bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Important Are in-Person Clinic Visits during Maintenance Therapy for Pediatric Acute Lymphoblastic Leukemia?
Authors: Rabinowicz Ron , Hitzler Johann K , Punnett Angela 
Published: November 2021

Abstract

B ackground
Acute Lymphoblastic Leukemia (ALL) is the most common cancer seen in the pediatric age group. The treatment consists of an initial intensive phase of chemotherapy followed by a prolonged period of maintenance chemotherapy intended to reduce the risk of relapse. Children are commonly seen in clinic every 4-6 weeks for bloodwork and physical examination during the maintenance phase. The COVID-19 pandemic has prompted consideration of alternative means of providing medical care. The objective of this study was to determine the proportion of in-person clinic visits during ALL maintenance therapy for which the outcome of the physical examination resulted in a change of patient management.

Methods
A retrospective chart review of children diagnosed with precursor-B ALL between January 2017 and December 2018, and who were in maintenance therapy between September 2019 and February 2020, was conducted. All routine maintenance visits were reviewed to identify new physical examination findings and patient outcomes and classified as either "could be managed virtually" or "essential in-person visit". For the latter, a second classification was conducted to distinguish between visits necessitating a change of management versus not.
Results
Eighty-five children were diagnosed with precursor B ALL and continued to maintenance treatment during the study period. 10 children were excluded as not meeting the inclusion criteria or not evaluable. Of the remaining 75 children, 54 were male (72%) and 21 female (28%). The median age at diagnosis was 4.83 years (0.73 - 14.8 years). 39 patients (52%) had standard risk ALL, 35 patients (46.7%) had high risk ALL and one patient had Infant ALL (1.3%) A total of 240 routine maintenance visits were included in the final analysis. An abnormal physical exam finding was noted in 20 visits (8.3%) and of these, new findings were noted in 14 (5.8%). 6 visits were classified as essential in-person visits (2 for new bruising, 1 for new limp, 1 for new lymphadenopathy, 1 for acute otitis media, and 1 for new wheezing). Among the 14 visits with new exam findings, only 5 had an impact on patient management and of these, only 2 (0.8%) were classified as obligate in-person visit for requiring immediate management (acute otitis media and wheezing).

Conclusion
Our results demonstrate that most in-person visits can be provided as virtual visits without affecting patient outcomes. The results of this study provide the foundation for a prospective study that will evaluate the benefits, risks and families' preferences associated with virtual visits and delineate the optimal frequency and timing of in-person clinic visits during ALL maintenance therapy.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Efficacy and Safety of Generic Dasatinib As First-Line Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase: Final Analysis with 2-Year Follow-up
Authors: Jin Jie , Meng Li , Yu Wenjuan , Liu Peng , Du Xin , Lou Jin , Wang Weiguang 
Published: November 2021

