bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Prognostic Factors of Venetoclax Combined with Azacitidine in Unfit AML Based on Real-World Data from a Chinese Population
Authors: Zheng Boyue , JIyi FU , Wu Jiafei , Yu Wang , Wang Jun , Jiang Chuanyan , Huan Wang , Haiqing Yang , Yang Xi , Zheng Hong , Hui Li 
Published: December 2024

Background: Venetoclax combined with azacitidine (VA) has become the standard first-line treatment for elderly unfit acute myeloid leukemia (AML) patients. In the era of targeted therapy, it is essential to explore new prognostic factors.
Objective: To investigate the factors influencing overall survival (OS) in newly diagnosed unfit AML (ND unfit AML) patients induced with VA, and in unfit AML patients who achieved composite complete remission (cCR unfit AML) and received VA maintenance therapy.
Methods: We retrospectively analyzed the clinical data of 112 ND unfit AML at Sichuan Provincial People's Hospital from January 2022 to May 2024. We observed treatment efficacy and survival outcomes, and utilized the COX regression model for statistical analysis to identify influencing factors.
Results: The median age of the included patients was 68 years (range: 43-86), with 57 male patients (51%). Eleven patients (10%) had secondary AML, and 81 patients (72%) had an ECOG score of 0-1. According to ELN-2022 cytogenetic risk stratification, 21 patients (19%) were low-risk, 44 patients (39%) were intermediate-risk, and 47 patients (42%) were high-risk. The cCR rate in ND unfit AML patients was 79% (including 24% CR and 55% CRi), with an MRD negativity rate of 47%. Seven patients (6%) received allogeneic transplantation after remission. The median follow-up was 16.2 months (95% CI: 14.7-17.7), and the median OS was 12.9 months (95% CI: 8.0-17.8). Patients who achieved cCR had a significantly longer median OS compared to incomplete remission (IR) (42.4 months vs. 2.0 months, p&lt;0.0001). There was no significant difference in survival curves among different ELN risk stratifications (NR vs. 12.1 months vs. 11.2 months, p = 0.3150). Among cCR unfit AML patients, those with MRD negativity had significantly better OS compared to those without MRD negativity (NR vs. 8.7 months, p&lt;0.0001). COX regression analysis indicated that IR, MRD positivity, t(8;21)(q22;q22)/AML1-ETO positivity, U2AF1 mutation, and post-treatment ECOG (＞1) were independent adverse prognostic factors in ND unfit AML patients. For cCR unfit AML patients, MRD positivity, U2AF1 mutation, and post-treatment ECOG (＞1) were independent adverse prognostic factors.
Conclusion: The VA regimen is effective in treating unfit AML patients. Patient OS is influenced by treatment response, performance status, and cytogenetic factors.
Evaluation of Obexelimab in Patients with Warm Autoimmune Hemolytic Anemia: Preliminary Results from an Open Label Phase 2 Study
Authors: Fattizzo Bruno , Evans Gillian , Wells Audrey , Poma Allen , Quinn Shauna , Zhang Dale , Yamashita Mason , Fischer Tanya Z. 
Published: December 2024

Introduction. Warm autoimmune hemolytic anemia (wAIHA) is a rare, serious autoimmune disorder characterized by the binding of autoantibodies to red blood cells (RBCs) at core body temperature (37°C), leading to hemolysis and signs/symptoms of anemia, including severe fatigue, dyspnea, pallor, and jaundice. There are currently no FDA-approved treatments for wAIHA, and anemia is typically managed with corticosteroids. Relapse is common and long-term steroid use carries significant risk of side effects and other complications. There is a need for new, safe and effective therapies. Obexelimab is a bifunctional, non-depleting humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B-lineage cell activity. Obexelimab is an investigational product and not approved for any indication. Here we report on the safety and efficacy of obexelimab in an open-label Phase 2 study in patients with wAIHA (NCT05786573).
Methods. The ongoing, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamic (PD), and efficacy (including improvement in hemoglobin (Hgb)) of obexelimab in patients with wAIHA. The study is expected to enroll 14 patients with primary or secondary wAIHA due to autoimmune disorders. Eligible patients are 18 years of age or older, have been clinically diagnosed with wAIHA for at least 3 months with documentation of a positive direct antiglobulin test and have failed at least 1 previous wAIHA therapy. Patients must have at least one sign/symptom of anemia with a hemoglobin level of ≥ 7 to &lt; 10 g/dL on Day 1. Eligible patients self-administer obexelimab via weekly subcutaneous (SC) injections.
