bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infantile Hemangioma: A Tumor Involving Hemogenic Endothelium with Erythropoetic Potential
Authors: Itinteang Tinte , Vishvanath Anasuya , Brasch Helen D , Day Darren J , Tan Swee T 
Published: October 2019

Abstract
Abstract 4305

Background
Infantile hemangioma (IH) is a tumor of the microvasculature predominantly composed of proliferating endothelial cells, but also contains progenitor cells of mesenchymal and hematopoietic lineages. We have previously shown that IH has a primitive mesodermal origin. Here we investigated expression of hematopoietic associated proteins (Tal-1, GATA-2, CD133 & CD34) as well as the erythropoietin receptor (EPOR) and the embryonically-associated hemoglobin zeta chain (HBZ) by both the cells of the endothelium and the cells emanating from proliferating IH explants. Additionally we investigated if the cells emanating from the explants generate erythrocytes in vitro.

Purpose
To investigate the expression of hematopoietic associated proteins and the primitive erythropoietic capacity of proliferating IH.

Methods
Proliferating IH biopsies from 5 patients were (i) processed for IHC staining for Tal-1, GATA-2, CD133, CD34, HBZ and EPOR; (ii) used to determine the relative expression of Tal-1, GATA-2, CD133, CD34, HBZ & EPOR transcripts by qRT-PCR; (ii) cultured as explants using our in vitro model and differentiated the cells down the erythropoietic lineage.

Results
IHC showed that the cells that line the endothelium forming the capillaries of proliferating IH expressed Tal-1, GATA-2, CD133, CD34, HBZ and EPOR. qRT-PCR confirmed the IHC data as abundant expression mRNA transcripts for the same proteins was detected in both the tissue and the cells emanating from the cultured explants. Following 5 months in culture morphological biconcave cells were visible, and were confirmed to be erythrocytes by immunoreactivity to the erythrocyte-specific cell surface marker glycophorin A.

Conclusion
The mRNA and protein expression of hematopoietic associated proteins in proliferating IH supports our previous studies showing this tumor expressing markers of primitive mesoderm and confirms a hemogenic endothelium phenotype. The expression of the primitive erythropoiesis-associated proteins HBZ and EPOR by proliferating IH and its functional ability of proliferating IH explants to form erythrocytes in vitro confirms the erythropoietic potential. Proliferating IH thus represents an extra-medullary site of tumor-associated erythropoiesis.

Disclosures:
No relevant conflicts of interest to declare.
EFFECTS of Zoledronic ACID On eNOS Exppression and Vascular Contractility IN Rat Aorta
Authors: Avcu Ferit , Soner Burak Cem , Yildiz Oguzhan , Ozturk Kamile , Elci Pinar , Sarper Meral , Ural Ali Ugur 
Published: October 2019

Abstract
Abstract 4318
Zoledronic acid (ZOL) is a potent nitrogen-containing bisphosphonate used in the treatment of skeletal metabolic disorders and bone metastatic diseases. It has been shown that the nitrogenous bisphosphonates inhibits enzymes of mevalonate pathway. Similar with statin derivatives, ZOL affects the biological activity of geranyl-geranylated proteins in mevalonate pathway, as shown for the small GTPase RhoA. Although, beneficial effects of statin derivatives on vascular tissue have been reported, there is no study on effects and of ZOL on endothelial functions in vascular tissue and mechanisms of its action. It is important to elucidate the mechanism regulating NO production for endothelial cells to develop new therapeutic strategies for the treatment of impaired endothelial function associated with the vascular diseases. The aim of this study is to demonstrate the molecular mechanism of ZOL in the regulation of endothelial responses and eNOS expression in rat aorta. For his aim, potassium chloride and phenyleprine induced vasoconstriction was evaluated in endothelium intact and denuded isolated rat aorta preparations (n=6) after incubation with ZOL 100 μM and the results were compared with those without ZOL incubation. In addition, to evaluate endothelium dependent or independent effects of ZOL, vasodilator effects of acetylcholine and sodium nitroprussid were tested in the presence and absence of ZOL. To evaluate the influence of protein geranylation in effect of ZOL, contractile effect of phenylephrine vasocontractions was tested after incubation with ZOL in the presence of geranylgeranyl pyrophosphate and farnesyl pyrophosphate, important enzymes of mevolonate pathway. In addition, eNOS mRNA expressions were evaluated with RT-PCR in intact rat aorta or after incubation with ZOL. According to our results, incubation with ZOL decreased potassium chloride and phenylephrine-induced contractions significantly. This decrease was reversed NO-syntase inhibitor Nı,-nitro-L-arginine methyl esther (L-NAME) 0.1mM. Additionally, incubation with ZOL, increased endothelium-dependent acethycholine-induced relaxations and this effect of ZOL was inhibited by L-NAME. In rat aorta preparations incubated with ZOL, eNOS mRNA expression was increased significantly (1.52 fold) compared with control group. According to these results, we herein provide the first experimental evidence for the physiological role of ZOL in the regulation of eNOS expression and the contractility in the vascular tissues. This effect of ZOL is probably via its influence on RhoA. Since the restoration of NO bioactivity is a major target of present pharmacological and non-pharmacological treatments in cardiovascular medicine, further laboratory and clinical studies to explore the effect of ZOL on vascular endothelium may be helpful to demonstrate the possible benefits.

