bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological Analysis and Overall Survival of Leukemia in Adults in a Developing Middle Eastern Country over 18 Years
Authors: Abdulelah Ahmed A , Abdulelah Zaid A , Saadeh Aseel , Al Ta'ani Omar , AlQirem Lina , Alhajahjeh Abdulrahman , Abdel-Razeq Hikmat , Haddadin Michael 
Published: December 2024

Introduction: Leukemia in adults imposes significant global health burden not only due to the presenting clinical characteristics, but also due to the resultant morbidity and mortality. Therefore, the identification of the epidemiological features, including the overall survival and crude incidence, in developing middle eastern countries such as Jordan is of paramount importance and significance in the risk stratification and introduction of effective measures.
Methods: Thorough data on a cohort of 4146 adult individuals of different nationalities residing in Jordan who were diagnosed with leukemia during the period of 2000-2018 was retrieved from the Jordan Cancer Registry, the formal cancer epidemiology reporting entity in Jordan. Statistical analysis was performed to establish the epidemiological characteristics of leukemia in adults in Jordan over a period of 18 years.
Results: A total of 4146 adult patients with a mean age of 49.5 ± 18 years old and a male predominance of 59.5% were included in the analysis. A considerable portion, 50.5%, of the study population were non-smokers at the time of diagnosis. Acute myeloid leukemia was the most commonly encountered leukemia as it accounted for 35.2% of all cases, followed by chronic myeloid leukemia in 20.8% of the patients, and subsequently followed by chronic lymphocytic leukemia and acute lymphocytic leukemia that were reported in 17.2% and 15.7% of the patients, respectively. Hairy cell leukemia was identified in 102 (2.5%) of the patients. A statistically significant decline in the crude incidence of adult leukemia over 18 years was evident with a crude incidence estimated effect of -0.048. The overall survival was 88.0%, 84.7%, 84.1%, 83.8%, and 83.4% at 1-year, 2-year, 3-year, 4-year, and 5-year interval, respectively.
Conclusion: Over a span of 18 years, adult leukemia in Jordan demonstrated a relatively young average age at diagnosis and thus mandates thorough vigilance. Interestingly however, Jordan demonstrates a higher 5-year survival rate than the witnessed overall survival rates internationally.
Evaluating Recent Drug Approvals for Hematologic Malignancies Utilizing the New European Society of Medical Oncology Magnitude of Clinical Benefit Scale for Hematology (ESMO-MCBS:H)
Authors: Hirsh Ryan , Moyers Justin , Benjamin David , Pourhassan Hoda 
Published: December 2024

Introduction:
Over the last decade, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have steadily leaned towards granting regulatory approval based on earlier phase trials and surrogate endpoints. Despite obtaining regulatory approval, many countries hold additional standards to assess the value of a new drug approval. The ESMO-MCBS is a tool created to evaluate the values and reduce bias or hype of drug approvals using various metrics: efficacy, quality of life, and duration of response. In 2023, the ESMO-MCBS:H was created for hematological malignancies. We aimed to evaluate recent drug approvals using the new ESMO-MCBS:H criteria for hematologic malignancies.
Methods:
We included all drugs approved for a hematologic malignancy between 2019 and 2024. Drugs were assessed using ESMO-MCBS:H forms 2a, 2b, 2c, or 3 depending on the trial type and primary endpoints leading to drug approval. Approvals were independently scored by two reviewers with a third reviewer to adjudicate scoring differences.
Results:
66 drugs were approved by either FDA or EMA during this time. 88% (n=58) were approved by both EMA and FDA, 12% (n=8) by FDA alone. No drugs were approved by the EMA alone without preceding or subsequent FDA approval. 4 drug approvals were for pediatric indications. 36 approvals (n=35/66, 53 %) were based on early phase 1 and/or 2 trial data. Approvals were for leukemias (n=16; 24%), lymphomas (n=25, 38%), myeloma (n=18, 27%), or CLL/SLL (n=6; 9%). 13% of approvals (n=9/66) were for drugs with a biomarker matched indication.
Substantial benefit criteria were met by 17 of 66 approvals (26%). Substantial benefit criteria were met by 0% (N=0/8) of drug indication by approved by FDA alone versus 29% of drugs approved by both the FDA and EMA (n=17/58), however was not statistically significant (p=0.08).
Approvals based on early phase (phase 1 and/or 2) trials met criteria in 17% (n=6/35) of trials and 36% of later phase (phase 3) trials met criteria (n=11/31) without statistical significance (p=0.09).
No significant difference in approvals meeting substantial benefit were seen for biomarker matched therapies (33%; n=3/9) versus unmatched therapies (25%; n=14/57) (p=0.58).
No therapies approved for a pediatric indication met criteria for substantial benefit (n=0/4).
Conclusion:
Few drugs approved by both agencies met the rigorous ESMO-MCBS:H criteria for substantial benefit. Recent approvals meeting substantial benefit criteria were not statistically correlated with approval agency, phase of trial utilized for approval, or biomarker selection of therapies. Drug approvals must balance proven benefit to access to innovative and new therapies.
CAR-Tscm Cells As an Effective Immune Treatment to Multiple Myeloma Patients
Authors: Zhaoyun Liu , Fu Rong 
Published: December 2024

