bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Impact of TP53 Mutation in Adult Acute Lymphoblastic Leukemia Treated with Pediatric-Inspired Regimen
Authors: Ou Jiawang , Xu Xiuli , Zhou Ya , Liu Qifa , Zhou Hongsheng 
Published: December 2023

Abstract
Background: TP53 is one of the most extensively studied genes in human cancer. However, the prognostic impact of TP53 mutations (TP53mut) in adult acute lymphoblastic leukemia (ALL) remained debatable, especially in those treated with pediatric-inspired regimen. Herein, we determined the characteristic of TP53mut in adult acute ALL patients and investigated the clinical significance of these TP53mut in newly diagnosed ALL.
Patients and Methods: We performed TP53 mutation analysis in 283 adult ALL patients (B-ALL n=227; T-ALL n=56) including 57 diagnose-relapse pairs using targeted next-generation sequencing (NGS). TP53 mutations were analyzed for their association with adult ALL enrolled in pediatric-inspired regimen evaluating clinical characteristics and treatment outcomes.
Results: A total of 35 TP53mut sites were detected in 31 diagnosed samples among 283 diagnosed patients and 17 among 57 paired diagnose-relapse samples, with a significant difference (11.0% vs 29.8%; c2=13.9, P&lt;0.001). The major variant was missense mutation (n=32), followed by frameshift (n=11), nonsense mutation (n=4), in-frame (n=3), and splicing mutation (n=2). In paired diagnose-relapse samples, we identified acquired and/or loss of TP53mut in the samples at the time of relapse. In 283 newly diagnosed patients, patients with TP53mut had a higher proportion of the older population, complex karyotype, and MRD positivity before consolidation therapy (P=0.023, 0.002, 0.024). Survival analysis revealed that TP53mut was associated with inferior outcomes in the whole cohort of newly diagnosed ALL (4-year OS rates, 43.6% vs 63.6%, P=0.0086; 4-year EFS rates, 30.4% vs 52.2%, P=0.0056). Additional survival analysis showed that TP53mut did not confer poor outcomes in the AYA population (4-year OS rates, 60.6% vs 68.1%, P=0.55; 4-year EFS rates, 52.5% vs 55.5%, P=0.57). For the older patients, however, TP53mut predicted inferior OS and EFS in older patients (4-year OS rates, 18.2% vs 46.2%, P=0.0033; 4-year EFS rates, 0 vs 39.6%, P=0.00028).
Conclusion: Our data revealed that TP53mut was present at a low incidence at diagnosis and increase at relapse. TP53mut were potential biomarkers associated with poor prognosis in older patients with newly diagnosed ALL treated with pediatric-inspired regimen.
This research was supported by the National Natural Science Foundation of China(NFSC82170163, 81970147), Clinical Study of Nanfang Hospital(LC2016ZD009/2019CR012).
【 Key words 】TP53; Acute lymphoblastic leukemia; Pediatric-inspired regimen; Next-generation sequencing; Prognosis
Gender and Racial Disparities in Risk and Outcomes of Thrombotic Thrombocytopenic Purpura Admissions: An Analysis of the National Inpatient Sample 2016-2019
Authors: Jain Tripti , Kharel Himal , Abdelhay Ali , Mahmoud Amir 
Published: December 2023

Introduction:
Thrombotic thrombocytopenic purpura (TTP) is a rare disorder associated with severe deficiency in ADAMTS13 leading to microangiopathic hemolytic anemia, thrombocytopenia and end organ damage. The purpose of this study is to compare incidence and outcomes of TTP hospitalization between genders and races.
Methods:
We studied the National Inpatient Sample (NIS) from 2016 to 2019 for hospitalizations with the primary diagnosis of TTP. We fitted a multivariable logistic regression model to compare the risk of TTP amongst different races and genders. The model also accounted for age and comorbidities including solid or hematologic malignancies, history of thrombophilia, obesity, diabetes mellitus, hypertension, hyperlipidemia, chronic coronary artery disease, chronic liver disease, and chronic kidney disease. To compare mortality outcomes, we narrowed our analysis to TTP admissions only and fitted a multivariable logistic regression model with similar parameters. All reported confidence intervals were adjusted for multiplicity using the Bonferroni method.
