bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Low Dose Versus High Dose Corticosteroid for Graft Versus Host Disease (GVHD): A Systematic Review
Authors: Shah Ghulam , Solangi Ahda , Devi Amirta , Kumar Arun , Sah Ranjit , Khanal Pradeep , Shah Sangam , Sah Sanjit , Mirza Usama , Solangi Zeeshan 
Published: December 2024

Abstract
Background
Graft-versus-host disease (GVHD) is an immune-mediated complication of allogeneic hematopoietic stem cell transplantations. Current standard dose of corticosteroids used by the most hospitals for GVHD patients is 1-2 mg/kg/day. The prednisone dose used in the treatment of a GVHD has been a matter of debate. In this systematic review, we aimed to compare low dose (1mg/kg/day) prednisone to high/standard dose (2mg/kg/day) prednisone in terms of multiple prognostic outcomes of the patients undergoing allogenic hematopoietic stem-cell transplantations.
Methods
We searched the databases PubMed, Cochrane library, and clinicaltrials.gov for all studies investigating the efficacy and safety of low dose and high dose steroid for GVHD. We set the search strategy incorporating the search terms, Graft-versus-host disease,“ ”low dose cortico-steroid,“ and ”high dose corticosteroid“, and operated using the Boolean operators ‘AND’, and ‘OR’. Thus, retrieved articles were then exported on an Excel® sheet, and duplicates were removed. The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel version.
Results
The search revealed 547 studies and 3 studies that met the eligibility criteria of this review have been included.During relapse, chronic GVHD, mortality, and malignancy outcomes were generally similar between doses, low-dose prednisone showed benefits for leukemia-free, relapse-free, and overall survival. Overall, the randomized trial by Chang et al. found lower risks of HZV and pulmonary infections with low-dose prednisone compared to standard-dose. Other infections were similar between groups.
Conclusion
Low-dose prednisone showed similar efficacy to standard-dose for most GVHD outcomes (relapse risk, mortality), with potential benefits on survival, reduced HZV/pulmonary infections, and reduced adverse effect of higher cumulative dose of corticosteroids.
Keywords: low dose, high dose, steroid, graft versus host disease
Development and Evaluation of a Risk Predictive Model for High Level of Self-Reported Symptom Cluster Distress in Patients with Hematologic Malignancies
Authors: Qianqian Zhang , Zhao Jinying , Liu Yating , Song Zhen , Jiang Bo , Xiao Zhijian , Jiang Erlie , Xie Wenjun 
Published: December 2024

Object To develop and evaluate a risk predictive model for high level of self-reported symptom cluster distress in patients with hematologic malignancies.
Methods 354 patients who met the inclusion and exclusion criteria were selected at 5 tertiary hospitals in Beijing，Tianjin，Shandong，Jiangsu，and Anhui provinces in China from June to August 2023．Cases were randomly assigned to a modeling group and a validation group based on 5-old cross-validation method at a ratio of 8：2．The random forest algorithm was used to develop the risk predictive model in the modeling group．The receiver operating characteristic curve，Hosmer-Lemeshow goodness-of-fit test，calibration curve，and decision curve were used to comprehensively evaluate the prediction performance of the model in the validation group．Risk factors were identified based on the order of the importance of each influencing factors．
Results The incidence of high symptom cluster distress was 35.37％in the modeling group and 31.29％in the validation group．The area under the receiver operating characteristic curve of the prediction model was 0.91；the sensitivity was 68.6%，the specificity was 94.6％；Hosmer-Lemeshow goodness-of-fit test was insignificant(P=0.1375)；the decision curve was above the reference line．
Conclusion The risk predictive model based on random forest algorithm has good predictive performance，which is of great significance to help identify hematologic malignancies subgroups at high risk of symptom cluster distress，and will potentially promote symptom management．
The Burden of Inpatient Classical Hematology Referrals at a 700-Bed University Hospital: Opportunities for Growth
Authors: West Chase , Butler Matthew , Kaur Supreet , Bowhay-Carnes Elizabeth , Perepu Usha , Karnad Anand 
Published: December 2024