Objective：
Since T memory stem cell (TSCM) is a kind of cell with strong self-renewal ability, long-term persistence, proliferation ability and anti-tumor activity, and is an ideal candidate cell for cancer immunotherapy. We aimed to explore the amount of TSCM cells in multiplt myeloma（MM） and the established a method to expansion TSCM in vitro, and to further explore the effect of CAR-T cells prepared by TSCM on MM cells.
Methods：
TSCM cells (CD45RA+CCR7+CD62L+CD95+) were detected with Flow cytometry, further induced TSCM cells expansion in vitro by using IL-2+MEKi+Il-15 combination, TSCM cell-based CAR-T cells were constructed in vitro, further the therapeutic effect of CAR-Tscm cells in MM-loaded NSG mouse model were explored.
Results：
The proportion of TSCM cells is reduced in patients with MM, but their function is stronger than that of CTL cells, and the use of IL-2+ Meki+Il-15 in vitro can induce the expansion of TSCM cells and promote their antitumor capacity; Further, Targeting BCMA CAR-Tscm cells as an effective immune treatment to multiple myeloma patients. CAR-T cells were constructed using TSCM cells in vitro, and in vitro experiments confirmed that they had similar killing effects to conventional CAR-T cells on MM cells in an NSG mouse model of MM tumor burden; CAR-Tscm cells were demonstrated to have similar effects to conventional CAR-T therapy, and demonstrated stronger antitumor effects than conventional CAR-T in contralateral tumorigenic models.
Conclusion：
CAR-Tscm cells are a potentially effective treatment for multiple myeloma.
Efficacy of Outpatient Haploidentical Transplantation in Patients with Refractory Hodgkin Lymphoma
Authors: Tejada Vasquez Ana Cristina , Gutierrez-Aguirre César Homero , Ugarte Pelaez Luis Paulo , Vega Mateos Antonio , Lopez-Garcia Yadith Karina , Garcia-Salas Gerardo , Colunga-Pedraza Perla R. Rocio , Gomez-De Leon Andres , Cantu Olga , Jaime-Pérez José Carlos , Gomez-Almaguer David 
Published: December 2024

Background: Hodgkin lymphoma (HL) is a neoplasm potentially curable with first-line chemotherapy. For relapsed or refractory (R/R) patients, rescue chemotherapy and autologous transplant remain the standard. R/R patients face a poor prognosis, and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) offers a potentially curative option.
Methods: A retrospective single-center analysis was performed in adults with R/R HL who underwent haplo-HSCT from 2015 to 2022. Conditioning was based on cyclophosphamide 350 mg/m² plus fludarabine 25 mg/m² for 3 days, followed by either melphalan 140-200 mg/m2 or busulfan 8 mg/m2, GVHD prophylaxis was given with cyclophosphamide 40mg/m2 at day +3 and +4 after infusion of CD34+. The primary outcome was overall survival (OS). Secondary endpoints included engraftment rates, infections, and transplant-related mortality (TRM). Progression-free survival (PFS) and graft-versus-host disease (GVHD) incidence.
Results: 17 patients were included, 52.9% (n=9) female and 47% (n=8) male, with a median age of 27 years (range: 11 to 62). Eight (47%) presented relapse after a previous autologous hematopoietic stem cell transplant (auto-HSCT). The average number of prior lines of treatment was 5 (range, 3-7). Conditioning included melphalan 140 mg/m² in 70% of patients, 200 mg/ m² in 18%, and busulfan 8 mg/m² (11%). The median CD34+x10^6kg infused was 10 million (3 - 16 x10^6). Engraftment of neutrophils and platelets occurred in a median of 14.6 (12-19) and 15 (12-23) days, respectively. The median follow-up was 18 months.
The 4-year OS was 62%, and the median OS was not reached. The 4-year PFS was 42%, with a median PFS of 17 months (95% CI 0-40). The incidence of aGVHD at 100 days was 58%, with the skin being the most frequent organ affected; 42% (n=8), and 18% presented chronic GVHD (cGVHD) during the year of follow-up. Five patients (29%) presented clinically significant infectious complications, including BK virus, cytomegalovirus infection, sepsis due to E. Coli ESBL, and invasive aspergillosis. Four patients relapsed (25%). TRM at 100 days was 23.52% (n=4).
Conclusions: The results highlight the effectiveness of haplo-HSCTin patients with refractory Hodgkin Lymphoma. A high incidence of aGVHD and cGVHD and infectious complications were documented. Haplo-HSCT transplant is a viable option for patients; however, it is essential to prioritize quality of life and minimize the toxicities associated with it. Additional studies are needed to optimize treatment protocols and management of long-term complications.
Public Health Insurance and Cancer-Specific Mortality Risk Among Patients with Lymphoma:a Prospective Cohort Study in Chongqing, Southwest China
Authors: Xiao Chunyan , Zhao Yulan , Ding Yao , Zeng Chensi , Zhang Lingqian , Nan Yingyu , Lei Haike , Liu Yao 
Published: December 2024