Abstract
Purpose: Generic dasatinib, a second-generation tyrosine kinase inhibitor (TKI), was approved as a second-line treatment for chronic myeloid leukemia (CML) patients in chronic phase (CP) in china. We initiated a prospective, multi-center and single-arm clinical trial (NCT04925141) from May 2016 to October 2018 to evaluate efficacy and safety of generic dasatinib as first-line treatment in China. The primary endpoint was achieved, here we reported the 2 years follow-up results to see its long-term clinical benefit in Chinese patients.
Methods:The study included the newly diagnosed CML-CP patients who was diagnosed by the presence of Philadelphia (Ph) chromosome and/or presence of BCR-ABL fusion gene. Key inclusion criteria were as follows: 1) Age ≥ 18 years; 2) The CML subjects in chronic phase with the Ph+ definitive diagnosis were within 6 months before the onset of administration of the study drug; 3) The ECOG performance grades of 0-2; 4) Sufficient main organ functions. All newly diagnosed patients were given 100mg/d (initial dose) of the generic dasatinib. The primary endpoint was molecular major response (MMR) calculated based on the BCR-ABL1 ≤ 0.1% at the 12th month. Secondary endpoints were proportion of subjects who achieved and maintained MMR at 3, 6, and 18 months; Cumulative MMR rates at 6, 12, and 24 months were determined. All patients were followed up through the hospital outpatient departments at second, fourth and eighth weeks, and third, sixth, ninth, twelfth, eighteenth, and twenty-fourth months. The follow-up ended on December 6, 2019. The SAS 9.2 software was utilized for all statistical analyses in this study, and the two-sided test was performed to see variances.
Results: A total of 59 patients were included in this trail, with median age of 44 (19 - 70), and 7% of the subjects were at high risk based on the Sokal index for the disease prognosis. The primary endpoint MMR rate at the 12th month was 80.8% which had been published. At 12 months, the cumulative response rate (CCyR) was 85.5% (47/55) and the cumulative MMR was 76.4% (42/55). Here we are reporting the 2 years follow ups. At 24 months, the complete hematological response (CHR) was 88.4%, the cumulative MMR rate was 73.7%, the cumulative MR4.0 rate was 63.6%, the cumulative MR4.5 rate was 58.2%, and the cumulative complete molecular response (CMR) rate was 58.2%. The most common adverse events (AEs) was thrombocytopenia (42.4%) in hematology and pleural effusion (20.3%) in non-hematology, only 11.9% and 1.7% of whom were grade III~IV respectively.
Conclusion: This was the first report on domestic dasatinib as the first-line treatment for CML-CP patients received a clinical benefit with 24 months in China. Safety was similar with that of the original study data.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Treatment with the Recombinant SLIT2 Protein Delays AML Leukemogenesis In Vivo
Authors: Simoes Luise A de Albuquerque , Weinhäuser Isabel , Pereira-Martins Diego A , Ortiz Rojas César Alexander , Bianco Thiago Mantello , Cavaglieri Rita de Cassia , Rego Eduardo M 
Published: November 2021

Abstract
Accumulating evidence suggest that the axon guidance molecules SLIT and ROBO are not only implicated in physiological process but also in cancer progression. Depending on the type of cancer the SLIT-ROBO axis can either act as a tumor suppressor gene, in which case the SLIT2 promoter site is frequently hypermethylated or as an oncogene, whereby high expression is often associated with poor prognosis. In the context of acute myeloid leukemia (AML), low expression of SLIT2 has been associated with low overall survival (OS) (Golos et al., 2019), while the functional role of SLIT2 remains largely unknown. Recently, we showed that the knockdown of SLIT2 increased cell proliferation of acute promyelocytic leukemia (APL) cells resulting in a more aggressive course of disease progression in vivo using the murine transgenic APL model (Weinhäuser et al., 2020). Here, we aimed to study the functional role of SLIT2 in a more heterogeneous disease, such as AML.
Using different publicly available datasets. (GSE58477, normal karyotype blasts: 62, healthy CD34 +: 10; GSE63409, LSC: 14, HSC: 5) we detected increased methylation at the SLIT2 promoter site of AML leukemic cells compared to healthy CD34 + cells suggesting SLIT2 tumor suppressive functions. In addition, we measured decreased levels of SLIT2 in the bone marrow (BM) plasma of AML patients compared to healthy donors. To assess the biological role of SLIT2, we treated AML cell lines (KASUMI1, MV411, and MOLM13) with recombinant SLIT2 (50 ng/mL) in vitro. Administration of SLIT2 reduced AML cell growth, colony formation and induced cell cycle arrest in the G1 phase for all AML cell lines. Conversely, the knockdown of SLIT2 promoted increased THP-1 and OCI-AML3 cell proliferation. Next, we determined whether the treatment with SLIT2 could delay leukemogenesis in vivo using the AML cell line MV4-11. Engraftment was monitored by luciferase bioluminescent signal and NSGS mice were either treated with recombinant SLIT2 using a dose of 25 ng/g of body weight or vehicle (control group). SLIT2 therapy resulted in a lower disease burden, decreased leukemic infiltration in the BM and spleen, reduced spleen size, and increased OS compared to the control group (p&lt;0.05). In conclusion, we showed that SLIT2 methylation is recurrent in AML patients and that the level of SLIT2 in the plasma of AML patients is reduced. Moreover, SLIT2 treatment appears to have a cytostatic effect on different AML cell lines delaying leukemogenesis in vivo. Overall, our study reveals the therapeutic potential of SLIT2 in hematological malignancies, which could be used as an adjuvant in the clinic.