Background: Classical hematology (CH) represents a significant proportion of hematology/oncology-related referrals in the outpatient setting. Hematologists also must contend with a high demand for CH referrals in the inpatient setting, and the combination of this high demand with an overall CH-workforce shortage puts immense strain on the referral systems and quality of CH-related care. It also affects the career satisfaction of hematologists and the decision-making of trainees interested in a hematology/oncology career. The objective of this study was to conduct an analysis of CH inpatient referrals in order to inform strategy on addressing the CH-workforce shortage and handling hematology inpatient referral demand.
Methods: Providers submit documentation of inpatient hematology referrals at our university hospital (UH), including the reason for referral, into our electronic medical record. To capture all referrals (including informal curbside referrals that resulted in formal consultation), new patient referrals were reviewed daily. Documented inpatient hematology referrals from September 14, 2023 to July 22, 2024 were categorized by reason for referral given by referring provider by one of the authors (C.V.W) and demographic information on referred patients was collected.
Results: A total of 261 CH referrals were documented in the 9 month period. Of these, 134 (51%) were female and 130 (49%) were male with median age 52 (range: 18 - 92 yrs). During the study period, there were 121 malignant hematology referrals, making CH referrals 69% of all hematology referrals during the study period. The most common reason for referral was anemia (40, 16%), followed by thrombocytopenia (40, 15%).
Conclusions: CH referrals make up the majority of inpatient hematology referrals at the CC. Hematologist-developed workup and treatment algorithms may help alleviate the need for CH consultation for more routine hematologic problems. This study demonstrates the heavy demand for inpatient hematology consultation and the need for an increase in CH-focused faculty. This demand suggests a need to expand CH-focused training and education at the UH and nationally.
Characteristics and Outcome of Diffuse Large B Cell Lymphoma: A Retrospective Single-Institutional Experience
Authors: Wu Xue , Ge Zheng 
Published: December 2024

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for approximately 30-40% of all in different geographic regions [Cancer Causes Control 2019;30(5):489-99], while its clinical data from Asian countries in recent years are lacking. It is unclear whether outcomes and disease natural history is similar to reported series with numbers of new drugs come out to be used [Haematologica 2016;101(10):1244-50].
Methods: In this retrospective study, we investigated the pathology, clinical characteristics, and treatment outcomes of patients with newly-diagnosed DLBCL.
Results: Three hundred and three patients with DLBCL diagnosed between January 2010 and October 2022 were identified. Median age at diagnosis was 65 years, and 55% were males. Eighty-two patients (27%) had stage I/II disease and were treated with combined chemotherapy (n=71), BTK inhibitor combined with chemotherapy (n=7) or lenalidomide combined with chemotherapy (n=4). Two hundred and twenty-one patients (73%) had stage III/IV disease and were treated with combined chemotherapy (n=167), BTK inhibitor combined with chemotherapy (n=44) or lenalidomide combined with chemotherapy (n=10). The median follow-up for the entire cohort was 47 months. Patients with stage I/II disease, compared to those with stage III/IV disease, had superior 2-year progression free survival (PFS) 55% vs 24% (P = 0.03) and overall survival (OS) 55% vs. 21% (P= 0.002). Outcomes were significantly different between stage III/IV patients who received combined chemotherapy vs. BTK inhibitor combined with chemotherapy with 2-year PFS (17% vs. 55%; P= 0.001) and OS (14% vs. 61%; P= 0.04). No significant differences in outcomes were noted based on gender or EBER positive/negative.
Conclusions: This series represents the experience of DLBCL treated at our center. Our data are consistent with multi-center studies. Further research is necessary to identify more pathological markers, IPI score, CD4+ lymphocyte and the ratio of neutrophils/lymphocytes.
A Novel Anti-CD20 Monoclonal Antibody for Treating Relapsed Immune Thrombocytopenia
Authors: Liu Jia , Yao Han , Liu Jia , Tao Jun , Feng Yimei , Zhang Xi 
Published: December 2024

