bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reporting Bleeding Outcomes in Adult and Pediatric Studies of Primary Immune Thrombocytopenia: A Systematic Review
Authors: Noroozi Nastaran , Neunert Cindy , Goy Jennifer K , Buchanan George R. , Blanchette Victor S. , Arnold Donald M. 
Published: October 2019

Abstract
Abstract 4281

Background:
Bleeding is arguably the most clinically meaningful outcome in ITP clinical studies since it impacts morbidity, mortality and quality of life. Yet, the measurement of bleeding is not standardized, and its prevalence as a study outcome has not been well characterized.

Methods:
We performed a systematic review of all English language, prospective clinical studies enrolling 20 or more adults or children with primary ITP to determine if and how bleeding data were reported. In duplicate and independently, we searched MEDLINE, EMBASE, Cochrane and Cinahl databases until January 2012. Titles were screened for relevance and abstracts and full text articles were reviewed in duplicate for eligibility. Study selection and data abstraction were performed in duplicate. Patient demographics, use of a bleeding measurement tool and frequency of bleeding were collected from all studies.

Results:
We identified 167 prospective studies, including 29 (33%) randomized trials enrolling 13,976 patients with primary ITP (including 3,723 adults; 9,730 children; and 523 combined adults and children). Of 167 studies, 87 (52.1%) reported bleeding either as an efficacy endpoint (n=77), a safety endpoint (n=5) or both (n=5). Of the 87 studies that reported bleeding, 17 (19.5%) used an ITP-specific bleeding measurement tool. Such a tool was used in 4 of the 29 randomized trials. Less common were the Common Terminology Criteria for Adverse Events score (n=4) and the World Health Organization score (n=4); but the majority of studies did not use a predefined tool to measure bleeding. Bleeding was reported as present or absent (n=8 studies, 9.1%); by anatomical site only (n=39, 44%); by severity only (n=1, 1.1%); or by severity and anatomical site (n=29, 33%). Ten (29.8%) studies did not specify how bleeding was measured. Forty-three studies reported some association between platelet count and bleeding; however, none provided a statistical association with severity of thrombocytopenia.

Summary:
This study represents a summative description of the English-language world literature on bleeding outcomes in ITP studies. Of all studies, just over half (52.1%) reported bleeding outcomes. Only 20% of studies used a bleeding measurement tool that was specific for ITP patients. A standardized approach to bleeding and other patient-centered outcomes will help direct future research in ITP.
Funding support from the McMaster Division of Hematology & Thromboembolism.

Disclosures:
Arnold: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffman-LaRoche: Research Funding.
Comparison of Complications Related to Peripherally Inserted Central Catheters, Infusion Ports, and Hickman Catheters in Acute Myeloid Leukemia Patients
Authors: Khalil Mohammad O. , Pierson Namali , Maymani Hossein , Holter Jennifer L. , Cherry Mohamad Ali 
Published: October 2019

Abstract
Abstract 4288

Background:
Intravenous catheters are widely used in acute myeloid leukemia (AML) patients. Complications associated with these catheters are frequently encountered and contribute to morbidity, mortality, and increased cost of treatment. Studies exploring and comparing complications in the different types of catheters in this unique patient population are lacking. We retrospectively studied infectious and thrombotic catheter-related complications in AML patients treated at the largest tertiary referral center for AML in Oklahoma.

Methods:
AML patients above the age of 18 who were referred to The University of Oklahoma Health Sciences Center from January, 2000 to June, 2012 were identified and medical records were reviewed. Patients were stratified according to type of first catheter inserted (peripherally inserted central catheter (PICC), infusion port (IP), or Hickman). First catheter-related blood stream infection and deep venous thrombosis (DVT) events were reported (subsequent catheter-related complications were not included). Statistical analysis was performed using SAS 9.2 software (SAS Institute Inc). Fisher exact test was used to compare patients with different types of catheters.

