bluuebunny/crossref_metadata_2025_split huggingface dataset:
Romiplostim Treatment Mimicking Cyclic Thrombocytopenia In 3 Patients with Chronic Idiopatic Thrombocytopenic Purpura
Authors: Iuliano Francesco , Mingrone Tecla , Infusino Stefania , Perricelli Alessia , Pomillo Angelo , Luci Maria , Maio Massimo Di 
Published: October 2019

Abstract
Abstract 4665

Introduction
The thrombopoietic growth factors (TGFs) are a novel class of compounds for the treatment of chronic immune thrombocytopenia (ITP). The first of these agents to receive regulatory approval, romiplostim and eltrombopag, have demonstrated impressive efficacy and tolerability in randomized controlled trials and open-label extension studies of several years duration and stand poised to revolutionize the management of ITP. Nonetheless, critical questions regarding the safety of these agents, remain partially unanswered. The aim of this report is to focus on the incidence of thrombocytosis and rebound thrombocytopenia mimicking cyclic thrombocytopenia in a series of 15 patients treated with romiplostim in a single institution.

Methods
15 patients (8 M and 7 F, median age 45 years range 21–76) with chronic ITP (median onset 6 years, range 1–11), 1/15 splenectomized, plts median 2 ×109/L, (range 18–24) were treated with Romiplostim initial dose of 1 mg/kg, weekly checks, with only weekly increase of 1 mg/kg to reach a platelet count ≥ 50 × 109/L. The target platelet count range was 50 to 250 × 109/L. Twenty-two percent of patients (3/15) were receiving concurrent treatment for ITP (corticosteroids, danazol) at the time of first romiplostim dose. These medications were discontinued after platelet counts reached 50 × 109/L.

Results
A platelet response had been achieved by 30% of patients after the first dose and by 51% of patients after the third dose. Treatment response was observed in 100% of pts treated after 6 weeks. In three patients after the eighth week, with average values plts 120×109/l, the subsequent administration of the drug led to an increase in platelet count > 1000×109/l, with rapid fall to <30 ×109/l at the third week suspension in 2/3, while the third patient is in CR at six months follow-up despite treatment was stopped.

Conclusion
According to an analysis of all patients with ITP treated with romiplostim in 4 controlled trials have been reported 3 thrombocytosis events in 271 pts (1.1%). In our series the percentage was 20% (3/15), much higher than that reported in the literature, with no thrombotic complications related. Interesting in a case CR was still maintained at 8 months of follow-up despite cessation of treatment. It would be very useful to create a network of information between users of romiplostim to evaluate on a larger series, the true incidence of thrombocytosis and any related thrombotic phenomena associated in a day by day clinical practice.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Characteristics of Thrombotic Thrombocytopenic Purpura with Severe ADAMTS13 Deficiency
Authors: Jang Moon , Chong So Young , Kim Inho , Jung Chul W. , Oh Doyeun 
Published: October 2019

Abstract
Abstract 4666
The clinical significance of ADAMTS13 activity for response to treatment, mortality rate, recurrence, and prognosis is unclear. Therefore, we investigated the characteristics of severe ADAMTS13 deficiency and evaluated its clinical significance in Thrombotic thrombocytopenic purpura (TTP). The Korean TTP Registry includes 66 patients from 13 teaching hospitals in Korea who received the diagnosis of TTP from January 2005 to December 2008. Blood samples obtained upon admission were sent for ADAMTS13 analysis (multimer analysis by sodium dodecyl sulfate electrophoresis and/or ELISA) to a central laboratory along with patient clinical information. After 6 months, patient data regarding treatment, response, and prognosis were collected on standardized report forms. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels (P=0.001) and WBC counts (P=0.050) than patients with non-severe ADAMTS13 deficiency. Although severe ADAMTS13 deficiency was associated with better response rate (75% vs 53%, P=0.145), remission rate (81% vs 61%, P=0.209), and mortality rate (19% vs 31%, P=0.508) than non-severe ADAMTS13 deficiency, treatment outcomes did not differ significantly between groups. After adjusting for clinical and laboratory features, multivariate analysis did not reveal any independent risk factors for TTP-associated mortality. Patients with severe ADAMTS13 deficient had lower serum creatinine levels and WBC counts at presentation but Severe ADAMTS13 activity deficiency at TTP diagnosis does not appear to have prognostic significance.