Disclosures
No relevant conflicts of interest to declare.
Anticoagulation Practices Using Activated Clotting Time in Veno-Venous Extracorporeal Membrane Oxygenation for Patients with Respiratory Failure: A Systematic Review and Met-Analysis
Authors: Parmar Kanak , Vutthikraivit Wasawat , Singh Amritpal , Morataya Christina , Del Rio Pertuz Gaspar , Cavazos Annia , Tijani Lukman , Nugent Kenneth , Argueta Erwin 
Published: November 2021

Abstract
Background
Veno-Venous Extracorporeal Membrane Oxygenation (ECMO) technology provides as a alternative approach in the intensive care of patients with respiratory failure due to varied causes who are not responsive to conventional treatment. As per the 2014 Extracorporeal Life Support Organization (ELSO) guidelines, in order to to maintain circuit patency and minimize thromboembolic complications, anticoagulation is used, but the optimal strategy remains to be defined. Activated clotting time (ACT) is the most utilized bedside test to adjust anticoagulation. Therefore, we performed an extended analysis of all published studies on the incidence of thromboembolic and bleeding events in patients with acute respiratory distress syndrome who were put on ECMO.
Methods
A comprehensive search of several databases from inception to November 25, 2020, limited to English language and excluding animal studies, was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The studies were classified into low anticoagulation target (ACT&lt;180) or high anticoagulation target (ACT&gt;180). A meta-analysis was performed of all eligible studies with the data on the incidences of thromboembolic and bleeding complications in patients with ARDS on VV-ECMO during different intensities of anticoagulation.
Results
A total of 6 eligible studies (4 retrospective and 2 case series) were identified, including in total 190 patients for 100 patient years. Our study showed that there is two times higher chances of bleeding when ACT goal is &gt;180 versus a lower ACT range of &lt;180 (Risk ratio 2.07, 95% CI 1.23-3.46, P 0.0056). The incidence of thrombosis did not change in the two group (Risk ratio 1.17, 95% CI 0.45-3, P 0.7516).
Conclusions
Currently there is a lack of data for anticoagulation strategies during VV-ECMO for patients in respiratory failure. Our study aimed to find an appropriate anticoagulation target for this patient group. The results show that although anticoagulation is required for circuit patency, there is an increased risk of bleeding when higher anticoagulation targets are set.

Disclosures
No relevant conflicts of interest to declare.
Relative Interfering Effects of In Vivo Direct Oral Anticoagulants on Routine Coagulation Tests
Authors: Kim Jinju , Song Yejin , Kim Hyun-Jeong , Yang Mi-Sook , Song Jaewoo 
Published: November 2021

