bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alemtuzumab and Rituximab in the treatment of refractory autoimmune Cytopenias.
Authors: Gomez-Almaguer David , Solano-Genesta Manuel , Cantu-Rodriguez Olga , Gutierrez-Aguilar Cesar Homero , Jaime-Perez Jose Carlos , Tarin-Arzaga Luz Carmen , Gomez-Guijosa Miguel Angel 
Published: October 2019

Abstract
Abstract 4458

Introduction
The combination of rituximab and alemtuzumab have been used to treat CLL. This combination is feasible without excessive toxicity. Both antibodies have been used as monotherapy for the treatment of autoimmune diseases, including autoimmune hemolytic anemia (AHA) and Immune thrombocytopenic purpura (ITP).

Objective
Evaluate the efficacy and safety of the combination of low dose alemtuzumab and rituximab in patients with AHA and ITP.

Material and methods
patients diagnosed with AHA (clinical and biochemical data of hemolysis) or ITP (less than < 50 K/μl) who failed or relapsed after first line therapy (steroids) were included. Basal lymphocyte count and immunoglobulin levels were assessed. Patients received alemtuzumab 10 mg SC on days 1,2 and 3 followed by rituximab 100 mg IV on days 4,11,18 and 25. Complete response (CR) was defined as normal hemoglobin in the absence of hemolysis and platelet count >150K/μl; and partial response (PR): increase of 2 g/dl of hemoglobin and platelets 50-149K/μl The effect of the antibodies combination was evaluated by lymphocyte B, T and NK count 8 and 24 weeks after their administration. Prophylactic bactrim, acyclovir and itraconazole were given for the first 2 months.

Results
We included 13 patients, and eleven were evaluable, 5 patients in the AHA group and 6 in the ITP group, demographic data is shown on table 1. For AHA the 5 patients achieved CR with a median follow up of 37 weeks; only 1 patient relapsed after the 49th week of follow up. For the ITP group 2 patients achieved CR, 2 patients PR and 2 were classified as non responders. Alemtuzumab and rituximab combination quickly depleted B lymphocites falling to zero or near zero at the 8th week determination, with a sustained decrease at 24th week, in which levels did not return to pre-treatment levels.

Conclusions
These initial results indicate that low dose alemtuzumab and rituximab combination is safe and demonstrate promising activity for AHA and ITP refractory patients including durable complete responses and as a steroid spring therapy.

Disclosures:
Off Label Use: alemtuzumab for refractory autoimmune cytopenias rituximab for refractory autoimmune cytopenias.
Racial Disparities in Pediatric Immune Thrombocytopenic Purpura.
Authors: Perkins Tiffany , Jayabose Somasundaram , Ozkaynak Mehmet , Tugal Oya , Sandoval Claudio 
Published: October 2019

Abstract
Abstract 4464

Background
Immune thrombocytopenic purpura (ITP) occurs in children with an estimated incidence of 5/100,000; however, it is not known whether racial disparities in the incidence of pediatric ITP exist. We hypothesize that because petechiae may go unrecognized in black children the observed incidence of ITP in this race may be less. The purpose of this study was to analyze an established pediatric ITP population at New York Medical College in order to assess whether such disparities exist amongst races and to determine the presenting features of ITP in black children.

Methods
Retrospective chart review of 630 pediatric ITP patients diagnosed and treated at New York Medical College from 1985 to 2009 was performed to determine the incidence in various races and to study the presenting features in black children. The patients' race was determined by review of medical records, physician recollection and when necessary by contacting patients by phone. Observed rates of ITP in various races were compared to expected rates given the incidence of ITP and the area's demographic construct. Census of children younger than 19 years residing in the Hudson Valley (Westchester, Putnam, Dutchess, and Rockland counties and Danbury, Connecticut) was obtained from the United States Census Bureau. We used a χ2 “goodness-of-fit” test to determine whether the sample distribution differed from the population distribution.