Objective: Lymphoma, comprising Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), is one of the common cancers worldwide.Little is known about how health insurance policies and self-paying rate influence lymphoma prognosis. Here, we examined the association between individual health insurance status and lymphoma-specific mortality in China.
Materials and Methods: A prospective longitudinal cohort study was conducted in Chongqing University Cancer Hospital, China from 2015 to 2021.The health insurance plan of patient was classified as either urban resident-based basic medical insurance (URBMI) or urban employee-based basic medical insurance (UEBMI) and was also categorized as self-paying rate (ie, the non-covered/ total charge) below or above the median.lymphoma-specific mortality was the primary outcome.After following the inclusion and exclusion criteria, the chi-square test was used to describe the demographic and clinical characteristics of patients with different insurance types and different self-paying rates. Multivariate logistic regression was used to analyze the relationship between patients with different insurance types, self-paying rates, and lymphoma treatment methods. Finally, the Cox proportional hazard model and the competitive risk model are used to calculate the cumulative hazard ratio of all-cause death and lymphoma-specific death for different insurance types and different self-paying rate groups.
Results:After following the inclusion and exclusion criteria, we included 2947 patients first diagnosed with lymphoma.We found that no matter patients received URBMI or UEBMI, they all more received treatment at the lymphoma later stage. After adjusting for clinical features and lymphoma treatment, compared with patients with insufficient self-paying rate, patients with a higher self-paying rate had a 54% lower risk of lymphoma-specific death (HRs = 0.460, 95%CI: 0.358-0.593, P &lt; 0.001). Every 10% increase in self-paying rate of URBMI reduces the risk of lymphoma-specific death by 19.7%, while every 10% increase in self-paying rate of UEBMI reduces the risk of lymphoma-specific death by 30.2%.
Conclusions: Underinsured and poor patients face a higher risk of lymphoma-specific mortality in china.The National Medical Security Administration should, under the condition of limited medical insurance funds, try to include the original self-paid innovative anti-tumor drugs and Outpatient examinations into the national medical insurance coverage, at the same time, address the high cost of new anticancer medicines is urgent.This can not only reduce the mortality rate of lymphoma patients, but also reduce the family burden of lymphoma patients.
SHMT2-Folate-Folate Receptor Axis Impaired Erythropoiesis in Myelodysplastic Syndrome
Authors: Yang Chaoying , Li Haobo , Wang Yanpeng , Nie Ling , Wang Zeyuan , Guo Zhiming , Han Xu , An Xiuli , Liu Jing , Zhang Ji 
Published: December 2024