Results:
A total of 7845 patients met the inclusion criteria of which 65.4% were female and 34.6% were males. The distribution of age and co-morbidities were different between the different racial groups. On adjusted analysis, females had higher rates of hospitalization due to TTP, with OR 1.32 (95% CI 1.24 to 1.41) compared to males, while there was no significant difference in mortality with OR 0.98 (95% CI 0.76 to 1.28). African American patients had significantly higher rates of hospitalization compared to Caucasian patients with OR of 3.62 (95% CI 3.38 to 3.88), followed by Asian and Hispanic patients respectively. Interestingly, the mortality in the African American patients was lower compared to Caucasian patients with OR of 0.74 (95% CI 0.55 to 0.98). There was no significant difference in mortality in other races.
Conclusion:
African American patients and females experienced significantly higher rates of hospitalization with TTP. However, African American patients experienced lower mortality. More research is needed to understand the cause behind these differences and modify our diagnostic and management to improve outcomes for patients with TTP.
Low-Dose IA with Venetoclax Regimen As Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia
Authors: Zheng Weiyan 
Published: December 2023

Abstract
Background: The IA regimen (combination of idarubicin and cytarabine) is used as the most common induction of remission therapy for acute myeloid leukemia, with the complete response (CR) rates of up to 70%. Addition of the BCL-2 inhibitor venetoclax(Ven) to chemotherapy can increase apoptosis priming. In order to further improve the remission rate and prolong survival, our center uses a low-dose IA regimen combined with Venetoclax to treat newly diagnosed primary acute myeloid leukemia under 60 years old.
Methods: We retrospectively analyzed 15 patients with newly diagnosed AML, who was under 60 years old. Patients received idarubicin (6mg/m2 IV for 3-days) and cytarabine (60mg/m2 IV for 5-days) with oral venetoclax (400mg daily for 2 weeks) for induction, followed by the same chemo-free regimen for consolidation if patients responded to induction therapy. And then analyze the effects of this regimen on complete remission (CR) rate, minimal residual disease (MRD) negative CR rate, relapse-free survival (RFS), overall survival (OS), and adverse events.
Findings: Between January, 2021 and June, 2023, 15 patients were treated with this regimen. The median age was 43 years (IQR, 36-43) and the median follow-up was 4.25 (IQR, 2.73-15.6) months. Among all patients, the ORR was 86.7% (95% CI 62, 96), the CR rate was 80.0% (95% CI 55, 93), and the MRD negative rate was 66.7% (95% CI 42, 85). According to 2022 ELN risk classification by genetics, the ORR in favorable risk patients were 50.0% (1/2), intermediate risk patients were 100% (7/7), adverse risk patients were 83.3%(5/6). Those who had epigenetic modification mutations (NPM1, FLT3-ITD, CEBPA) were more likely to benefit from this regimen. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia.
Conclusion: As induction and consolidation therapy whose adverse reactions were tolerable, the low-dose IA with Venetoclax regimen produces deep remission for the patients with newly diagnosed primary AML.
CLL Incidence Based-Mortality By Gender: Is There a Change in the Probability of Dying from CLL Today Among Men and Women?
Authors: Kenmoe Jerry , Ghimire Calvin , Yadav Monica , Vinjam Tejaswi , Kunadi Arvind 
Published: December 2023

CLL Incidence Based-Mortality by Gender: Is there a change in the probability of dying from CLL today among men and women?
Background:
About one-fourth of newly diagnosed cases of leukemia are CLL. The lifetime risk of developing CLL is approximately 1 in 175 (0.57%) for the average person. Men are slightly more at risk than women are.
