bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Clinical Study of Zanubrutinib Combined with R-CHOP Regimen in the Treatment of Newly Diagnosed Double Expression Diffuse Large B-Cell Lymphoma
Authors: Wu Yingying , Zhang Ao , Zhang Liling , Cui Guohui , Liu Fang , Chen Zhichao , Chen Zhipeng , Zhang Lu , Liu Lin , He Wenjuan , Hu Yu , Xia Linghui , Fang Jun 
Published: December 2024

Objective
To explore the efficacy and safety of Zanubrutinib combined with the R-CHOP regimen (ZR-CHOP) in the treatment of newly diagnosed diffuse large B-cell lymphoma with MYC/BCL2 double expression (DE-DLBCL).
Methods
This is a prospective single-arm clinical study. Patients aged 18-80 years with newly diagnosed DE-DLBCL were enrolled and treated with 6 cycles of ZR-CHOP plus 2 cycles of rituximab. The immunohistochemical criteria for DE-DLBCL are MYC expression of 40% or higher, and BCL2 expression of 50% or higher. High-grade B-cell lymphoma with MYC and BCL2 rearrangements was excluded. Treatment response was evaluated using PET/CT after 4 cycles and 6 cycles.
Results
From April 15, 2022, to July 25, 2024, 15 patients were enrolled in the study. The median age was 56 years (range 35-70), and 13 patients (86.7%) were female. At diagnosis, 9 patients (60.0%) were in Ann Arbor stage III-IV, 5 patients (33.3%) had an ECOG score of 2 or higher, and 5 patients (33.3%) had an IPI score of 3 or higher. Additionally, 6 patients (40.0%) presented with B symptoms, 5 patients (33.3%) had extra nodal involvement, and 10 patients (66.7%) had the non-GCB subtype. All 15 patients (100%) completed 4 cycles of treatment, and 13 patients (86.67%) completed 6 cycles of treatment. The overall response rate (ORR) was 100.0%, with 13 patients (86.67%) achieving complete response (CR) and 2 patients (13.33%) achieving partial response (PR). As of the follow-up date on July 25, 2024, the median follow-up duration was 15.8 months (range 4.0-27.8). The 1-year estimated PFS and overall survival (OS) rates were both 92.3%, while the 2-year estimated PFS and OS rates were 69.2% and 92.3% respectively. One patient relapsed after 18.9 months of induced remission, and one patient died from accident. Common adverse events of grade 3-4 included anemia (46.7%), leukopenia (40.0%), neutropenia (46.7%), thrombocytopenia (33.3%), and pulmonary infection (26.7%, all are grade 3). Febrile neutropenia, atrial fibrillation and severe bleeding were not observed.
Conclusion
Zanubrutinib combined with R-CHOP regimen demonstrates a significant efficacy and good safety in the treatment of newly diagnosed DE-DLBCL, warranting further exploration.
Outcome in Patients with Multiple Myeloma Receiving Salvage Therapy after Exposure to BCMA-Targeted CAR-T Therapy
Authors: Jiang Yiwen , Gao Wen , Zhu Honghu , Chen Wenming 
Published: December 2024

Novel immunotherapies such as B-cell maturation antigen (BCMA) targeted directed chimeric antigen receptor T-cell (CAR T) therapy has shown favorable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Despite their remarkable efficacy, disease progression still occurs in some patients with limited treatment options.
To investigate optimal strategies of subsequent therapies. We retrospectively performed a comprehensive analysis of the clinical characteristics, post-CAR T treatments, and outcomes of 31 patients from our center who experienced disease progression following BCMA-directed CAR T cell therapy.
A total of 48 patients with R/RMM were treated with BCMA-directed CAR-T in our study. 31 patients suffered progressive disease (PD) with 5 (range 2~9) prior lines of therapy and received subsequent salvage therapies, including one patient who lacked of following treatment details after relapse post BCMA-directed CAR T therapy but had available survival data. There was a median time of 41.5 months (7.7- 175.8 months) between the time of MM diagnosis and CAR-T infusion.
The median overall survival from relapse after BCMA CAR-T for the cohort of 31 patients was 19.5 months (95% confidence interval [CI], 15.7-NE months). Among them, 13 (42%) patients suffered death, although receiving antimyeloma treatment after PD. The overall response rate (ORR) and the median progression-free survival (PFS) for first line salvage therapy after BCMA CAR-T relapse was 46.7% and 5.5 months (95% CI 3.9-27.5 months). Carfilzomib-containing therapy is the most commonly used first line salvage treatment, with the highest ORR of 72.7%, demonstrating a median PFS that was not reached (95% CI 2.03months-NE) and no patients suffered death. Overall, a total of 78 salvage treatment lines were used among the 30 patients at any time post-CAR T relapse with an ORR of 39.4%.
This analysis indicates that Carfilzomib-containing therapy after previous BCMA-targeted treatments offers clinical benefit with higher objective response rates in patients who have few other options.
Gender Influences Clinical Characteristics of Classical Ph Negative Myeloproliferative Neoplasms
Authors: Cai Yanan , Wang Yuebo , Lu Wenyi , Zhang Ping , Zhu Zunmin 
Published: December 2024

