bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial (Non-Clostridium Difficile) and Parasitic Stool Studies Have Limited Utility in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Nagy Matthew , Wychera Chiara , Schemm Jeffrey , Brewster Ryan , Duncan Christine 
Published: December 2024

Background: Diarrhea is a common complication among pediatric hematopoietic stem cell transplantation (HCT) recipients. Although the majority of cases are secondary to graft versus host disease (GVHD), stool microbiological studies are often performed to evaluate an underlying infectious etiology. The aim of this study was to assess the frequency and utility of stool studies in children who have undergone HCT.
Methods: Demographics, clinical characteristics, and results for bacterial (Shigella, Salmonella enterica, Yersinia enterocolitica, Enterohemorrhagic Escherichia coli (SSYCE), and Clostridium Difficile), viral (Rotavirus, Cytomegalovirus, Norovirus, and Adenovirus), and parasitic (ova & parasite examination, of all patients who underwent HCT at a large, academic, freestanding children's hospital and affiliate cancer center and were admitted to the hospital for more than one day between Jan 2006 and Dec 2023 were obtained. Statistical analysis conducted included t-tests, chi-square and linear regression.
Findings: Overall, 1381 HCT recipients (9.2 ± 6.6 years) were included. Altogether, 6509 stool studies were obtained among 741 (54%) patients. Those with stool studies sent were more likely to have undergone an allogeneic transplant (63% vs 72%, p&lt;0.001). Of those with allogeneic transplant, those with stool studies sent had higher incidence of GVHD, both acute (27% vs 17%, p=0.001) and chronic (23% vs. 11%, p&lt;0.001). SSYCE studies were sent on 363 (26%, 2252 studies) patients with one (0.04%) positive result for Yersinia enterocolitica. Clostridium Difficile was sent on 706 (51%, 2055 studies) patients, with 156 positive results (7.6%). Stool ova and parasite was sent on 143 (10%, 242 studies) patients, with two positive results of Giardia lamblia (0.8%), however, in both instances the studies prior to HCT showed positivity for the same parasite . Viral studies were sent on 638 (46%, 1960 studies) patients, with 107 positive studies (5.5%) Over the years, there was a significant increase in studies sent for yersinia (p = 0.013) and adenovirus (p=0.007), and decrease for rotavirus (p=0.011) and clostridium difficile (p&lt;0.001).
Interpretation: We identified a negligible rate of positivity for SSYCE and parasitic stool studies, despite the use of these tests in more than a quarter of all HCT patients admitted in the prior 8 years. Given the overall low diagnostic value, we argue that routine use of these studies in post-HCT pediatrics patients should be avoided, barring specific clinical circumstances, which would also serve to avoid unnecessary testing costs.
The Disparity of Circulating Immune Cell Subsets and Inflammatory Status between HIV-Positive and HIV-Negative Patients with Lymphoma
Authors: Xiao Qing , Quan Xi , Chen Shuang , Wang Chaoyu , Jun Li , Zhang Xiaomei , Yang Zailin , Liu Yao 
Published: December 2024

Background:
Differences in circulating immune cell subsets and inflammatory status, and their impact on prognosis in HIV+ lymphoma patients compared to HIV-negative lymphoma patients are not fully understood.
Aims:
We analyzed the expression of circulating immune cell subsets and inflammatory status in newly diagnosed HIV+ lymphoma patients and HIV- lymphoma patients in our department, and we also analyzed the influence of circulating immune cell subsets and inflammatory status on the prognosis of lymphoma.
Methods:
The study subjects enrolled 99 patients with newly diagnosed lymphoma from July 2022 to December 2023 at the Department of Hematology-Oncology of Chongqing University Cancer Hospital, including 33 patients with HIV+ lymphoma and 66 patients with HIV- lymphoma matched by sex and age. The clinical information of these patients was collected, and the peripheral blood lymphocyte subsets, expression of granzyme, perforin and inflammatory status were detected at the time of new diagnosis. Meanwhile, the curative effect and survival of the patients were followed up. Then, the differences of lymphocyte subsets and other indicators between the two groups were analyzed, and the relationship between the lymphocyte subsets and the complete response (CR) rate after four courses of chemotherapy was analyzed, and the relationship between the lymphocyte subsets and other clinical characteristics of patients was analyzed.