We looked at the incidence-based mortality rates (probability of dying from) of CLL by gender in adult populations in the United States from 2000-2019 via SEER.gov database.
Methods:
We used Incidence -Based Mortality SEER Research Data, 17 Registries, Nov 2021 Sub (2000-2019), which provides the broadest geographic coverage for incidence-based mortality rates and is roughly 26.5% of the US population (based on the 2020 Census) for the calculation of incidence rates of CLL. SEER*Stat 8.4.1 was used to obtain age-adjusted rates for different age-groups, races and genders. We used Join-point software, version 5.0.2. by the National Cancer Institute, annually to create log-linear time trends.
There are no P-values noted for the CI as Joinpoint does not currently produce a test statistic or p-value for Empirical Quantile confidence intervals.
Results:
Fig 1: CLL Incidence Based Mortality Rate per 100,000 and age-adjusted to the 2000 US standard population for males and females 2000-2019
Our study showed increasing incidence based mortality rates, with higher rates in males compared to females. We also noted significant Joinpoints in 2002, 2005 and 2012 for males and2003, and 2010 for females. It is of note that at the Joinpoints, the slope for the rate significantly changes or drops.
The Average Annual Percent Change (AAPC) for males and females were 10.64%*(95% CI 9.95 to 11.53) and 10.09%*( 95% CI 9.41 to 11.44)
Conclusion:
Our study reveals that the slope of incidence-based mortality has significantly reduced over the years from 2000-2019. This means the probability of dying from CLL has also significantly dropped over the years.
This pattern points to changes in guidelines or therapy that have significantly impacted the probability of dying from CLL. This suggests that more investigation is warranted to understand the underlying causes for the trends appreciated.
Distinguishing the Variances in Patient Care between Hematologists and Hospitalists for Individuals with Sickle Cell Disease Hospitalized Due to Vaso-Occlusive Crisis
Authors: Bou Zerdan Maroun , Niforatos Stephanie , Ashok Kumar Prashanth , Siegenthaler Alanna , Ombada Mulham , Kirk Melanie , Jones Andrulisa , Poudyal Bhavya , Levine Elad , Liu Cathy , Repicky Joseph , Mammadli Mahinbanu , Sampat Parth , Sherazi Mahnoor , Ramm Matthew , Rao Gergal Gopalakrishna Rao Sanjay , Layoun Habib , Gentile Teresa 
Published: December 2023

Introduction:
Sickle cell disease (SCD) is a chronic condition characterized by multiple vaso-occlusive complications. Patients often experience recurrent, severe pain that can be disabling and necessitate opioid treatment. Hospitalization for vaso-occlusive crisis (VOC) is a common occurrence for individuals with SCD. In recent times, the care of hospitalized SCD patients has increasingly shifted from adult hematology specialists to hospitalists. At our institution, we are yet to make this transition, with hospitalists rarely taking over the care of inpatients with SCD. Initially, recommendations to the hospitalist service were provided through informal opinions or formal consultations when requested.
Hospitalists have demonstrated efficient inpatient management; however, some may have knowledge gaps and biases that can influence their interactions with SCD patients. To gain a better understanding of the differences in care practices between hematologists and hospitalists and to identify potential areas for improvement in the care of SCD patients, we conducted a formal comparison of their approaches.
Methods: We performed a single-institution, retrospective review of patients with SCD hospitalized for VOC between January 1, 2014, and September 31, 2022.
Results: Table 1 portrays the significant results.
Conclusion: We observed significant distinctions in the care provided by hematologists and hospitalists to patients admitted for VOC in SCD. Hematologists tended to transfer fewer patients to the intensive care unit compared to hospitalists. On the other hand, hospitalists more frequently sought consultations from the pain service than hematologists. Interestingly, patients under the care of hematologists received longer hours of patient-controlled analgesia for pain management. Additionally, patients managed by hematologists exhibited higher hemoglobin levels at the time of discharge when compared to those treated by hospitalists.
