bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a Dynamic Ctdna Monitoring System to Predict the Prognosis of CAR-T Cell Therapy in R/R B-NHL Patients
Authors: Zhou Linghui , Cheng Tao , HU Yongxian , Huang He 
Published: December 2023

Introduction: The objective of this study is to establish a prediction system using circulating tumor DNA (ctDNA) to determine the effectiveness of CAR-T cell therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Furthermore, the study aims to compare the mutation characteristics between different therapeutic groups to provide guidance for the prevention and follow-up treatment of patients who fail CAR-T cell therapy.
Methods: In this part of the study, a total of 79 (192 serum samples) R/R B-NHL patients with CAR-T cell therapy were collected for ctDNA detection (187 lymphoma-related gene panel), including 62 samples before treatment (T0), 69 samples at 1 week (T1) and 62 samples at 4 weeks (T2) after reinfusion. Differences of categorical variables were tested using the chi-square test or Fisher's exact test, and differences in survival events between different groups were compared using Kaplan-Meier analysis and log-rank test.
Results: The results of Kaplan-Meier analysis showed that patients with ctDNA mutation genes &gt;10 before CAR-T cell therapy had poorer OS (1-year OS rate: 0% vs 74.9%, 2-year OS rate: 0% vs 68%, P&lt;0.001) and PFS (1-year PFS rate: 0% vs 52.5%, 2-year PFS rate: 0% vs 36.6%, P=0.0056). Patients with MYD88, FAT1 and BTG2 mutation before CAR-T cell therapy had poorer OS, while patients with MUC16 mutation had better OS. The CR rate in patients with TP53 mutation before CAR-T cell treatment was significantly lower than that of patients without TP53 mutation (33.3% vs 68.1%, P=0.02). However, the TP53 mutation status before treatment did not have an impact on the long-term survival of patients. All patients with TP53 mutations at 4 weeks after CAR-T cell therapy failed to achieve CR, and OS was poorer (1-year OS rate: 37.5% vs 66.4%; 2-year OS rate: 12.5% vs 56.3%, P=0.0023). For CR patients, patients with BCR mutation at 4 weeks after treatment had poorer OS (2-year OS rate: 40.9% vs 76.1%, P=0.035). At one week after CAR-T cell therapy(Figure 1), patients without mutations of CDKN2A, CBLB, APC, SPEN, KMT2D, CARD11, FOXO1 and PDGFRB, were more likely to achieve CR (76.6% vs 28.6%, P&lt;0.001), and had better OS (1-year OS rate: 81.5% vs 38.9%, 2-year OS rate: 62.2% vs 5%, P&lt;0.001) and PFS (1-year PFS rate: 67.2% vs 0%, P&lt;0.001).
Conclusions: In this study, we evaluated the characteristics of gene mutation between different therapeutic groups, and a gene set was screened to predict the efficacy of CAR-T cell therapy in R/R B-NHL patients, helping clinicians accurately evaluate the efficacy and assisting in decision-making of treatment options.
Efficacy of Hetrombopag in Treatment of Cancer Therapy-Induced Thrombocytopenia in Lymphoma and Multiple Myeloma Patients
Authors: Huang Wen-Rong , Chen Junli 
Published: December 2023

Background: Chemotherapy and its combination are the mainstay of lymphoma and multiple myeloma (MM) treatment, with high-intensity regimens frequently causing cancer therapy-induced thrombocytopenia（CTIT）, which results in dose reductions and treatment delays. Hetrombopag, a novel oral non-peptide thrombopoietin receptor agonist, is approved in China for immune thrombocytopenic purpura and severe aplastic anemia. This study retrospectively evaluated the efficacy of hetrombopag in treating CTIT among lymphoma and MM patients.
Methods: In this retrospective study, lymphoma and MM patients experiencing≥grade 2 thrombocytopenia (PLT&lt;75×10 9/L) after anti-tumor treatment at the Fifth Medical Center of PLA General Hospital from July 2021 to May 2022 who received hetrombopag were included. All patients were treated with 5 mg hetrombopag once daily until PLT≥100×10 9/L or treatment discontinuation as directed by physicians.