Results:
195 patients with AML were identified; of which 125 were included in the analysis (Patients referred for stem cell transplant (SCT) were excluded if not treated with prior chemotherapy at our institution). Median age at diagnosis was 51 years. 87 (70%) were males and 38 (30%) were females. 97 (78%) were White, 11 (9%) Native Americans, and 10 (8%) African Americans. 73 (58%) had PICC, 34 (27%) had Hickman, and 17 (14%) had IP. Blood stream infection occurred in 34% of all patients. Blood stream infection rates in each group were 32% in patients with PICC, 47% with IP, and 31% with Hickman (p=0.47). When divided by age group, infections occurred in 41% of patients 55 years of age or older and in 29% of those <55 years (p=0.19). Gram-positive cocci accounted for 57% and Gram-negative rods for 30% of all infections. DVT occurred in 14% of all cases. DVT rates in each group were 22% in patients with PICC, 6% with IP, and none with Hickman (p=0.002). When divided by age group, thrombosis rates were 9% in patients 55 years of age or older and 17% in those <55 years (p=0.29). 39% of patients with platelet count >20,000/microL at the time of event had DVT compared to only 8% of those with platelet count <20,000/microL (p=0.0005).

Conclusion:
Among AML patients referred to our institution, PICCs were associated with significantly higher rate of DVT compared to IPs and Hickmans. Platelet count >20,000/microL was also associated with significantly higher rate of thrombosis. There was no difference in blood stream infections across the different catheter types.

Disclosures:
No relevant conflicts of interest to declare.
Impact of Body Mass Index (BMI) On Overall Survival in Myeloma
Authors: Kumar Mukesh , Nooka Ajay K. , Langston Amelia , Gleason Charise , Watson Melanie , Collins Hannah , Casbourne Daniela , Boise Lawrence H. , Kaufman Jonathan L. , Waller Edmund K. , Lonial Sagar 
Published: October 2019

Abstract
Abstract 4289

Introduction:
Excess body weight has been identified as a risk factor for developing myeloma. From a meta-analysis of 15 cohort studies evaluating myeloma incidence and 5 others on mortality, the risk of multiple myeloma was significantly elevated among overweight patients and obese patients. Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. A polymorphism (allele 174C) in the IL-6 gene promoter is associated with obesity and hence, the hypothesis that overweight may be a surrogate for IL-6 promoter genotypes, and associated with increased risk of plasma cell neoplasms has been proposed. However, data is limited in evaluating the outcomes in these patients, based on BMI. We have evaluated the impact of BMI on overall survival in patients with myeloma.

Methods:
We have evaluated a total of 589 patients that underwent ASCT during the period January 2005 through June 2011 from our myeloma database. The median time of follow up is 50 months in all patients and 23 months post ASCT. We used IBM SPSS version 20 to generate the survival statistics.

Results:
The median patient age at the time of diagnosis and at ASCT is 57 years (range, 26–77) and 59 years (range, 26–78), respectively. Patient characteristics: 55%/45% male/female; 56%/36% white/black; ISS stage I/II/III 38%/19%/43%; ASCT conditioning melphalan 140/200 15%/85%. At a median follow up of 50 months from the time of diagnosis and 23 months from the time of ASCT, 75% of the patients are expected to be alive at 109 months. OS was not statistically different between the groups stratified on gender and race. OS from the time of diagnosis and from the time of ASCT was not statistically significant in patients stratified by BMI 18.5–24.9; 25–29.9; 30–34.9; 35–39.9 and ≥40. However, for the patient group with BMI&lt;18.4 vs. ≥18.5; the OS from the time of diagnosis (75% survival: 55 months vs. 109 months; p=0.018) and from the time of ASCT (median OS: 43 months vs. NR; p=0.017) was significantly different, in favor of the BMI≥18.5 group.

Conclusion:
Our results suggest that patients that received ASCT have significant survival benefit. Higher BMI does not confer a negative impact on the prognosis of obese patients, as they actually have better survival after ASCT. Patients that are underweight (BMI&lt;18.4) have inferior survival as those with higher BMI. This effect is possibly related to cancer cachexia or malnutrition, or increased toxicity from the conditioning regimen.

