bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presentation and Outcome of Idiopathic Thrombocytopenic Purpura in Children: A Single Institution Experience
Authors: Bradham Kari , Wilson Felicia L. , Imran Hamayun 
Published: October 2019

Abstract
Abstract 4683

PURPOSE:
To review the presenting features, response to treatment and outcome in children diagnosed with idiopathic thrombocytopenic purpura (ITP) at the University of South Alabama, Children’s and Women’s Hospital and Specialty Clinic.

METHODS:
Using ICD code 287.3, data were collected from the specialty clinic’s medical records and hospital database for children diagnosed with ITP between January 2005 and September 2010. Recurrent and chronic ITP were defined as thrombocytopenia recurring within or more than 6 months of diagnosis, respectively. Univariate and multivariate logistic regression analyses were performed to evaluate variables associated with chronic ITP.

RESULTS:
Eight four patients were identified (M,F 1:1) with an average age of 70 months at diagnosis. Mean platelet count at presentation was 14k. Oral or nasal mucosal bleeding occurred in 19(23%) patients but none experienced a serious hemorrhage. Thirty three (39%) patients had an associated illness prior to diagnosis of ITP. Treatment consisted of intravenous immunoglobulin (IVIG) in 38(45%), WinRho in 11(13%), IVIG or WinRho followed by the other in 20(24%), data not available 8(10%) and no therapy in 7 patients (8%). Average platelet count at discharge and within 2 weeks after IVIG and WinRho was 57k, 337k and 57k, 375 respectively. Forty three (51%) were acute, 17(20%) became recurrent, and 24(29%) became chronic ITP. Bone marrow examination was performed in 26(30%) patients upon subsequent relapse but the diagnosis remained unaltered in all cases. Rituximab therapy was provided to five and splenectomy was performed in 7 patients. Four patients failed both modalities, all of whom currently are IVIG dependant.
Age <5year (OR 0.12, 95%CI 0.22, 0.67, p=0.01) was protective against development of chronic ITP while platelet count >20k at presentation (OR 6.50, 95%CI 1.35, 31.30, p=0.02) and race other than white (OR 36.63, 95%CI 4.61, 291.09, p=0.001) were found to be significantly associated with the development of chronic ITP. Gender, mean platelet volume, total white cell count, and absolute lymphocyte count had no significant association.

CONCLUSION:
Our study supports the published data that patients with an initial platelet count >20k, older age and non-white race have an increased risk of progression to chronic ITP. Other published variables had no significant association in our analyses. Response to IVIG and WinRho was no different in our patients while rituximab or splenectomy did not lead to a complete resolution in refractory cases. Since bone marrow examination did not alter the diagnosis in any patient, we suggest that routine performance of this procedure may be omitted when a diagnosis of ITP is consistent with clinical history, physical examination and laboratory data.

Disclosures:
No relevant conflicts of interest to declare.
Association of Birthdays with Late Relapses of Immune Thrombocytopenia
Authors: Varma Mala 
Published: October 2019

Abstract
Abstract 4685
Adult immune thrombocytopenia (ITP) typically takes a chronic or relapsing course. Etiologies of initial presentations and/or late relapses have not been identified. Emotional stress has been associated with adult ITP, but it is not known if there is a causal relationship.1,2 Birthdays have been described as psychosocial stressors that have been linked with vascular events including stroke and myocardial infarction.3 Based on our observation that a disproportionately high number of late relapses were occurring within 3 weeks of patients’ birthdays, we conducted a retrospective cohort study to determine if birthdays are associated with the onset and/or late relapses of ITP.
Thirty-five consecutive patients with ITP followed between July 1, 2003 through August 11, 2011 were included in the study. Median age at presentation was 48 years (range 22 to 83 yrs). The female:male ratio was 1.9:1. One patient had human immunodeficiency virus. The median duration of follow-up was 28.3 months (range 1.25 to 72 mos). Dates of initial presentation were available for 22 patients. Only 3 (13.6%) presented within 3 weeks of their birthdays. Eleven of 35 patients had a relapse (defined as a platelet count < 30,000/μL or a 50–70% decrease in platelet count from baseline) after an unmaintained remission exceeding 1 year. Four (36%) of these 11 patients had relapses within 3 weeks of their birthdays (binomial test for significance = 0.002). Two of these 4 patients presented 3 weeks following their birthdays, but had noted fatigue 1 week before presenting. Fatigue has been associated with thrombocytopenic exacerbations of ITP;4 these patients therefore were likely relapsing at the onset of fatigue, closer to their birthdays. The other two patients relapsed 3 – 10 days following their birthdays. One was pregnant; pregnancy may have contributed to her relapse. None of the 4 patients had concurrent infections, autoimmune disease, or malignancies.
This study is the first to show that birthdays are associated with relapses of ITP after long unmaintained remissions. Birthdays may be accompanied by stress of anticipation, indulgence, and overexertion. Stress is associated with ITP, and may have a causative role in relapsing ITP.