Disclosures:
No relevant conflicts of interest to declare.
Which Hematological Malignancies Are Implicated In Acute Hemolytic Reactions Following Rh (D) Immune Globulin for ITP
Authors: Astacio Hugo , Muller Carmen , Little Gregg , Sinclair Chris , Genereux Maurice 
Published: October 2019

Abstract
Abstract 4670

Background:
Acute Hemolytic Reactions (AHR) and Intravascular Hemolysis (IVH) have been reported rarely with Rh (D) Immune Globulin (WinRho® SDF) administration for normalization of platelet count in ITP. The sporadic and unpredictable occurrence of these events has led to an analysis of our WinRho® SDF safety database to identify populations that may be at higher risk for occurrence of AHR's. A disproportionality analysis revealed that malignancies were disproportionally over represented in cases with AHR compared to Non Hemolytic Reactions and was reported in another abstract.

Aims:
To determine which malignancies were disproportionally overrepresented in patients who developed AHR's.

Methods:
Medical Histories cases with AHR with malignancies were reviewed and classified by type of malignancy. AHR's included both the expected post infusion hemolysis and infrequently reported cases involving clinically compromising hemolysis including IVH.
Hematological malignancies were present in 39/45 of AHR's (86.6 %) and non-hematological malignancies 6 of 45 of AHR (13.3%). 90% of AHR's in patients with Malignancies were adult, 5% children and 5% age unknown. Adults above the age of 65 years accounted for 45% of these cases. CLL was present in 66% of patients with leukemia and Non Hodgkins Lymphoma was present in 92% of patients with Lymphomas. Proliferative disorders were diagnosed in 27% of patients with AHR. Solid tumors were present in 14% of patients with AHR's.

Conclusions:
Hematological malignancies including CLL and NHL are disproportionally over represented in cases presenting with AHR post WinRho® SDF. Alternate therapies to Rh (D) Immune Globulin should be considered in patients with thrombocytopenia and these hematological malignancies due to increased risk of AHR, such as IVH.

Disclosures:
Astacio: Cangene Corporation: Employment. Muller:Cangene Corporation: Employment. Little:Cangene Corporation: Employment. Sinclair:Cangene Corporation: Employment. Genereux:Cangene Corporation: Employment.
Thrombotic Thrombocytopenic Purpura INDUCED PANCREATITIS– A Rare Complication
Authors: Gotlieb Vladimir K. , erma Vaibhav , Jacob Robin , Reddy Padi , Taha Hesham , Ullah Asmat 
Published: October 2019