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal bone marrow diseases with a high risk of progressing to acute myeloid leukemia. Current therapies for MDS patients include bone marrow transplantation and hypomethylation chemotherapy, however, since MDS is very common in elderly people, many patients cannot tolerate transplantation related complications or acquire drug resistance, making it urgent to develop novel therapy. Abnormal metabolic regulation had been reported to be involved the pathogenesis of many diseases including MDS, but the underlying mechanisms are not fully characterized.
To explore underlying mechanisms and develop novel therapy to treat MDS, we utilized NUP98-HOXD13 knock-in mice which was a well-known MDS mouse model. We purified bone marrow lineage negative cells from MDS and control mice and performed RNA sequencing. After data processing, we found SHMT2 was dramatically up regulated in MDS mice. SHMT2 involved the one-carbon unit cycling and regulated the contents of glycine, serine and folate. Followed metabolomic profiling showed that, only folate, but not glycine and serine, was significantly increased in MDS mice. Furthermore, SHMT2 expression and folate were also significantly increased in MDS patients compared to the healthy cases. These findings indicated that increased SHMT2 expression and overloaded folate may involve MDS pathogenesis. Indeed, high folate diet or folate intraperitoneal injection decreased red blood cell (RBC) number and hemoglobin content, inhibited bone marrow erythropoiesis and shortened the survival of wild mice. And folate intraperitoneal injection into the MDS mice exacerbated anemia symptom. More importantly, using the CRISPR/Cas9 technique and bone marrow transplantation assay, we found that knock-out SHMT2 in MDS mice decreased folate content and alleviated MDS phenotypes. Through a series of assays, we further found that high dose of folate binds to folate receptor 2 (FOLR2) and leads its translocation from membrane to nucleus where FOLR2 regulated gene expression as a transcription factor. FOLR2 up-regulated IRF2 and IRF2BP2 expression levels and inhibited normal erythropoiesis.
Taken together, our findings demonstrated that SHMT2-folate-folate receptor axis inhibited erythropoiesis in MDS, and targeting SHMT2 had therapeutic effectiveness for MDS treatment. Our findings also provided more comprehensive understanding on the relationship between folate and erythropoiesis.
Post-COVID-19 Infant with a Hemizygous PRF1 Mutation and Overlapping Features between MIS-C and Hemophagocytic Lymphohistiocytosis
Authors: Janssen Jesslyn , Nwachukwu Chiamaka , Falcon Corey Paul 
Published: December 2024

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disorder that requires a high index of suspicion and comprehensive evaluation for timely recognition. Its rarity, diverse clinical manifestations, and overlapping symptoms with other hyperinflammatory syndromes, such as the recently emerged Multisystem Inflammatory Syndrome in Children (MIS-C) during the COVID-19 pandemic, present unique diagnostic challenges.
Herein, we report the case of an 8-month-old infant initially suspected of MIS-C following acute liver failure after COVID-19 exposure. The diagnosis was later revised to secondary HLH with an atypical presentation. Despite initial management for MIS-C, the patient's condition deteriorated, prompting further investigation. Laboratory findings, including elevated ferritin levels, low fibrinogen, and worsening thrombocytopenia, suggested HLH, leading to targeted diagnostic evaluations. Genetic testing revealed a heterozygous PRF1 mutation, and additional laboratory investigations showed markedly elevated IL-2 receptor and CXCL9, with decreased CD107a and perforin expression in NK cells. The patient met four out of five diagnostic criteria for HLH. Treatment with intravenous immunoglobulin (IVIG) and high-dose steroids resulted in significant clinical improvement, and the patient has remained symptom-free since the episode.
This case highlights the diagnostic challenges in differentiating hyperinflammatory syndromes in pediatric patients with COVID-19 exposure. It underscores the importance of considering HLH in the differential diagnosis, even when standard HLH diagnostic criteria are not fully met at presentation and when standard treatments fail in patients suspected of having MIS-C. Given the frequent occurrence of atypical HLH presentations, early evaluation for HLH is crucial in children with hyperinflammation, such as MIS-C, especially when patients exhibit hyperferritinemia, hypofibrinogenemia, cytopenia, acute liver failure or are unresponsive to MIS-C treatment. Thorough assessment and careful consideration are essential to prevent misdiagnosis or delayed recognition of HLH, a condition that can result in severe outcomes, including death. Multidisciplinary collaboration is vital to optimize HLH diagnostic strategies and improve patient outcomes. Further research is needed to elucidate the clinical relevance of heterozygous mutations of HLH-associated genes in HLH and MIS-C.
Impact of Sglt-2 Inhibitors on Sickle Cell Disease Patients with Type 2 Diabetes: A Retrospective Matched Cohort Study
Authors: Nawab Athar , Ivers Lauren , Rizwan Umer , Shafique Nouman 
Published: December 2024