Background and Objective: The anti-CD20 monoclonal antibody, such as rituximab, is a guideline-recommended reagent for refractory/relapsed immune thrombocytopenia (ITP) treatment. As a novel anti-CD20 monoclonal antibody developed in China, Ripertamab (chemical name) has the amino acid threonine replacing alanine at position 219 in the constant region, which is the most common sequence extracted from Chinese blood cells. It has lower immunogenicity and is more suitable for Chinese patients. Compared with rituximab, Ripertamab has demonstrated comparable efficacy and safety in patients with B-cell non-Hodgkin's lymphoma. However, there are currently no reports of Ripertamab in the treatment of relapsed ITP; therefore, the purpose of this study is to observe the efficacy and safety of this domestically produced novel anti-CD20 monoclonal antibody in the treatment of ITP.
Methods: From September 2022 to July 2024, relapsed ITP patients were enrolled and treated with Ripertamab (200 mg weekly for four consecutive weeks). The primary observation indicator is platelet response, and the secondary outcome is adverse reactions. Response criteria were: complete response (CR), platelet count ≥100 ×109/L; partial response (PR), 30-99×109/L, or at least double the baseline level, with no bleeding symptoms; no response (NR), platelet count &lt;30×109/L, less than double the baseline level, or bleeding symptoms present.
Results: The median follow-up was 5 months (1-23 months). 14 adult patients (6 males and 8 females; median age 38 [13-77] years old) were analyzed. Four patients (28.6%) had previously received treatment with two medications, while ten patients (71.4%) had been treated with three or more different medications, including immunoglobulins, all-trans retinoic acid (ATRA), cyclosporine, sirolimus, and thrombopoietin receptor agonists (TPO-RAs), etc. Before Ripertamab treatment, the average platelet count was 20×109/L. The median time of initial response was 2 weeks (1-8 weeks), and the average platelet count reached 52×109/L.
The median response duration was 3 months (range: 2-16 months). One month after the first Ripertamab dose, 11 responses (3 CR, 8 PR; ORR 78.6%) and 3 NR (21.4%) were recorded. Two months after the first dose, 12 responses (5 CR, 7 PR; ORR 85.7%) and 2 NR (14.3%) were observed, and the median platelet count reached 94×109/L. During the follow-up period, a total of 4 patients relapsed, with three of them occurring in the third month after the initial treatment and one in the first month after the initial treatment. Adverse events included an infusion-related reaction (fever in 14.2% of patients) during the first dose and an upper respiratory tract infection (7.1%).
Conclusion: Ripertamab can effectively induce remission of relapsed ITP and demonstrate tolerable safety, although more data is required to verify this.
Health Information Needs of Patients with Hematological Diseases: What Exactly Do They Want?– a Cross-Sectional Survey
Authors: Liang Taoyun , Wang Yingli , Yu Yan , Liu Shurong , Mao Ling 
Published: December 2024

In 2023, there were more than 1.64 million patients worldwide suffering from hematological malignancies, according to WHO estimates. Patients with hematological diseases may have various unmet needs during long-term treatment and rehabilitation due to the physical, psychological and social maladjustment caused by the disease itself and its treatment. Among them, the need for health-related information is of paramount importance. All knowledge about health or illness, news about health, statistics about health, and details about people's physical and emotional well-being are often referred to as health information. But our understanding is limited.
This is a cross-sectional study, which investigated the health information needs of 409 patients with hematological diseases. We found that these patients have high information needs, especially in self-care, treatment, medical examination and prognosis. It's interesting that patients' desire for self-care information-primarily nutrition-related information-is highest ranked. Patients' health literacy, their communication skills with healthcare providers, their ability to evaluate and apply health information, their anxiety or depression about their physical condition, and whether they have medical background knowledge all have an impact on their health information needs.
The results of this study underline the importance of providing relevant health information to patients with hematological diseases. Understanding patients' information needs can help healthcare professionals to better address their needs, improve their health literacy, promote effective communication between patients and medical teams, and thus improve patient outcomes and overall health.
Keywords: hematological disorders, hematological tumors, information needs, health literacy, quality of life
Genome-Wide Association Study Identifies Novel Genetic Variants Associated with Avascular Necrosis in Sickle Cell Disease
Authors: Sowa Anna , Hu Yue , Gladwin Mark T. , Gordeuk Victor R. , Nouraie Seyed Mehdi , Zhang Yingze , Pashankar Farzana D. , Krishnamurti Lakshmanan , Gruen Jeffrey 
Published: December 2024