Results. Six patients have been enrolled to date. The median age at the time of enrollment was 70.5 years. Other demographics include: 5/6 (83.3%) of patients were female; 5/6 (83.3%) were white; 1/6 (16.7%) was Asian. All patients had a diagnosis of primary wAIHA, and the median disease duration was approximately 3 years. Median Hgb at baseline was 9.50 g/dL, and 4 patients were on background therapy (including glucocorticoids, EPO, mycophenolate) at the time they entered the study.
All 6 patients have been on study for a minimum of 10 weeks (range 10 - 24 weeks). Hemoglobin improvement from baseline have been observed in 3 of the 6 patients.
Four out of 6 patients (67%) experienced a total of 18 treatment emergent adverse events (TEAEs). 3 TEAEs were considered related, and all these were grade 1. There was one serious and not related event of cholecystitis. There were no discontinuations due to adverse events.
Conclusions. Data from the ongoing study suggests that obexelimab administered SC is well-tolerated and may provide improvement in Hgb and other biomarkers of anemia in patients with primary wAIHA, who have failed at least one prior therapy.
A Single-Arm, Multi-Center, Retrospective Clinical Study of Cba Preconditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Acute Leukemia
Authors: Zhuo Dingjun , Tan Xu , Chen Guo , Ma Yingying , Wang Maihong , Chen Siyu , Wen Qin , Liu Hong , Zhang Cheng , Zhang Xi 
Published: December 2024

Abstract
Background: Consolidation regimens for patients with acute leukemia (AL) after complete remission (CR) include conventional chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT), and allogeneic hematopoietic stem cell transplantation (allo-HSCT), Limited by HLA-matching donor, physical status, ages, costs, treatment-related mortality (TRM), and graft-versus-host disease (GVHD), many patients are ineligible for allo-HSCT, auto-HSCT has become a therapeutic option for first-line consolidation in AL patients. However, there is no effective preconditioning regimens followed by autologous hematopoietic stem cell transplantation for AL patients at present.
Aims: To investigate the clinical efficacy,prognosis and safety of Cladribine combined with Cytosine arabinoside (Ara-C) and Busulfan (CBA) preconditioning regimens followed by autologous hematopoietic stem cell transplantation in patients off AL.
Methods: Patients with acute leukemia patients with complete remission and negative residual lesions were selected for autologous hematopoietic stem cell transplantation using CBA (Cladribine: 5mg/m2*5d, Busulfan:130mg/m2*3d, Ara-C:1g/m2*5d) pretreatment regimen, and the therapeutic effect, transplantation complications and prognosis were observed.
Results: A total of 16 patients with acute leukemia were enrolled in the study, there were 7 males and 9 females, with a median age of 50 (19-70) years old. included 10 patients (62.5%) with acute myeloid leukemia (AML),4 patients (25%) with acute lymphoblastic leukemia (ALL) and 2 patients (12.5%) with myelodysplastic syndromes (MDS). Among whom, low risk 4 cases (25%), low risk 5 cases (31.3%), high risk 7 cases (43.7%). Hematopoietic reconstruction was achieved in all 16 patients, and the median time of neutrophil engraftment was 12 (10-33) days, and their median time of platelet engraftment was 16 (12-36) days. 6 patients (37.5%) developed lever, and positive blood cultures were identified in 3 infected patients and included 2 cases of Escherichia coli, 1cases of Corynebacterium-afermentans. 3 patients (18.8%) had digestive tract hemorrhage of different degrees, and 1 patient（6.3%）had drug-induced liver damage. All these symptoms were cured after the symptomatic treatment. With a median follow-up of 5.3(1.2-13.2) months, 2 patients (12.5%) were lost to follow-up, 4 patients (25%) had disease recurrence, and there was no transplant-associated death occurred in any of the 16 patients.
Conclusion：
For patients with acute leukemia, undergoing autologous hematopoietic stem cell transplantation. CBA pretreatment regimen has tolerable adverse reactions, can promote implantation, reduce recurrence rale, and improve the overall quality of life of patients.
Keyword: acute leukemia, autologous hematopoietic stem cell transplantation(auto-HSCT), preconditioning regimen.