Results: A total of 60 patients (4 Hodgkin's lymphoma, 40 non-Hodgkin's lymphoma, and 16 MM) were analyzed. Their baseline characteristics are presented in Table 1. The median age was 58.0 years (range 14, 86), with 51 (85%) stage Ⅲ/Ⅳdiseases. Most patients received chemotherapy alone (40.0%, 24/60) or combined with targeted therapy (48.3%, 29/60). Notably, 90% patients received a combination of ≥3 chemotherapy drugs. The mean PLT before hetrombopag treatment was (38.8±15.6) ×10 9/L, with 81.7% (49/60) of grade 3/4 thrombocytopenia (PLT＜50×10 9/L). The median treatment duration with hetrombopag was 8 days (range 2, 28). The median time for PLT recovery to 75×10 9/L, and 100×10 9/L from hetrombopag initiation was 7 days (range 3, 14), and 9 days (range 3, 13), respectively. The mean PLT counts on days 3, 5, and 10 of hetrombopag treatment showed notable increases to (40.9±30.9) ×10 9/L, (54.9±37.8) ×10 9/L, and (94.4±70.5) ×10 9/L, respectively. Only 3 patients (5%) developed bleeding events, and 50% of patients avoided platelet transfusion. No hetrombopag-related adverse events were observed.
Conclusion: With the limit of a retrospective evaluation, we observed that hetrombopag might increase PLT, shorten the duration of thrombocytopenia, with no significant toxicity, for lymphoma and MM patients who developed CTIT of ≥grade 2 in this study.
Trends in Diffuse Large B-Cell Lymphoma Mortality in the United States: A Comprehensive Review from 2000 to 2020
Authors: Al Armashi Abdul Rahman , Al Zubaidi Anas , Mahmood Omar , Thierheimer Marisa , Alkrekshi Akram , Abdulhaq Haifaa 
Published: December 2023

Introduction:
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma (NHL), accounting for approximately 30% of all cases. While NHL mortality rates have shown a downward trend over the last two decades, comprehensive investigations into DLBCL mortality trends and disparities across racial, ethnic, gender, and geographical categories in the United States are notably scarce.
Methods:
Utilizing the Centers for Disease Control and Prevention's (CDC) WONDER database we identified all patients who died from NHL and DLBCL from 2000 to 2020. Age-adjusted mortality rates per 100,000 persons (AAMR) were calculated and standardized to the 2000 US census data. The National Cancer Institute (NCI) Joinpoint Regression Program was used to analyze these data to calculate annual percent changes (APCs) and average annual percent changes (AAPCs). Statistically significant changes were confirmed when the confidence interval for the APC or AAPC did not encompass zero. Additionally, subgroup analyses were conducted based on race, ethnicity, gender, and geographic location.
Results:
The study identified 434,419 NHL and 46,252 DLBCL deaths. NHL mortality showed a statistically significant average annual decrease of 2.5% (95% CI: -2.7 to -2.4). DLBCL mortality trends varied, initially decreasing from 2000 to 2008, then notably increasing from 2008 to 2011, and subsequently rising moderately from 2011 to 2020. This pattern culminated in a statistically significant overall average annual increase of 3.5% (95% CI: 0.4 to 6.7) in DLBCL mortality. Subgroup analyses revealed that males, Blacks, and Asians or Pacific Islanders experienced the most marked upward trends in DLBCL mortality. Both metropolitan and non-metropolitan areas reported an increase in DLBCL mortality, with metropolitan areas showing a more pronounced rise.
Conclusion:
Representing the most comprehensive analysis of DLBCL mortality trends to date, our study revealed intriguing disparities among the subgroups we investigated, along with an upward trend in mortality rates that departs from previously reported data. The divergence could be attributed, in part, to the expansive population coverage of the database we utilized and the use of death certificates, which may present discrepant results from other cancer registries. These findings underscore the necessity for ongoing research, guiding the development of targeted intervention strategies for DLBCL and informing efforts to bridge the identified disparities.
