bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy and Safety of Selinexor Plus Ruxolitinib Regimen in Ruxolitinib-Resistant Myelofibrosis: A Retrospective Study
Authors: Wen Ziyu , Zhou Xuan , Lin Bingyu , Liu Xiaoli , Wang Qiang , Xu Na 
Published: December 2024

B ackgroundMyelofibrosis (MF) includes two types: primary MF (PMF) and post-polycythemia vera (PPV) and post-essential thrombocythemia (PET) MF, also known as secondary MF (SMF). Perturbation of the JAK/STAT signaling pathway is the hallmark of MF. Despite the meaningful improvements JAK inhibitors provide in managing splenomegaly and symptoms, they do not significantly impact disease progression. Consequently, issues such as treatment failure, poor efficacy, leukemia progression, and safety concerns persist in managing MF, particularly in patients who respond poorly or are intolerant to the JAK inhibitor ruxolitinib (RUX). In recent years,Combination therapy with different mechanisms has emerged as a new approach to improve prognosis post-ruxolitinib. Selinexor (SEL), an oral XPO1 inhibitor, may inhibit MF through various pathways. The 2024 CSCO Guidelines for hematological malignancies recommend SEL as first-line treatment for PMF. Cell experiments have confirmed that selinexor has the potential to overcome JAK resistance. A parallel cohort phase 2 study reported that 71.42% of RUX-intolerant/resistant MF patients receiving the SEL plus RUX regimen had reduced spleen volume, and 38.09% achieved spleen response. Here, we report on the efficacy and safety of SEL combined with RUX in RUX-resistant MF patients in a retrospective study.
Method This is a retrospective single-center study aimed at evaluating the efficacy and safety of SEL combined with RUX regimen in RUX-resistant MF patients. The study included 21 MF patients with a poor response to RUX: 12 with PMF, 4 with post-PV MF, and 5 with post-ET MF. Patients received SEL at 20 mg, 40 mg, or 60 mg QW plus RUX (dosage determined by the investigator).
Result The median age is 56 (range, 37-71) years and the median duration of previous RUX treatment is 11.3 (6-39) months. 47.6% of patients had peripheral blood blasts of 1-9%. 16 (76.2%) patients harbored JAK2 mutations, 2 (9.5%) patients CALR mutations and 1 (5%) patient MPL mutations. All patients had splenomegaly, and 8 (38.1%) were transfusion-dependent. According to the DIPSS risk score, 11 patients (52.4%) were classified as high-risk, 5 (23.8%) as intermediate-2 risk, and 5 (23.8%) as unknown risk. Spleen size reduced in 16 (76.2%) patients with a median response time of 2.3 (1-3) months. Three patients underwent bridging to transplantation and are currently surviving with good recovery. Peripheral blood blasts decreased in 10 (47.6%) patients after one month of treatment. The most common adverse events during treatment were gastrointestinal reactions and cytopenias.
Conclusion The combination of SEL and RUX showed promising efficacy and manageable safety profile in RUX-resistant patients with myelofibrosis.
Keyword Selinexor; ruxolitinib; ruxolitinib-resistant; myelofibrosis
Title:Revision of the Diagnostic Methods Used for the Detection of Pulmonary Embolism in Pregnant Women at the “Centre Hospitalier Universitaire De Sherbrooke”
Authors: Le Templier Genevieve 
Published: December 2024

Introduction: We aim to describe the incidence of pulmonary embolism in pregnant patients in which this diagnosis was suspected in our hospital and to compare it with the 5% incidence found in medical literature. We also want to describe the use of serum D-dimer assay in our hospital and assess whether there has been an increase in its use over time for these patients, particularly since the appearance of the ARTEMIS study in March 2019.
Methods: We collected data from our local computerized clinical record for all pregnant patients aged 18 to 45 who underwent an investigation for pulmonary embolism between January 2015 and November 2019.
Results: Of the 186 of these patients, 4 (2.2%; 95% CI [0.84% - 5.40%]) were diagnosed with a confirmed pulmonary embolism. There was no statistically significant difference with the value of 5% found in the literature (p value at 0.07). Before March 2019, serum D-dimer was measured in 57.7% of pregnant patients in whom there was suspicion of pulmonary embolism. After March 2019, D-dimer was measured in 82.6% of these patients, representing a statistically significant increase in their use before and after March 2019, with a p-value of 0.02.
Conclusions: These results demonstrate that there is no statistically significant difference between the incidence of pulmonary embolism in pregnant women in which this diagnosis is suspected in our hospital and that found in medical literature. In recent years, some studies have shown that the serum D-dimer assay could be useful for the purpose of identifying pregnant patients who would benefit from imaging that could expose them to ionizing radiation, and indeed we have found an increase in the use of D-dimer in the diagnostic approach for pulmonary embolism in pregnant patients in our hospital after March 2019.
Outcome of Relapsed Childhood Acute Lymphoblastic Leukemia in Resource-Poor Country : Warrants the Need for Immunotherapy
Authors: Abu Shanap Mayada , Sultan Iyad 
Published: December 2024

