bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Electronic Medical Records Study of Treatment Patterns Among CLL Patients in the CancerLinQ Research Database
Authors: Kabadi Shaum M , Kumar Supriya R , Wong Jennifer L 
Published: November 2019

Background: Chronic lymphocytic leukemia treatment has changed dramatically with the emergence of novel targeted therapies. Data generated on CLL treatments are mostly from clinical trials, which are primarily conducted at academic centers. There are limited data on contemporary CLL treatment patterns in the community practice setting in the United States (US).
Methods: Adults with CLL who initiated treatment between November 1, 2013 and March 31, 2018 were identified retrospectively from electronic health records (EHR) from the CancerLinQ Discovery Research Database and followed up until March 31, 2019. A random sample of patients were selected for further study. Patients enrolled in clinical trials or who had another primary cancer diagnosis within 2 years of CLL treatment start were excluded. Index date was record of first treatment for CLL. Baseline demographics, comorbidities, and treatment characteristics were derived from structured data elements of the EHR or abstracted from clinical notes in the EHR.
Results: 338 patients with a median follow-up of 26.9 months (range, 0.5-63.8), were included. Median age at treatment initiation was 69.7 years; 57.1% were male (Table 1). Of patients (n=110) with a known Eastern Cooperative Oncology Group (ECOG) score at diagnosis, 53.6% and 35.5% had an ECOG performance status of 0 and 1, respectively. The 3 most common treatments used for CLL regardless of line of therapy were rituximab (63.9%), ibrutinib (36.4%), and bendamustine (34.0%). Furthermore, the 3 most common comorbidities at index were hypertension (19.2%), anemia (16.0%), and thrombocytopenia (5.6%).
Conclusions: This is the first published real-world observational study in CLL using the CancerLinQ Discovery Research Database, providing information on baseline characteristics of patients with CLL receiving treatment in the community setting in the US. Additional analyses evaluating treatment-related adverse events and associated outcomes for CLL-directed treatments by line of therapy are ongoing.

Disclosures
Kabadi: AstraZeneca: Employment, Equity Ownership. Kumar:AstraZeneca: Employment, Equity Ownership. Wong:AstraZeneca: Employment, Equity Ownership.
Change in Treatments and Complications after Regionalizing High-Intensity Induction of Acute Myeloid Leukemia in a Community-Based Population, 2013-2017
Authors: Law Lisa Y , Uong Stephen , Ho Gwendolyn , Vempaty Hyma T. , Baer David M. , Liu Vincent , Herrinton Lisa 
Published: November 2019

Introduction: Patients with acute myeloid leukemia (AML) may receive more appropriate care when treated regionally instead of locally, but studies have not adequately accounted for baseline differences between regional and local cohorts. In 2015, Kaiser Permanente Northern California, an integrated healthcare delivery system, started to shift AML induction from local (N=21) to regional (N=3) centers. We assessed the association of regionalization with the frequency of use of induction therapy and bone marrow transplantation, and with 60-day mortality.
Methods: Information for all adult health plan members with ≥1 year of enrollment before receiving a diagnosis of AML during 2013-17 was obtained from the electronic health record. Multivariable methods were used to compare risk of induction, bone marrow transplantation, and death before and after 2015 (i.e., 2013-14 and 2016-17) after adjustment for baseline characteristics.
Results: Of 662 patients, 38% were ≥75 years, 30% had an Elixhauser comorbidity index ≥5, and 10% died within the week following diagnosis. Among non-APL patients, we observed increased use of induction therapy (65% vs 49%, p=0.0003) and bone marrow transplantation (23% vs 13%, p=0.007) after 2015, while the 60-day mortality rate did not change (before 2015, 94 of 278 [32.7%]; after 2015, 82 of 249 [32.9%]; p=0.83).
Conclusion: In this community-based population that includes advanced elderly patients with substantial comorbidity, regionalization was associated with increased use of induction therapy and bone marrow transplantation but no increase in the risk of 60-day mortality. Older patients can benefit from AML induction therapy at specialized centers.
Figure