A Novel Nomogram Predicting Rituximab-Associated Interstitial Pneumonia in Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Analysis of Single-Center
Authors: Guo Jia , Wang Chengji , Liang Yuanzheng , Wang Liang 
Published: December 2023

Background: The incidence rate of rituximab-induced interstitial lung disease (RILD) was reported to be 3.7%-16.7%. The onset of RILD was insidious, and the clinical symptoms were atypical. The course of the RILD progressed rapidly without timely treatment. However, there were no models reported to predict the risk of RILD. Herein, we investigated the incidence of RILD in consecutive patients with diffuse large B-cell lymphoma (DLBCL) and its correlation with clinicopathological features, and a novel nomogram was constructed to successfully predict the risk of RILD.
Methods: The clinicopathological data of 110 consecutive patients with DLBCL who were treated in the Department of Hematology of Beijing Tongren Hospital from January 2020 to December 2022 were retrospectively collected, and all patients received first-line treatment regimens containing rituximab. The occurrence of interstitial pneumonia was assessed by chest CT or interim PET-CT. Efficacy was assessed according to Lugano criteria, and chi-square test was used to assess the difference in RILD in different characteristic groups.
Results: The complete remission rate of 110 patients with DLBCL after treatment was 84.2%. Twenty-one patients (19.1%) developed RILD during treatment, and the median time of occurrence was the 4th cycle（range: 2~8). The median duration of treatment for RILD was 10 days (range: 5~60). Except for 5 patients with no obvious symptoms, all 16 patients received glucocorticoid-containing regimens, and all patients improved after treatment. The incidence of RILD was significantly higher in patients who received liposomal doxorubicin-containing regimens than those treated with adriamycin regimens (29.7% versus 13.7%, P=0.043). Smoking ( P=0.298) and advanced age ( P=0.156) were associated with a high incidence of RILD. Then we developed a RILD risk prediction model according to the risk factors, and the patients were divided into high-risk and low-risk groups, and the incidence of RILD was significantly different between the two groups ( P=0.027). Finally, a novel nomogram related to the occurrence of RILD in DLBCL patients was developed to scientifically and accurately predict the incidence of RILD.
Conclusion: Patients with DLBCL should be alert to the occurrence of RILD after chemotherapy with rituximab-containing regimen, especially in smoking and elderly patients, and the prevention and monitoring of RILD should be strengthened after the application of liposomal doxorubicin.
Lack of Standardized Coding Limits Accuracy of Electronic Clinical Quality Measure for Pulmonary Embolism Diagnosis
Authors: Baumann Kreuziger Lisa , Keenan Megan , Dykhoff Hayley , Hall Marie , Campbell Kyle , Cahill Emily , Hanson Ryan , McEvoy Dustin , He Wei , Dutta Sayon , Rosovsky Rachel P. , Houghton Damon E. 
Published: December 2023

Introduction: ASH Guidelines for diagnosis of pulmonary embolism (PE) start with risk assessment using a pretest probability tool (PTP) followed by D-dimer testing or CT pulmonary angiography (CTPA) depending on risk. We aimed to develop an electronic clinical quality measure (eCQM) to encourage broader use of a validated PTP scoring tool in emergency departments (EDs). The Centers for Medicare & Medicaid Services require reporting of eCQMs which consist of value sets or lists of standardized codes linked to patient data within the electronic health record. We sought to identify a standardized way to identify CTPA and abnormal D-dimer tests using administrative codes (i.e. CPT, LOINC, SNOMEDCT codes) across three institutions.
Methods: Value sets identifying CTPA and D-dimers were reviewed from existing eCQMs. Three institutions representing 38 EDs from across the country submitted data from all ED encounters between September 12, 2022 and January 11, 2023. Imaging types were reviewed from each of the CPT codes and LOINC (Logical Observation Identifiers Names and Codes). We determined the number of ED encounters, pre-test probability tool use, and diagnosis of PE using different codes. We calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV, respectively).
Results: Over the 4-month study period, 270,214 encounters were identified across 38 EDs. Each institution identified CTPA with site-specific codes (Table 1). The Full CTPA Value Set identified 55% more encounters than the site-specific codes (Full set 15,054/9679 site-specific codes). LOINC code 88322-3 was only used at one site. CPT code 71275 had the best sensitivity and specificity, but still had false positives (PPV 82%) (Table 2).