Results
Racial demographics were available for 530 of 630 (84%) ITP patients. The estimated racial demographics of children younger than 19 years residing in the Hudson Valley are as follows: total population, 468,550; 75% Caucasian; 10% Hispanic 10% black; and 5% Asian. Of the 530 identified, 406 (76.6%) were found to be Caucasian, 55 (10%) Hispanic, 36 (7.5%) Black, and 33 (6.2%) Asian. If ITP is detected equally amongst races, one would expect to find 397.5 White patients (observed expected difference [O – E] 8.5 with a residual of 0.426), 53 Hispanic (O - E 2 with a residual of 0.275), 53 black patients (O – E -17 with a residual of -2.335), and 26 Asian (O – E 6.5 with a residual of 1.263). The distribution of our sample over race groups compared with the distribution of the population over race groups had a p-value of 0.063 with the largest contribution due to under-representation of black children in our sample. Of the 36 black children with ITP 18 (50%) were found to present with bruising/petechiae, 4 (11%) presented with a combination of wet purpura and bruising/petechiae, 3 (8%) presented with wet purpura alone, and 11 (31%) were asymptomatic.

Conclusion
The incidence of ITP in black children may be less than in Caucasian, Hispanic, and Asian children.

Disclosures:
No relevant conflicts of interest to declare.
Heparin Induced Thrombocytopenia; A Diagnostic Dilemma.
Authors: Reagan John L. , Dalia Samir , Butera James N. 
Published: October 2019

Abstract
Abstract 4468

Introduction
The diagnosis of HIT can be challenging. Short of the serotonin release assay, which can be difficult to get in a timely manner, the 4T method developed by Lo et al., in conjunction with the HIT elisa assay (EIA), is the best established criteria for the rapid diagnosis of Heparin Induced Thrombocytopenia (HIT). We sought to determine how often the 4Ts were being applied at a large academic institution. In addition, we sought to understand the outcome of patients started on direct thrombin inhibitors (DTIs) who did not meet the 4T/EIA criteria for HIT.

Methods
A retrospective case series identified patients placed on DTI for HIT treatment from 10/2006 to 5/2008. The 4T pretest probability was then applied retrospectively. HIT EIA Ab testing, optical densities, duration of DTI treatment, and bleeding incidence were recorded. Liberal and modified conservative criteria from Lo et al.'s study were used to define patients with HIT. Overdiagnosis of HIT was then recorded based on the above criteria.

Results
76 patients were included for analysis. The average age was 61.4 years. Based on the 4T pretest probability, 30 patients were classified as low risk, 37 intermediate risk, and 9 high risk for HIT. The average HIT OD for low, intermediate, and high pretest probability was 0.49, 1.17, and 2.05.
76% and 36% of patients treated with DTIs for HIT met the liberal and modified conservative HIT definitions, respectively. 18 patients (24%) did not meet liberal HIT criteria but remained on DTI treatment for 1 to 60 days. Cost of DTI overuse in this subset was $84,960. Cost of DTI use in patients who did not meet modified conservative criteria was $462,246. All 16 patients who developed bleeding complications fulfilled a liberal diagnosis of HIT while only 6 of these patients fulfilled the modified conservative definition of HIT.

Conclusions
1) The 4T method for diagnosing HIT is not being applied to a large percentage of patients in a tertiary academic center. 2) There is an overdiagnosis of HIT regardless of definition criteria with 24% of patients treated for HIT not meeting the liberal definition while 64% of patients did not meet the modified conservative definition. This overdiagnosis has both a significant monetary and morbidity cost.

Disclosures:
No relevant conflicts of interest to declare.
The Significance of Anti-Platelet Antibodies Associated with Antibiotic Use, A Descriptive Analysis.
Authors: Shah Ruta M , Szczepiorkowski Zbigniew M , Leach, MS, MT Miriam K , Zuckerman Richard A 
Published: October 2019

Abstract
Abstract 4470

Introduction
Antibiotics (Abx) have been implicated in immune thrombocytopenia via drug dependent platelet antibodies (DDPA). Our institution has had a DDPA assay available since 1994 which is used to guide clinical decisions. We performed a retrospective review to determine the significance of DDPA.

Methods
We reviewed the medical records of patients (pts) who tested positive for abx DDPA between 1994 and 2006 and performed a descriptive analysis. Detection of DDPAs was performed using a previously described, modified solid phase red cell adherence assay that detects hapten or immune complex reactions.