Disclosures:
No relevant conflicts of interest to declare.
Adjuvant Corticosteroid Therapy for Chronic Disseminated Candidiasis in Patients with Acute Leukemia
Authors: Qian Shenxian , Chen Kuang 
Published: October 2019

Abstract
Abstract 4723
Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. Our objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. We performed a study involving 6 adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST therapy was initiated. All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia.The common manifestations in these six patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with appearance of painful and diffuse cataneous nodules, expectoration and dyspnoea. The abnormal laboratory test observed of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the five patients; one of them showed multiple nodular patchy shadows in bone. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Three patients had positive blood candida tropicalis cultures. liver biopsy in one patient was negative for fungal. Two patients received Fluconazole therapy empirically, but it was replaced by Itraconazole later in one because of unresponsiveness to the drug. Three patients received Itraconazole therapy and in one received voriconazole therapy empirically. CDC-attributable clinical symptoms resolved with CST, which was started an average of 31 day since antifungal therapy was initiated. Fever and abdominal pain disappeared a median of 5–6 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14–30 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 45 days (range, 27–167 days). All the six patients received further chemotherapy smoothly after the treatment antifungal therapy combined with CST,No relapses of CDC were observed during a median duration of follow-up of 3.2 years (range, 2.6–3.8 years).CONCLUSION: In adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of > or =0.25 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome.

Disclosures:
No relevant conflicts of interest to declare.
Location, Location, Location: Reassessing Erythropoiesis Stimulating Agents (ESAs) in the United States (US), Canada, and Europe (2007−2011)
Authors: Norris Leann , Mattison Donald , Qureshi Zaina Parvez , Bennett Charles 
Published: October 2019

Abstract
Abstract 4753

Background:
Erythropoiesis stimulating agents (ESAs) are approved for preventing transfusions (United States (US)) or treating symptomatic anemia (Canada/Europe) among chemotherapy or chronic kidney disease (CKD) patients. Extensive reassessments of safety, efficacy, dosing, and target hemoglobin levels have occurred.

Methods:
Regulatory agencies', ESA manufacturer notifications, clinical guidelines, phase III trials and meta-analyses cited in clinical guidelines were reviewed (2007 to 2011).

Results:
CKD and Cancer: Quality of life benefits are reported in Europe and Canada. In the US, product labels report exercise capacity improvements for CKD patients. CKD: Clinical trials reported cardiovascular, cerebrovascular, and mortality risks with ESAs targeting high versus low hemoglobin levels or cardiovascular and mortality risks with ESAs versus placebo. 2011 US' advisories recommend ESA doses sufficient to prevent transfusions among dialysis patients and caution with ESA administration to non-dialysis patients. Canadian and European recommendations target hemoglobin levels between 10 and 12 g/dl and 11 to 12 g/dl, respectively. Following these recommendations among non-dialysis US patients, ESA use decreased 16%. Most US dialysis CKD patients receive ESAs, with lower achieved hemoglobin levels, and 30% decreased ESA usage since 2008. In Europe and Canada, which initially had substantially lower ESA use, there has been a gradual increase. Cancer: Trials identified mortality, tumor progression, and venous thromboembolism risks with ESAs targeting higher versus lower hemoglobin levels. US labels warn against administering ESAs with potentially curative chemotherapy. European guidelines recommend ESAs for symptomatic patients at hemoglobin levels of 9 to 11 g/dL and consider for asymptomatic patients at levels of 11 to 11.9 g/dL. Canadian advisories report cost-utility ratios exceeding accepted standards. ESA use decreased by 70% in the US. Current ESA utilization rates for cancer are higher in Europe and lower in Canada.