Results:
There were no significant differences in gender, age, or bone marrow invasion at initial diagnosis between HIV+ lymphoma patients and HIV- lymphoma patients. The CR rate of HIV+ lymphoma patients after 4 courses of chemotherapy was lower than that of HIV- lymphoma patients. In terms of lymphocyte subsets, compared with HIV- lymphoma group, the total number of lymphocytes, the proportions and counts of CD4+ T lymphocytes, and the CD4/CD8 ratio in HIV+ lymphoma group were lower；the proportions and counts of CD8+ T lymphocytes were higher in HIV+ lymphoma. HIV+ lymphoma patients had lower NK cell counts, lower double-negative T (DNT) lymphocyte counts, and lower Treg cell counts. With regard to inflammatory factors, the expressions of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) were higher in HIV-positive lymphoma patients than in HIV-negative lymphoma patients.
Conclusion:
In summary, our study showed that compared to HIV- lymphoma patients, HIV+ lymphoma patients had lower CR rates after four courses of chemotherapy, and their counts of CD4+ T lymphocytes, NK cells, DNT cells and Treg cells in peripheral blood were all decreased to varying degrees, and CD4/CD8 ratios were also lower, but CD8+ T lymphocyte counts increased significantly. In addition, HIV+ lymphoma patients had elevated levels of some inflammatory factors, suggesting a higher inflammatory status in vivo.
Efficacy and Safety of Carfilzomib-Based Regiments for the Treatment of Relapsed or Refractory Multiple Myeloma: Single-Center Real-Word Data
Authors: Zhao Weiwei , Liu Juan , Chen Liyan , Wang Lianjie , Xue Yanming , Tian Yaoyao , Liu Yao , Dong Xiushuai , Chang Yuying , Chen Xi , Yu Liqian , Zhang Xiaomin , Jin Yinglan , Song Yan , Han Biqing , Yao Dandan , Wang Wei 
Published: December 2024

Introduction:
Carfilzomib has been approved for the treatment of relapsed or refractory multiple myeloma (RRMM) in China1 and become a new trend for the treatment of RRMM in clinical practice. In this study, we retrospectively analyzed the clinical data of 60 RRMM patients in real world to investigate the clinical efficacy and safety of carfilzomib-based therapies, with a view to further optimizing the treatment of RRMM.
Methods:
we retrospectively collected and analyzed clinical data of 60 RRMM patients treated with carfilzomib based chemotherapy regimens in the Hematology Department of the Second Affiliated Hospital of Harbin Medical University from January 2023 to June 2024. The efficacy was evaluated at the end of each cycle of treatment, and the adverse effects were recorded in detail during the treatment process. The primary endpoint is Overall Response Rate (ORR), while the secondary endpoints are Overall Survival (OS) and Progress Free Survival (PFS) according to 2016 IMWG criteria.
Results:
Sixty RRMM were available for efficacy and safety assessment. Carfilzomib based therapies includes KRd (carfilzomib, lenalidomide and dexamethasone; 8 cases), KCd (carfilzomib, cyclophosphamide, and dexamethasone; 10 cases), DKd (carfilzomib, daratumumab, and dexamethasone; 8 cases), KPd(carfilzomib, pomalidomide, and dexamethasone; 8 cases), KBd (carfilzomib, bendamustine, cyclophosphamide, and dexamethasone; 4 cases), KDD(carfilzomib, dexamethasone and liposomal doxorubicin; 4 cases) and Kd (carfilzomib and dexamethasone; 20 cases). The median number of cycles was 4 (2-9). The ORR was 83.3%(50/60) of which 6 (10.0%) complete response (CR) in 6 cases, 10 (16.7%) very good partial response (VGPR) , and 34 (56.7%) partial response (PR). Patients of older than 60 years old, R-ISS stage III, high-risk cytogenetic abnormalities, and previous ≥3 lines of therapy account for 60%, 73.3%, 63.3%, and 26.7% respectively. The ORR was significantly lower in patients who previously had received third-line and higher treatment (50%) than in those who had received first- and second-line treatment(95.5%, p＜0.05). Median PFS was 8 months and the data of OS was unmature. The most common hematological and non-hematological adverse effects were thrombocytopenia (50.0%) and upper respiratory tract infection (30%) respectively which were resolved or relieved in vast majority of patients after symptomatic treatment without affecting the course of treatment.