Notably, only 39.8% of patients had a formal hematology consult requested during their hospital stay, indicating a potential need for better collaboration between hematologists and hospitalists. This study emphasizes the importance of enhancing cooperation between these two specialties to elevate the quality of care for patients hospitalized with VOC.
Impact of Srs-CoV2 Infection on Pain Crises and Acute Chest Syndome in Patients with Sickle Cell Anemia: A Retrospective Multi-Cohort Study Based on USA Data from 2020-2022
Authors: Onimoe Grace ifeyinwa , Yerigeri Keval 
Published: December 2023

Objective: To determine the impact of SARS-CoV-2 infection on vaso-occlusive pain crisis (VOC) and acute chest syndrome (ACS), incidence, and outcomes in sickle cell anemia (SCA) patients.
Method: This retrospective study used the TriNetX USA health research network database to identify SCA patients (Hb-SS, Sβ0-thal) ages 1-50 with and without concomitant SARS-CoV-2 infection from May 2020 to May 2022. A total of 6 cohorts were created: pain crisis with/without SARS-CoV-2, ACS with/without SARS-CoV-2, and SARS-CoV-2 without pain crisis/ACS. Patients with SARS-CoV-2 and pain crisis/ACS were compared to 2 cohorts (SARS-CoV-2 without pain crisis/ACS) for demographic characteristics, baseline laboratory parameters, disease-modifying drug use, and influenza/COVID-19 vaccination status by t-tests. Pain crisis/ACS patients with SARS-CoV-2 were then compared to 2 cohorts (pain crisis/ACS without concomitant infection) for demographic characteristics, and relative risk for acute settings of care, pain control, laboratory parameters/outcomes (including hemolytic and inflammatory markers), procedures (blood transfusion) and mortality.
Results : The incidence of pain crises and ACS in SCA patients following SARS-CoV-2 infection was 34 and 27 per 100 patients, respectively. The risk of developing ACS was significantly increased by SARS-CoV-2 infection (2.57% vs. 1.17%, RR 2.2), but not the risk of developing a pain crisis (RR 1.04). Pain crisis and ACS patients with concomitant SARS-CoV-2 infection had a greater risk for inpatient services, subsequent hospital visits, opioid and non-opioid analgesia, blood transfusions, and concerning hemolytic and inflammatory markers compared to those without the infection. Patients with SARS-CoV-2 who did not develop pain crises/ACS had higher baseline hemoglobin levels prior to infection compared to patients who developed pain crisis/ACS. There was a higher rate of COVID-19 and influenza vaccination in the cohorts who did not develop pain crisis/ACS and might have improved pain crisis rates (but not ACS) following SARS-CoV-2 infection.
Conclusions: COVID-19 illness had an impact on the incidence of both pain crises and ACS, significantly increased the risk of developing ACS, and influenced morbidity outcomes for both pain crises and ACS. Prior vaccination against influenza and COVID-19 may represent a protective factor for developing pain crises.
Utility of Assessing Primary Hemostasis By Determining Platelet Function and Von Willebrand Factor in Patients with Myeloproliferative Neoplasms
Authors: Nomdedeu Meritxell , Moreno Castaño Ana Belén , Garrote Marta , Arellano-Rodrigo Eduardo , Carbonell-Ordeig Sara , de Moner Blanca , Escolar Ginés , Esteve Jordi , Tassies Dolors , Diaz-Ricart Maribel , Reverter Joan Carles , Alvarez-Larran Alberto 
Published: December 2023

VWF
Changes in primary hemostasis have been implicated in thrombotic and bleeding complications in myeloproliferative neoplasms (MPN), so their evaluation could be useful in the management of these patients.