Disclosures
No relevant conflicts of interest to declare.
Myeloablative Conditioning Is Preferred for Allogeneic Transplantation of Acute Myeloid Leukemia and Myelodysplastic Syndromes with Low/Intermediate but Not High Disease Risk Index
Authors: Bejanyan Nelli , Zhang Mei-Jie , Bo-Subait Khalid , Wang Hai-Lin , Warlick Erica D. , Brunstein Claudio G , Sandmaier Brenda M , Litzow Mark , Kebriaei Partow , Saber Wael , Weisdorf Daniel J. 
Published: November 2019

Although some data (Scott, JCO 2017) suggest that myeloablative conditioning (MAC) is preferred for allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), these data were not informed by analysis of disease specific risk factors. We analyzed AML and MDS HCT outcomes stratified by the disease risk index (DRI) in order to identify the preferred transplant conditioning intensity (reduced-intensity conditioning [RIC] vs. MAC). In this large CIBMTR registry study we identified 4387 adult patients (age 40-65 years) who received HCT for AML (68%) or MDS (32%) between 2009 and 2015. DRI was stratified as low/ intermediate risk (1539 MAC and 999 RIC) and high/ very high risk (1121 MAC and 728 RIC). Examining the low/ intermediate risk DRI cohort (Table), RIC was associated with lower risk of TRM (HR=0.74, 95% CI 0.62-0.88; p<0.001) but significantly higher risk of relapse (HR=1.54, 95% CI 1.35-1.76; p<0.001). As a result, RFS in this cohort was significantly worse with RIC (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/ very high risk DRI cohort, RIC resulted in similar TRM (HR=0.83, 95% CI 0.68-1.00; p=0.051) but again significantly higher risk of relapse (HR=1.23, 95% CI 1.08-1.41; p=0.002). RFS in high/ very high risk DRI cohort was similar between RIC and MAC. Adjusted outcome curves for the 3 endpoints are shown in the Figure.
In this large study of HCT for AML or MDS stratified by DRI, RIC was independent predictor of lower TRM, but significantly higher risk of relapse. The MAC was an independent predictor of lower relapse in both low/ intermediate and high/very high DRI groups. However, MAC only resulted in RFS benefit in the low/ intermediate group where the magnitude of impact on relapse was not offset by the higher TRM.
In adults with AML or MDS aged 40-65 years, these data support MAC as the preferred conditioning intensity for low/ intermediate risk DRI, whereas MAC does not provide significant benefit in those with high/ very high risk DRI. Safer, yet still potent MAC regimens could benefit this higher risk group.

Disclosures
Bejanyan: Kiadis Pharma: Other: advisory board. Brunstein:Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria; Pfizer: Honoraria; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.
Development of an Immunotherapeutic Monoclonal Antibody Recognizing DKK1-HLA-A2 Complex to Treat Human Hematologic Malignancies
Authors: Qian Jianfei , Wang Qiang , Liu Lintao , Bi Enguang , Ma Xingzhe , Su Pan , Yang Maojie , Yi Qing 
Published: November 2019

Immunotherapy is a promising option for cancer treatment. Our previous studies demonstrated that DKK1 is widely expressed by various tumor cells including multiple myeloma (MM) and other hematological malignancies but not normal tissues, and DKK1 peptide (such as P20 and P66v, which bind with HLA-A2 molecule) specific cytotoxic T cells specifically kill myeloma and other cancer cells that express DKK1 and HLA-A2, but not HLA-A2+ normal cells, indicating that DKK1+ tumor cells naturally express these peptides, in the context of HLA-A2 molecules, on their surface. To develop cancer therapeutic antibodies, DKK1 peptide P20-HLA-A2 monomer was synthesized and used to immunize mice. Hybridomas secreting monoclonal antibodies (mAbs) recognizing soluble and cell surface-expressed DKKl P20-HLA-A2 complex were obtained and analyzed. The mAbs bind specifically with DKK1-expressing, HLAA2+ cancer cells but not DKK1-expressing, HLA-A2- cancer cells or DKK1- HLA-A2+ normal blood cells. The mAbs exhibited potent in vitro tumoricidal activity on HLA-A2+DKK1+ U266 multiple myeloma cells, HLA-A2+DKK1+ PC-3 prostate cancer cells and T2 cells loaded with DKK1-P20 peptides. Our results also showed that the anti-DKK1-HLA-A2 mAbs effectively lysed cancer cells via antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which were correlated with and dependent on the surface expression of DKK1-HLA-A2 complex on cancer cells. Furthermore, anti-DKK1/HLA-A2 mAbs were also active and therapeutic in vivo. In MM xenografted SCID mouse model, the mAbs were able to eradicate U266 MM cells and more than 60% of mAb-treated mice survived for 3 months, while control mice all died within 2 months. Toxicity and safety assay in MM xenografted A2-SCID mouse model showed that the mAbs had no significant negative effects on different normal tissues. Therefore, these results support clinical development of anti- DKK1-HLA-A2 mAbs as therapeutic agents to treat hematological malignancies and possibly solid tumors that express surface DKK1-HLA-A2.