D-dimer values were identified as LOINC code 48065-7 and 91556-1 at Site 1 and 48067-3 at Site 2. SNOMEDCT codes were not used at any site despite being the way other eCQMs identify elevated D-dimer results. Different D-dimer tests with different normal ranges were used at each site. All sites did not have an electronically extractable positive indicator for D-dimer.
Conclusion: Due to persistent false positives using CPT Code 71275 for identification of CTPA, using this code would lead to inclusion of patients for whom PTP was not required or recommended. Additionally, coding for an abnormal D-dimer test result are not standardized across institutions. Therefore, administrative codes cannot be used to develop eCQMs whose aim is to evaluate whether CTPA is ordered appropriately based on the PTP risk level and laboratory testing.
A Preliminary Report of Clinical Study on Immunosuppressive Therapy Combined with Avatrombopag As the First-Line Treatment for Severe Aplastic Anaemia in Elderly Patients
Authors: Ye Lei , Zhao Xin , Jing Liping , Peng Guangxin , Zhang Fengkui , Zhang Li 
Published: December 2023

Objective The objective is to evaluate the early hematologic response (HR) rate and safety of immunosuppressive therapy (IST) combined with avatrombopag as the first-line treatment for severe/very sever aplastic anaemia(V/SAA) in elderly patients. Methods Prospective，multi-center, single-arm, clinical research. IST treatment regimen: pig anti-human lymphocyte globulin (ALG-p, Wuhan Institute of Biological Products Co., Ltd. China) 20 mg/kg/d for five days and cyclosporin A (CsA) 3 mg/kg/d with adjusted concentration of 150-250 ng/mL, and oral avatrombopag 40 mg/d from the first day of IST initiation up to six months. The patients' treatment responses were evaluated and the major adverse events were collected. Results Ten patients have been enrolled in the study at our centre from June 2022 to October 2022.Among 10 patients, six had SAA and four had VSAA; male: female = 1:1, median age of 68 (60-82) years, and median time from diagnosis to treatment of 44 (20-480) days. The patients' treatment responses were evaluated after initiation of IST, at 3 months: 7 HR [1 complete response (CR), 3 good partial response (GPR), 3 partial response (PR), and 3 no response (NR)]; and at 6 months: 8 HR (1 CR, 5 GPR, 2 PR) and 2 deaths due to infection. The median time of red-cell transfusion independence was 60 (3-168) days in HR patients and that of platelets was 60 (16-153) days. No relapse and clonal evolution occurred within six months. Major adverse events within three months were infection in five cases, electrolyte disturbance in five cases, and cardiac insufficiency in three cases. Liver function abnormalities occurred in two cases, both of which showed elevated alanine aminotransferase up to 174 μ/L and 208.7 μ/L on day 8 and 20 of IST treatment, respectively. Two of the five infected patients had sepsis caused by Enterobacter cloacae. Except for infection, the remaining adverse events were of grade I-II. All the adverse events were effectively controlled. Table 1 summarises the characteristics and clinical status of patients before and after the treatment.
Conclusion This preliminary study of IST combined with avatrombopag for the treatment of elderly patients with V/SAA showed the potential of the combination to improve haematologic response rate and quality in elderly patients with AA, and it is well tolerated as well.
Keywords: immunosuppressive therapy, severe aplastic anaemia, avatrombopag, elderly
Safety and Efficacy of Human Amniotic Epithelial Stem Cells Eye Dropin Ocular Chronic Graft-Versus-Host Disease
Authors: Cheng Xianjing , Huang Ruihao , Fan Wei , Zhao Yuancheng , Huang Shiqin , Yuan Rongdi , Wang Xiaoqi , Zhang Xi 
Published: December 2023

Background
Approximately 50% of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) suffer from ocular chronic GVHD (ocGVHD), which causes severe dryness and visual impairment. However, current clinical treatments for ocGVHD, such as artificial tears, immunosuppression therapy, and punctual occlusion, typically offer only limited benefits. Amniotic membrane transplantation (AMT) can significantly alleviate ocular symptoms in patients with ocGVHD, but it is an invasive procedure that is not appropriate for all patients with ocGVHD. Therefore, we designed a clinical trial to demonstrate the safety and efficacy of eye drops containing human amniotic epithelial stem cells (hAESC) in ocGVHD.