Objectives:
To explore the influence of gender on the clinical characteristics of patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), based on The Surveillance, Epidemiology and End Results (SEER).
Methods:
We used the ICD (International Classification of Diseases) for Oncology, third edition (codes 9950, 9961, and 9962) to assemble a retrospective cohort of patients with PV, ET and PMF diagnosed between 2000 and 2018 in SEER 18. Other exclusion criteria included unknown age and diagnosis by autopsy or death certificate only.
Results:
The cohorts enrolled 35645 patients with myeloproliferative neoplasms (MPNs), including 17416 male patients (48.9%) and 18229 female patients (51.1%). In male patients with MPNs, 9218 (52.9%), 5935 (34.1%) and 2263 (13.0%) patients were diagnosed as PV,ET and PMF respectively, in contrast with female patients with MPNs [6817 (37.4%), 9844 (54.0%) and 1568 (8.6%) respectively, P＜0.001]. Male patients developed MPNs at an earlier age than female patients [63(0-99) versus 67(0-99) years old，P＜0.001]. In subgroup analysis, the median age of onset in male patients with PV and ET was significantly younger than female patients [60(0-99) versus 68(0-99) years old and 64(0-99) versus 65(0-99) years old respectively，P＜0.001]. However, the median age at diagnosis in male patients with PMF did not differ with female patients [68(0-95) versus 69(0-99) years old，P=0.272]. Survival analysis showed similar overall survival (OS) between male and female patients with MPNs [59 (0-227) versus 58 (0-227) months，P=0.382]. But in PV patients, OS in male patients was superior to female patients, whereas male patients with ET and PMF suffered shortened OS than female patients [55 (0-221) versus 59 (0-227) months and 29 (0-222) versus 37 (0-213) months，all P value＜0.001].
Conclusion:
Gender influences clinical spectrum, age and OS of MPNs.
SUVR (SUVmax Lymphoma/SUVmax Liver) Vs Deauville Score for Predicting Relapse in Hodgkin Lymphoma
Authors: Rizzolo Angelo , Ben-Ezra Noah , Liu Richard , Salaciak Matthew , Maliha Peter , Probst Stephan , Johnson Nathalie A. 
Published: December 2024