Background:
Avascular necrosis (AVN) is a debilitating complication of sickle cell disease (SCD). The incidence of AVN in individuals with SCD is markedly higher than in the general population, affecting even young children and up to 30% of those over the age of 45. While candidate gene studies have explored genetic associations with AVN in SCD, no genome-wide association studies (GWAS) have been conducted.
Methods:
We performed a GWAS on 405 patients with diagnosis of SCD using data from the screening phase Walk-PHaSST study (NCT00492531). Patients were 12 years or older, median age of 35 years, 53% female, 73% had hemoglobin (Hb) SS, 18% had Hb SC, 4.0% had Hb Sβ + thalassemia, and 4.9% had other SCD forms. All samples had a genotype call rate greater than 95%. SNPs deviating from Hardy-Weinberg equilibrium (P &lt; 0.00001) or with a minor allele frequency less than 0.05 were excluded. Following quality control, 9,874,538 SNPs remained for analysis. genomic inflation factor lambda was 1.023, indicating adequate control for population stratification. We performed multivariable logistic regression analysis (PLINK version 1.9) to investigate the association between SNPs and the presence of AVN of the hip and/or shoulder, adjusting for age, sex, SCD type, alpha-thalassemia, hemoglobin level, hydroxyurea use, and the first 10 principal components.
Results:
There were 88 (21.7%) individuals with AVN of the hip and/or shoulder. Two SNPs on chromosome 1 reached genome-wide significance: rs74436238 (OR=7.43, 95% CI: 3.75-14.70, p=8.11×10^-9) and rs112449951 (OR=6.67, 95% CI: 3.44-12.93, p=1.87×10^-8). These SNPs are in high linkage disequilibrium and located within a long non-coding RNA gene (ENSG00000232537) and an enhancer region (GH01J209266), respectively. The enhancer region is suggested to regulate CAMK1G expression, a gene involved in bone metabolism.
Conclusions:
To the best of our knowledge, this is the first GWAS of AVN to identify a locus that exceeds genome-wide significance threshold. Analyzing a small but well phenotyped cohort of individuals with SCD, we identified a novel locus for AVN on chromosome 1, potentially involving regulatory elements affecting bone metabolism. Further studies in larger cohorts and functional validation are needed to confirm these findings and explore their clinical implications.
The Efficacy and Safety of Cyclophosphamide in Treating Refractory Hepatic aGVHD
Authors: Lu Ni , Jiang Erlie 
Published: December 2024