M ethods
Register Number: ChiCTR2200057857. The enrolled eyes received 1*10 6 cells/mL of hAESC eye drops four times daily for one to three treatment cycles (A cycle was defined as two weeks of continuous administration and two weeks without hAESC eye drops). The primary outcome measure is safety following treatment with hAESC eye drops. In addition, other clinical indices, such as the ocular surface disease index (OSDI), NIH score(eye), Schirmer's test, corneal fluorescein staining (CFS) score, fluorescein tear breakup time (FTBUT), and in vivo confocal microscopy (IVCM) were essential parameters.
Results ：
19 of the 25 patients included in the study completed at least one round of treatment. The average length of follow-up was 9.4 months. There were no adverse events associated with hAESC. After one round of treatment(n=19), there was a significant decrease in OSDI score (P=0.0003) and eye NIH score (P0.0001), an increase in Schirmer basal secretion score (P=0.0237), and a significant improvement in CFS score (P0.0001), corneal subbasal nerve density(P=0.006), and corneal epithelial cell density(P=0.0349). It also produced statistically significant improvements in FTUBT after two rounds of treatment (n=14) (P= 0.024). After three rounds of treatment (n=11), we observed additional improvements in the OSDI (P=0.0001) and CFS (P0.001) scores.
Conclusion ：
The findings of this study indicated that hAESC eye drops are safe and effective at alleviating symptoms and signs in patients with ocGVHD, making them a promising therapeutic option for the treatment of ocGVHD.
Patient Characteristics and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Qazilbash Muzaffar H. , Khan Hina N. , Milton Denái R. , Pasvolsky Oren , Tanner Mark R. , Popat Uday R. , Kebriaei Partow , Hosing Chitra , Khouri Issa F. , Rezvani Katayoun , Nieto Yago , Oran Betul , Srour Samer A. , Saini Neeraj Y. , Olson Amanda L. , Ahmed Sairah , Alatrash Gheath , Rondon Gabriela , Konopleva Marina Y. , Champlin Richard E. , Shpall Elizabeth J. , Bashir Qaiser , Pemmaraju Naveen 
Published: December 2023

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy arising from plasmacytoid dendritic cells. It commonly presents as skin lesions with or without bone marrow, lymph node, central nervous system (CNS), or systemic involvement. Limited retrospective data have shown durable remissions after allogeneic (allo) hematopoietic cell transplantation (HCT).
Methods: In this retrospective single-center analysis, we evaluated outcomes of 31 BPDCN patients treated with allo-HCT between September 2000 and June 2023 at our institution.
Results: Median age of our cohort was 52 years [range 16-76 y]. Patient characteristics are summarized in the attached Table. Only 6 patients (19%) had their disease confined to skin and 4 (13%) had CNS/CSF involvement at diagnosis. Four patients (13%) had prior hematologic malignancies (HM), and 9 patients (29%) had a cytogenetic abnormality at baseline. Thirteen (42%) patients, who were evaluated by a next-generation sequencing Leukemia Mutation Panel, had TET2 mutation. Median time from diagnosis to HCT was 6.2 (3.2-42.4) months. Eight (26%) patients received tagraxofusp, matched unrelated donor was the most common donor type (39%), and fludarabine + busulfan-based conditioning was used in 17 (55%) patients. Post-transplant cyclophosphamide (PTCy) was used for GVHD prophylaxis in 23 (74%) patients. Median follow up was 23.9 (0.9-119.9) months. One-hundred day and 1-year non-relapse mortality was 9.7% and 23.1%, respectively. Grade 2 acute GVHD was seen in 9 patients (29%), and no grade 3-4 GVHD has been seen so far. Limited or extensive chronic GVHD was seen in 6 (21%) of 28 evaluable patients. Only 6 of the 31 (19%) allo-HCT patients progressed after HCT. Two-year PFS and OS was 56% and 67%, respectively. Patients receiving allo-HCT in first remission had significantly better median PFS (not reached vs. 11.3 months; p=0.034) and OS (not reached vs. 12.6 months; p=0.045).
Conclusions: These results demonstrate the safety and efficacy of allo-HCT in BPDCN. Patients undergoing allo-HCT in first remission had significantly better outcomes. Prospective studies are needed to better define the role of allo-HCT in BPDCN.