Conclusion:
The efficacy of carfilzomib-based regimens in RRMM is promising and adverse effects are manageable.
References：
1.Carfilzomib (Kyprolis®) label.
A Systematic Review of Barriers and Enablers to Reproductive Care for Women with Cancer Identified Data Gaps in Best Practice
Authors: Sanil Parammal Shilpa , Anazodo Antoinette , Chadwick Verity , Rodgers Rachael , Dear Rachel , Hamad Nada 
Published: December 2024

Background: Holistic care is becoming increasingly a priority in cancer treatment, including blood cancers, especially for women of reproductive potential (defined as women aged 15-49 years) who deal withunique challenges and circumstances. These challenges include fertility, sexual health, contraceptive counselling and use, and menstrual health. This is especially important in blood cancers because of their incidence during reproductive years.
Objective: This systematic review aimed to explore the barriers and enablers of healthcare providers taking thorough reproductive histories of women with reproductive potential.
Methods: Fifteen studies were included in this review, after searching PubMed, Embase, and CINAHL from 02 April 2024 to April 18, 2024, resulting in 565 articles. Searches were refined to include clinicians treating women with reproductive potential for cancer.
Results: Most studies focused on fertility history taking and counselling, and one study examined contraception in this population. The key barriers were categorized ashealthcare provider-related, patient-related, clinical/medical, organizational and accessibility-related. The most common barrier identified was healthcare providers' lack of knowledge around reproductive health in the context of cancer care, followed by consultation time limitations. The majority of the barriers can be traced back to personal beliefs and assumptions made by the healthcare provider regarding patient demographics and characteristics. Of the 15 studies, only three discussed enablers aiding clinicians in obtaining reproductive histories, including onsite obstetrics and gynecology services and standardized referral processes.
Conclusion: This review highlights an urgent need for the education of healthcare providers working in cancer care with patients of reproductive potential to ensure that reproductive health is not surpassed by the current cancer diagnosis. There is also a need for tangible guidelines regarding reproductive care for cancer patients, and for reproductive history and counselling to be mandatory in cancer care and ensure equitable access to holistic cancer care. Furthermore, there has to be increased research to understand the enablers to clinicians who are able to obtain thorough reproductive histories, which can form the basis for effective interventions to be put into place.
Predictive Model for Infection Risk in CAR-T Therapy Patients
Authors: An Ning , Li Chunrui , Luo Hui , Wang Xinran , Wang Di , Zhang Peiling , Mu Wei , Yu Qiuxia , Bao Yuhan , Gao Yang 
Published: December 2024

Background:
Chimeric antigen receptor T-cell (CAR-T) therapy is a powerful treatment for hematologic malignancies, but it often leads to serious infections, a major cause of non-relapse mortality. These infections typically occur within the first 30 days post-therapy, a period also characterized by cytokine release syndrome (CRS). Early fever after CAR-T therapy can indicate either an infection or CRS, complicating diagnosis, especially in neutropenic patients. A predictive model is needed to accurately identify infections for prompt and effective management.
Methods:
This multicenter retrospective study involved three phases: model development, internal validation, and external validation. The internal cohort included 443 patients treated with CAR-T therapy at Tongji Hospital, Huazhong University of Science and Technology, from June 2016 to December 2023. The study excluded patients with pre-existing infections, fever unrelated to CRS or infection, incomplete data, or no fever within 30 days post-CAR-T therapy. An external validation cohort of 30 patients was recruited from three hospitals. Febrile events (temperature &gt;38°C) within 30 days post-infusion were recorded, with daily assessments of blood counts and inflammation markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and ferritin. Febrile episodes were classified as infection or CRS. A multivariate logistic regression model identified independent predictors of infection and established a scoring system.
