bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rondaptivon Pegol (BT200) to Correct Thrombocytopenia in a Peri-Interventional Setting in Type 2B Von Willebrand Disease (VWD)
Authors: Moser Miriam , Ay Cihan , Schoergenhofer Christian , Gilbert James C , Zhu Shuhao , Jilma Bernd 
Published: December 2024

Introduction
Type 2B von Willebrand disease (VWD) is a qualitative VWF defect with increased binding of VWF to platelets, increased platelet clearance, potential thrombocytopenia and a substantial risk of bleeding. Rondaptivon pegol (BT200) is an aptamer binding to the A1 domain of von Willebrand Factor (VWF), which increases VWF antigen, GpIbM, collagen binding activity, multimers and platelet counts in type 2B VWD.
Methods, intervention and outcome
Two thrombocytopenic patients with type 2B VWD received BT200 peri-interventionally. Patient #1 had a suspect lesion in the lung and required bronchoscopy. As she had received BT200 in a previous phase 2 trial, she now received a loading dose of 10 mg BT200 prior to the procedure, which increased platelet counts from 46 to 108 x10E9/L after one week. Subsequent doses of BT200 normalized her platelet counts. Two months later, she received a loading dose of 12mg, 7.5 and 7.5mg BT200 at weekly intervals before an enteroscopy with thermocoagulation because of frequent bleedings due to jejunal angiodysplasia. Her platelet counts reached 160 before and 153 x10E9/L after the intervention. In both cases BT200 made it possible to conduct those diagnostic procedures, for which threshold platelet counts above the patient's baseline are required. No bleeding complications occurred.
The second patient had a femoral neck fracture that required hip surgery under prophylactic substitution wirh Haemate P, which increased VWF activity to 101%. Nevertheless, platelet counts continued to fall to 14 x10E9/L, and the patient not only showed extensive local hematomas, but also developed bleedings at distant sites (buccal, extremities). This strongly indicates that those bleedings resulted from severe thrombocytopenia, because VWF activity was normal under substitution therapy. BT200 (4.5mg) was injected four days after surgery which increased platelet counts from 25 to 49 x10E9/L after one week. A second dose of 7.5 mg increased platelet counts to 278 x10E9/L after another week.
Conclusion
BT200 corrected platelet counts facilitating two successful interventions without bleeding complications in one patient and a cessation of bleeding in a second patient, which indicates the utility of BT200 in the peri-interventional setting.
Literature
Ay C, et al. The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease. Blood Advances. 2022;27;6(18):5467-5476.
Cihon A, et al. Aptamer BT200 blocks interaction of K1405-1408 in the VWF-A1 domain with macrophage LRP1. Blood. 2024 Jul 12:blood.2024024055
Characterization of Bleeding in Thrombotic Thrombocytopenic Purpura Treated without Caplacizumab
Authors: Mahmoud Amir , Shah Purva , Eltaher Basant , Mostafa Mariam A , Abdelhay Ali , Abou-Ismail Mouhamed Yazan , Chaturvedi Shruti 
Published: December 2024

Introduction: The addition of caplacizumab to immune thrombotic thrombocytopenia (iTTP) treatment options has led to a renewed interest in characterizing the epidemiology and risk factors for bleeding in iTTP. Limited data exist on the bleeding risk in iTTP due to systemic underreporting in earlier cohorts.
Methods: To describe the incidence, patterns, and predictors of bleeding in hospitalized iTTP patients, independent of caplacizumab (pre-caplacoizumab era), we retrospectively analyzed the National Inpatient Sample database (2012-2019) and identified all patients aged ≥18 years with a diagnosis of iTTP. Bleeding was identified using ICD-9/10 codes and characterized as major bleeding or non-major bleeding. Factors associated with bleeding were determined by multivariable logistic regression analysis.
Results: We identified 3103 iTTP hospitalizations between 2012-2019. Median age was 49 years (range 18 - 90) and 65.9% were female. Bleeding occurred in 594 (19.1%) episodes and 157 (5.1%) were characterized by major bleeding. Mucocutaneous bleeding (7.6%) was the most frequent type of bleeding and included heavy menstrual bleeding (2.6%), gingival (2.3%), epistaxis (1.4%), and skin/procedure-related bleeding (1.3%). This was followed closely by gastrointestinal bleeding (5.6%). Among patients with major bleeding (table S1), CNS bleeding was the most common at 67 (42.7%), followed by hemothorax/hemopericardium in 55 (35.0%), and hemoperitoneum in 25 (15.9%). Only 37 (1.2%) hospitalizations with bleeding required percutaneous, endoscopic, or surgical intervention for bleeding. More patients in the bleeding group (table 1) received blood transfusions (48.8% vs 33.6%; P&lt;0.001) and platelet transfusions (21.2% vs 12.2%; P&lt;0.001). Major bleeding was independently associated with mortality (OR, 2.62; 95% CI 1.65-4.16).