Results
A total of 71 pts were included in this analysis. Multiple classes of abx were tested. Platelet nadir was &lt;50 in 70%, between 50 and 100 in 26% and over 100 in 4% of pts. Pts had between 1 and 4 abx tested: 37% had 1, 37% had 2, 15% had 3, and 11% had 4 tested; 65% of pts had one abx positive and 35% had &gt;1 abx positive for DDPA. Of those with &gt;1 abx tested (n=45), 14 (31%) had all tested abx positive. 53% of abx testing took place on or after the abx stop date and 32% of abx tested were administered for &lt;=3 days. Only 29 of 38 pts receiving heparin were tested for heparin-associated antibodies, and 14 had positive results. 49 pts had other non-abx drugs tested, 19 with positive DDPA. Thus, 35% had alternative non-abx testing positive for DDPA. 31% of pts had bleeding complications and 35% of pts died during hospitalization. Excluding pts who died and those with non-abx positive DDPA left 25 pts, median platelet counts were: abx start=142; nadir=22, abx discontinuation=46, hospital discharge=192.

Conclusions
Antibiotic DDPA testing is usually performed in ill pts with multiple medical complications and comorbidities. Abx were stopped for concern of DDPA in a number of pts for whom typical immune thrombocytopenia was not present or alternative explanations could be found. Though some pts exhibited improvement in platelet count after abx were stopped, a clear understanding of which pts may benefit from DDPA testing could not be determined based on the retrospective nature of this study and the complexity of pts histories. Further research is necessary to clarify the clinical applicability of DPPA testing.

Disclosures:
Szczepiorkowski: Cersus Corporation: Research Funding; CaridianBCT: Research Funding; BASF: Research Funding; Terumo Corporation: Research Funding; Fenwel, Inc - Scientific Advisory Board: Research Funding.
Bone Marrow Transplant Induces Pulmonary Vascular Remodeling in Mice.
Authors: Aliotta Jason M , Del Tatto Michael , Dooner Mark , Pereira Mandy , Quesenberry Peter J. 
Published: October 2019

Abstract
Abstract 4480

Objective
Pulmonary complications are common in bone marrow transplant (BMT) recipients and often of an infectious etiology or attributed to intensive conditioning regimens. Cases of pulmonary arterial hypertension have been described in the setting of autologous BMT but are believed to be the result of acquired infections or previously-administered chemotherapy. Whether transplanted marrow cells themselves are toxic to the recipient's lungs is unknown.

Methods
To address this, non-irradiated female BALB/C mice were transplanted with 5-6×107 whole bone marrow (WBM) cells from male BALB/C mice daily for four days on week zero, then again on week eight (4.5×108 cells total/mouse), or an equal volume of diluent (control). On week 24, transplanted mice received 1000 cGy of chest-only radiation or no radiation. On week 32, histochemical and immunohistochemical analyses were performed on recipient's lungs.

Results
Bone marrow chimerism was not significantly different in the irradiated and non-irradiated cohorts at the time of sacrifice (average 45.11+6.25% Y chromosome+, all mice). Recipient lungs contained few non-hematopoietic donor marrow-derived cells. These cells were exclusively epithelial (Y+/cytokeratin+), primarily type II pneumocytes (Y+/prosurfactant C+), while no endothelial (Y+/von Willebrand+) or vascular smooth muscle (Y+/alpha-actin+) cells were identified. Irradiated and non-irradiated cohorts had similar quantities of these cells (0.80+0.22% vs. 0.51+0.08% Y+/cytokeratin+; 0.37+0.08% vs. 0.32+0.12% Y+/prosurfactant C+, p>0.2). Pulmonary vessel wall thickness-to-blood vessel diameter ratios (PVWT/D) were significantly increased in the non-irradiated cohort compared with controls and these ratios were further increased in the irradiated cohort (141+5.75%, 161+5.34% of control, p<0.05 comparing all groups).

Conclusions
These data indicated that marrow cell infusion alone results in pulmonary vascular remodeling and this effect is augmented by radiation injury. These changes are independent of transplanted marrow cell conversion to pulmonary vascular endothelial, smooth muscle cells. These studies suggest that transplanted cells may be lung toxic entities in the setting clinical BMT.