Disclosures:
Kaufman: Millenium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Onyx Pharmaceuticals: Consultancy. Waller:Outsuka: Research Funding.
Study On the Recovery of Immune System After Chemotherapy in Pediatric Acute Lymphoblastic Leukemia
Authors: Jiang Qian , Qun Yang , Zheng Huyong 
Published: October 2019

Abstract
Abstract 4299

Background:
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Nowadays, the cornerstone treatment of ALL is chemotherapy, which will destroy immune system at the same time of killing leukemic cells. After the cessation of chemotherapy, the immune system will rebuild gradually. Our previous study based on the BCH 93 and BCH 98 protocols showed immune system reconstruction would take 2–3 years after the cessation of chemotherapy. In recent years, the intensive chemotherapy is decreased because of accurate classification of ALL, resulting in much more proper treatment which can both cure the leukemia and reduce side effects, such as immune depression. In this study we investigate the recovery of immune system of ALL patients treated by an update CCLG-ALL-2008 protocol in Beijing Children's Hospital of Capital Medical University.

Methods:
There were 104 ALL patients enrolled in this study. Their immunenoglobins (Ig) and T lymphocyte subtypes in peripheral blood were examined at the time points of 0 month, 12 months and 24 months after cessation of chemotherapy, respectively. The data was analyzed by statistical software of SPSS19.0.

Results:
Immunenoglobins of IgA, IgG, IgM and IgE were lower at the cessation of chemotherapy, and increased significantly at 12 months of stopping treatment. The IgA, IgG, IgM and IgE recovered to normal level in 61.54%, 89.23%, 90.77%, and 89.83% of ALL patients, respectively at 12 months of stopping treatment. The total B cells, T cells, CD4, CD8 and NK cells recovered to normal level in 84.85%, 92.54%, 71.64%, 67.16% and 69.23% of ALL patients, respectively at 12 months of stopping treatment. The level of immunenoglobins and T lymphocyte subtypes were no statistical differences between the time points of 12 and 24 months after cessation of chemotherapy.

Conclusion:
Most of ALL patients rebuild their immune system within 12 months after the cessation of chemotherapy. Current protocol of CCLG- ALL-2008 based on the risk classification is more reasonable that shorten the time of immune reconstruction, compared to the results in published literatures based on our previous protocols of BCH93 and BCH 98.

Disclosures:
Zheng: Beijing Health System High-level Technical Personel Plan: Research Funding.
Low MDR1 and BAALC expression Identifies a New Subgroup of Adult Cytogenetically Normal Acute Myeloid Leukemia with a Favorable Outcome
Authors: Guo Xutao , Chen Feili , Shi Pengcheng , Zha Jie , Liu Bingshan , Zheng Haiqing , Xu Bing 
Published: October 2019

Abstract
Abstract 4312

OBJECTIVE:
Cytogenetically normal acute myeloid leukemia (AML) is a heterogeneous disease, in terms of genetic/molecular abnormalities resulting into marked differences in outcome. We demonstrated that MDR1, BAALC expression was of prognostic significance and high MDR1 expression correlated with a high BAALC expression (r=0.487, P<0.001) in cytogenetically normal AML in the prophase study then we hypothesized that MDR1 and BAALC expression together would better identify the patient's risk profile.

METHODS:
Pretreatment bone marrow samples from 92 cytogenetically normal AML patients were analyzed for MDR1 and BAALC mRNA expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into low MDR1 and BAALC expression group and combined group (high MDR1 and/or high BAALC expression) according to MDR1 and BAALC levels and were compared for clinical outcome.

RESULTS:
73 cases of 92 cytogenetically normal AML patients got CR after the first block with a CR rate being 79.3%. However, 29 cases of the CR patients relapsed with the relapsed rate being 39.7%. In contrast, Patients with low expression of both MDR1 and BAALC had a higher CR rate (93.3%vs72.6%, P=0.021), lower relapse rate (7.1% vs. 42.5%, P=0.000), longer OS (50.3% vs 17.8%,P=0.001) than high MDR1 and/or high BAALC expression (combined group) in cytogenecally normal AML. Results showed no statistical difference in CR rate (93.3%vs85.7%, P=0.341),relapse rate (7.1% vs. 8.8%, P=0.000) and OS (50.3% vs 63.1%,P=0.431) for cytogenetically normal patients with both MDR1 and BAALC low expression comparing to those with low-risk cytogenetically abnormal.