In multivariable analysis, Asian/Pacific Islander/Native American race (OR, 2.04; 95% CI 1.04-4.01), coronary artery disease (OR, 1.70; 95% CI 1.06-2.74), autoimmune disease (OR, 2.61; 95% CI 1.58-4.30), Charlson comorbidity index ≥ 3 (OR, 2.08; 95% CI 1.25-3.46), and delay ≥ 2 days in plasma exchange initiation (OR, 1.63; 95% CI 1.13-2.34), were significantly associated with major bleeding.
Conclusion: In conclusion, bleeding is a relatively common issue in acute iTTP that has not been adequately addressed in existing literature. Bleeding is mostly mild, with mucocutaneous bleeding being the most common phenotype. However, major bleeding occurs in over 5% and is associated with mortality. Further studies are needed to establish risk factors for bleeding in iTTP, especially given the increasing use of caplacizumab in the treatment of iTTP.
Rituximab, Chidamide, and Zanubrutinib±CHOP Could be a Promising Regimen for Newly Diagnosed Double-Expressor DLBCL (DE DLBCL)
Authors: Li Zhiming , Sun Peng , Zhang Lu , Fu Xiangjun , Jiang Yirong , Guo Zhi , LIU Panpan , Wang Yu , Yang Hang , Huang Kangming 
Published: December 2024

Background: DLBCL patients with co-expression of MYC (≥40%) and BCL2(≥50%) by immunohistochemistry are considered as double expressor lymphomas (DE DLBCL). The prognosis of DE DLBCL is usually worse than non-DE DLBCL. The Smart Start trial had explored the feasibility of chemotherapy-free targeted therapy before frontline chemotherapy. The BTK inhibitor Zanubrutinib (Z) or epigenetic drug Chidamide (C) with R-CHOP regimen has a potential synergistic effect in the treatment of DE DLBCL. Under the inspiration of Smart Start, this trial aim to explore the feasibility of RCZ±CHOP regimen in newly diagnosed DE DLBCL.
Methods: This is a multicenter, open-label, single-arm phase II study (NCT05527912) conducted in China. If patients achieve complete response (CR) after cycle-2 (C2), RCZ will be continued for up to 8 cycles. Otherwise, RCZ-CHOP will be given for another 6 cycles. The primary endpoint is CR rate at the end of treatment (CRR-EOT); secondary endpoints included ORR (overall response rate) ,2y-PFS, and 2y-OS. Plasma samples were collected at baseline, after C2 and the EOT. In evaluable samples, circulating tumor DNA (ctDNA) assays were performed.
Results: From February 2023 till now, 43 newly diagnosed DE DLBCL patients were enrolled, with 38 patients evaluable. The median age was 55y (range: 22-68), 51.2% were male, 67.4% were Non-GCB. 18 patients who achieved CR by C2 were continued with RCZ chemo-free therapy, and CHOP were added to the 16 PR and 2 SD patients. In the 38 evaluable patients, ORR after C2 of RCZ was 89.5%(CR 47.4%, PR 42.1%, SD 5.3%, PD 5.3%). Up to now, 11 patients have completed RCZ chemo-free therapy 8 cycles (C8) and all of them have achieved CR, both ORR and CR are 100% (11/11). 17 patients have completed RCZ chemo-free therapy 2 cycles and RCZ-CHOP therapy 6 cycles, with a remarkable CR rate of 82.4% and 2 patients withdrew due to PD. For safety information in the trial, the majority of G-3/4 AEs is hematological events, including leukopenia(46.9%), neutropenia(21.9%) and thrombocytopenia(50%), mostly occurred in RCZ-CHOP period. The CR rate at C2 was 66.7% in patients with negative baseline plasma test results (n=32). The patients with BCL6 fusion of ctDNA at baseline were more prone to PD. C2 plasma ctDNA levels decreased significantly from baseline. 29 patients were evaluable for ctDNA after C2, 100%(12/12) of C2-CR patients and 58.8%(10/17) of non-C2-CR patients were negative, P=0.023. The number of detected mutations and the average VAF in plasma were also decreased in Non-C2-CR patients.