Abstract
Background:
The interfering effects of DOACs on the screening coagulation tests, such as prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen assay, have been shown mainly by in vitro spiking experiments. However, the effects of DOACs on coagulation tests in real-world samples from anticoagulated patients are unknown because of the difficulty in selectively eliminating DOAC from blood samples already containing DOACs.
Method:
Citrated blood samples were drawn from patients on anticoagulation therapy (rivaroxaban and edoxaban). In addition, blood samples from patients not on anticoagulation were collected. PT INR and APTT were measured from those samples by coagulometers from two manufacturers (Roche t711, Swiss and ACL-TOP, USA). We also measured DOAC levels from the same samples by anti-FXa activity (Hyphen Biomed, France). Then, we compared the test results in relation to the DOAC levels.
Results:
The PT INR, APTT, and fibrinogen assay results from non-anticoagulated patients measured by the two coagulometers were comparable (PT INR: y = -3.353 + 1.029 x; APTT: y = -6.276 + 1.101x; fibrinogen: y = -3.353 + 1.029 x; Passing Bablok). We included blood samples from 61 patients on rivaroxaban and 75 patients on edoxaban. From the rivaroxaban samples we observed the regression line change for PT INR (y = 0.6303 + 0.3712x) and for APTT (y = -10.71+1.358x). The comparability of fibrinogen assay was not affected significantly (y = -17.39+1.01x). From the edoxaban samples we also observed the similar change of the regression line (PT INR: y = 0.4728 + 0.5661x; APTT: y = -133.07+2.014x). Fibrinogen levels were comparable (y = -28.95+1.082x).
Conclusion:
The susceptibility of screening coagulation tests to the interfering effects of in vivo DOAC is dependent on the reagents and coagulometers.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Clinical Analysis of Air-Leak Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients
Authors: Zhao Wei , Chen Man , Zhao Yanli , Wang Hui , Lu Peihua , Xiong Min 
Published: November 2021

Abstract
Background: Air-leak syndrome (ALS) occurs when there is leakage of gas from the alveoli, which results in clinical symptoms including cough and sputum, dyspnea, and hypoxemia. ALS is rare but potentially life-threatening in patients who have received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is an independent prognosis factor of patients undergoing HSCT. However, the clinical features and risk factors for post-transplant ALS among pediatric patients have rarely been explored.
Aims: This study analyzed the clinical characteristics, risk factors, clinical treatment options and prognosis to provide a scientific basis for ALS prevention and treatment for pediatric patients.
Methods: We retrospectively reviewed patients who were diagnosed with ALS following allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in the prognosis of the HSCT.
Results: A total of 2026 pediatric patients received an HSCT between January 2013 and December 2019. The ALS incidence rate was 1.4% (28 of 2,206 patients) with a survival rate of 64.3% (10 of 28 patients). The median overall survival (OS) time was 429 days (range: 55-1614 days). Sixteen patients were males and 12 were female. The median patients age was 12 years old (range: 1-16 years), and the median follow-up time was 871 days (range: 55-2973 days).We divided ALS into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). There was a significant difference in OS between the twogroups (80% among BOS patients versus 46% among IPS patients; P=0.037). Logical regression analysis showed that gender, an unmatched transplant donor and recipients (P=0.049), time to first occurrence of graft-versus-host disease after transplantation (P=0.021), and dosage of methylprednisolone &gt;0.5mg/kg at the onset of ALS (P=0.049), were independent risk factors for poor prognosis in ALS. In addition, we found fluticasone, azithromycin, and montelukast (FAM) could significantly improve the prognosis following ALS (P=0.005). Compared with IPS, our results showed that some patients with BOS may benefit from imatinib (P=0.055), ruxolitinib (P=0.009), or pirfenidone (P=0.044).
Conclusion: ALS is a rare manifestation of pulmonary complications following HSCT among pediatric patients. Our analysis demonstrates that early diagnosis and FAM treatment may improve the survival rate of ALS following HSCT among pediatric patients.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Combination of Haploidentical Hematopoietic with Low-Dose TBI and Cord Blood Transplantation for Hematologic Malignancies
Authors: Qian Shenxian , Yang Fan , Shi Pengfei 
Published: November 2021