We studied primary hemostasis in 248 patients with essential thrombocythemia-type MPN (TE n=129), polycythemia vera (PV n=71) and myelofibrosis (MF n=48). Von Willebrand antigen (VWF:Ag) (normal: 60-160 U/dL), von Willebrand factor (VWF) activity (VWF:GPIbM) (normal: 60-160 U/dL) and closure time with the platelet function analyzer (PFA-200) (pathological: collagen-Epinephrine channel &gt; 200 seconds; collagen-ADP channel &gt; 140 seconds) were assessed. VWF:GPIbM &lt; 60 U/dL and a VWF:GPIbM / VWF:Ag ratio &lt; 0.7 were considered to be suggestive of acquired von Willebrand disease (aVWD). In antiplatelet patients with acetyl salicílic acid (ASA), we defined in vitro resistance as a PFA-200 Col-Epi time &lt; 200 seconds. The results were correlated with the diagnosis, hematological values, conventional or NGS genotype (n=176) and treatment at the time of the study. Patients with thrombocytopenia &lt; 50x10 9/L were excluded from the PFA-200 analysis.
Table 1 describes the clinical variables of the patients.
GPIbM was decreased in 14 cases, increased in 85 cases, and normal in the rest. We identified a direct correlation with age (β=0.29, R2=0.08, p=0.001), and an inverse correlation with the number of platelets (β=-0.45, R2=0.20, p&lt;0.001), independent of the genotype. . We found elongated PFA-200 in the Col-Epi and Col-ADP channels in 129 (54%) and 63 (26%) cases, respectively. In 10 (4%) patients we found parameters suggestive of avWD. All of them had thrombocytosis. Elevated platelet count (&gt;600x109/L) was associated with VWF values suggestive of aVWD, with a sensitivity and specificity of 90% and 83%, respectively (AUC: 0.938, 95%CI: 0.896-0.980).
Of the 99 patients not on antiplatelet therapy, 31 (31%) had an elongated PFA-200. Elongated PFA-200 was associated with lower Hb, higher leukocytes, higher platelets, higher JAK2 mutational load, lower VWF:GPIbM, and CALR genotype. This alteration was observed in 71% of patients with the CALR genotype. In multivariate analysis, decreased VWF:GPIbM (OR: 0.98, 95%CI: 0.97-0.99, p=0.001) and CALR mutation (OR: 0.98, 95%CI: 0.97- 0.99, p=0.001), maintained their value.
Of the 130 patients receiving ASA, in vitro resistance was found in 31 cases (24%) (PV 30%, TE 25%, MF 0%). ASA resistance was associated with a higher platelet count and higher VWF:GPIbM. 50% of the patients with increased VWF:GPIbM (&gt;160 U/dL) had resistance to ASA, showing VWF:GPIbM as an independent variable in the multivariate analysis.
Patients with Sickle Cell Disease Can Demonstrate a Constellation of Symptoms Associated with Hyper-Hemolysis without Recent Transfusion
Authors: Garrett Erin R. , Chonat Satheesh , Briones Michael , Rollins Margo R. 
Published: December 2023

Background
A hallmark characteristic in patients with Sickle Cell Disease (SCD) is chronic hemolysis, the severe exacerbation of which has been linked to RBC transfusion in some cases. This hyper-hemolysis (HH) is defined as a rapid decline of hemoglobin (Hb) and HbA% below pre-transfusion values. HH has been considered a severe form of antibody negative DHTR (Ab (-) DHTR) in patients with SCD and defined by the American Society of Hematology as hemolysis within 21 days of transfusion, negative DAT and absence of new alloantibody. Herein, we present a case series of 5 SCD patients with transfusion &gt; 21 days from presentation demonstrating symptoms and lab findings consistent with HH. The purpose of this study is to characterize patients with SCD diagnosed with HH as a working diagnosis without temporal relation to transfusion. To our knowledge, this is the first and largest case series of its kind.
Methods
An IRB approved retrospective EMR review collected demographic and clinical data for patients with SCD admitted for concern for HH or DHTR to a large multi-site Pediatric Hospital in the Southeastern USA (2020-2023). All patients in this study were identified from Transfusion Medicine consults to investigate DHTR. Patient admission diagnosis was obtained from EMR review.