Results:
Among the 443 patients, 514 febrile episodes were recorded, with 86% occurring during the first episode. Infections accounted for 21% of initial episodes, often co-occurring with CRS. The predictive model for infection during the first febrile episode included factors like pre-fever neutropenia (N), ferritin change (FCV) on the second day of fever, lymphocyte count (L), platelet count (Plt), IL-6 level, and CRP level. The model achieved an area under the curve (AUC) of 0.9, with 87% sensitivity and 81% specificity in the training set. The external validation cohort showed an AUC of 0.93, with sensitivity and specificity of 75% and 84%, respectively. The Hosmer-Lemeshow test confirmed a good model fit (P = 0.950), and decision curve analysis indicated a significant net benefit.
Conclusion:
This study developed and validated a robust risk assessment model for predicting infections within 30 days post-CAR-T therapy. The model, based on routine blood tests and febrile episodes, is practical for clinical use and offers high accuracy across different patient cohorts.
Clinical Analysis of CAR-T Cell Therapy in Patients with Acute B-Lymphoblastic Leukemia and Central Nervous System Infiltration
Authors: Yan Hong , Li Biyi , Zheng Ruyue , Lin Yuehui , Deng Biping , Tong Chunrong , Wu Tong , Zhao Defeng 
Published: December 2024

Background: Acute B-lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) has traditionally been treated with whole-brain and spinal radiotherapy, combined with intrathecal chemotherapy, systemic chemotherapeutic drugs, and allogeneic hematopoietic stem cell transplantation for long-term survival. There are few reports of clinical cure and long-term survival in patients treated primarily with CAR-T therapy.
Objective: To observe the efficacy of CAR-T therapy in patients with B-ALL and CNSL.Methods and Results:A retrospective analysis was conducted on four cases of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL) with CNSL treated with CAR-T cell therapy at Beijing Boren Hospital from April 2018 to June 2023. Three patients were adult males, and one was a 6-year-old female, with a median age of 33.5 years (range: 6-48 years). Case 1 and 3 had PH+ B-ALL, case 2 had MEF2D-BCL9 fusion gene, and all three relapsed post-transplant. Case 4 relapsed during chemotherapy. Case 1 and 4 had isolated CNSL relapse (50%), case 3 had minimal residual disease (MRD) in bone marrow, and case 2 had hematologic relapse with bone marrow involvement and bilateral kidney and pancreatic infiltration. The clinical outcomes of single and sequential two-course CAR-T cell therapy were observed. The median follow-up for the four patients was 26 months (range: 18-64 months), with all achieving complete remission and a median remission duration of 25 months (range: 17-62 months). The overall survival rate at the end of follow-up was 100% (4/4). Case 1 had a sustained molecular remission for 62 months, case 2 for 21 months, case 3 for 32 months, and case 4 for 18 months. Case 1 experienced reversible ICANS, and the other three had CRS grades 0-1. The event-free survival (EFS) was greater than 18 months (100%), with one case reaching clinical cure criteria. The overall survival rate (OS) was 100%.
Conclusion:CAR-T cell therapy can be considered a primary treatment method for patients with B-ALL and CNSL. In this group of four patients, sustained remission was achieved without cranial radiotherapy or allogeneic hematopoietic stem cell transplantation, thus avoiding radiotherapy-related neurological damage, bone marrow suppression, and graft-versus-host disease (GVHD), improving overall patient quality of life.
CMV-Specific TCR-T Cells for the Treatment of CMV Reactivation after Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Tang Jingwen , Dou Liping , Liu Daihong 
Published: December 2024

Cytomegalovirus (CMV) reactivation remains the leading cause of death after haploidentical stem cell transplantation (HSCT). Current therapies, including antiviral drugs and relay cell therapy using CMV-specific cytotoxic T lymphocytes (CTLs), have shown only limited benefit to patients, and T-cell receptor (TCR)-T-cell therapy offers a promising option for the treatment of CMV reactivation.