Introduction:
The overall survival (OS) rate for children with acute lymphoblastic leukemia (ALL) treated at King Hussein Cancer Center is approximately 80%, aligning with published results of the Total XV regimen.
Method:
From December 2003 until August 2023, children/adolescents (&lt;18 years at diagnosis) with ALL in first and subsequent relapses were studied. Treatment of relapse consisted of reinduction regimens followed by intensive continuation therapy and hematopoietic stem cell transplantation (HSCT) in selected patients. The poor prognostic group (PPG) included patients who did not achieve remission after salvage chemotherapy and were referred to palliative care.
Results:
The study included 160 patients with a median age of 5 years (range: 0.4-19.8 years), followed for a median of 71 months (range: 4-248 months). Sites of relapse were: bone marrow (BM) in 64%(N=103) of the patients, combined relapse in 19 %( N=30) and isolated extra-medullary Relapse (IEM) relapse 17%(N=27). Complete remission (CR2) rates for all patients were 64% and vary according to time and site of relapse (100% for IEM, 56% for isolated BM/combined: 90% for late relapses, and 39% for early/very early relapses). The estimated 5-year-EFS and OS for the whole group were 30% and 40 %, respectively. Five-year-OS for patients with BM relapse was 29%, combined relapse 58%, and IEM 66%. Five-year-OS for patients with very early relapse was 12%, early relapse 36%, and late 74%.
Forty patients (39%) continued on chemotherapy after achieving CR2, and sixty-two patients (61%) underwent HSCT, with 60 (59%) alive in continuous complete remission (CCR) at last follow-up. All patients (N=58) in the PPG died of the disease.
In univariable analysis, worse OS was observed in patients &lt;1 or≥10-years at diagnosis, those T-cell-immunophenotype, CNS 3 at diagnosis, BM and very early relapses. In multivariable analysis : age (p=0.02), site of Relapse( p=0.019) and time of relapse(p=0.009) were prognostic.
In univariable analysis, worse EFS was observed in patients &lt;1 or≥10-years at diagnosis, T-cell-immunophenotype, CNS 3 at diagnosis, unfavorable cytogenetic at diagnosis, BM and very early relapses. In multivariable analysis Site of Relapse ( p=0.02)and time of relapse(p&lt;0.001) were prognostic.
Conclusions
At our center, more than one-third of relapsed ALL patients were cured. However, survival rates are low in high-risk relapsed ALL (very early and isolated BM relapses). Conventional chemotherapy and adequate supportive care failed to salvage this high-risk group, indicating the need for immunotherapy as a bridge to allogeneic hematopoietic stem cell transplantation.
Leveraging Clonal Competition between Chip and Aggressive Malignant Clones As a Novel Therapeutic Approach
Authors: Guillermo Kiana Kalei , Huang Xin (Helen) , Heidmann Jianhong C , Fleischman Angela G. 
Published: December 2024