Inpatient Outcomes of Spontaneous Bacterial Peritonitis in Patients with Sickle Cell Disease
Authors: Dave Prashil , Uddin Anwar , Uddin Rahat , Ahad Afgal , Shastri Dipsa , Mahmoud Yasmin , Winer Andrew 
Published: December 2024

Introduction: Spontaneous bacterial peritonitis (SBP) is a severe complication that can occur in patients with sickle cell disease (SCD), particularly those experiencing splenic dysfunction and portal hypertension. This condition is characterized by infection of the peritoneal cavity without an obvious source, often leading to significant morbidity and mortality. Using the nationwide database, this study evaluated inpatient outcomes associated with SBP in SCD patients.
Methods: The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) was used to identify adult patients with SCD during 2016 - 2020 using ICD-10-CM codes (D57). ICD-10-CM codes were used to identify patients who had SBP. The primary outcomes were in-hospital mortality, length of stay (LOS), and hospital costs. The secondary outcomes included renal cancer, pancreatic cancer, acute liver failure, liver cirrhosis, hepatic steatosis, and hepatitis B and C. The association between spontaneous bacterial peritonitis and SCD was evaluated using survey-based multivariate logistic regression models for in-hospital mortality and secondary outcomes, Poisson regression for LOS, and a generalized linear model with gamma distribution and log link for hospitalization cost. Models were adjusted for age, sex, race and ethnicity, primary payer, Charlson comorbidity index, hospital bed size, hospital region, and hospital teaching status.
Results: A total of 899,610 SCD patients were identified as required hospitalization between 2016 and 2020 in the United States, and 320 (0.04%) of them had SBP. Inpatient mortality and length of stay were significantly higher in SCD patients with SBP compared to those without SBP (inpatient mortality: 11% vs 0.6%, adjusted OR: 5.27, 95% CI: 2.30 - 12.00, P &lt; 0.001; length of stay: 11.5 vs 5.1 days, p = 0.033). SCD patients with SBP had an increased cost of hospitalization ($36,769 ± 12,018 vs $11,818 ± 105, P &lt; 0.045). SCD patients with SBP had increased odds of having liver cirrhosis and acute liver failure (55% vs 1.1%, 17% vs 0.3%, respectively, p &lt; 0.001).
Conclusion: This analysis shows thatwhile the incidence of SBP in this population is low, it is associated with significantly higher inpatient mortality, prolonged hospital stays, increased hospitalization costs, and elevated rates of hepatic complications. Further research is essential to explore the gastrointestinal complications arising from hepatic and splenic dysfunction in this cohort and identify any preventative strategies to mitigate these risks.
Transcriptional Profiling of Plasma Cells in AL Amyloidosis and Multiple Myeloma: A Single-Cell RNA Sequencing Approach
Authors: Kim Ka Young , Park Sung-Soo , Kim Na Yung , Lim Ji-Young , Lee Jung Yeon , Yun Sujin , Chung Yeun-Jun , Jung Seung-Hyun , Yoon Jae-Ho , Kim Hee-Je , Min Chang-Ki 
Published: December 2024

Background
AL amyloidosis, characterized by the deposition of amyloid fibrils derived from monoclonal light chains, often results in multi-organ dysfunction. Timely diagnosis is crucial for effective management. The gold standard for AL amyloidosis diagnosis involves the demonstration of amyloid deposits by biopsy, usually in affected organs. Despite their potential co-occurrence between multiple myeloma (MM) and AL amyloidosis, distinguishing AL amyloidosis within the context of MM poses diagnostic challenges.
Method
By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 8 treatment-naïve AL amyloidosis, 18 treatment-naïve MM. Publicly available scRNA-seq data of BM-MNCs from 23 healthy donors were used as normal control.
Results
Utilizing single-cell RNA sequencing, we identified 37 distinct subtypes of plasma cells, with the majority being MM-specific and showing patient-specific independence. In contrast, control and AL groups exhibited a more convergent pattern, comprising 1-2 plasma cell subsets. We discovered gene expression differences among plasma cells in control, AL, and MM groups. Through comparative analysis of up-regulated and down-regulated genes, we identified 2,342 potential candidates specific to AL amyloidosis, of which 1,598 were up-regulated and 744 were down-regulated. Focusing on tier-1 genes with possible driver mutations and confirming gene nature related to protein metabolism disorders, we selected 54 genes unique to AL amyloidosis compared to MM or healthy controls. To develop a transcriptional biomarker panel for AL amyloidosis, we further refined the selection to 31 genes that facilitated panel construction, including two housekeeping genes and 14 genes with the highest statistical significance for panel development QC. Ultimately, we assembled a transcriptome panel consisting of 47 genes, specific to the diagnosis of AL amyloidosis.