Background
Post-transplant liver dysfunction affects approximately 50%-80% of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Hepatic acute graft-versus-host disease (aGVHD) is a substantial contributor to this dysfunction and is associated with poor prognosis and reduced survival rates for patients after allo-HSCT. Cyclophosphamide (CTX) is a well-established immunosuppressive and cytotoxic agent commonly used in pretransplant conditioning regimens. However, its potential efficacy in managing refractory hepatic aGVHD remains unexplored.
Methods
We conducted a prospective, single-arm trial to investigate the efficacy and safety of intravenous cyclophosphamide (CTX) at a weekly dose of 100-400 mg in patients with refractory hepatic aGVHD（refractory to second-line therapies） following allo-HSCT. The median cumulative dose of CTX administered was 900 mg (range: 200-2600 mg). The primary endpoint was overall response (complete response or partial response) at day 28 and day 56. Secondary endpoints included overall survival (OS), relapse, and non-relapse mortality.
Results
Between January 2018 and November 2023, 50 patients (median age [range], 34 [10-58] years; 19 [38.0%] women) received CTX treatment and were included in this study. 44 patients (88%) presented with Grade III or IV aGVHD before treatment. A total of 20 patients (40.0%) had a complete remission, and 14 (28.0%) had a partial remission, with an ORR(overall response rate) of 68.0% (34 patients; 95% CI, 53.3%-80.4%) at day 28, and 70% patients(35 patients; 95% CI, 55.4%-82.1%) achieved ORR at day 56. Patients who responded at day 56 received a relatively higher dose CTX (p=0.044). The median follow-up for this cohort was 22.9 months (range, 1.1-60.2) months, with the median OS of 4.7 months (range, 1.1-34.1) months. 5 patients (10%) experienced relapse and the non-relapse mortality rate was 48%. Hepatic-variant of liver aGVHD demonstrated prolonged survival compared to classic liver aGVHD (p=0.045). Prolonged survival was also observed in patients with skin aGVHD(p&lt;0.01), whereas gastrointestinal involved had poorer survival(p&lt;0.01). The most common adverse events up to day 28 were neutropenia (in 34 [68.0%] patients) and cytomegalovirus infection (in 26 [52.0%] patients).
Conclusions
Cyclophosphamide demonstrated a significant response in patients with refractory hepatic aGVHD and a reasonably well-tolerated safety profile. These findings contribute to the evidence supporting CTX as a promising therapeutic choice for refractory hepatic aGVHD.
An Erythrocyte-Based Delivery Platform for Leukemia Treatment
Authors: Chen Mengran , Zhao Lei , Qu Ying , Wu Yu 
Published: December 2024

Background：Leukemia is a highly malignant hematologic neoplasm commonly treated with intensive chemotherapy as frontline therapy, albeit associated with significant side effects that may be poorly tolerated by elderly patients. Erythrocytes, the most abundant cells in blood, possess excellent biocompatibility and provide ample storage capacity due to their lack of organelles. Their biconcave disc morphology confers elastic properties beneficial for drug encapsulation. Utilizing erythrocyte as carrier can significantly extend drug half-life and address challenges in the in vivo distribution of water-soluble drugs across the blood-brain and bone marrow barriers, presenting numerous advantages in leukemia therapy. At present, there is still a lack of exploration on using intact erythrocyte to deliver chemotherapy drugs for leukemia treatment. Thus we designed an erythrocyte-based drug delivery system using intact and biologically active erythrocytes to encapsulate the chemotherapeutic agent Doxorubicin (E-Dox), with the goal of achieving enhanced therapeutic efficacy and reduced toxicity.
Methods：E-Dox was prepared using a hypotonic-hypertonic method. Characterization and release assays confirmed the successful preparation of E-Dox. Subsequent investigations evaluated the tumor inhibitory capacity, pharmacokinetics, and biodistribution in vivo. We also analyzed the immune environment in the bone marrow and spleen using flow cytometry and IHC staining. Furthermore, the safety profile of the system was validated.
Results：E-Dox preparation preserved the biconcave disc morphology, with minimal differences in cellular protein, notably CD47, compared to normal erythrocyte as determined by Western Blot analysis. Furthermore, the system exhibited high encapsulation efficiency, reaching 80%. E-Dox also demonstrated significant tumor inhibitory effects. Following treatment with E-Dox, there was an increase in early apoptotic cells among tumor cells and elevated production of reactive oxygen species within the tumor cells compared with free Dox. Importantly, E-Dox markedly prolonged drug half-life, achieving a four-fold extension compared to free drug formulations. Leukemia mice treated with E-Dox showed attenuated tumor progression and prolonged survival period. Interestingly, by analyzing the immune environment in the bone marrow and spleen, we observed an increase in activated T cells and cytotoxic T cells in mice treated with E-Dox. And Hepatic and renal function tests, along with histopathological analysis, indicated favorable biocompatibility of E-Dox and alleviated doxorubicin-induced cardiac toxicity.
Conclusion：This study elucidates an optimal strategy for preparing E-Dox, successfully creating an intact and functional erythrocyte-based delivery platform. The system significantly extends drug action duration, effectively suppresses leukemia in mouse models, and demonstrates biocompatibility, thereby mitigating chemotherapy-induced organ toxicity.