Conclusions:
International differences in interpreting efficacy and safety data and ESA utilization exist. The changes have been most apparent in the US.

Disclosures:
No relevant conflicts of interest to declare.
Translating Research Into Policy: A Review of Pharmacovigilance Efforts From the Southern Network On Adverse Reactions (SONAR) Group
Authors: Bennett Charles , Norris Leann , Qureshi Zaina Parvez , Miller April , Bookstaver Brandon , Mattison Donald 
Published: October 2019

Abstract
Abstract 4756

Introduction:
SONAR, the only state-funded (South Carolina) pharmacovigilance initiative in the nation, focuses on identifying near fatal side effects of hematology and oncology therapeutics. Most safety findings are like “trees falling in the forest” – with no one hearing the noise. Our objective was to describe the outcomes from the findings of the pharmacovigilance efforts from the SONAR group.

Methods:
SONAR investigators reviewed practice and policy outcomes to our identification of adverse drug reactions with hematologic implications. Data sources used were PubMed, the Food and Drud Administration (FDA) files, and the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

Results:

Conclusions:
Most SONAR findings have been followed by FDA notifications and market responses. Identifying and reporting sADRs can have marked beneficial effects on medical care.

Disclosures:
No relevant conflicts of interest to declare.
Bone-Marrow Derived Cells Can Reconstitute GCLM Function in the Sickle Lung
Authors: Adisa Olufolake , Ghosh Samit , Tan Fang , Chappa Prasanthi , Archer David R. , Ofori-Acquah Solomon F 
Published: October 2019

Abstract
Abstract 4836
Sickle cell disease (SCD) is a chronic hemolytic and inflammatory disorder characterized by repeated episodes of vaso-occlusion and hemolysis, resulting in oxidative stress and endothelial dysfunction. We have recently demonstrated that the heme scavenging capacity in SCD is severely impaired, highlighting the danger posed by excess heme in this disorder. Paradoxically, heme induces expression of several cyto-protective enzymes including the modifier subunit of glutamate cysteine ligase (GCLM), the rate-limiting enzyme in glutathione (GSH) synthesis, which is a crucial antioxidant in the lung. While the induction of cytoprotective enzymes is thought to attenuate the deleterious effects of heme in SCD the somatic origin of this protection has not previously been defined. Using transgenic mouse models we show for the first time that the level of GCLM in the sickle lung is markedly up-regulated due primarily to enhanced expression of the enzyme in the epithelium and blood mononuclear cells, but not in the endothelium. Based on these findings, we tested the hypothesis that leukocyte-derived GCLM was sufficient to protect the sickle lung from oxidative stress. Thus, bone marrow chimeric SCD mice with GCLM deficiency were generated by transplanting bone marrow from Berkeley SCD transgenic mice into GCLM null mice recipients. We confirmed that the chimeric GCLM-null-SCD mice had a SCD phenotype as determined by >95% engraftment of donor white blood cells, reticulocyte counts, urine osmolality and hemoglobin gel electrophoresis. Whole lung GCLM and total GSH levels in the chimeric mice were identical to the levels in the wild-type SCD mice. Moreover, lung function, as determined by oxygen saturation and breath rate, were identical in the two mouse strains. These results show that loss of GCLM expression in resident lung cells does not compromise production of GSH or the function of the lung in SCD.