Abstract
Abstract 4683
Thrombotic Thrombocytopenic Purpura (TTP) is a rare clinical disorder characterized by clinical combination of fever, microangiopathic hemolytic anemia, thrombocytopenia, renal failure and neurological changes.
Pancreatitis may occur as a result of TTP or may rarely trigger TTP. We present a case of acute Pancreatitis as a complication of TTP.
A 29 year-old African-American female with history of alcohol abuse presented with three days of nausea, vomiting, diarrhea, headache and fever. Vitals: BP-120/80mmHg, HR-75/min, Temp-98F, and RR-14/min. Examination was remarkable for lethargy and mild epigastric tenderness. Pertinent laboratory: Hgb-12.4g/dL (Day1) - 8.5g/dL (Day3), reticulocyte count-3.35, Platelets-13,000mm3, BUN/Cr-69/6.3 (mg/dL), LDH-1523U/L, indirect hyperbilrubinemia-3.6mg/dL, Amylase/Lipase-117/87(U/L), fibrinogen-462, D-dimer-15.39, PT/PTT-normal and Haptoglobulin<8mg/dL. Peripheral smear showed 3+ schistocytes. Imaging: CXR, CT Head and CT Abdomen were unremarkable. Work-up for various infections and autoimmune diseases was negative.
TTP was diagnosed and patient was admitted to ICU. Plasmapheresis was initiated with clinical improvement by day 3 with subsequent deterioration by day 7. On day 10, patient developed severe abdominal pain with increase in Amylase (145U/L) and lipase (281U/L). Repeat CT Abdomen showed acute pancreatitis. Day 13 - Rapid worsening in clinical status with death of the patient. Autopsy revealed micothrombi and infarcts in multiple organs including kidney, pancreas, and heart.
Acute Pancreatitis is a rare complication of TTP suggested to occur in 2% of cases of TTP but no case has ever been reported in the literature. There are cases that have been reported where Acute Pancreatitis have triggered TTP-HUS syndrome and chronic relapsing TTP. Idiopathic cases of TTP have a deficiency of ADAMS 13, a metalloprotease enzyme that cleaves von Willebrand factor (vWF) resulting in abnormal vWF multimers causing hyaline thrombi formation with end-organ damage due to ischemia. Pancreatic inflammation in TTP has been regarded as ischemic in nature, due to microthrombi of pancreatic small vessels. It is common to see the inflammation of pancreas in the histological specimens on autopsy, but very rare to develop pancreatitis with clinical symptoms, increase in pancreatic enzymes and CT findings of Pancreatitis. Prognosis of Patients with Acute Pancreatitis in TTP is guarded. Patient should be closely monitored in ICU setting aiming to control TTP by Plasmapheresis and Immunosuppressive therapy (Rituximab) in refractory cases.
Acute Pancreatitis is a rare complication of TTP and carries a worse prognosis.
In patients developing abdominal pain during the course of TTP, Acute Pancreatitis should always be considered in the differential diagnosis.

Disclosures:
No relevant conflicts of interest to declare.
Prolonged Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: Association with Reduced Ploidy and Immaturation of Megakaryocytes
Authors: Zhang Xiao-hui , Fu Haixia , Xu Lan-Ping , Liu Dai-Hong , Liu Kaiyan , Huang Xiao Jun 
Published: October 2019

Abstract
Abstract 4695
Prolonged thrombocytopenia is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its pathogenesis has remained obscure. In present study, by using a flow cytometry technique, we determined the frequency of bone marrow megakaryocytes (MKs) and MKs ploidy distributions in allo-HSCT recipients with or without prolonged thrombocytopenia (n=32 and 27, respectively) and in 13 healthy volunteers. Along with that, the expression of c-Mpl in MKs was measured. The result showed a significant difference in MKs ploidy distributions between the 3 groups. Both the allo-HSCT patients with or without prolonged thrombocytopenia showed a significant shift to low ploidy cells (left shift) with 55.63±18.62% and 44.63±19.38% of their MKs in ploidy classes 2N to 8N, respectively. In contrast, the healthy volunteers had only 25.97±10.70% of their MKs in ploidy classes 2N to 8N. And the patients with prolonged thrombocytopenia showed a marked increase in cells ≤8N, a significant decrease in the 16N and ≥32N cells comparing to patients without prolonged thombocytopenia, which told us there were more less mature MKs in the allo-HSCT recipients with prolonged thrombocytopenia. We concluded that prolonged thrombocytopenia and slow platelet engraftment after allo-HSCT may be related to reduced ploidy and immaturation of MKs.

Disclosures:
No relevant conflicts of interest to declare.
Selectively T Cell Depleted Allografts From HLA-Matched Sibling Donors Followed by Low-Dose Post Transplant Immunosuppression to Limit Disease Relapse In Patients with Hematological Malignancies
Authors: McIver Zachariah A. , Mielke Stephan , Shenoy Aarthi , Fellows Vicki , Stroncek David , Leitman Susan , Childs Richard , Battiwalla Minoo , Koklanaris Eleftheria K. , Haggerty Janice , Savani Bipin N. , Rezvani Katy , Barrett A. John 
Published: October 2019