CONCLUSION:
The combined assessment of BAALC and MDR1 expression can improve treatment stratification in adult cytogenetically normal AML. Low expression of both MDR1 and BAALC identifies cytogenetically normal AML patients with a favorable long-term outcome.

Disclosures:
No relevant conflicts of interest to declare.
Azacitidine in Relapsed and Refractory AML: Efficacy for Patients Relapsing As MDS Post AML
Authors: Ivanoff Sarah , Lemasle Emilie , Gruson Berengere , Merlusca Lavinia , Charbonnier Amandine , Parcelier Anne , Damaj Gandhi , Royer Bruno , Marolleau Jean Pierre 
Published: October 2019

Abstract
Abstract 4332

Background:
Azacitidine (Aza), inhibitor of DNA methyltransferases, plays an important role in epigenetic regulation of gene expression and tumorogenesis, and is active in myeloid neoplasia such as myelodysplasia (MDS) and de novo acute myeloid leukemia (AML). Efficacy of Aza for relapsed and refractory AML has not been so far reported.

Methods:
We report in 2 french centers (Amiens, Rouen) retrospective study, the results of Aza for relapsed or refractory patients. All patients received Aza (75 mg/m2 per day over 7 days for 4 weeks cycles), until progression, and at least one cycle. Leukocyte blood count was < 10109/l. The primary endpoint was overall response rate (ORR), according to IWG 2006: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), hematological improvement (HI). Secondary endpoints were duration of response and overall survival (OS).

Results:
41 patients (26 males and 15 females) with a median age of 59 years (range 28–78) were studied from August, 2007 and November, 2011 (Table): 15 had refractory and 26 relapsed AML. At relapse 11/26 had MDS, defined by blast count <20% and cytological morphology of MDS in bone marrow aspirate, and 15/26 AML.
Patients received in average 6 cycles (1–30): 4 (1–7) for refractory; 7 (1–30) for relapsed (11 (3–30) for MDS post AML; 3 (3–5) for relapsed AML).
Overall, the ORR was 34% (7 CR, 5 RP, and 9 HI). For patients with MDS post AML OR was 82% (7 CR, 2 RP, 7 HI), 13% (1 RP, 1 HI) for relapsed AML, and 13% (2 PR and 1HI) for refractory AML.
The average duration of response was 4 months (0–39) for the 41 patients: 14 months (0–39) for MDS post AML, 0.3 for relapsed AML, and 0.5 for refractory.
Overall survival from diagnosis was 29 months (6.9–87): 38.2 (12–57) for MDS post AML, 30.1 (6.9–87) for relapsed AML and 13.3 (6.9–35.5) for refractory (no significant differences).
Overall survival from initiation of Aza was 9.4 months (1.1–39.2): 22.6 (4.8–39.2) for MDS post relapsed and 3.9 (0.3–11.3) for relapsed AML and 6.2 (1.1–13.3) for refractory patients. The differences are not statically significant probably due to small effective of our study. Contrarily to the others 2 groups, 6 patients (55%) with MDS post AML are alive in CR at the latest report; moreover three of them underwent an allogeneic transplantation.

Conclusion:
Aza seems to efficient for relapsed AML patient, especially for MDS post AML, but inappropriate for refractory patients.

Disclosures:
No relevant conflicts of interest to declare.
Breakthrough Stroke During Rivaroxaban Therapy in a Patient with Non-Valvular Atrial Fibrillation
Authors: Ahn Inhye E , Kim Myungsun 
Published: October 2019

Abstract
Abstract 4370

Introduction.
Rivaroxaban is the first orally active direct factor Xa inhibitor FDA approved for anticoagulation in non-valvular atrial fibrillation. Rivaroxaban has several remarkable aspects-it has less incidence of fatal bleeding and intracranial hemorrhage compared to Warfarin, excellent pharmacodynamic profile as an oral agent (high bioavailability (80–100%) and short half-life (7 to 11 hours), and it is reversible- which highlights Rivaroxaban as a promising future anticoagulant. However, 1.71% of Rivaroxaban arm in ROCKET-AF (New Eng J Med 2011;365:883-91) trial developed breakthrough stroke or systemic embolism while on therapeutic dose. We present the first report of breakthrough stroke in a patient with non-valvular atrial fibrillation anticoagulated with Rivaroxaban.