To evaluate the efficacy and safety of CMV-targeted T-cell receptor-engineered T (CMV-TCR-T) cell therapy as a first-line pre-emptive therapy ,we conducted a single-arm, open-label, phase I clinical trial for patients with CMV reactivation after HSCT. Ten patients with CMV reactivation after HSCT were adoptively transferred by one to three doses of HSCT donors-derived CMV-TCR-T cells. Meanwhile, 2 patients who had failed standard antiviral drugs used CMV-TCR-T cells as second-line therapy.
Eight of the first-line treatment patients responded within one month after infusion of CMV-TCR-T cells without administration of any antiviral drugs; the other two patients who initially did not respond to CMV-TCR-T cell therapy were given salvage ganciclovir and phosphonate, followed by rapid clearance of CMV. Second-line treatment patients were controlled with TCR-T cells after 2 weeks of ineffective use of antiviral drugs. CMV-TCR-T cells demonstrated overall robust expansion and persistence in peripheral blood after infusion. CMV-TCR-T cells were first detected in the peripheral blood of these patients 3-7 days after the initial CMV-TCR-T infusion, expanded rapidly and persisted for at least 1-4 months, providing long-term protection against CMV reactivation. In 2 patients, CMV-TCR-T cells began to expand even while anti-graft-versus-host disease reagents were still in use, further demonstrating the proliferative potential of CMV-TCR-T cells. No adverse events were observed except for grade 1 cytokine release syndrome in one patient and mild fever in two patients.
Median follow-up was 318 days. Six patients survived for more than 1 year and 2 patients died (2 in the first-line treatment group and 1 in the second-line treatment group).This study demonstrates the great potential of CMV infection after HSCT or other organ transplantation in terms of treatment and prevention.
Prognosis Prediction By Two Single Factors Could Predict the Survival of PCNSL Patients Received HD-MTX Therapy without HSCT
Authors: Renjie Bian , Qu Yi , Wu Danyang , Yu Jinxiang , Wang Xiaoxue , Wang Lei , He Juan , Wang Jun , Yan Xiaojing 
Published: December 2024

Objective：Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal non-Hodgkin lymphoma and and there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL) except for the high-dose methotrexate (HD-MTX). Post-remission consolidation with autologous hematopoietic stem cell transplantation (auto-HSCT) was associated with the best survival outcome. However, not all the patients are available for auto-HSCT and PCNSL displays a wide variability in outcome. This study aimed to identify prognostic factors among individuals with PCNSL undergoing HD-MTX-based regimens without auto-HSCT.
Methods: This retrospective, single-center study included 93 patients diagnosed with PCNSL who underwent HD-MTX-based chemotherapy. Treatment options include: R-MT, R-M, R2-M or RMZ (R rituximab, M methotrexate, T temozolomide, R2 rituximab and lenalidomide, Z zanubrutinib). The dosage of HD-MTX was standardized at 3.5g/m2 (adjusted according to the patient's physical condition) and administered every 2-3 weeks per cycle. We collected the patients' clinical characteristics, imaging data, pathology data, treatment plan and follow-up data. Statistical analyses were conducted to identify independent predictors influencing PCNSL prognosis and to establish a prognostic scoring system.
Results: Univariate prognostic analysis of OS showed that male, KPS &lt;70 or ECOG &gt;1, deep brain tissue involvement, GCB phenotype, CD10-positive and Bcl-6-negative were poor prognostic factors for PCNSL. Besides, univariate prognostic analysis of PFS exhibited that males, KPS &lt;70 or ECOG &gt;1 and deep brain tissue involvement have a greater risk of disease progression. Cox multifactorial analysis identified shorter OS in males and Bcl-6-negative cases and shorter PFS in males. Consequently, male gender and Bcl-6 negativity were included in the predictive scoring system, each assigned a value of 1. The median OS was 10 months, 33 months, and not reached (NR) for low-risk, medium-risk and high-risk groups.
Conclusion: Gender disparity was observed in the prognosis of PCNSL patients who received HD-MTX, with males exhibiting worse outcomes in both OS and PFS compared to females. Bcl-6 negativity also correlated with shorter OS. When females with no BCL-6 expression, it generally predicts a worse prognosis.