Disclosures:
No relevant conflicts of interest to declare.
Childhood B-Precursor-ALL Presenting as Hepatitis - A Diagnostic and Therapeutic Challenge
Authors: Schneider Henriette , Adam Ruediger , Marx Alexander , Duerken Matthias 
Published: October 2019

Abstract
Abstract 4331
Liver involvement in childhood acute lymphoblastic leukemia (ALL) at presentation is common with hepatomegaly but severe impairment or hepatitis is rare with only 9 reported cases. The need to start anti-leukemic treatment despite the potential hazard of severe liver failure poses a clinical dilemma. We report a 6 year old girl who presented with jaundice, fever, vomiting and diarrhoea, cytopenia, hyperbilirubinemia of 5.7 mg/dl (direct 5.2), ASAT of 3389, ALAT of 2747 U/L, increased INR to 1.33, but normal ammonia. An acute common-ALL was diagnosed and serology, PCR-studies and cultures were negative for viruses causing hepatitis. Liver biopsy revealed diffuse hepatic blast infiltration, piecemeal necrosis and hepatocellular cholestasis without signs of infectious hepatitis. We treated the patient according to the ALL-BFM-2000-protocol without dose reductions and on day 8, hyperbilirubinemia had completely normalized and liver enzymes had significantly decreased. Further therapy was uneventful and the patient is alive and well 12 month after diagnosis, without any signs of hepatic dysfunction. Reviewing the literature on children with ALL presenting with hepatitis revealed 9 patients with a mean age of 8.8 years (range 4 to 15), female to male ratio of 2.0 and precursor B-cell immunophenotype in 8/9 patients. Patients had a mean bilirubin of 8.7 mg/dl (range 2 – 16.5), 3 had highly elevated transaminases above 2000 U/L, and two of them died initially. Another patient with moderately increased liver enzymes but hepatic encephalopathy needed transient hemofiltration, but survived. In none of the reported cases a viral organism has been identified and abnormal liver function normalized during chemotherapy in most of the patients. This indicates, that leukemia rather than infection was responsible for hepatitis. In conclusion, severe hepatitis in children with ALL is rare, seems to affect the older girl, and highly elevated liver enzymes are associated with early death. After infective organisms have been excluded, instant start of an effective induction therapy is required, even despite severe hepatitis, most probably caused by blast infiltration.

Disclosures:
No relevant conflicts of interest to declare.
Outcome of Adults with Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Therapy: A Single Institution Experience
Authors: Ruiz-Delgado Guillermo J. , Macias-Gallardo Julio , Lutz-Presno Julia , Montes-Montiel Maryel , Ruiz-Arg\)elles Guillermo J. 
Published: October 2019

Abstract
Abstract 4337
The results of treatment of adults with ALL remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. Eighty adult ALL patients were prospectively treated in a single institution in a 16-year period with a schedule based on the St. Jude's TOTAL XI pediatric protocol employing vincristine, prednisone, asparaginase, daunorubicin, etoposide, cytarabine, methotrexate, mercaptopurine and triple intratecal therapy. Median age was 31 years (range 18 – 86); 92% were B-cell malignancies and 14% were Ph1 (+). Ten patients did not complete the first course of chemotherapy and 4 exited early. 44 of 66 patents (67%) achieved a complete remission; relapses presented in 57%. The median probability of overall survival (OS) was 28 months, whereas the 144-month OS was 27%. The median probability of leukemia-free survival (LFS) was 28 months, and the 144-month LFS 35%. Ph1 (+) patients did worse than Ph1-negative and T-cell leukemias did better than B-cell ones. Concerning toxicity, eight patients had toxic deaths (12%), two developed acute pancreatitis and one secondary diabetes. This pediatric-inspired therapy rendered better results than those obtained in similar socioeconomic circumstances using adult-oriented treatments; tolerance was acceptable and costs were low since it employs affordable drugs and can be delivered as outpatients.