Conclusion
This panel has the potential to aid in the identification of patients with asymptomatic plasma cell dyscrasia who should undergo amyloidosis tissue testing. However, its validation status necessitates further assessment in a validation cohort.
5-y Follow-up of Combination of Ibrutinib, Obinutuzumab and Venetoclax for Patients with Newly Diagnosed Mantle Cell Lymphoma, the Oasis Trial
Authors: Tessoulin Benoit , Morschhauser Franck , Chiron David , Bouabdallah Krimo , Cartron Guillaume , Rossi Cedric , Milin Caroline , Fouillet Ludovic , Herbaux Charles , Tchernonog Emmanuelle , McCulloch Rory , Gastinne Thomas , Callanan Mary B. , Le Gouill Steven 
Published: December 2024

Background:
Targeted therapies (such as Ibrutinib and Venetoclax) have improved Mantle Cell Lymphoma (MCL) patients' outcomes. OAsIs trial has evaluated the efficacy and toxicity of the Ibrutinib Obinutuzumab plus venetoclax combination in both R/R and untreated MCL patients (NCT02558816, Le Gouill et al. Blood 2021). In the present work, we updated the outcome of patients enrolled in OASIS trial, especially for patients with newly diagnosed MCL.
Methods:
The OASIS trial was a 3 arms multicenter prospective phase 1/2 trial. Arm A (n=9) enrolled R/R patients who were treated with Obinutuzumab (Obi, 1000mg) and Ibrutinib (Ibru, 560mg). Patients in Arm B (R/R; n=24) and C (newly diagnosed MCL; n=15) were treated with Obi+Ibru+Venetoclax (Ven, 400mg). Patients' characteristics have been described in the original manuscript.
Results:
In R/R cohorts A (n=9) and B (n=24), overall response rates were 89% and 71%, respectively. Median Follow-ups were 72 and 58 m, the 6-y PFS were 53% and 40%, respectively. No safety signals appeared during long term FU. Patients who progressed were treated with Bendamustine-containing regimen (6 out of 10) and one patient received Odronextamab and anti-CD22xCD3 bispecific antibodies.
For Cohort C (n=15), all patients presented with a medium or high-risk MIPI, the median follow-up was 61 m (48-68m). The overall response rate was 93%, with 87% of CR. Median PFS and DOR were not reached, the estimated 60m-PFS and DOR were 80%. Two patients prematurely discontinued, one early PD (after 4m) and one for Adverse Event (neuropathy after 9m). The early PD patient harbored no adverse event, especially no TP53 alteration. One patient with TP53 mutation is still experiencing disease control. One patient experienced atrial fibrillation and one patient had acute cardiac failure. Regarding infections, one patient died of a progressive multifocal leukoencephalopathy (PML) after the completion of treatment. Two patients prematurely discontinued the treatment, one patient had a PD at C4 and has subsequently been treated with R-CHOP, one patient relapsed after treatment completion and has been treated with Glofitamab. In all, 2 patients progressed and 1 died in arm C (PML), hence, the 5-y OS is 93%.
Conclusion:
The Ibrutinib-Venetoclax-Obinutuzumab triplet is associated with a highl and sustained disease control in newly diagnosed (5y-PFS of 80%) patients presenting with high risk-profiles. The anti-CD20+Ibrutinib vs anti-CD20+Ibrutinib+Venetoclax combinations are currently under investigation in OASIS-II trial (NCT04802590) for untreated patients with MCL and may represent a bona-fide alternative to Chemo-based treatments.
Comparison of Alternative Mayo Staging Classification Systems USED in LIGHT-Chain Amyloidosis
Authors: Laires Pedro A , Thompson Jeffrey , Catini Julia , Manwani Richa , Zhang Yu , Yang Feifei 
Published: December 2024

Background: Light chain amyloidosis (AL), a rare, life-threatening disorder, is characterized by deposition of abnormal amyloid fibrils in various organs, notably the heart. Morbidity and mortality in AL patients are closely linked to the magnitude of heart involvement. The Mayo staging system is widely used for stratifying the severity and prognosis of patients with AL. The initial approach, developed in 2004 (Mayo 2004), was later revised into two separate approaches (Mayo 2004 European, Mayo 2012). Currently, no consensus exists on which staging system to use, with clinical trials utilizing either European Modification Mayo 2004 or Mayo 2012 as part of their patient inclusion criteria.