Background
The Deauville score (DS) assessed by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is the current standard method for evaluating treatment response in patients with Hodgkin lymphoma (HL). However, DS is a qualitative and somewhat subjective evaluation. Recent evidence supports the use of the standardized uptake value ratio (SUVR) as a more quantitative and objective assessment of treatment response.
Objective
To compare the diagnostic performance of DS and SUVR at the EOT FDG PET/CT in predicting PFS in patients with HL.
Methods
We included patients with classical HL treated with curative intent between 2000 and 2019 who had EOT PET/CT scans. Each EOT scan was re-scored according to DS and SUVR. SUVR was defined as lesional SUVmax divided by liver SUVmax. Receiver operator curve (ROC) analysis determined the optimal SUVR cut-off value using Youden's index. We computed sensitivity, specificity, positive, and negative predictive values (PPV & NPV) for DS (positive ≥ 4) and SUVR (positive ≥ 1.13). Kaplan-Meier curves and Cox-regression analysis evaluated the PFS predictive ability of the two response-assessment modalities. Informed consent was obtained from all patients.
Results
157 patients had available data at the EOT timepoint. Median age was 31, and 30% had limited favorable disease at diagnosis, defined as Stage I-IIA, non-bulky. Most patients received frontline ABVD chemotherapy (4-6 cycles) and 16 patients (10%) received radiation therapy. There were 35 PFS events, including 5 deaths. The optimal SUVR cut-off at EOT was 1.13. Median PFS among patients with positive DS or SUVR was 8.1 and 8.2 months, respectively. Diagnostic parameters for DS and SUVR were similar (PPV: 77% and 78%, respectively). Both DS and SUVR predicted PFS (HR 2.46 [95% CI 0.29-20.66] and HR 9.06 [95% CI 1.08-75.87], respectively).
Conclusion
Both SUVR with a positivity threshold of 1.13 and DS are predictive of PFS at EOT and have similar diagnostic parameters in patients with HL. However, SUVR offers a more objective assessment of treatment response.
Combination of Geriatric Assessment and Clinical Factors to Predict the Survival of Elderly Patients with Myeloma
Authors: Jin Yuanyuan , Liu Ruoru , Li Jianyong , Fan Lei , Chen Lijuan 
Published: December 2024

Purpose
Elderly patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes due to their potential risk, and lack of the standard-of-care risk stratification model. In this study, we proposed the prognostic model by analyzing the additive value of geriatric assessment and clinical factors.
Patients and Methods
The collected individual data from 131 elderly patients(≥65) with NDMM enrolled. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed.
Results
At a median follow-up of 23.7 months, age, ADL, PLT, CRP, CPC had the highest impact on OS and were used to construct OS risk model. Likewise, age, ADL, PLT, CRP, CPC for PFS risk model. A value was assigned to each risk feature according to their OS impact (age&gt;75 5 points, ADL&gt;4 3 points, PLT&lt;100×109/L 4 points, elevated CRP 3 points, CPC≥0.105% 2 points). And for PFS risk model, age&gt;75, CCI ≥2, β2≥3.5mg/L, PLT&lt;100×109/L and CPC≥0.105% were assigned 2, 2, 3, 2, 2 points repectively. Patients were stratified into three risk groups according to the total additive score. Median OS was not reached versus NR versus 54 versus 56 months, and median PFS was NR versus 47 versus 23 months, respectively. Nomogram was also constructed using the same variables. the AUC values obtained from our nomogram were 0.742, 0.773 and 0.807 for predicting the 1-, 2- and 3-year OS rates, respectively, which were higher than those of both the MRP model (0.692, 0.691, 0.683) and IMWG-GA model (0.649, 0.634, 0.659). Additionally, 1-, 2- and 3-year PFS in our cohort yield value of 0.775, 0.782,0.774, respectively, which also exhibited superior performance compared to both the MRP model(0.646, 0.607, and 0.602), and the IMWG-GA model( 0.636, 0.506, and 0.576).
Conclusion
Our simple prognostic staging system allowing a better stratification of patients with elderly NDMM. The additive geriatric metrics of this score fosters its future implementation with new prognostic variables.
Single-Cell RNA Sequencing Elucidates Cellular Origin and Heterogeneity in Acute Myeloid Leukemia
Authors: Min Kyoung Il , Kwag Daehun , Lee Jung Yeon , Min Gi June , Park Sung-Soo , Park Silvia , Lee Sung-Eun , Cho Byoung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Kim Hee-Je 
Published: December 2024