Introduction:
Hematopoietic stem cells are in constant clonal competition, as a result variant clones resistant to inflammatory pressures emerge with aging resulting in clonal hematopoiesis. Multiple independent clones can coexist, and potentially come into equilibrium. However, with an acute leukemia a clone overtakes the system, thus inhibiting normal hematopoiesis. We sought to explore the possibility of leveraging the increased competitive ability of CHIP clones to dampen expansion of an aggressive malignant clone. As proof of principle, we tested whether introduction of Tet2-/- cells as competitors could dampen the expansion of MPLW515L cells, an aggressive MPN mouse model.
Methods:
We used a transduction-transformation model of MPL W515L as an aggressive MPN model. This mouse model usually results in death approximately 3-4 weeks post-transplant. Whole bone marrow from wild-type C57B/6 (CD45.1) mice was transduced with Green Fluorescent Protein (GFP) tagged retrovirus to induce expression of hMPLW515L. We transduced bone marrow with a low viral multiplicity of infection (MOI) resulting in approximately 1-5% GFP+ cells to extend survival beyond the expected 3-4 weeks post-transplant. The transduced bone marrow was mixed with unmanipulated whole bone marrow from either WT or Tet2-/- (both in CD45.1/2) to result in a 90%/10% mixture and transplanted into lethally irradiated CD45.2 mice. Peripheral blood counts, % GFP+ cells, and chimerism was followed biweekly. Surviving mice were sacrificed and analyzed at 5 months post-transplant.
Results:
There was early death from expansion of MPLW515L GFP+ cells within 3-4 weeks in 10% of both the WT and Tet2-/- competitor groups. However, of the surviving mice the percentage of GFP+ cells in the peripheral blood was consistently lower in the Tet2-/- competitor group compared to the WT competitor group (for example mean of 55% GFP+ in WT competitor group vs 23% at day 105 post-transplant). At five months post-transplant we sacrificed the cohort to assess the composition of MPLW515L cells in the hematopoietic stem and progenitor compartments. The percentage of GFP+ cells was higher in all cell populations assessed in the WT competitor group compared to the Tet2-/- competitor group. Moreover, spleen and liver weights were higher in the WT versus Tet2-/- competitor group.
Conclusions:
This work demonstrates proof of principle that clones with increased competitive ability and low malignant potential, such as Tet2-/- cells, can be used as a buffer for the expansion of highly aggressive clones. This concept of introduction of non-malignant competitor clones could be potentially be explored as a novel therapeutic approach in aggressive hematologic malignancies.
Parvovirus B19 Originates from Infected Hematopoietic Stem Cells Following Hematopoietic Stem Cell Transplantation
Authors: Pei Xuying , Huang Xiaojun , Liu Zhuojun , Fu Qiang , Zhao Xiaosu , Sun Yuqian 
Published: December 2024

Background: Human parvovirus B19 (B19) can lead to severe refractory anemia, aplastic crisis, and systemic lethal syndromes due to persistent infection of erythroid progenitor cells after hematopoietic stem cell transplantation (HSCT), however, the causes of pancytopenia have not yet demonstrated. Previous studies on post-transplant B19 infection have mainly been case reports, leaving its clinical characteristics and pathogenesis largely unexplored.
Methods: We examined the clinical manifestations, risk factors, and prognosis of 136 adult patients infected with B19 at our institution from 2017 to 2023. A control group of 408 patients without B19 infection was selected using propensity score matching. Single cell full-length RNA sequence (scFAST-seq) of four B19-infected patients and four B19-negative patients after HSCT were adopted to profile B19-infected cell spectrum and functional characteristics. Polymerase chain reaction (PCR) were performed to validate scFAST-seq results.
Results: Our study revealed a 2.6% incidence of B19 DNA viremia after allo-HSCT, with a median onset of 94 days post-transplant. Severe anemia, granulocytopenia, and thrombocytopenia were observed in 69.1%, 80.9%, and 96.3% of B19-positive patients, respectively. Persistent B19 infection, defined as B19 DNAemia lasting for 28 days or more occurred in 48 patients, often accompanied by severe pancytopenia (97.9%) and organ complications (54.1%). Importantly, B19 infection significantly correlated with poorer transplant outcomes, evidenced by higher non-relapse mortality and lower overall survival at 1, 3, and 5 years compared to the control group. Based on scFAST-seq data, we found that in adition to erythroid-lineage cells, which are well-known targets of B19, this virus could infect a broad spectrum of the hematopoietic system, including giant bone marrow myeloid and lymphoid-lineage cells, and even hematopoietic stem cells (HSCs). Interestingly, the scFAST-seq data showed a dramatic decrease in hematopoietic stem cells in patients infected with B19, which suggest that B19 may impair the survival of HSCs, potentially leading to pancytopenia. Moreover, B19-infected HSCs exhibited a higher expression levels of differentiation pathways toward downstream lineages, which may suggest that B19 disease originates from the infected HSCs.
Conclusion: This study provides a comprehensive clinical overview of B19 infection following HSCT and indicates poorer transplant outcomes in patients with B19 infection. Importantly, our findings suggest that B19 can infect a broad spectrum of the hematopoietic system post-HSCT, potentially originating from infected hematopoietic stem cells in patients with persistent B19 infection.
Trends in Mortality Due to Hematologic Malignancies Among Patients Aged 25 and Older in the United States: Geographic and Metropolitan Area Disparities Insights from CDC Wonder Database
Authors: Durugu Satya R , Sinha Shrishti , Ali Hassan , Ahmed Faizan , Agrawal Shubham , Abboud Brian , Rojulpote Krishna V , Thirumaran Rajesh 
Published: December 2024