Conclusions: This trial demonstrates the RCZ±CHOP therapy could be a promising regimen with an active antitumor effect and acceptable toxicity in newly diagnosed DE DLBCL patients.
Real-World Efficacy and Safety of Letermovir Prophylaxis in Adolescent Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: A Single Center Observational Study
Authors: Xu Ziwei , Wang Huafang 
Published: December 2024

Letermovir, an inhibitor of the cytomegalovirus (CMV) terminase complex, has demonstrated remarkable efficacy in the prevention of CMV infections in adult patients through randomized controlled trials. Nevertheless, its application in adolescent patients has been relatively limited. This observational study, conducted at a single center, sought to assess and compare the efficacy and safety of letermovir (n=20) and valganciclovir (n=32) for CMV prophylaxis in adolescent patients (aged 14-18 years) undergoing allogenic hematopoietic stem cell transplantation (aHCT).
The incidence of CMV DNAemia following aHCT was 45.0% in the letermovir group and 59.4% in the control group receiving valganciclovir. Notably, 20.0% of patients receiving letermovir required preemptive therapy (PET), in contrast to 40.6% of those receiving valganciclovir. Furthermore, 10 patients in the letermovir group and 15 in the valganciclovir group developed grades Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD). Among patients with grades Ⅱ-Ⅳ aGVHD, the proportion of adolescents requiring PET was significantly lower in the letermovir group compared to the valganciclovir group (10% vs 53.3%, p=0.04). The 1-year overall survival rates were 87.4% and 85% in the letermovir and valganciclovir groups, respectively (p=0.928). Importantly, no patients succumbed to CMV infection in both groups . The most common adverse events observed in the letermovir group were aGVHD (60.0%), diarrhea (25.0%), and nausea (15.0%). Leukopenia was reported in only one patient, and did not necessitate an adjustment of letermovir dosage. In this single-center real-world study, letermovir exhibited a superior efficacy and safety profile for CMV prophylaxis in adolescent patients undergoing aHCT, as compared to valganciclovir. In particular, for patients with grades Ⅱ-Ⅳ aGVHD, the administration of letermovir prophylaxis can significantly decrease the likelihood of PET. However, further prospective multi-center studies are warranted to validate the efficacy and safety of letermovir for CMV prevention in adolescent patients.
Limited Quality of Life Sacrifice for Optimizing Long-Term Survival: The Impact of p-Alg Compared to r-ATG in High-Risk Hematological Malignancy Patients Undergoing Matched Sibling Donor Transplantation
Authors: Cheng Qian , Yan Lingyan , Li Xin 
Published: December 2024

Background: Disease relapse and graft-versus-host disease (GVHD) represent significant clinical challenges for high-risk hematological malignancies(HM) patients undergoing HLA-matched sibling donor transplantation (MDST). The inclusion of lymphocyte depleting antibodies significantly reduce the incidence of GVHD in MDST. However, the resulting T-cell depletion weakens the graft-versus-leukaemia (GVL) effect, potentially increasing the rate of disease relapse.How to balance the effect of GVHD and GVL remain unclear for high-risk HM patients receiving MDST. Here, we conducted a retrospective study to compare the efficacy of two lymphocyte depleting antibodies(r-ATG and p-ALG) as the GVHD prevention strategy.
Methods:A retrospective analysis was conducted on 48 patients with high-risk HM patients who underwent MSDT at our center from January 2019 to January 2024. Among them, 22 patients were in the p-ALG group (45mg/kg), and 26 patients were in the r-ATG group (3.5-4.5mg/kg). Data of GVHD, immune reconstitution, survival and recurrence after transplantation were analysed and compared between these two groups.
Results: Our results showed that p-ALG was more likely than r-ATG to induce chronic GVHD of moderate and prolonged duration, the p-ALG group had a higher 3-year cumulative incidence of chronic GVHD than the r-ATG group (64.4±12. 6% vs. 35.7±10.7%, p=0.063). However, there was no significant difference in total acute GVHD (aGVHD) (40.9±10.5% vs. 25.3±9%, p=0.209) and 3-year extensive cGVHD (25.5±11.4% vs. 9.3±6.4%, p=0.188) between the two groups. In terms of patient prognosis, the p-ALG group showed a higher 3-year overall survival rate compared to the r-ATG group (100% vs. 75.5%±8.8%, p=0.039). Although there was no statistically significant difference in the 3-year cumulative relapse rate (CIR) between the two groups, the p-ALG group showed a longer duration of disease remission after transplantation, with a lower 3-year cumulative incidence of post-MRD+ compared to the r-ATG group (4.5%±4.4% vs. 40.5%±11%, p=0.022).High-risk cytogenetic alterations were a significant factor associated with relapse, as 66.7% of patients who experienced a relapse had these high-risk alterations. Further stratified analysis showed that the risk of relapse was significantly increased in the high-risk genetic subgroup compared with the standard-risk group (OR=15.21, 95% CI [1.14-164.057], p=0.025). However, compared with r-ATG, the use of p-ALG has a protective effect in these high-risk patients (OR=0.33, 95% CI [0.002-0.563], p=0.019).