Disclosures
No relevant conflicts of interest to declare.
Human Interleukin 15 (IL15) Humanized NCG Mice Support the Human Natural Killer Cells Reconstitution and Development
Authors: Ju Cunxiang , Zhang Mingkun , Wu Dan , Tang Jing , Li Shuai , Zhao Jing , Wang Demin , Gao Xiang 
Published: November 2019

NCG (GPT strain ID: T001475), one of the highly immune-deficient mouse models generated so far, is ideal for engraftment of human tissues and cells, such as patient derived tumors (PDX), human cancer cell lines (CDX), human peripheral blood mononuclear cells (PBMC) and human hematopoietic stem cells (HSCs). NK cells that are a critical component of the innate immune system have diverse biological functions, such as recognizing and killing viral-infected and neoplastic cells. Human HSCs (CD34+) could reconstitute human T but not NK cells in NCG mice. The cytokine Interleukin 15 (IL-15) plays a critical role in the generation of NK cells from HSCs. IL-15 is produced by non-lymphoid cells, including monocytes, dendritic and bone marrow stromal cells. Human and mouse IL-15 are only 70% identical to each other in primary amino acid sequence. Mouse IL-15 poorly supports the reconstitution of human NK cells.
To overcome this problem, several lines of transgenic mice that express human IL-15 (hIL-15) have been established. However, the non-physiological levels of hIL-15 expression are detrimental to human immune system reconstitution.In the current study, we developed hIL-15 knock-in in NCG mice (NCG-hIL-15), in which the mouse IL-15 (mIL-15) gene was replaced by the hIL-15 gene. We quantified the mRNA expression of hIL-15 and found that the levels of hIL-15 expression in the BM, liver, lung, and small intestine of NCG-hIL-15 mice were similar to those of mIL-15 in NCG mice.Based on these data, we expect that NCG-hIL-15 mice can efficiently support the development, maturation and function of human NK cells. In the future, we will further study human NK cell engraftment and human NK cell-mediated cancer immunotherapy in NCG-hIL-15 mice.
Taken together, our newly developed NCG-hIL-15 mice offer a novel mouse model for studying human NK cell biology and human NK-mediated cancer immunotherapy in vivo.

Disclosures
Ju: GemPharmatech Co., Ltd: Employment. Zhang:GemPharmatech Co., Ltd: Employment. Wu:GemPharmatech Co., Ltd: Employment. Tang:GemPharmatech Co., Ltd: Employment. Li:GemPharmatech Co., Ltd: Employment. Zhao:GemPharmatech Co., Ltd: Employment. Wang:GemPharmatech Co., Ltd: Employment. Gao:GemPharmatech Co., Ltd: Employment.
Real-Time Electronic Health Registry Improves Care for Children with Sickle Cell Disease
Authors: Singh Ashima , Danda Vanaja , Panepinto Julie 
Published: November 2019