Case presentation.
A 52-year-old Caucasian male with non-valvular atrial fibrillation presented with aphasia, right-sided weakness and right facial droop. The patient was newly started on Rivaroxaban for two weeks followed by successful elective cardioversion a day prior to admission. One hour prior to admission, the patient was found with global aphasia, right hemianopsia and hemiparesis consistent with left MCA stroke. Ischemic CVA was confirmed with non-contrast CT. The patient underwent emergent cerebral angiogram and successful mechanical thrombolysis (Solitaire) of left MCA embolus. A week later, neurologic condition improved to hemiparetic and independent gait with residual dysarthria and right facial droop. Given his breakthrough embolic event, the choice of anticoaulgation was changed to Dabigatran.

Conclusion.
We have demonstrated the first case of breakthrough stroke while on therapeutic dose of Rivaroxaban in a patient with non-valvular atrial fibrillation. In a subset of patients with ischemic stroke while on therapeutic doses of oral anticoagulants, mechanical thrombolysis is crucial and intravenous thrombolytics should be avoided to minimize risk of intracranial hemorrhage. The effectiveness of alternative anticoagulation after failing Rivaroxaban needs to determined with further studies.

Disclosures:
No relevant conflicts of interest to declare.
The Benefit of RED CELL Antigen Testing in A Transfusion Service of A Large Cancer Center
Authors: Aung Fleur M. , Reddy Virgil M , Lichtiger Benjamin 
Published: October 2019

Abstract
Abstract 4374

Introduction:
DNA-based tests are increasingly being used to predict blood group phenotypes in patients who have been recently transfused to aid in alloantibody identification, to distinguish an alloantibody from an autoantibody, in patients who have received hematopoietic stem cell transplants, when RBCS are coated with immunoglobulin (+DAT) and to detect weakly expressed antigens when the patient is unlikely to make antibodies to antigen- positive RBC's transfused. The molecular bases associated with most antigens have been determined and PCR-assays available for testing RBC antigens are a powerful adjunct to the conventional hemagglutination, the gold standard technique to type RBCs for the presence or absence of blood group antigens.

Purpose:
This retrospective review of Red Blood cell (RBC) antigen testing data was conducted on all patients typed between January 2010 and December 2011 at MD Anderson Cancer Center. The purpose was to review the concordance between the antibody (ies) identified by serologic testing and the antigen negativity from phenotype predicted from DNA analysis for selecting antigen negative RBCs for transfusion. In addition we also wanted to review whether the extended phenotype red cell units transfused to patients with unidentified alloantibody (ies)/RACT and autoantibodies formed additional red cell alloantibody (ies) after transfusion.

Methods:
The technology of BioArray Solutions (Bioarray Solutions, Immuncor, Norcross, GA, USA) and the Human Erythrocyte Antigen (HEA) v1.2 BeadChip was used to assess the genotype and predicted phenotype of patients. We performed RBC antigen testing on all of our recently transfused patients with alloantibody (ies), patients whose red cell antibody panels showed reaction with all red cells tested (RACT) or unidentified antibodies, patients with positive direct antiglobulin test (DAT) and whose elution studies showing RACT or unidentified antibody (ies) and in patients with autoimmune hemolytic anemia.

Results:
Atotal of 912 BioArray tests were performed on 912 patients [444 (49%) males:468 (51%) females; median age 60 years (range 1–92)]. Antibody screen was positive in 424 (46%) and negative in 488 (54%) patients. A DAT was performed in 126 patients with a positive antibody screen to establish immune from non-immune hemolytic anemia. The results are listed in Tables 1,2 and 3.

Conclusion:
We found 100% concordance between the predicted antigen negativity phenotype and the patient's RBC alloantibody (ies) identified by serologic testing. The RBC antigen typing has allowed us to transfuse patients with unidentified antibodies and RACT with extended phenotype matched red cell units preventing the development of additional red cell alloantibody (ies) as well as allowed us to transfuse antigen-negative units preventing patient/blood donor incompatibility issues.

Disclosures:
No relevant conflicts of interest to declare.