Abstract
Abstract 4705
We evaluated a photodepletion technique to selectively deplete graft-versus-host disease (GVHD) alloreacting T cells from stem cell transplants. Donor lymphocytes were stimulated with irradiated in-vitro expanded recipient T lymphocytes. Alloactivated T cells preferentially retaining the photosensitizer 4, 5-dibromorhodamine 123 (TH9402) (Kiadis Pharma, NL) were eliminated by light exposure. Twenty-four patients with hematological malignancies (16 high-risk) conditioned with fludarabine, cyclophosphamide and total body, irradiation received a CD34-selected stem cell allograft from an HLA identical sibling and 5×106/kg selectively depleted (SD) donor T cells. Low-dose cyclosporine was used as the only post-transplant immunosuppression. The overall probability of grade III-IV a-GVHD was 13%. Fourteen patients developed chronic GVHD (c-GVHD). Five patients relapsed, 2 of whom remain alive in remission after further treatment. Thirteen patients survive at a median of 22 months. Overall survival and disease free survival probabilities (+/− SEM) were 43 +/− 13% and 35 +/− 13% respectively. The SD technique resulted in a low incidence of relapse (24 +/− 10%), but was complicated by late non-relapse mortality associated with c-GVHD and infection of 50 +/− 14% at 4 years follow up. These results suggest that SD may effectively reduce severe a-GVHD while conserving graft-versus leukemia effects, but the depletion strategy has yet to be optimized.

Disclosures:
Mielke: Kiadis Pharma: Research Funding.
Studies on the Role of TGF-β1/TGF-βR1/Smad4 In the Occurance and Development of Myelocytic Leukemia and Breast Cancer
Authors: Xiaoli Liu , Xia Liping , Zhang Jinfang , Du Qingfeng , Li Rong , Xu Na , Huang Bintao 
Published: October 2019

Abstract
Abstract 4714
Previous studies showed that the function of TGF-β/Smad passway is aberrant in many human cancers, the expresses of TGF-β1, TGF-βR1 and Smad4 proteins were related to the clinicopathologic characteristic of tumors and prognosis. The aim of the present work was to study the role of TGF-β1, TGF-βR1 and Smad4 in the occurance and development of myelocytic leukemia and breast cancer. Firstly, 2 myelocytic leukemia cell lines (KG1, HL60), 2 breast cancer cell lines (SKBR-3, MCF-7) and 293 cells (normal control) were selected. Secondly, we detected the expression levels of mRNA and protein in the 4 cell lines by fluorescence quantitative PCR (qRT-PCR), immunohistochemistry, and Western blotting. qRT-PCR showed that the gene copies of TGF-β1, TGF-βR1 and Smad4 in SKBR-3 cells and KG1 cells, which were poorly differentiated, were lower than that in MCF-7 cells and HL60 cells, which were well differentiated (P<0.01); and the gene copies in 293 cells were higher than all of the four cell lines (P<0.01). Western blotting showed that the protein expression levels of TGF-β1, TGF-βR1 and Smad4 in SKBR-3 and KG1 cells were also lower than in MCF-7 cells and HL60 cells (P<0.01), and higher in 293 cells (P<0.01). The same results could also be abtained by immunohistochemistry. This studies may indicate that TGF-β1, TGF-βR1 and Smad4 act possibly as the role of anti-oncogene in myelocytic leukemia and breast cancer, which also may be associated with the biological behaviors of the development of myelocytic leukemia and breast cancer. TGF-β/Smad passway might be a promising candidate target for the controling progression of malignant tumor.

Disclosures:
No relevant conflicts of interest to declare.
Accuracy and Precision Study: Body Fluid White Blood Cell (WBC) Analysis (Peritoneal, Pleural and Peritoneal Dialysate) Using a Light Scatter Technology (ADVIA®2120/2120i) Versus Hemocytometer Manual Counts
Authors: Castellone Donna D , Peerschke Ellinor I.B. , Francisco Nenita , Canfield William , Kling Gail 
Published: October 2019

Abstract
Abstract 4730

Background:
The ADVIA® 2120/2120i body fluid application is an in vitro diagnostic test for the enumeration of the total nucleated cell (TNC) or white blood cell (WBC) count and RBC (red blood cell) count for pleural, peritoneal and peritoneal dialysis (PD) specimens collected in K2 EDTA. Total nucleated cell (TNC) and RBC counts are used in the laboratory assessment of these fluids. The TNC count is an absolute count of the nucleated blood cells, mesothelial cells, and other non-hematopoietic cells in these fluids.

Objective:
The objective is to demonstrate concordance between the manual (hemocytometer) method versus the light scatter principle used on the ADIVA® 2120i analyzer.