Objective: Published literature shows low and variable compliance with the recommended guidelines for care of children with sickle cell disease (SCD). Our objective was to use an electronic health record (EHR)-based registry to track and improve compliance with the recommendations for the pediatric population of SCD at our institution, using annual transcranial doppler screening (TCD) as an example.
Methods: We developed an in-EPIC real time registry for children with SCD in the year 2016 to enhance point of care and improve quality. Since 2017, we have been conducting plan-do-study-act (PDSA) cycles using the registry to improve TCD compliance. We extract data quarterly to examine TCD rates and share with the clinical team the list of children who have not received a TCD screening in the past 18 months. This allows the clinical team to provide case-management to reduce non-compliance. We recently added Child Life support to increase TCD compliance among children <7 years. We use control charts to examine TCD rates after the aforementioned interventions. We also continually refine the registry to broaden the provision of quality care to the patient population.
Results: One year into the registry, which we considered baseline and the start of the first PDSA cycle, 63% of children were compliant with the recommendation of an annual TCD screen. The TCD rates steadily increased to 80% by the third-quarter of 2017. We observed a dip in TCD rates by the second-quarter 2018 (66%), felt to be in part driven by failure of screening young children. Since the initiation of Child Life Support for young children, the overall TCD rates increased to 74% (first-quarter 2019). Our data demonstrate a sustained improvement in TCD rates since 2016 and meet criteria for special cause variation (Figure 1). We have recently added other metrics such as acute care encounters external to our institution, magnetic resonance imaging, and an indicator for active hydroxyurea use to the registry.
Conclusion: Use of an EHR-based registry to track and provide feedback on quality of care metrics such as annual TCD screening can result in sustained improvement in compliance with the recommended guidelines. Preliminary evidence indicates that Child Life involvement further improves TCD rates. Future work will determine if audit and feedback for other metrics added to the registry can improve compliance and improve outcomes.

Disclosures
Panepinto: NIH: Research Funding.
Intravenous Iron Infusions in Pediatric Patients: A Single Institution Assessment of Efficacy and Adverse Effects of IV Iron Infusions
Authors: Nestor Jennifer A , Afridi Faraz A , Suarez Richard , Karem Joey Bou , Hardiman Michael , Hunter Krystal , Rickette Christine , Ahmed Rafat 
Published: November 2019

Background:
Iron deficiency, even without a diagnosis of anemia, can be neurodevelopmentally dangerous in pediatric populations. Oral iron supplementation has been the treatment of choice but is associated with poor adherence for several reasons including metallic taste of the tablets, gastric irritation, severe constipation, and daily dosing for several weeks. Intravenous iron has been safely used in adult populations for iron supplementation, but has less commonly been used in pediatric populations. It is hypothesized that pediatric patients with iron deficiency anemia (IDA) who receive intravenous iron infusions will show normalization of hematologic parameters.
Methods:
EMR of patients aged 1-21 who received at least one intravenous iron infusion at Cooper University Hospital between 2016 and January 2019 were reviewed for retrospective data collection. Pre-infusion lab values including Hgb, MCV, RBCs and RDW were compared to post-infusion values to determine if values normalized after intravenous iron infusion. Patient demographics including ethnicity, cause of IDA, prior oral iron treatments, and adverse effects of oral and IV iron were analyzed.
Results:
There were 33 subjects in this study. The average age of the subjects was 12.8 (+/- 5.1) years of age and 79% were female. The most prevalent indication for IV iron was menorrhagia (55%), while GI issues were 18% and insufficient diet accounted for 27%. The mean baseline HGB was 8.3 (+/- 1.7) while the mean final HGB increased to 11.5 (+/- 1.4) (p<0.001). The mean baseline MCV was 69.2 (+/- 9.3) and the mean last MCV was 76.1 (+/- 6.8) (p<0.001). The mean baseline RBC was 4.2 (+/- 0.82) and the mean last RBC was 4.9 (+/- 0.6) (p<0.001).
Conclusion:
IV iron sucrose infusions administered to pediatric outpatients were safe and effective in children and adolescents with IDA. Adherence to intravenous iron did not significantly improve. Hematologic parameters improved with infusions. Further analysis of patient demographics and characteristics of diagnosis needs to be performed to elucidate benefits of this therapy. As a single institution study, the results are limited to a regional patient population and their specific demographics.

Disclosures
No relevant conflicts of interest to declare.
Hematocrit and Incidence of Venous Thromboembolism
Authors: Cushman Mary , Wang Wendy , Parikh Romil , Lutsey Pamela L , Beckman Joan D , Folsom Aaron R 
Published: November 2019