Disclosures:
No relevant conflicts of interest to declare.
Results of the Treatment for Relapsed Acute Lymphoblastic Leukemia (ALL) in Childhood
Authors: Guitter Myriam Ruth , Alfaro Elizabeth M , Rossi Jorge , Gallego Marta , Alonso Cristina , Felice Maria S 
Published: October 2019

Abstract
Abstract 4339

INTRODUCTION:
Relapses occur in 25–30% of childhood ALL. We evaluated the outcome of this group of patients (pts) according to the duration of the 1st CR, immunophenotype and site of relapse in our Institution.

PATIENTS AND METHODS:
From Sept’94 to Aug’09, 245 ALL relapses were diagnosed: 73 cases were not evaluable due to: different treatments received (n: 36), palliative care (n: 26) and insufficient data (n: 11); 172 pts were evaluable (54 F/118 M), with a mean age at the moment of the relapse of 9.8 (range 1.8–20.8) years. Induction therapy combined a pre-phase with 10 days of prednisone and 1 block of high doses of chemotherapy, followed by 5 blocks of similar intensity, CNS or testicular (preventive/therapeutic) radiotherapy, and weekly rotational maintenance, until completing two years from the moment of diagnosis. High-risk relapsed pts who had an available identical donor received HSCT.

RESULTS:
Immunophenotype was B-cell precursor (Bcp) in 89% of the pts and T-cell in 11 %. The duration of the 1st CR was <18 mo in 41 (24%), 18–36 mo in 79 (46%), >36 mo in 52 (30%) pts. The sites of relapse were bone marrow (BM) in 106 pts (61%), combined bone marrow (cBM) in 27 pts (17%) and isolated extramedullar in 39 pts (22%). The response to induction was: CR 134 pts (78%), death during induction 20 pts (12%) and partial/null response 18 pts (10%). Among the 134 pts who achieved CR, 69 (52%) presented a second relapse at 18,8 (r 0.7–88.8) mo from the 2nd CR, 10 (7%) died in CR and 1 developed a 2nd neoplasm. With a mean follow-up of 49 (r 2–155) mo, 54 pts remain in CR, 37 of them out of therapy. Of the 26 pts who received HSCT, 12 relapsed and 3 died in CR. The EFSp (SE) for the total group of pts was 25 (3)% and LFS probability (SE) 33 (4)%; for Bcp relapses it was 28%, and for T relapses 6% (P=0.0025); for BM+cBM cases it was 21%, and 40% for extramedullar (P=0.0061). However, testicular relapses achieved EFSp of 80%, and 12% for the remaining extramedullar cases (P=0.0004). The EFSp for relapses at <18mo of 1st CR was 5%, between 18–36 mo 25% and >36 m 41% (P=0.0001).

CONCLUSIONS:
The immunophenotype, the duration of the 1st CR and site of relapse significantly influenced the EFSp. Isolated testicular relapses achieved the best EFSp. HSCT is an eligible option for a small group of pts. New therapeutic approaches must be developed to improve outcome of most of relapsed ALL patients.

Disclosures:
No relevant conflicts of interest to declare.
Predictive Factors for Achieving Complete Remission In 69 Mexican Patients with Adult Acute Lymphoblastic Leukemia Treated with Hyper-CVAD
Authors: Chávez-Güitrón Eduardo , Rocha Fernando Perez 
Published: October 2019

Abstract
Abstract 4340

Background.
Acute adult lymphocytic leukemia (ALL) is an infrequent oncologic entity whose rates of global response and cure remain unsatisfactory, when compared to results obtained in treatment of other neoplastic disorders, and of ALL itself in pediatric population, where cure rates approach 90%. Most current induction protocols achieve remission rates of 70 to 90% worldwide, but 5-year disease free survival remains unchanged. MD Anderson Cancer Center (MDACC) published their results with HyperCVAD more than a decade ago, reporting rates of complete remission of 92%, and 5-year disease free survival of 38%. We have used HyperCVAD at our center since 1999, but have not reported the baseline patient characteristics and outcomes.

Methods.
We conducted a retrospective analysis on 69 patients treated with HyperCVAD from 2005 to 2009, evaluating traits at baseline and response to treatment, using descriptive statistics. Survival analysis (overall survival and disease free survival) were described using the Kaplan-Meier method. Baseline traits and their association to response were measured using Chi-square test. Comparison between the original cohort described by MDACC and ours was also analyzed by this test.