Disclosures:
No relevant conflicts of interest to declare.
Gene Therapy of Chronic Myelogenous Leukemia Using Pseudotyped Recombinant Adeno-Associated Viral Vectors.
Authors: Sellner Leopold , Veldwijk Marlon R , Kleinschmidt Jürgen A. , Laufs Stephanie , Topaly Julian , Zeller W. Jens , Wenz Frederik , Fruehauf Stefan 
Published: October 2019

Abstract
Abstract 4506

Introduction
Gene transfer into malignant leukemia cells can be of relevance to overcome conventional therapy-resistance. Either suicide or immune stimulating gene therapy vectors may be a tool for second line treatment of imatinib-resistant chronic myelogenous leukemia (CML). Unfortunately, for gene transfer into CML cells, most current vector systems either lack sufficient transduction efficiency or an acceptable safety profile. Conventional adeno-associated virus (AAV) based vectors have an advantageous safety profile, yet lack the required efficiency.

Methods
Pseudotyped recombinant adeno-associated viruses of the serotypes 2/1 to 2/6 (rAAV2/1 to rAAV2/6) were screened on a panel of human CML cell lines and primary CML cells to determine their gene transfer efficacy. Additionally, double-stranded self complementary rAAV (scAAV) were used to determine possible second strand synthesis limitations.

Results
On CML cell lines, generally rAAV2/2 and rAAV2/6 were most efficient (Fig. 1). For both, an interesting difference in transduction efficiency between the imatinib-resistant LAMA84-R and imatinib-sensitive LAMA84-S cells were observed. On primary human CML cells, rAAV2/6 proved to be significantly more efficient than the other tested vectors (4.6% ± 5.3% GFP-positive cells, p=0.011). Additionally, the transduction efficiency could be significantly increased by using scAAV vectors (scAAV2/6: 43.1% ± 25.9% GFP-positive cells, p<0.001 vs rAAV2/6; Fig. 2). Our data suggest that both the conversion of the single stranded AAV genome to double stranded DNA, as well as cell binding/entry are rate limiting steps in efficient transduction of primary human CML cells with AAV vectors. Furthermore, donor-dependent differences in gene transfer efficiency were observed. Of note, data from experiments on CML cell lines seems to provide limited information about the transduction efficiency of rAAV vectors on primary CML cells.

Conclusions
Overall, pseudotyped rAAV and scAAV vectors offer efficient clinically relevant gene transfer into human CML cells with a potential for future clinical application.

Disclosures:
No relevant conflicts of interest to declare.
Influence of Magnetic Fe3O4 Nanoparticle On the Lymphocyte and Macrophage Function of Mice.
Authors: Chen Bao-An , Jin Nan , Wang Jun , Ding Jia-Hua , Gao Chong , Cheng Jian , Chen Ning-Na , Zhao Gang , Wang Xue-Mei , Pei Xiao-Ping 
Published: October 2019

Abstract
Abstract 4519

Objective
In this paper we investigate effects of magnetic nanoparticle of Fe3O4 (MNP-Fe3O4) on the murine immune system especially in lymphocyte and macrophage function.

Methods
ICR mice were assigned randomly into four groups which were treated with normal saline, the dose of 300mg/kg, 600mg/kg and 1200mg/kg MNP-Fe3O4. The mice were killed when they were exposed by intragastric administration after 2 weeks. The ratios of spleen to body weight, lymphocyte transformation rate in spleen suspension, phagocytic index of macrophage in belly cavity were detected.

Results
The ratios of spleen to body weight in all experimental groups were not significantly difference in comparison to the control group(P>0. 05). The lymphocyte transformation rate in spleen suspension in experimental groups were all higher than that of the control group, especially in the media dose group(600mg/kg)(P < 0. 05). And the results of phagocytic index of macrophage in belly cavity indicated that though all experimental groups showed that they enhanced the phagocytic function of macrophage more than the control group, media dose group(600mg/kg) could increase the phagocytic index more than the other two experimental group(P < 0. 05).

Conclusion
It is concluded that suitable dose of MNP-Fe3O4 supplement enhance cellular immune function and phagocytic funtion of macrophage of mice.

