic veno-occlusive disease/ sinusoidal obstruction syndrome (VOD/SOS) is a rare but severe complication after hematopoietic cell transplantation (HCT) showing high fatality. Recently reported incidence of VOD/SOS in the Korea was 8.9% (7.8% in adults and 14.0% in pediatrics). Estimated 1-year overall survival (OS) of VOD/SOS was around 41% and the outcome was much dismal when it progressed to severe (36.8%) or very severe grade VOD/SOS (5.7%) based on the revised EBMT severity criteria. Defibrotide (DF) is the only approved agent for the treatment of severe to very severe VOD/SOS, and we tried to analyze the real-world outcome in Korea.
Methods: DF was approved in Korea since 2016, and we tried to retrospectively analyze the outcome of severe to very severe VOD/SOS treated with defibrotide from 2016 to 2023. Totally 73 adult patients were identified. DF was indicated in Korea in patients who satisfied 4 or more out of 6 severity parameters - Time from diagnosis to VOD, total bilirubin, bilirubin doubling time, elevation of aminotransferase, weight gain, and decreased renal function, which was amended to 2 or more out of 5 parameters (excluding weight gain). The diagnosis the severity was assessed by revised EBMT criteria.
Results: Median time from HCT to VOD/SOS diagnosis was 21 days (range D-1 to D+414), and the median time from diagnosis to defibrotide was 1 day (range 0 to 40). There were 40 severe and 33 very severe VOD/SOS at DF start, and they progressed to 20 severe and 53 very severe at worst period (WP). Overall response was observed in 34 (46.5%), and complete resolution (CR) was in 29 (39.7%) - 52.5% in severe and 24.2% in very severe. OS at 100-day was 34.2% (40.3% for severe-DF and 26.4% for very severe-DF, while 62.4% for severe-WP and 23.2% for very severe-WP, p&lt;0.001). When only based on the total bilirubin level (&lt;3, 3-5, 5-8, &gt;8mg/dL), the CR rate (71.4%, 50%, 42.9%, and 25%) and 3-year OS (100%, 25%, 16.7%, and 13.2%) were well distinguished to predict prognosis. We also identified that early DF application within 2 days showed higher CR (55.6% vs. 30.4%) and better OS (37.0% vs. 26.1%).
Conclusion: Real-world outcome of defibrotide demonstrated early administration according to current indications showed good therapeutic effects.
Factors Associated with in-Hospital Mortality from Gastrointestinal Bleeding in Patients with Sickle Cell Disease
Authors: Uche Ifeanyi Nnamdi , Hehr Rohan , Becerra Henry , Gold-Olufadi Shakirat , Oluwadeyi Esther Yemisi , Wasifuddin Mustafa , Saparov Dosbai 
Published: December 2024

Introduction
Gastrointestinal bleeding (GIB) is a common complication and potential cause of mortality in hospitalized patients. Previous studies have shown that patients with SCD have an increased risk of developing GIB. There is a paucity of literature addressing factors that could predict GIB mortality in patients with SCD. Our study aims to identify these factors and other clinical characteristics of GIB in patients with SCD.
Methods
Data for this study were obtained from the National Inpatient Sample (NIS) database. We identified patients with SCD aged 18 years and older who had GIB between 2016 and 2020. The primary outcome was in-hospital mortality. Patient demographics, clinical and hospital characteristics were compared using x2 test. The association between SCD and in-hospital mortality was assessed using logistic regression controlling for other covariate. A two-sided p≤0.05 was considered statistically significant.
Results
We identified 1284 patients with SCD who had GIB during the study period. 51.25% (n=658) were aged ≥40 years old 48.75% (n=626) were &lt;40 years. 42.21% (n=542) of patients had lower GIB compared to 38.01% (n=488) with upper GIB. 5.61% (n=72) of patients died from GIB. Patients with cerebrovascular disease (CVD) (aOR= 3.62 [95% CI: 1.23-10.67] p-value: 0.019), sepsis(aOR= 14.48 [95% CI:7.70-27.21] p-value: &lt;0.001) and acute kidney injury (AKI) (aOR= 3.54 [95%CI:1.87-6.70]p-value:0.0001) had a increased risk of inpatient mortality from GIB compared to other patients. Vaso-occlusive crisis and acute chest syndrome did not show a significant risk for mortality from GIB. There was no significant association between race, gender, income, or insurance with inpatient mortality.
Conclusion
Our study demonstrates a relationship between AKI, Sepsis and CVD and in-hospital mortality of GIB in patients with SCD. Understanding these factors will assist clinicians in anticipating potential mortality in patients with SCD who develop GIB. Our study was limited by a small sample size. More research is needed to identify factors that could improve survival of GIB in patients with SCD.