Methods:
The ADVIA® 2120/2120i Body Fluid Application uses the Basophil/Lobularity and RBC/PLT channels to enumerate the WBC and RBC counts. WBC counts are derived from the Basophil/Lobularity channel by a process in which the cytoplasmic membrane is stripped and the suspension of cells is intercepted by light from the laser diode where the low-angle light scatter (2° to 3°) and high-angle light scatter (5° to 15°) signals of each cell are counted. The manual method uses a hemocytometer in which a chamber is charged with fluid and both areas of the chamber are counted and the result averaged. De-identified remnant peritoneal, pleural and peritoneal dialysate samples were processed within 2 hours in the Hematology Laboratory according to their standard operating procedure. Samples with TNC counts that fell in the range of 0.030 to 400 × 103 cells/μ L (30 to 400,000) for each type of fluid were included. Ten consecutive runs were performed for each type of fluid to determine precision.

Results:
The WBC reproducibility study (n=10) demonstrates that within the run, precision of the body fluid counts demonstrates a coefficient of variation (CV) ≤ 10 CV. Regression analysis (n=34) demonstrates an r=.93 using samples across the reportable range.

Conclusion:
These results suggest that the light scatter technology used on the ADVIA® 2120/2120i gives both accurate and precise WBC determinations and compares very well to the manual method for determination of WBC analysis in peritoneal, peritoneal, dialysate, and pleural fluids. Utilizing this method will decrease turn-around time for this process, resulting in a faster time to result and ultimately better patient outcomes.

Disclosures:
Castellone: Siemens Healthcare: Employment. Canfield:Siemens: Employment. Kling:Siemens: Employment.
Hemophilia A: Patient Impact and Economic Burden of the Disease
Authors: Strandberg-Larsen Martin , Gater Adam , Marlow Emma , Thomson Andrew 
Published: October 2019

Abstract
Abstract 4763

Introduction:
Hemophilia A is a rare but serious bleeding disorder caused by a deficiency in blood clotting factor VIII (FVIII). To examine the impact of hemophilia A and replacement FVIII therapies from a humanistic and economic perspective, a targeted literature review was conducted.

Methods:
Searches were conducted in MEDLINE® and the National Health Service Economic Evaluation Database, using combinations of disease, patient-reported outcome and economic-related key words, limited to articles published in English between January 2000 and January 2010 (inclusive). A total of 34 full-text articles (from 653 abstracts retrieved) were selected for detailed consideration.

Results:
Findings revealed increased mortality rates and decreased life expectancy among people with hemophilia A, compared with the general population. This is largely a result of the transmission of blood-borne viruses (e.g. HIV and Hepatitis-C) due to use of plasma-derived FVIII (pdFVIII) concentrates. Improvements in viral attenuation processes plus donor screening practices for pdFVIII products have reduced the risks of viral transmission, but risk of transmission still exists in relation to non-enveloped viruses and other unknown pathogens. Newly developed recombinant FVIII therapies minimizes these risks; however, such therapies are not currently widely available globally. All available FVIII therapies use demanding regimens requiring regular time-consuming injections, which can be detrimental to patients’ health-related quality of life and limit adherence to replacement FVIII therapy. Non-adherence to factor replacement therapy is associated with diminished product efficacy, poorer health outcomes and increasing economic expenditure. Treating hemophilia A is costly, primarily due to the high acquisition cost of replacement FVIII products. However, indirect costs related to patient disability and level of care also contribute to economic burden. Prophylactic treatment initially may appear to be more expensive than on-demand treatment but is associated with greater clinical efficacy and improved long-term outcomes, which may lead to cost savings over the course of a patient's lifetime.

Conclusions:
Hemophilia A is associated with considerable humanistic and economic burden. There remain substantial unmet needs with regard to the safety, convenience, global access to treatment incl. reliable product supply and total care costs associated with factor replacement therapies.

Disclosures:
Strandberg-Larsen: Novo Nordisk A/S: Employment. Gater:Novo Nordisk A/S: Research Funding. Marlow:Novo Nordisk A/S: Research Funding. Thomson:Novo Nordisk A/S: Research Funding.