bluuebunny/crossref_metadata_2025 huggingface dataset:
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>75 5 points, ADL>4 3 points, PLT<100×109/L 4 points, elevated CRP 3 points, CPC≥0.105% 2 points). And for PFS risk model, age>75, CCI ≥2, β2≥3.5mg/L, PLT<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.
Identification of Metabolic Biomarkers Associated with the Efficacy of Intravenous Immunoglobulin in the Treatment of Immune Thrombocytopenia Based on Machine Learning
Authors: Li Yang , Jia Chen , Sun Ting , Chen Yunfei , Zhang Lei
Published: December 2024

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder characterized by isolated thrombocytopenia, resulting from the breakdown of immune tolerance. Intravenous immunoglobulin (IVIG) is one of the first-line treatment strategies for ITP patients. Given that no studies have investigated the differences in response to IVIG treatment in ITP patients from a plasma metabolomics perspective, this prospective study aims to evaluate the efficacy of IVIG 5% in patients with persistent and chronic ITP from the National Longitudinal Cohort of Hematological Diseases. It also compares the plasma metabolic profiles of patients in the responsive and unresponsive IVIG treatment groups and uses machine learning algorithms to identify metabolic biomarkers that can effectively distinguish the efficacy of IVIG treatment. A total of 37 ITP patients (75.7% female, median age 36 years) were enrolled. Intent-to-treat analysis indicated that 32 out of 37 patients (86.5%) achieved a response, with a median time to response of 3 days and a median response duration of 9.5 days. From the plasma samples of 37 ITP patients, we quantified a total of 2,701 metabolites, including 1,280 metabolites in the positive mode and 1,421 metabolites in the negative mode. Metabolic patterns varied significantly between groups of responsive and unresponsive, with 35 metabolites upregulated and 173 metabolites downregulated in the IVIG-unresponsive group. 9-[(3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one was significantly upregulated in the IVIG-unresponsive group, while 3,4-Dihydroxymandelic acid, 2-Thiouracil, Gulose, Carnitine C6:1, and others were significantly downregulated. Enrichment factors and P-values revealed the top metabolically enriched pathways to be purine metabolism, arginine biosynthesis, the mTOR signaling pathway, ether lipid metabolism. In summary, this study revealed the metabolic pathways in plasma associated with differences in IVIG efficacy and identified potential metabolic biomarkers distinguishing IVIG response.
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.
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 <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.
Polycythemia Vera in Patients Aged > 80 Years: Real-Life Experience of the NPM Ph Negative Latial Group
Authors: Tatarelli Caterina , Breccia Massimo , Santopietro Michelina , Paciaroni Katia , Di Veroli Ambra , Maurillo Luca , Romano Atelda , Andriani Alessandro , Tafuri Agostino , Latagliata Roberto
Published: December 2024