Outcomes of Acute Myeloid Leukemia Patients Aged 60 Years and Above: An Analysis of SEER Data
Authors: Gopishetty Swathi , Jaiyesimi Ishmael A. , Ezekwudo Daniel 
Published: December 2024

Background: Acute Myeloid Leukemia (AML) is an aggressive and most common hematologic malignancy in adults with a higher incidence in older adults with a median age of diagnosis of 68 years. It accounts for the largest number of annual deaths from leukemias in the United States. Several new therapies have been approved after many years and are expected to impact patient outcomes, especially in patients aged 60 and above.
Design/Methods: We conducted a retrospective analysis of AML patients aged 60 years and above, diagnosed between 2000 and 2021, using the SEER database. Variables such age, gender, race, chemotherapy, and survival outcomes in the last 5 years were extracted and analyzed. Kaplan-Meier survival analysis was performed to evaluate overall survival (OS).
Results: The study included 51,778 AML patients aged 60 years and above. 55.9% were male, and 44.1% were female. The racial distribution was 85.3% white, 6.8% black, 7.2% Asian/Pacific Islander, and 0.6% from other racial backgrounds. Among these only 58.4% of patients received chemotherapy in patients aged 60 and above. Patients who received chemotherapy had median OS of 7 months compared to 1 month in patients who did not receive chemotherapy. Patients who received chemotherapy has significantly reduced risk of death, with hazard ratio of 0.53 (95% CI: 0.42-0.68) and a p-value &lt; 0.01, indicating a 47% reduction in risk of death. The median overall survival (OS) in older patients including patients with and without chemotherapy was 2 months, and 5-year survival rate is 8.3% for Age ≥ 60 years. The results from the multivariate Cox proportional hazards model indicate that, compared to the reference group aged 60-64 years, the hazard ratios (HR) for the age groups 65-69, 70-74, 75-79, 80-84, and 85+ are 1.23 (95% CI: 1.19-1.28), 1.48 (95% CI: 1.43-1.53), 1.79 (95% CI: 1.73-1.85), 2.00 (95% CI: 1.93-2.07), and 2.40 (95% CI: 2.32-2.50) respectively, with all p-values &lt; 0.01. This indicates a statistically significant increase in risk with advancing age, with the 85+ age group having a 140% higher risk compared to the reference group.
Conclusion: This analysis of SEER data highlights that despite advances in treatment, survival outcomes remain poor, in older patients aged 60 and above with AML. A significant percentage was unable to get chemotherapy, and it determines significant challenges in managing this population. These findings emphasize the need for novel therapeutic approaches and strategies to improve outcomes in older AML patients.
Uncovering MHC-1 Racially Defined Leukemogenic Pathways in Adults Patient Diagnosed with Myeloid Hemopoietic Malignancies
Authors: Thalberg Alexandra , Williams Lacey Scott , Sackstein Paul , Renteria Anne S. , Bhatty Hafsa , Rivero Gustavo A. 
Published: December 2024

Background: Outcome in African Ancestry (AA) Acute Myelogenous Leukemia and Myelodysplastic Syndrome patients (pt) is inferior. In particular, AML data suggests differential enrichment of genomic abnormalities [i.e., lower incidence of Core binding factor AML, worse outcome among NPM1 mutated cases etc.). The immune system plays a crucial role in recognizing and eliminating cancer cells. HLA class I molecules present endogenous antigens to CD8+ T cells. HLA gene diversity possibly reflects differences in antigen presentation and immune response. Therefore, mapping HLA-I alleles used by “pathogenic variants in hematopoietic cells” during leukemogenesis may inform “prioritized MHC restricted pathways” susceptible to T cell targeting. In this study, we hypothesized that Class I alleles may be classified as disadvantageous when they do not present mutated neoantigens, promoting immune escape, and that such alleles will be differentially found in African Ancestry (AA) pt at higher frequencies compared non-AA population.
Methods: After IRB approval, 31 patients with available Class I HLA typing and clinical data were included in analysis. The mutational profile obtained by NGS was analyzed for each patient to determine mutated protein sequences for the downstream analysis of neopeptides. MHCNetPan software was used to predict MHC-neopeptide binding. To compare HLA frequencies between AA vs non-AA pt, allele frequencies were analyzed using Fisher's exact test.