Introduction: Sickle cell disease (SCD) is associated with an increased risk of chronic kidney disease (CKD), with 12% of patients developing CKD by a median age of 37 years in one large 40 year longitudinal study. Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated reno-protective benefits in type 2 diabetes mellitus (T2DM) and CKD, but their efficacy in SCD nephropathy is not well studied. A retrospective analysis of 7 SCD patients with T2DM found observed treatment with GLP-1 agonists or SGLT-2 inhibitors improved estimated glomerular filtration rate (eGFR) slope, but increased the rate of vaso-occlusive pain episodes (VOEs). Additionally, a large placebo-controlled study showed that empagliflozin increased hemoglobin (Hgb) levels in patients with T2DM, but no SCD. In the previous study, serum erythropoietin (EPO) levels were found to be inappropriately normal or increased in all 27 patients with EPO tested, with a median of 10.3 mIU/mL (6.1-37.3 mIU/mL)
Methods: Using a large federated network database, we identified 75 patients with SCD and T2DM. Less than 20 patients had CKD. For our control group, we had 2,366 patients with SCD and T2DM, who were not on SGLT2 inhibitor therapy. There were 1,754 patients with CKD in this group. In this retrospective study, we matched 65 patient in SGLT2 cohort to 65 control group patients based on sex assigned at birth, age and co-morbidities including stage of CKD (if present), hypertension, obstructive lung disease and heart failure.
Results: We did not observe statistically significant differences in the risk of progression or development of CKD. Similarly, we observed no significant difference in proteinuria, A1c and microalbuminuria between the two groups when comparing mean lab-values on student t-test. However, patients on SGLT-2 inhibitors had significantly higher mean Hgb levels (12.459 g/dL) compared to controls (10.358 g/dL; p&lt;0.0001).
Discussion: Putative mechanisms for this erythrocytosis include increased erythropoietin production, modulation of iron metabolism, and hemoconcentration. The inappropriately normal or increased EPO levels observed in previous study support the role of EPO in the erythrocytosis associated with SGLT-2 inhibitor therapy. The observed increase in Hgb levels in SCD patients with T2DM treated with SGLT-2 inhibitors could potentially increase the risk of VOEs, as seen in a previous small study. Further research is needed to elucidate the risks and benefits of SGLT-2 inhibitor therapy on SCD-related nephropathy.
Evaluating Daratumumab Effectiveness in Relapsed/Refractory Multiple Myeloma: A Meta-Analysis of Clinical Outcomes and Prognostic Indicators
Authors: Shah Vedant , Fernandes Bolivia Crocete Aloysia , Ali Muhammad Ashar , Shah Abhi , Patel Kaushal , Mansabdar Aditya , Alla Arya , Panchal Viraj , Cheriyath Pramil 
Published: December 2024

Introduction: Daratumumab, a human IgG monoclonal antibody against CD38 has direct and indirect antimyeloma activity. Daratumumab monotherapy in heavily pretreated patients with multiple myeloma has shown substantial efficacy. We conducted a meta-analysis to demonstrate its efficacy in combination therapy in patients with relapsed or refractory multiple myeloma focusing on clinical outcomes and prognostic factors.
Methods: A comprehensive search was carried out in PubMed, Cochrane and Clinicaltrials.gov using the following MeSH terms: “daratumumab” or “Darzalex” and “multiple myeloma” from 2000 to 2024. Studies comparing daratumumab with combination therapy versus combination therapy alone were taken into consideration. Mantel-Haenzel formula was used to calculate the pooled risk ratio (RR), and Generic Inverse Variance method was used to assess pooled hazard ratio for disease progression in RevMan version 5.4 at 95% confidence interval (CI). P value &lt;0.05 was considered to be significant.
Result: We analyzed 7 phase-III RCTs including 2048 patients. The hazard ratio for progression or death with daratumumab group versus control was significantly lower (HR= 0.44; 95% CI= 0.33 to 0.60; p&lt;0.00001). The RR of overall response rate (ORR) was higher in daratumumab group versus control (RR= 1.25; 95% CI= 1.16 to 1.34; p&lt;0.00001), as were the rates of complete response (CR) (RR= 2.49; 95% CI= 1.91 to 3.24; p&lt;0.00001), very good partial response (VGPR) (RR= 1.64; 95% CI= 1.44 to 1.87; p&lt;0.00001). In terms of prognostic factors, the rate for minimal residual disease (MRD)-negativity rate was also higher for the daratumumab group compared to the control group (RR= 5.32; 95% CI= 3.73 to 7.58; p&lt;0.0001).
Conclusion: Daratumumab affects diverse facets of multiple myeloma and has shown a favorable efficacy in patients with relapsed or relapsed and refractory multiple myeloma. In combination therapy, daratumumab resulted in significantly prolonged disease progression, improved clinical outcomes and prognostic factors through increasing MRD-negativity rates.