Findings
Cohort patients were 15-19 years with HbSS or HbS-beta thalassemia zero. All patients had transfusion &gt;21 days from presentation. Of note, patient #5 received a transfusion during their first admission and was readmitted for signs and symptoms of HH/Ab (-) DHTR within 24hrs of discharge. All patients admitted for &gt;1 day demonstrated an average 47% fall in hemoglobin (range: 24-69%), negative antibody screen/DAT, reticulocytopenia and mild to moderate thrombocytopenia. Four patients demonstrated elevated LDH. One patient died prior to discharge. Day of stay (DOS) of labs is in brackets []. Refer to table 1 for detailed patient data.
Conclusion
This case series demonstrates that patients with SCD can experience a constellation of symptoms identified in patients with HH without temporal relation to transfusion. These include hemolysis, reticulocytopenia, and thrombocytopenia as well as elevation of complement proteins. Given the overlap in presentation, HH in patients with SCD should be considered independently of proximity to transfusion for prompt diagnosis. Further study should include a retrospective review for further characterization. In addition, given the finding of elevations in C5a, further study into complement as a mechanism and target of therapy would be valuable.
Increased Proliferative Drive of Lymphocytes in Sickle Cell Disease
Authors: Ginda Ashley , Zhang Jingyue , Meng Wenzhao , Kearns Charlotte , Weissman Samuel , Swiggard Liam , Richards Clarice , Moore Jeffrey , Murter Melissa , Luning Prak Eline T. , O'Doherty Una 
Published: December 2023

Introduction
Patients with sickle cell disease (SCD) have higher levels of inflammation which plays a prominent role in disease pathogenesis. It is well known that individuals with SCD have a higher erythropoietic drive given the ~20 day life span of their red blood cells. We asked whether this increased proliferative drive also occurred in white blood cells (WBC). To characterize WBC turnover we focused on the longest-lived CD4+ and CD8+ T cells.
Methods
Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll gradient from red cell waste products from consented individuals with sickle cell disease and from leukapheresis products of healthy donors. In ten healthy donors and ten donors with SCD, CD4 and CD8 T cells were purified using EasySep Cell Isolation, labeled with eFluor 670 proliferation dye, and cultured in RPMI with 30% FBS for seven days. Samples were collected daily and stained with naïve and memory T cell markers. CountBright beads were added to obtain absolute cell counts and eFluor 780 live/dead dye was used to capture daily snapshots of cell death. Flow cytometric analysis was performed to track absolute cell numbers, cell division and indirectly monitor cell death. B cells, NK, macrophages, and dendritic cells were similarly tracked. To further probe T cell turnover, T cell receptor (TCR) sequencing was performed on twelve separate aliquots from purified CD4+ T cells at two different timepoints in healthy donors and individuals with SCD. Turnover of clonal sequences was analyzed using the Morisita index.
Results
CD4+ and CD8+ lymphocytes from individuals with SCD experienced more death in culture by day 7 compared to healthy donor controls. In addition, T lymphocytes from donors with SCD were observed to undergo 15-fold more proliferation compared to healthy donors (p=0.0002, unpaired t-test). Immunophenotyping performed on the CD4 and CD8 T lymphocytes showed a propensity for memory cells to undergo proliferation. We also found individuals with SCD had higher turnover in TCR sequences in two timepoints compared to healthy donors (p=0.05, Chi-square). Notably, we also saw increased proliferation of B cells, NK cells, macrophages, and dendritic cells in individuals with SCD.
Conclusion
Our data suggest that T lymphocytes and other PBMCs undergo faster turnover in SCD than in healthy donors, suggesting a stronger hematopoietic drive. Our findings may have important implications for gene therapy since an increased proliferative drive may contribute to an increased risk of developing leukemia in SCD.