Introduction:
Acute myeloid leukemia (AML) is a heterogeneous malignancy arising from hematopoietic stem and progenitor cells (HSPCs) that acquire genetic abnormalities during hematopoiesis. Understanding the heterogeneous nature of AML is crucial, and predicting the cell of origin for each AML subtype could significantly enhance our comprehension of the disease. Recent studies utilizing single-cell RNA sequencing (scRNA-seq) have characterized hematopoiesis at single-cell resolution. However, many scRNA-seq studies involve a limited number of patients and lack comprehensive clinical information. Investigating large-scale bulk RNA-seq data with clinical annotations based on scRNA-seq studies will provide deeper insights into the heterogeneous nature of AML.
Methods:
A reference transcriptomic map of hematopoiesis was created using publicly available scRNA-seq data from the Human Cell Atlas and Tabula Sapiens. Data from various studies were aggregated using BBKNN and Scanorama and visualized using UMAP. Bulk RNA-seq data from the BeatAML project were projected onto the reference UMAP and clustered based on the annotations from the reference map to infer the cell of origin for each AML patient. This classification was validated using Pearson correlation of pooled transcriptomic data from the reference cells and NMF factorization of gene expression of reference cell types.
Results:
The reference map comprised 330,000 cells, capturing a wide variety of hematopoietic processes. UMAP projection of bulk RNA samples primarily divided the samples into granulocytic and monocytic origins with varying degrees of differentiation inferred from pseudotime analysis. Overall survival analysis revealed a favorable outcome for diseases originating from granulocytic lineages. To investigate transcriptomic changes from initial diagnosis to relapse, 30 paired initial and relapsed bulk RNA-seq samples were compared. Relapse samples were more likely to be located in proximal pseudotime, indicating a loss of differentiation, and showed a mixture of cell origins, indicating a loss of original transcriptomic characteristics.
Discussion:
This study provides a comprehensive single-cell resolution map of hematopoiesis and reclassifies existing AML bulk RNA-seq data based on the cell of origin. This reclassification allows for comparison of clinical outcomes, such as overall survival and relapse rates, between different groups. Furthermore, the investigation of transcriptomic changes from initial diagnosis to relapse offers insights into the evolution of AML and highlights the importance of targeting specific subpopulations for therapy.
Polatuzumab Vedotin As an Effective Salvage Therapy for Relapsed/Refractory Mantle Cell Lymphoma Resistantance to BTK and BCL Inhibitors
Authors: Yang Ping , Li Chunyuan , Yang Yuan , Liu Shuozi , Wang Jing , Chen Yingtong , Zhang Weilong , Jing Hongmei 
Published: December 2024

Background Novel immunotherapies and small molecular inhibitors including BTK inhibitors, BCL2 inhibtors and lenalidomide have substantially improved survival in relapsed/refractory MCL patients. Patient who resisted to BTK and BCL inhibitors, had more aggressive clinical features and poor prognosis. Previous study showed Polatuzumab vedotin (Pola) was effectiveness in the treatment of MCL. However, there are little previous reports on the efficacy of pola-combination therapy in the patients resistance to BTKi and BCL-2i.
Method This study is a prospective single center study, evaluating the efficacy of pola combined with obinutuzumab ± chemotherapy for 2-6 cycles. The primary endpoint was overall response after 2 cycles assessed by Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment.
Result The study included 9 patients with relapsed or refractory mantle-cell lymphoma. Patients were 44 to 73 years with a male-to-female ratio of 3:1. Clinical features were aggressive, 44.4% of patients were blastoid/pleomorphic histology, 77.7% of patients had ki-67 ≥50%, and 66.7% of patients had TP53 mutation. The lines of previous treatments were 4(2-9), and all patients were resistance to BTKi and BCL-2i. After 2 cycles, 55.6% patients obtained partial remission. Among of them, three patients received CD19-CART therapy and one patients (11.1%) got complete remission after 6 cycles. The most common grade 3-4 adverse events were neutropenia (in 2 [22.2%] of 9 patients), thrombocytopenia (in 2 [22.2%] of 9 patients), infections (in 1 [11.1%] patients).
ConclusionsOur results provide preliminary evidence that the combination of polatuzumab vedotin is an effective salvage therapy for high-risk relapsed/refractory mantle cell lymphoma resistantance to BTK and BCL inhibitors, especially as an optimum bridging choice before CART therapy. The result should be evaluated in a large-sample study.
Clinical Characteristics and Prognosis of 52 Patients with Primary Central Nervous System Lymphoma: 10-Year Experience from a Single Center Study
Authors: Li Sen , Bao Fang , Jing Hongmei 
Published: December 2024