Results: Median age of studied patients was 63 years (range 28-89). Fifty-one percent were males. AML and MDS were observed in 74% and 26% patients respectively. By ethnicity, 58% were non-AA and 42% were AA. The median number of mutations was 4. Studied patients had mutations in driver genes. Most mutant driver genes in our cohort were methylation genes (TET2 and DNMT3A), chromatin regulation genes (ASXL1, EZH2), transcription factors (TP53 and RUNX1). Alleles that approached “disadvantageous” significance for AA were A*11:01 (p=0.01), A*25:01 (p=0.01), B*13:02 (p=0.001), B*14:02 (p=0.0006), C*02:02 (p=&lt;0.0001), and C*08:02 (p=0.01). Alleles approaching “advantageous” significance for AA cases: A*33:03 (p=&lt;0.0001) and A*02:02 (p=&lt;0.0001).
Conclusion: In conclusion, some HLA alleles, including A*11:01, A*25:01, B*13:02, B*14:02, C*02:02 and C*08:02 are more common in AA pt, suggesting that these alleles may predispose individuals to develop leukemias. On average, these alleles present “lower” number of bindings [i.e., proportion of 1, 2, 3, 5, and 6 bindings in AA vs non-AA, 26% v 72%, 23% v 77%, 0% v 100%, and 31% vs 69%, &lt;p=0.0001]. Differential MHC frequencies in AML/MDS AA vs non-AA pt implicate the involvement of neoantigen presentation in leukemic cells. While our data requires adjustment for local “normal” allele frequencies, they could potentially be used for patient risk stratification and treatments.
Bruton's Tyrosine Kinase (BTK) Inhibitors Plus RM (rituximab and methotrexate) for the First-Line Treatment of Primary Central Nervous System Lymphoma (PCNSL)
Authors: Guan Fangshu , Guo Xing , Li Yi , Chen Jing , He Jingsong , Wu Wenjun , Cai Zhen , Zhao Yi 
Published: December 2024

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare invasive non Hodgkin's lymphoma (NHL), with the vast majority being diffuse large B-cell lymphoma. Due to its invasive biological behavior, the median survival time is only 2-3 months without therapy. Currently, the standard regimen for newly diagnosed (ND) PCNSL was high dose methotrexate (HD-MTX) combined with rituximab (R), and more effective regimens also have been explored since its poor prognosis. Genomic studies in PCNSL demonstrated that recurrent and CDKN2A deletions, MYD88 and CD79B mutations, and mutations that activate BCR signaling. BTK mediates downstream signaling of MYD88 and, and is an important regulator of the BCR signaling pathway. To date, three BTKs, Ibrutinib (I), Zebutinib (Z), and Obutinib (O) are approved for clinical using in China and have shown promising anti-tumor activity in NHL, and PCNSL in particular. So we analyze the efficacy and safety of BTKs combined with RM for ND PCNSL.
Methods: ND PCNSL patients who received BTKi-RM (I 420mg po qd (1 patient) , Z 160mg po bid (4 patients) or O 150mg po qd (17 patients), rituximab 375 mg/m2 iv day 0, MTX 3.5 g/m2 iv day1, 21 days per cycle) regimens in our center between March 2021 and February 2024 were included.Tumor evaluation was performed usually every two cycles during the induction therapy, at end of treatment and every 3 to 6 months after that by MRI or PET/CT, PET/MR.The overall remission rate (ORR), complete remission (CR) rate, progression-free survival (PFS), and overall survival (OS) were described.
Results:Twenty patients (11 males), with a median age of 61 (rang, 44-74) years were included, the median number of treatment was 6 (rang, 3-8). Eleven and six patients were considered moderate and high risk respectively according IELSG scores. Eleven patients were non-GCB subtype, and 14 were double-expression. Twelve samples were performed genetic analysis and classified by LymphGen algorithm, 9 (75%) were MCD genetic subtype, 2 were non-subtyped and the other was assigned to BN2.Ten patients underwent ASCT and 15 patients received maintenance therapy (BTKi or Lenalidomide) after induction therapy. After median follow-up of 16.3 months, a CR rate of 60% (12/20 patients) and a ORR of 95% (19/20 patients) was achieved, and 1-year PFS and OS were 71.5% (95% CI 53.1%-96.3%) and 94.7% (95% CI 85.2%-100%), respectively. All patients had response to O-RM (ORR 100%, CR rate 66.7%) in the O-RM cohort, and 8 patients (88.9%) achieved CR in MCD subgroup. There were no treatment-related deaths occurred.Conclusion: This real-word analysis demonstrates that BTKi-RM regimen is effective and safe for the treatment of patients with ND PCNSL.