Background: Increasing life expectancy has lead to a progressive increment in the proportion of patients (pts) with myeloproliferative neoplasms (MPN) aged ≥ 80 years at diagnosis. However, so far, few studies have evaluated very elderly pts with polycythemia vera (PV) Aim: To describe the clinical features and the course of disease in a real-life cohort of PV pts aged ≥80 years Methods: From 1/2000 to 12/2023, 100 consecutive pts aged ≥ 80 years were diagnosed in 7 hematologic Centres and enrolled in the retrospective and prospective databases of the Latial group for Ph-negative MPN. Diagnosis was revised according to WHO 2022 criteria. Results: Main features at diagnosis were as follows: M/F 42/58, median age 83.1 years [interquartile range (IQR) 81.3 - 85.9], median Hb value 17.5 g/dl (IQR 16.0 - 18.5), median Ht 53.7% (IQR 50.5 - 57.9), median WBC count 10.2 x 109/l (IQR 8.7 - 13.5), median PLT count 520 x 109/l (IQR 370 - 690).Marrow biopsy was performed in 13/89 evaluable cases (14.5%), median JAK2 V617F allele burden was 40% (IQR 17.8-66.2). Symptoms at diagnosis were present in 18/86 evaluable pts (20.9%), with pruritus accounting for 50% of cases (9/18). Arterial hypertension, diabetes, dyslipidemia and smoke attitude were present in 69.7%, 13.1%, 32.0% and 23.1% of pts, respectively. Previous thrombotic events were reported in 28/90 evaluable pts (38.1%). Hydroxyurea (HU) was started in 96/100 pts, after a median time of 1 month (IQR 0.1 - 3.8) from diagnosis. HU was discontinued in 20/96 pts (20.8%), mostly due to intolerance (12/20). Only 3/20 pts (15%) received Ruxolitinib as 2nd line, while no other drug was used in 11/20 pts (55%). Thrombotic events during follow up were reported in 10/86 evaluable pts (11.6%), while evolution in fibrotic and blastic phase was observed in 2 cases. At the last follow up, 18 pts died, 40 were lost to FU and 42 were still alive: 60-month and 120-month cumulative overall survival were 82.2% (95%CI 92.6 - 71.8) and 52.3% (95%CI 73.9 - 30.7), respectively Conclusion: Our data in a relatively large real-life cohort of very elderly PV pts highlight some points of the current clinical practice: as expected, few pts underwent marrow biopsy at diagnosis and quite all pts received HU as frontline cytoreductive therapy at a short interval after diagnosis. However, responsible physicians were still reluctant after HU discontinuation in prescribing 2nd line treatment with ruxolitinib in this setting. The high number of cases lost to follow-up, probably due to difficulties in reaching hematologic Center by these aged pts, made difficult a correct evaluation of OS curve, which however was similar to that of general population in the same age group
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 < 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<0.01), whereas gastrointestinal involved had poorer survival(p<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.
The Role of Emicizumab in Patients with Acquired Hemophilia A
Authors: Su Malcolm , Yates Sean , Sanchez Melissa , Shen Yu-Min
Published: December 2024

Acquired hemophilia A (AHA) is a bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Emicizumab is a FVIII mimetic antibody used in the treatment of inherited hemophilia A that could potentially be used in AHA to achieve hemostasis and shorten hospital stay while reducing bypass therapies. We report on 12 cases of AHA patients treated with emicizumab in an academic center between January 2020 and June 2024. There were 5 male and 7 female patients, with median (interquartile range [IQR]) age and maximum inhibitor titer of 73 (60-76) years and 138 (36.75 -164.25) BU/mL, respectively. Patients had an initial FVIII activity level of <10 and <1 on chromogenic and blood clot-based assays, respectively. Ten patients were started on emicizumab while admitted inpatient, while 2 were started outpatient. The initial emicizumab dose was 3 mg/kg for 8 patients and 1.5 mg/kg for 4 patients; all patients then continued therapy with emicizumab 1.5 mg/kg every other week starting on day 8 and received immunosuppression with steroids and rituximab. Patients received a median (IQR) of 5 (2-6.5) emicizumab injections. FVIII activity recovered past 20% and 50% after a median (IQR) of 28 (13-64.5) and 52 (13-170) days after emicizumab initiation, respectively. Patients who began emicizumab therapy inpatient required a median (IQR) of 8 (6-9) days of bypass therapy and stopped bypass therapy 4 (1.75-6.25) days after emicizumab initiation. Furthermore, these patients were hospitalized for a median (IQR) of 10 (6.5-18.75) days and discharged 3 (2-6) days after starting emicizumab. One patient developed deep vein thrombosis and acute pulmonary thromboembolism while on emicizumab and was subsequently treated with anticoagulation. Three other patients died but unrelated to thromboembolism or bleeding complications. In conclusion, emicizumab appears to be an effective treatment in attaining hemostasis and reducing need of bypass therapy in patients with AHA. Emicizumab use in AHA may warrant monitoring for thromboembolic complications, and further study is needed to determine whether immunosuppression can be avoided.