Introduction
Hematologic malignancies represent a significant cause of mortality among adults aged 25 and older in the United States. This study examines geographic and metropolitan area disparities in mortality rates from 1999 to 2020.
Methods
A retrospective analysis of the CDC WONDER database was conducted to calculate age-adjusted mortality rates (AAMRs) per 100,000 persons. Trends were analyzed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC), stratified by geographical regions and metropolitan areas.
Results
From 1999 to 2020, hematologic malignancies caused 1,463,046 deaths among adults aged 25 and older. Geographic analysis revealed that all regions experienced a decrease in AAMR from 1999 to 2018, followed by slight, non-significant increase from 2018 to 2020. The Northeast showed a decrease from 36.72 to 26.38 (APC: -1.7256; 95% CI: -2.7731 to -0.2212; p = 0.0246), with a non-significant rise to 26.96 in 2020. The Midwest had similar trends, with the AAMR decreasing from 39.55 to 28.99 (APC: -1.6203; 95% CI: -1.7705 to -1.5059; p &lt; 0.001) from 1999 to 2018, followed by a non-significant rise to 30.55 in 2020. The South saw a decrease from 35.96 to 26.41 (APC: -1.6129; 95% CI: -2.0725 to -1.4489; p &lt; 0.001) from 1999 to 2018, with a non-significant rise to 27.17 in 2020. The West had a significant decrease from 35.85 to 25.82 (APC: -1.7130; 95% CI: -1.8933 to -1.6040; p &lt; 0.001) from 1999 to 2018, followed by a non-significant rise to 26.45 in 2020. Metropolitan areas consistently had lower AAMRs compared to non-metropolitan areas, with the AAMR in metropolitan areas decreasing from 36.43 in 1999 to 27.19 in 2020, while non-metropolitan areas decreased from 37.77 in 1999 to 30.30 in 2020.
Conclusion
This analysis reveals significant geographic and metropolitan area disparities in mortality rates due to hematologic malignancies among adults aged 25 and older in the U.S. Despite overall declines, there is a persistent higher mortality rate in non-metropolitan areas. Limited healthcare infrastructure, barriers to healthcare accessibility, and social determinants of health are suggested factors contributing to these results. This highlights the need for targeted public health interventions to address these disparities and improve outcomes in rural populations.
Reduced Incidence of Severe Hemorrhagic Cystitis in Prophylaxis Infusion of Mensenchymal Stromal Cells for Gvhd, a Secondary Endpoints in a Randomized,Multiple Center Clinical Tria
Authors: Yao Han , Wang Xiaoqi , Huang Ruihao , Feng Yimei , Deng Xiaojuan , Chen Ting , Zhu Lidan , Liu Jia , Liu Yuqing , Zhao Lu , Wang Lu , Zhang Cheng , Kong Peiyan , Gao Li , Gao Lei , Liu Qifa , Zhang Xiaohui , Zhang Xi 
Published: December 2024

Aim:MSCs are being explored for their potential to prevent and treat graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. A secondary endpoint was anaylzed in our multi-center prospective randomized controlled study (ChiCTR1900022292) aimed to evaluate the efficacy of MSC infusions in preventing hemorrhagic cystitis (HC), a common complication of allo-HSCT.
Methods:Based on the electronic data capture（EDC) ,clinical data, interleukin levels, and T lymphocyte subgroups were monitored to identify potential biomarkers and risk factors for predicting HC occurrence.
Results:A total of 192 patients were included in the analysis, of whom 36 (18.8%) developed HC. The results showed both a lower incidence of HC and severe HC in the MSCs group compared to the control group. Factors associated with severe HC included BK virus infection, older age, and slower platelet reconstitution(Table 1). Combination of these risk factors had an area under the curve (AUC) of 0.756 (95% CI: 0.586-0.851), with a specificity (1-specificity) of 0.688(Figure 1). Cytokine and T cell subset analysis revealed decreased levels of IL-4, TNF-α, and TNF-γ in patients with severe HC, as well as increases in CD3+ T cells, CD4/CD8 ratio, and CD19+ B cells.
Conclusions:This trial demonstrated the potential of MSCs to prevent severe HC in allo-HSCT patients. The identified biomarkers and risk factors may help predict and manage the development of HC in this population.
Key words:Hemorrhagic Cystitis,Mensenchymal Stromal Cells,Clinical Trial,prophylaxis
Trends in Mortality Due to Hematologic Malignancies Among Patients Aged 25 and Older in the United States: Annual Trends and Insights on Gender Disparities from the CDC Wonder Database
Authors: Durugu Satya R , Ali Hassan , Sinha Shrishti , Kalantri Shreyas , Ahmed Faizan , Abboud Brian , Rojulpote Krishna V , Thirumaran Rajesh 
Published: December 2024