Background. Polycythemia vera patients with high hematocrit have increased risk of venous thromboembolism (VTE). We tested whether high hematocrit in the general population is also associated with elevated VTE risk.
Methods. The prospective Atherosclerosis Risk in Communities (ARIC) Study performed a complete blood count in 13,891 adults aged 45-64 at baseline in 1987-89. We identified and validated incident hospitalized VTEs through 2015, with provoked VTE defined as occurring within 90 days of surgery, trauma, immobilization or with cancer. We performed proportional hazards regression analyses using race-sex specific categorization of hematocrit percentiles (i.e., <5, 5-24.9, 25-74.9, 75-94.9, and 95-100 percentiles, with the 25-74.9th percentile serving as the reference group).
Results. At baseline, higher hematocrit was associated with smoking prevalence, greater pack years smoked, higher body-mass index and higher prevalence of diabetes. With 26 years median follow-up, 800 participants had incident deep vein thrombosis of the leg and/or pulmonary embolism. The figure shows a J-shaped association of hematocrit with VTE incidence. The VTE incidence at the highest level of hematocrit was approximately double that at the mid level. Low hematocrit also was associated with elevated VTE incidence but the confidence interval overlapped 1. The Table shows modeling results. Accounting for other risk factors, the risk of overall VTE was elevated 72% for participants above the 95th percentile of hematocrit compared with the reference. Specifically, hazard ratios (95% confidence interval) of incident VTE were 1.27 (0.91,1.76), 1.06 (0.87,1.28), 1 (reference), 1.17 (0.98, 1.40) and 1.72 (1.30, 2.27) across the five hematocrit percentiles, adjusted for age, race, sex, body mass index, and other potential confounding variables including smoking status and pack-years. The association of high hematocrit with VTE was limited to provoked VTE, with little evidence for unprovoked VTE. Results were similar for hemoglobin (not shown).
Discussion. High hematocrit and hemoglobin in a general middle-aged population sample were associated with increased long-term risk of VTE, particularly provoked VTE. The reasons for this pattern require further study.

Disclosures
No relevant conflicts of interest to declare.
Treatment of Upper Extremity Deep Vein Thrombosis with Apixaban and Rivaroxaban
Authors: Houghton Damon E. , Cochuyt Jordan , Hodge David O. , Vlazny Danielle , Casanegra Ana I , Peterson Lisa , Froehling David A , McBane Robert D. , Wysokinski Waldemar E. 
Published: November 2019

Background: Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with UE-DVT. Limited observational data has been published on outcomes in this setting and no direct comparison to traditional anticoagulation has been performed.
Objective: Evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT compared to low-molecular weight (LWMH) and warfarin.
Methods: Consecutive patients with VTE were enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and July 22, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received either rivaroxaban, apixaban, LMWH or warfarin within the first 14 days after diagnosis and who completed at least 3 months of anticoagulant therapy or had an outcome event in that period were included into the analysis. Recurrent VTE, major bleeding, clinical relevant non-major bleeding (CRNMB), and death were assessed at 3 months, in person whenever feasible, or by mailing a written questionnaire or a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board.
Results: One hundred and thirty-four patients with acute UE-DVT were included. Forty-one were treated with apixaban, 32 with rivaroxaban, and 61 with LWMH and/or warfarin. The mean age was 58.3 years, mean BMI was 28.2, and 59% were male (Table 1). Patients treated with LMWH / warfarin were older (61.3 vs 55.8, p=0.04) and had a lower BMI (27.1 vs 29.0, p=0.0496). Twenty-six (19%) patients had catheter-associated UE-DVT, 93 (69.4%) had a diagnosis of malignancy, and 16 (11.9%) had concurrent pulmonary embolism, which were similar between groups. More patients on apixaban /rivaroxaban were receiving chemotherapy (53.4% vs 47.5%, p=0.04) and had recent surgery (13.7% vs 3.3%, p=0.04) compared to LMWH / warfarin. At 3 months of follow up, 1 recurrent VTE occurred in patients treated with LMWH /warfarin and none of those treated with apixaban /rivaroxaban (p=0.27). Major bleeding occurred in 2 patients treated with LMWH /warfarin and in none of those treated with apixaban /rivaroxaban (p=0.12). CRNMB occurred in 1 patient treated with LWMH /warfarin and 5 patients treated with apixaban / rivaroxaban (p=0.15). Two of the CRNMBs occurred with rivaroxaban and 3 occurred with apixaban. Death occurred in 5 patients treated with LMWH /warfarin and in none of the apixaban /rivaroxaban treated patients (p=0.01).
Conclusion: This single institution prospective study adds to the limited experience with apixaban and rivaroxaban for acute UE-DVT. Treatment of UE-DVT with rivaroxaban and apixaban appears to be as safe and effective as LMWH/warfarin after 3 months of anticoagulation.

Disclosures
McBane: BMS: Research Funding.