Disclosures:
Ofori-Acquah: Emory University: Patents & Royalties.
Identification of Chondroitin Sulfate Proteoglycan-4 In Acute Myeloid Leukemia Using Monoclonal Antibody 225.28
Authors: Fenton Moon , Gasparetto Maura , Hong Chang-Sook , Wang XinHui , Smith Clay , Whiteside Theresa , Ferrone Soldano , Boyiadzis Michael 
Published: October 2019

Abstract
Abstract 4885
Chondroitin sulfate proteoglycan-4 (CSPG4) is a membrane-bound proteoglycan that is expressed on the surface of differentiated malignant cells, progenitor cells, and cancer initiating cells in various types of solid tumors. CSPG4 is highly conserved through evolution; its structure, amino acid sequence and functional properties show a high degree of homology with its rat counterpart, named neuron-glial antigen 2 (NG2). CSPG4 has been shown to be involved in the activation of several signaling pathways that play an important role in tumor progression. Because of its high levels of expression on malignant cells and its restricted distribution in normal tissues, CSPG4 is potential candidate tumor marker and target for immune- and targeted therapy. CSPG4 has been shown previously to be expressed on AML cells using an antibody raised against the rat counterpart and levels of expression were correlated with the clinical course of the disease. In this report we extend these findings by identifying a monoclonal antibody (mAb) directed at a human CSPG4 epitope and then used this antibody to examine co-expression with other common markers in AML as well as important molecular/cytogenetic abnormalities. Initially we screened a panel of 15 CSPG4-specific mAb which recognize 7 distinct epitopes for reactivity with leukemic blasts. mAb 225.28 was shown to have the highest reactivity and was selected for further studies. CSPG4 expression using mb225.28 was detected in 18/18 peripheral blood samples containing AML blasts at levels ranging from 0.2% to 98%. 7 samples showed less than 10% CSPG4 positive cells, 2 showed 10 – 20% positivity, 4 showed 20 – 30% positivity, and 5 showed greater than 30% positivity. CSPG-4 expression was not confined to any single blast sub-population defined by co-staining with CD34, CD117 and CD33. The expression of CSPG4 was shown on leukemic cells with mixed lineage leukemia (MLL) gene rearrangements, FTL3 mutation, NPM1 mutation, and complex cytogenetic abnormalities. These results indicate that the expression of CSPG4 is not restricted to any sub-type of AML or confined to one developmental compartment and using the mAb 225.28 CSPG4 may constitute a potential marker for AML.

Disclosures:
No relevant conflicts of interest to declare.
Mast Cell Leukemia?—Malignant Mastocytosis with Leukemia-like Manifestations
Authors: EFRATI P. , KLAJMAN A. , SPITZ H. 
Published: October 2019

Abstract
A case of probable leukemia in an adult female is described which is classified as tissue mast cell leukemia. Clinical course and autopsy findings are analyzed and a detailed morphologic description is given of the different stages of maturation of T.M.C. as found in the peripheral blood and in bone marrow aspirates.
The patient succumbed to massive gastrointestinal hemorrhage following cortisone treatment.
Histologic examination of spleen and loose areolar tissue suggested origin of T.M.C. from both reticulum cells and fibroblasts.
Focal osteosclerosis in the vertebrae probably represents a lesion related to the basic disorder.
Unique Sequence of Pernicious Anemia, Polycythemia, and Acute Leukemia
Authors: ZARAFONETIS CHRIS J. D. , OVERMAN ROBERT L. , MOLTHAN LYNDALL 
Published: October 2019

Abstract
The development of three primary blood dyscrasias, namely, pernicious anemia, polycythemia vera, and acute myeloblastic leukemia, in one patient has been reported.
Leukocyte Antibodies in Human Sera and in Immune Rabbit Sera
Authors: WALFORD ROY L. , PETERSON E. TAYLOR , DOYLE PATRICIA 
Published: October 2019