Abstract
Objective: To evaluate the efficacy and safety of the combination of haploidentical hematopoietic with low-doseTotal body irradiation（TBI）and cord blood transplantation for hematologic malignancies.
Methods: This study was conducted as a retrospective review of medical records of 5 patients with hematologic malignancies who received a combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation at Affiliated HangZhou first people's hospital of Zhejiang University school of medicine, from March to June 2021.
Results: 5 patients were included for the analysis. There were 1 acute myeloid leukemia (AML),2 acute lymphoblastic leukemia (ALL) and 2 Non-Hodgkin's Lymphoma(NHL). The minimal residual disease (MRD) of the two patients with ALL was positive before allo-HCT.Median age of patients at the time of allo-HCT was 30 years (range 21-63 years). All patients received low-dose TBI(4-6GY) +antithymocyte globulin（ATG）based conditioning.Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. The median values of absolute total nucleated cell counts were 139.0 (80.8-240.0) × 10 7 / kg in The haploidentical grafts and 2.25 (1.32-3.10)× 10 7 / kg in the cord blood units,respectively. The median doses of CD34+ cells infused were 28.6 (22.0-51.1) × 10 5 / kg in the haploidentical grafts and 1.5 (1.0-3.5)×10 5/kg in the cord blood units, respectively.All patients attained complete engraftment,of which 3 were haploidentical engraftment and 2 were mixed hematopoietic chimerism that included haploidentical and cord blood engraftment.The median time to neutrophil engraftment was 12 (10-22) days and 13 (11-22) days for platelets. All patients were in complete remission with MRD-negetive during a median follow-up of 83 (34-136) days.No patients developed grade II-IV acute graft versus host desease.
Conclusion:The results suggested that the combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation may potentially improve the outcome of HSCT. It offers a transplant alternative for patients with hematologic malignancies who lack matching donors.

Disclosures
No relevant conflicts of interest to declare.
Bone Marrow Adipocyte Promotes Epithelial-Mesenchymal-Transition-like Activation in Multiple Myeloma Via CXCL-12/CXCR4 Axis
Authors: Shu Ling-Ling , Chen Shuzhao , Li Jinyuan , Wang Weida , Liu Yang , Li Yang , Huang Han-Ying , Wu Xiaoping , Liang Yang 
Published: November 2021

Abstract
Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. The bone marrow microenvironment is a key regulator of myeloma metastatic progression through the secretion of growth factors that activate epithelial-mesenchymal transition (EMT)-like characters. Bone marrow adipocyte (BMA) accumulates in obese patients and displays distinct immune regulatory properties rather than provides energy substrates, forming a bulk portion of the bone marrow microenvironment. Emerging evidence indicates the potential for adipocytes to influence cancer cell progression through the secretion of adipokines that can induce EMT activation. The molecular mechanisms underlying how adipocytes enhance multiple myeloma progression is largely unknown. The present study aims to investigate the precise mechanism of BMA promoting myeloma EMT-like activation and new potential therapeutic strategies targeting bone marrow adipocytes.
Newly diagnosed MM patients in our cancer center were recruited and divided into lean or obese group according to their body mass index (BMI). The bioinformatics-based analysis of transcriptome sequencing data for bone marrow stromal cells (BMSCs) derived from lean and obese MM patients identified that obese patients showed more obvious EMT-like transcriptional regulation characteristics and altered the expression of genes regulating EMT (Fig A), which was further confirmed by the immunohistochemistry staining of bone marrow biopsy (Fig B). Co-culture bone marrow adipocytes with myeloma cells significantly enhanced the proliferation and migration (Fig C-D). The transcriptome sequencing data of BMA further demonstrated that CXCL12 was enriched in BMA derived from obese MM patients (Fig E). We further confirmed that CXCL12 secreted by adipocytes induce EMT-like activation in myeloma cells, and the effect of CXCL12 expression on EMT is mediated through activation of CXCR4 (Fig F-G). Blocking of CXCR4 signaling in myeloma cells, decreased proliferation and invasion capabilities of myeloma cells cultured with CXCL12 (Fig H-I). Together, our results suggest that bone marrow adipocytes can enhance the aggressive behavior of myeloma cells and induce an EMT-like activation through paracrine CXCL12/CXCR4 signaling (Fig J).
In conclusion, paracrine signaling by BMAs can induce EMT-like activation and results in increased proliferation and invasion characteristics of myeloma cells. These results suggested that targeting CXCL12/CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.