Conclusions: In comparison to r-ATG, the administration of p-ALG in high-risk HM patients receiving MDST is associated with an increased incidence of GVHD but results in a more favorable survival prognosis. We also found the potential superior benefits of p-ALG in MSDT particularly for HM patients with high-risk cytogenetic characteristics.
Polatuzumab Vedotin-Based Regimens As Bridging Therapy before Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma
Authors: Liu Xin-di , Cong Jia , Yang Jing , Wang Liang 
Published: December 2024

Background:
Chimeric antigen receptor T-cell therapy (CAR-T) has achieved great success in treating relapsed/refractory diffuse large B cell lymphoma (R/R-DLBCL). It was reported that 7% of patients did not survive while awaiting the completion of CAR T cell manufacturing, which underlines the need for shortening CAR-T cell production times and the potential importance of bridging therapy. The goal of bridging therapy is to prevent rapid disease progression prior to CAR-T cell infusion. Commonly used bridging therapy includes immunotherapy, chemotherapy and/or targeted therapy, and radiotherapy. However, no standard-of-care bridging therapy has been defined yet for R/R-DLBCL. Polatuzumab vedotin (POLA) has been shown effective both in the first-line setting and as salvage therapy for DLBCL. In this retrospective study, we reported the efficacy and safety profiles of POLA -based regimens as bridging therapy before CD19/ CD22 Bispecific CAR-T cell therapy for R/R-DLBCL.
Methods:
21 patients with R/R-DLBCL enrolled in a prospective clinical trial of CD19/ CD22 Bispecific CAR-T cell therapy (NCT06081478) received POLA -based regimens as bridging therapy, and herein we only reported the efficacy and safety profiles of the bridging therapy retrospectively.
Results:
21 patients with R/R-DLBCL were included in this analysis. The median age was 57 (22-77) years old, and female to male ratio was 11:10. The median prior lines of therapy was three (2-6), and 11 patients were primary refractory to all lines of therapy, and 15 patients were refractory to the last line therapy before CAR-T cell therapy. 19 patients had advanced disease and IPI score &gt;2. Commonly used regimens include: POLA+ Mitoxantrone Hydrochloride Liposome+dexamethasone (N=10), POLA+Obinutuzumab+BTK inhibitors (N=7), and POLA+other agents (N=4). All patients received one cycle bridging therapy, and 20 patients received subsequent CAR-T cell infusion. All patients were evaluated for efficacy of the bridging therapy before lymphodepleting conditioning therapy using PET-CT or CT scan. 15 patients (71.4%) responded to this POLA-based bridging therapy, among whom three patients (14.3%) got complete remission. Five patients got stable disease, but symptoms related to DLBCL got a little relieved. Concerning the safety profiles, five patients developed grade 3-4 bone marrow suppression (neutropenia or thrombocytopenia), and one patient infected with COVID-19 and got fever. All patients recovered to less than grade 2 adverse effects before lymphodepleting conditioning therapy.
Conclusions:
POLA-based regimens seemed to be effective and tolerable as bridging therapy before CAR-T cell therapy for R/R-DLBCL patients, and our findings need verification in large cohort studies.
A Pragmatic Monitoring Model for Non-Relapse Mortality Risk Based on Machine Learning in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Shao Yang-Liu , Yang Jingjing , Li Xiaobo , Guan Di , Zhang Xiawei , Tong Wu , Song Zeliang , Wang Dao , Wei Zhijie , Wang Jingbo , Liu Xiangjun , He Yuelin , Dou Liping , Liu Daihong 
Published: December 2024

Background：Prognostic biomarkers play a crucial role in assessing non-relapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).The concentrations of biomarkers fluctuate with the progression of complications and corresponding clinical interventions. However current predictive models are commonly built and applied based on biomarker concentrations measured at a single fixed time point, which may limit their predictive validity and utility for clinical applications.