Introduction
Hematologic malignancies are a major cause of mortality among adults aged 25 and older in the United States. This study investigates annual trends and gender disparities in mortality rates from 1999 to 2020.
Methods
A retrospective analysis of the CDC WONDER database was conducted to calculate age-adjusted mortality rates (AAMRs) per 100,000 persons. Trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) stratified by year and gender.
Results
From 1999 to 2020, hematologic malignancies caused 1,463,046 deaths among adults aged 25 and older. The overall AAMR decreased from 37.30 in 1999 to 28.0 in 2020, with an AAPC of -1.3641 (95% CI: -1.5184 to -1.2762; p &lt; 0.001). A significant decline occurred from 1999 to 2018 (APC: -1.6696; 95% CI: -1.7878 to -1.5890; p &lt; 0.001), followed by a slight increase from 2018 to 2020 (APC: 1.5861; 95% CI: -0.7262 to 2.6695; p = 0.2151). Men exhibited higher AAMRs compared to women (40.6 vs. 23.7). Both genders saw a decrease in AAMR from 1999 to 2020 [Men: AAPC: -1.2398 (95% CI: -1.3859 to -1.1540; p &lt; 0.001); Women: AAPC: -1.6315 (95% CI: -1.8334 to -1.5137; p &lt; 0.001)]. For women, the AAMR decreased significantly from 29.50 in 1999 to 19.90 in 2019, followed by a minor rise to 20.80 in 2020. Similarly, for men the AAMR decreased from 48.60 in 1999 to 35.4 in 2019 and then increased to 37.40 by 2020.
Conclusion
This analysis highlights significant annual trends and gender disparities in mortality rates due to hematologic malignancies among adults aged 25 and older in the U.S. Despite an overall decline, Despite an overall decline, men demonstrated a higher mortality due to hematologic malignancies in comparison to women. Globally, men have higher incidence and death rates for leukemia, multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) compared to women. From 1990 to 2019, the male-to-female ratio for these cancers increased, suggesting the influence of hormonal, genetic, and environmental factors. Existing literature shows evidence for specific leukemia subtypes exhibiting higher mortality rates in men, with notable age groups having the highest death rates. This disparity underscores the need for further research to understand and address these gender differences in hematological malignancies.
Zanubrutinib Can Rapidly Improve Clinical Features Especially Anemia in Newly Diagnosed Waldenström Macroglobulinemia
Authors: An Ran , Zhang Sujiang , Wei Rong , Yan Zeying , Sun Haimin , Liu Zhiyin , Tian Jie , Wang Ying 
Published: December 2024

Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disease with an ambiguous clinical presentation. It is well established that bone marrow infiltration is a key component of the pathophysiology of WM, which most commonly presents as anemia. The phase III ASPEN study has already demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with WM. Here, we presented a real-world study about zanubrutinib and WM in different center.
A total of 30 newly diagnosed WM patients from Ruijin Hospital and Shanghai Tenth People's Hospital was included in this retrospective study. All patients received zanubrutinib as monotherapy. The median age of the 30 patients was 65 years（range 36-85 years）with 17 patients &gt;65 years, the ratio of male to female was 1.5:1, and all patients met the indications for treatment. The majorities of patients (24/30, 80%) presented with non-specific symptoms such as fatigue, weight loss and fever. Additionally, three patients presented with significantly enlarged lymph nodes, 2 with bleeding and 1 with Reynolds phenomenon. According to IPSS, these patients can be categorized with high-risk (26.7%, 8/30), intermediate-risk (43.3%, 13/30) and low-risk (30%, 9/30). At the time of initial diagnosis, the median level of IgM was 20.3g/L (1.3-84.8g/L), while the median haemoglobin level was 95g/L (49-149g/L). In addition, MYD88 L265P mutation was detected in 81.5% (22/27) cases. All patients were treated with zanubrutinib as monotherapy, with a median time to first treatment (TTFT) of 3.3 months (range 0.4-28.1). The median duration of zanubrutinib therapy was 15.5 months (range 1.0-57.0). Zanubrutinib was well tolerated and no patients need to discontinue treatment. Further efficacy analysis demonstrated 24 patients showing strikingly improvement about hemoglobin levels and the median response time was 3.0 months (range 0.2-12 months). A significantly reduction of IgM level was also observed in 23 patients after 3 months treatment of zanubrutinib, with a median percentage reduction of 52% (50%-94%). We concluded that zanubrutinib can rapidly improve clinical features especially anemia in the treatment of newly diagnosed WM, which will largely boost confidence of clinicians as well as patients and finally be benefit to cure this disease.
Keywords:
Waldenström macroglobulinemia, Zanubrutinib, anemia