Objectives: This study aimed to characterize the most severe AL patients using different Mayo staging systems and to determine the agreement between European Modification Mayo 2004 and Mayo 2012.
Methods: A cross-sectional analysis (July 1, 2017 - June 30, 2023) was conducted using an anonymized dataset from the TriNetX Dataworks comprising about 95 million patients from 57 USA healthcare organizations. Adults diagnosed with AL between January 1, 2018, and December 31, 2022, with ≥2 records for AL (ICD-10-CM code E85.81) ≥30 days apart were included. Characteristics of interest, including organ involvement (i.e. cardiac, renal, hepatic), the Charlson Comorbidity Index (CCI) and lab values required for staging (NT-proBNP, cTNT, and dFLC) were captured ±180 days from AL diagnosis (ICD-10 E85.81). All patients with available data were staged according to the classification systems under comparison.
Results: Among 525 AL patients, 54.3% (n=285) and 54.1% (n=284) were classified as severe AL according to European Modification Mayo 2004 (stages IIIa: 29.9%; IIIb: 24.4%) and Mayo 2012 (stages III: 41.9%; IV: 12.2%), respectively. Most severe AL patients were predominantly male (65.6%/70.3%) with a mean age of 67.4/67.5 years, and mean CCI of 4/3 in stage IIIb (European Modification Mayo 2004) or stage IV (Mayo 2012), respectively. Renal involvement was observed in 76.6% / 56.2% and liver involvement in 8.6% / 4.7% of stage IIIb/IV patients. The overall agreement for all stages between the two systems was 46.8% (246 out of 525 patients), indicating low concordance.
Conclusion: Our findings reveal a notable lack of agreement among the AL Mayo staging systems. Given developments in the standard-of-care for AL since their inception, it is crucial to re-evaluate the prognostic value of these staging systems in the context of contemporary and upcoming treatments.
The Causality between Immune Thrombocytopenia and Thrombosis : A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Zhao Yajing , Han Shouqing , Liu Xinguang , Guo Li 
Published: December 2024

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, observational studies have shown that ITP patients have a significantly higher incidence of arterial and venous thromboembolism compared with the normal population, despite the low platelet counts. Treatments options, complications, and inflammatory status of ITP patients are considered to contribute the thromboembolism formation. This study aimed at investigating the causal associations of ITP with arterial and venous thromboembolism.
Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was designed by using summary-level data from large genome-wide association studies performed in European individuals. Inverse variance weighting with multiplicative random effect method was used to obtain the primary causal estimates, and weighted median, weighted mode, and MR egger regression were replenished as sensitivity analyses to test the robustness of the results. We also collected data from 302 ITP patient hospitalized in Qilu Hospital during October 2016 to September 2018 to observe the incidence of thrombotic events.
Results: Among the 302 ITP patients included in our retrospective study, 49 patients (16.2%) presented with coronary atherosclerosis, 12 patients with cerebral infarction, and 2 patients with deep venous thrombosis. In the MR analysis, we found no significant causal effects of ITP on coronary atherosclerosis (odds ratio [OR]: 1.000034, P = 0.74), arterial thrombosis (OR: 1.030618, P = 0.07), ischemic stroke (OR: 0.9999557, P = 0.07), myocardial infarction (OR: 0.9999557, P = 0.77), and venous thromboembolism (OR:1.0011961, P = 0. 82) including deep venous thrombosis (OR: 0.9998565, P = 0.02), pulmonary embolism (OR: 0.999987, P = 0.69), and portal venous thrombosis (OR:0.997588, P = 0.96). In the other direction, there were also no significant causal effects of thrombotic events on ITP.
Conclusion: This MR analysis demonstrated no significant causal associations of ITP with arterial or venous thromboembolism in both directions. Although the previous observational studies indicated a positive association between ITP and thromboembolism, the external effects may be dominant. Further investigations are still needed for the underlying pathogenesis of thrombosis in ITP.