Methods: A prospective, multicenter study (NCT04284904) involved 621 allo-HSCT patients from 7 Chinese transplant centers. Concentrations of biomarkers (ST2, REG3α, TNFR1, IL6, and IL8) were measured at day 7/14/28/60/90 post-HSCT; patients with acute GVHD were monitored at onset and weekly during the first treatment month.The time point of relative maximum concentration for each patient (MC) was determined based on the time at which the maximum metric was reached. A pragmatic monitoring model employing the relative maximum concentrations of ST2 and TNFR1 within three months post-transplantation was developed to forecast 6-month NRM in allo-HSCT patients: log10[-log10(1 - p)] = 1.4798(log10ST2) + 3.2733(log10TNFR1) - 21.632，where p = predicted probability of 6-month NRM.
Results：The 460 patients in the modeling cohort were randomly split into a training (n=310) and a test (n=150) set, with model validation performed on an independent cohort (n=159). In both the modeling and validation cohorts, the combination of ST2 and TNFR1 exhibited the highest AUC and C-index among the models (training set: 0.85, 0.80 ; test set: 0.85, 0.80; validation set: 0.95, 0.93).Patients were categorized into three risk groups based on model-derived thresholds: low risk (LR, ≤0.0567), moderate risk (MR, 0.0567-0.1309), and high risk (HR, ≥0.1309). The HR group experienced significantly higher 6-month NRM than the MR and LR groups in both the modeling cohort (40.62% vs. 13.11% vs. 1.57%, P &lt; 0.001) and the validation cohort (47.37% vs. 9.76% vs. 0.00%; P &lt; 0.001). Further, our investigation revealed that our predictive model effectively gauged NRM risk independently of HLA matching, recipient age, donor type, ATG-based GVHD prophylaxis, and other clinical considerations. Multivariate analysis identified model score as significant NRM predictors (P &lt; 0.0001). The model consistently identified high-risk NRM patients throughout post-HSCT time points. The model effectively stratifies NRM risk in patients with or without acute GVHD.
Conclusions: A pragmatic monitoring model for predicting NRM in allo-HSCT patients was established, showing potential for identifying high-risk individuals and improving personalized treatment.
The Race Against Time: Rapid Dflc Response in C1D7 Predicts Complete Hematologic Response in Systemic AL Amyloidosis
Authors: Liu Yang , Bi Jingyi , Mai Ashley , Peng Nan , Wen Lei , Liu KaiYan , Lu Jin 
Published: December 2024

Background: Daratumumab and bortezomib, the first-line regimens for AL amyloidosis, typically yield a complete hematologic response rate of nearly 60%. The median time to a hematologic response for the daratumumab based treatment is only 7-9 days. An early achievement of a complete hematologic response (CR) is particularly crucial in amyloidosis.
Methods: We retrospectively evaluated the relationship between dFLC (the difference between free light chain) reduction in C1D7 and complete hematologic response, organ response, and survival in newly diagnosed AL amyloidosis patients receiving daratumumab, bortezomib, and dexamethasone.
Results: The hematologic CR rate within six months for 48 patients was 66.7%. The median time to initial hematologic response among these patients was 7 days (range, 7-31), while the median time to achieve the best hematologic response was 2 months (range, 0.23-9). Using Receiver Operating Characteristic Curve (ROC) curve analysis, we predicted hematologic CR based on a dFLC reduction 7 days post-treatment (67.0% change, optimal sensitivity 87.5%, specificity 81.3%). We introduce the novel concept of “rapid hematologic dFLC response”, which is defined as a reduction in dFLC levels ≥ 67% after 7 days. The CR rate was 90.3% in rapid responders' groups while 23.5%in slow responders' group (P ＜0.01). After a median follow-up of 19 months (range: 0.3-57), cardiac and renal response achieved 72.0%, 62.8% in rapid responders' group while 43.8%, 40% in slow responders' group (P=0.104, P=0.025). The median major organ deterioration event-free survival (MOD-EFS) in rapid responders' group (not reached) was significantly superior than that in slow responders' group (19m, 95% CI: 1.785-23.14m, P=0.048).
Conclusion: Early dFLC reduction 7 days post-treatment indicates a high possibility of complete hematologic response and organ response. We propose a new concept of “the rapid hematologic dFLC response” in AL amyloidosis, based on treatment with daratumumab, bortezomib, and dexamethasone.