BackgroundPrimary central nervous system lymphoma (PCNSL) is an aggressive, rare form of Non-Hodgkin lymphoma. The aim of this study was to report a 10-year experience of PCNSL treatment, to evaluate clinical characteristics and treatment outcomes of these patients.
Methods Clinical and pathologic data of 52 patients with PCNSL admitted to Peking University Third Hospital from January 2013 to December 2023 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model.
ResultsAmong 52 patients with PCNSL, 44 received induction therapy with chemotherapy. This included 42 patients who were treated with methotrexate-based induction chemotherapy (20 of whom also received small molecule drugs including Bruton's tyrosine kinase inhibitors and immunomodulators), and 2patients who received other chemotherapy regimens. Of these 44 patients, 32 (72.7%) achieved complete remission (CR) and 7 (15.9%) achieved partial remission (PR). No significant difference in efficacy was observed between patients receiving methotrexate-based induction chemotherapy with or without small molecule drugs. An additional 5 patients were treated with a chemo-free regimen of small molecule drugs, achieving 40% CR and 20% PR. The 2-year progression-free survival (PFS) rate was 56.4%, with a median progression-free survival (mPFS) time of 31 months, while the 2-year overall survival (OS) rate was 75.5%, with a median OS (mOS) time of 79 months. Univariant analysis demonstrated that age over 60 years, International Extranodal Lymphoma Study Group (IELSG) prognostic model, Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model, and autologous stem cell transplantation (auto-HSCT) were significantly associated with OS in PCNSL patients. Multivariant analysis further indicated that methotrexate-based induction chemotherapy and auto-HSCT were independent favorable prognostic factor for OS.
Conclusions Our study indicated that patients with PCNSL would benefit from methotrexate-based induction chemotherapy and auto-HSCT as consolidation therapy. The efficacy of small molecule drugs in induction therapy still needs more studies to verify.
Effect of NPM1 mutation Subtype and Co-Mutation Patterns on the Outcomes of Patients with Acute Myeloid Leukemia; A Referral Center Experience
Authors: Yodsuwan Ratdanai , Mott Sarah L , Crawford Kathryn , Sutamtewagul Grerk , Dhakal Prajwal , Magalhaes-Silverman Margarida , Poonsombudlert Kittika 
Published: December 2024

Introduction
AML driven by NPM1 mutation (NPM1mut) in the absence of FLT3-ITD mutation has been categorized by the ELN 2022 criteria in the “favorable” group. However, our center's experience noted some patients with “unfavorable” outcomes prompting us to search for potential distinguishing factors that may help stratify patients with adverse risk NPM1mut.
Methods
We reviewed records of NPM1mut AML patients from 2015 to 2024 and factors associated with relapse-free survival (RFS) and overall survival (OS) were evaluated using Cox regression.
Results
We identified 141 patients with NPM1mut AML, subtype A was the most common (N=98), followed by subtype D (N=10), subtype B (N=6), and other subtypes (N=27) respectively. Ninety patients received chemotherapy (chemo), 41 received hypomethylating agent +/- venetoclax (HMA/ven) and 10 did not receive specific anti-AML therapy. We did not find statistically significant differences in RFS and OS among the different NPM1mut subtypes.
Fifty patients underwent allogeneic stem cell transplants (HSCT); 33 in CR1 (indicated by adverse cytogenetics or co-mutations) and 17 in CR2+ (4 with MRD+ disease pre-HSCT). Median RFS was 70.7 months after HSCT. On multivariable analysis, increased WBC at diagnosis and treatment with HMA/ven compared to chemo were associated with inferior RFS and OS. Co-mutation with KRAS and TET2 was associated with worse RFS. Co-mutation with IDH1/IDH2 was associated with better OS, while KRAS and SRSF2 were associated with worse OS.
Conclusion
We did not find a statistically significant difference in RFS and OS between subtype A vs other subtypes of NPM1mut. However, our results showed that prognoses of NPM1mut AML patients can be influenced by co-mutations other than FLT3-ITD. We noticed inferior RFS among TET2 co-mutated patients, which has not been previously reported, but, whether this is related to underlying clonal hematopoiesis vs true clinical significance remains to be explored. Our results agree with prior reports of favorable outcomes from co-occurring IDH mutations and adverse outcomes when SRSF2 and RAS pathways are altered. The inferior RFS and OS outcomes in the HMA/ven cohort warrant further investigation in a larger randomized trial.