Disclosures:
No relevant conflicts of interest to declare.
Erythropoietin Stimulating Agents (ESAs): Reassessment of Use in Cancer and Chronic Kidney Disease (CKD) Settings in the United States, Canada, and Europe.
Authors: Bennett Charles L , Samaras Athena T , McKoy June M , Edwards Beatrice J , Zheng Mi , Fisher Matthew J , Boyle Simone N , Trifilio Steven M , Boen Monica , Deleon Dianne , West Dennis P 
Published: October 2019

Abstract
Abstract 4538

Introduction
International reassessments of erythropoiesis stimulating agents (ESAs) for anemia have recently occurred. While ESAs prevent blood transfusions and, improve select quality of life domains among chronic kidney disease (CKD) patients, 8 trials individually identified increased mortality and/or tumor progression among cancer patients treated with ESAs. For CKD, one study of non-dialysis CKD patients targeted to higher versus lower hemoglobin (Hb) levels identified 34% increased relative risk (17.5% vs. 13.5%) for death, acute myocardial infarction, congestive heart failure hospitalization, or stroke with a higher Hb target.

Methods
Guidelines, notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and CKD settings within the U.S., Europe, and Canada were reviewed.

Results: Cancer Setting
In 2008, the Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to Hb levels < 10 g/dL. In the U.S., ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) reports that ESA benefits do not outweigh risks. In Europe, ESA reimbursement is included in global provider payments. Between 2001 and 2006, ESA use increased 51%; since 2006, use has decreased 10%. Canadian manufacturers recommend ESA usage based on patient preference. In Canada, reimbursement for myelosuppressive chemotherapy with ESAs is restricted to Hb levels of 10-11 g/dL in Alberta and 11-12.5 g/dL in British Columbia. Usage increased 20% between 2004 and 2007.

CKD Setting
The FDA recommends Hb levels < 12 g/dL and Medicare reimbursement is restricted to Hb levels ≥ 13 g/dL. Between 2001 and 2006, usage increased 480% (non-dialysis) and 40% (dialysis) in the U.S. Since 2007, ESA use has decreased 30% (non-dialysis) and 17% (dialysis). The EMEA recommends target Hb levels of 10-12 g/dL. In Europe, ESA usage has increased 10% since 2001. The 2009 Canadian label recommends Hb levels < 12 g/dL. Within Canada, ESA usage increased 30% since 2004.

Conclusions
While reassessments of ESA safety have occurred internationally, safety concerns in the U.S. have resulted in marked decrements in ESA use among cancer and CKD patients, whereas in Europe and Canada ESA use has increased over time.

Disclosures:
No relevant conflicts of interest to declare.
From Bench to Bedside: Hematopoietic Growth Factors (HGFs)- a Cause of Serious and Unanticipated Class Toxicities.
Authors: Bennett Charles L. , Polish Ari , Samaras Athena T , Zheng Mi , West Dennis P , Trifilio Steven M , Edwards Beatrice J , Boyle Simone N , Fisher Matthew J , McKoy June M 
Published: October 2019

Abstract
Abstract 4555

Introduction
HGFs have vastly improved the management of anemia, neutropenia, and thrombocytopenia, but are associated with unexpected toxicities.

Methods
Toxicities associated with granulocyte, erythroid, and thrombopoietic growth factors were reviewed. Data sources included systematic reviews, clinical trials, guidelines, and materials disseminated by the Food and Drug Administration (FDA), the European Medicines Agency (EMEA), and Canada Health and their advisory committees; product labels and safety notifications disseminated by manufacturers; and utilization data. Data abstracted were thromboembolic complications, immune-mediated cytopenias, bone marrow toxicities, systematic and synergistic toxicities, and regulatory responses.

Results

Granulopoiesis agents
Pulmonary infiltrates were associated with administration of HGFs with bleomycin or chest radiation. Increased myelodysplasia (MDS) or acute myeloid leukemia (AML) risks among chemotherapy (chemo)-treated breast cancer patients were reported.

ESAs
Increased mortality and tumor progression were seen when cancer patients received ESAs versus placebo; increased mortality and cardiovascular events were reported when chronic kidney disease (CKD) patients received ESAs targeted to complete anemia correction. Between 1998 and 2003, 191 CKD patients developed neutralizing antibodies and pure red cell aplasia (PRCA) following recombinant erythropoietin administration.

Thrombopoietins (TPO)
TPO receptor agonist administration is associated with bone marrow reticulin and collagen deposition. 3% of healthy volunteers who received repeated rHuMGDF developed neutralizing autoantibodies and severe thrombocytopenia.

Conclusions
While ESAs, granulopoietic factors, and thrombopoietins have important clinical benefits, they also retain the potential to exhibit serious and unanticipated toxicities.

Disclosures:
No relevant conflicts of interest to declare.