Abstract
A study of leukocyte antibodies is presented using (1) the sera of rabbits immunized with human leukocytes, and (2) the sera of three patients screened for the presence of such antibodies from among 36 patients with hematologic disease, 31 of whom (including the 3 studied in detail) had received multiple transfusions. The following technics are described and were employed: Leukoagglutination, leukoprecipitation including tube and agar-plate methods, agglutination of antigen-coated tanned and untanned sheep erythrocytes, the effect of antisera upon phagocytosis of heat-killed staphylococci by leukocytes, and upon ameboid motility of leukocytes.
The leukoagglutinin test gives reliable clearcut results providing that appropriate controls are included and certain criteria adhered to, in order to facilitate the recognition of clumping due to other factors than true antigen-antibody union.
No leukoprecipitins were detected in human sera with the technics used in this study. Immune rabbit sera, on the other hand, gave two reaction-lines in agar media, when set up against leukocyte extract.
Immune rabbit sera reacted strongly with antigen-coated tanned sheep red blood cells. Human sera did not so react. One of the three selected human sera reacted with antigen-coated untanned erythrocytes, suggesting the presence of a polysaccharide antigen extractable from human leukocytes and capable of stimulating antibody formation in the human. Immune rabbit sera, and other human sera, did not react in this test.
A suggestive but perhaps not a conclusive effect upon phagocytosis of bacteria by leukocytes exposed to human leukocyte antibody for 1 hour could be demonstrated.
By means of ameboid motility studies, a cytotoxic effect of the human antisera upon human leukocytes could be demonstrated after 18 hours of incubation, but not after 3 hours. This was interpreted as evidence of a delayed reaction.
Certain cardinal points from a clinical and theoretical standpoint with regard to the genesis of leukocyte antibodies in man are briefly reviewed. A possible analogy between leukocyte antibody formation and the homograft reaction is discussed. It is suggested that the rarity of leukocyte iso-antibody formation following transfusion is related to the fact that the intravenous pathway may be a poor route of immunization for these antigens.
Erythroblastopenia with Giant Pro-Erythroblasts in Kwashiorkor
Authors: LIEN-KENG KHO 
Published: October 2019

Abstract
Description of seven cases of kwashiorkor in children of one and a half to eight years of age, in which at one time or other an aplastic crisis (erythroblastopenia) occurred with the appearance of giant proerythroblasts or their precursors in the bone marrow. This condition independent of the treatment—reversed to normal in four cases and was followed by a reticulocytic crisis. Three of the children died during or shortly after the aplastic crisis. The author considers erythroblastopenia in these cases as due to insufficiency of the bone-marrow (lability) caused by chronic protein deficiency superimposed by frequent infections. The giant pro-erythroblasts are pathologic forms of erythropoiesis and are not identical with Ehrlich’s megaloblasts.
A Modified Urinary Excretion Test for Measuring Oral Cobalt60 Labeled Vitamin B12 Absorption and its Application in Certain Disease States
Authors: MILLER AARON , CORBUS HOWARD F. , SULLIVAN JOHN F. 
Published: October 2019

Abstract
1. Factors relating to the urinary excretion test for oral vitamin B12 absorption were studied. A modified procedure is presented giving a high percentage of urinary recovery of radioactivity in the normal.
2. Values in the pernicious anemia range were found in the presence of acute infection and severe renal insufficiency. Other limitations in the interpretation of the test are discussed.
The Dead Leukocyte Content of the Blood in Normal and Leukemic Patients
Authors: PETRAKIS NICHOLAS L. , LIEBERMAN ESTELLE , FULLERTON JEAN 
Published: October 2019

Abstract
The dead leukocyte content of the blood of normal and leukemic subjects was determined by the technic of the unstained-cell counts of Schrek. A small and constant number of dead leukocytes was found in the normal blood, averaging 46 per cu. mm. In patients with chronic lymphocytic leukemia and acute leukemia, higher numbers of dead leukocytes were commonly found, ranging from normal values to as high as 4,600 per cu. mm. No correlation was found between the numbers of smudge forms on blood smears from these patients and the number of dead leukocytes. The smudge forms on blood smears appear to result from the mechanical trauma produced in making the smears. The leukocytes from chronic lymphocytic leukemia and acute leukemia appear to be much more susceptible to the mechanical forces produced in the preparation of blood smears than are leukocytes from normals and patients with chronic granulocytic leukemia.