Results.
Sixty nine patients with a median follow up of 12 months (range 1–144) were evaluated. Complete remission rates were 77%; induction mortality 4.3%; the estimate of overall survival and disease free survival at 60 months was less than 10% in both cases. The pretreatment variables associated to an increased probability of achieving remission were age <30, baseline hemoglobin >10g/dL and pre B phenotype (p<0.001). Leukocyte count and baseline DHL did not predict ability to achieve remission as shown in the original MDACC study. A 15% difference in complete remission response rate between the original series and ours was found to be statistically significant (p<0.0001).

Discussion.
HyperCVAD as applied to Mexican patients has an efficacy similar to other remission induction protocols, as reported elsewhere, but is inferior to the original results published by MDACC. Survival analysis requires a longer median follow-up for valid conclusions to be drawn.

Disclosures:
Perez Rocha: genzyme: Employment, Honoraria.
Efficacy and Effectiveness of Azacitidine In Elderly Patients with Acute Myeloid Leukemia and Blasts Counts below 30%: Experience of the Spanish Registry
Authors: García Regina , Arnar Monserrat , Luño Elisa , Bargay Joan , Romero Ma Mar , Besalduch Juan , Amutio Elena , Garrido Raquel , Carnicero Fernando , Smd Grupo Andaluz de 
Published: October 2019

Abstract
Abstract 4354

Introduction:
The incidence of acute myeloid leukemia (AML) increases exponentially with age. Elderly patients normally have a previous hematologic condition like myelodysplastic syndrom (MDS), cytogenetic abnormalities that correlate with resistance to conventional chemotherapy schemes and a shorter duration of response. Not only responses are worse, also the hospitalization duration is longer, and the mortality associated to the treatment is higher (30%). Therefore, treating these patients with standard chemotherapy schemes is associated, in many cases, to a low probability of obtaining satisfactory results. Introducing less toxic and/or more efficient agents can change the course of the illness for this sub-group of patients. Azacitidine (AZA) is a hypomethylating drug recently approved in Europe for the treatment of AML with 20 – 30% blasts.

Materials and methods:
We present clinical data analysis of a longitudinal, multicenter and retrospective Spanish patients’ registry of patients with de novo and relapse AML. Data on the course of the disease and managment of patients with de novo and relapse AML with low blasts count (20-30%) treated with AZA under compasionate use were analized.

Result:
Twentyfive patients (male/female 13/12) with a median age of 67 years with AML were included in the registry. Ten patients (40%) had refractory/relapsed AML and had received previous treatment with intensive chemotherapy. Cytogenetic alterations were reported in 10 patients (4 monosomy-7). An average of 7 cycles of AZA were administered to the patients (range 1–25). The most frequently used dose was 75 mg (82%), of which 28% received a scheme of 5 days, 24% received a scheme of 5+2 and 48% of 7 days. The global responses were of 56% with 20% of complete responses. The most frequent toxicity described was hematologic.

Conclusion:
Our data corroborates, with a similar rate of responses, what Journal of Clinial Oncology published about the sub analysis of the AZA-001. 5-Azacitidine is an efficient and safe drug in patients with AML. Good response rates and a toxicity and mortality related to the acceptable treatment in this sub-group of patients.

Disclosures:
García: Celgene: Research Funding. Bargay:Celgene: Research Funding.
The Apoptosis of Acute Myeloid Leukemia Cell Line (SHI-1 cells) Induced by Bortezomib In Vitro
Authors: Yang Mingzhen , Zhang Xiaoyu , Huang Zhenqi , Li Qingsheng , Wang Lin , Liu Qinhua 
Published: October 2019

Abstract
Abstract 4382

Background:
The proteasome plays a critical role in the regulation of many cellular processes, including the cell cycle and tumor growth. The proteasome inhibitor Bortezomib has been used in multiple myeloma and other lymphoid malignancies because of its antitumor activity. Here we investigated the induction of apoptosis by proteasome inhibitor Bortezomib in human acute myeloid leukemia (AML) cell lines SHI-1 cells and try to explore the mechanism of anti-leukemia.

Method:
We incubated SHI-1 leukemic cells with different concentration of bortezomib. cell proliferation was detected with MTT, apoptosis was measured by FCM, the protein expression of PI3K and p-Akt were determined by Western blot.

Result:
0.5ug/ml bortezomib suppressed SHI-1 cells proliferation and induced SHI-1 cells apoptosis after incubated 24hr, 100ug/ml bortezomib suppressed 61.7% SHI-1 cells proliferation. Apoptosis increased obviously with the increasing bortezomib concentration and the culture time, about 39.77% SHI-1 cells were apoptosis when bortezomib concentration was 100ug/ml, the leukemia cell apoptosis was significant at 150ng/ml bortezomib, the protein expression of PI3K, and p-Akt gradually declined with bortezomib concentration increasing, The protein expression of PI3K and p-Akt in SHI-1 cells decreased 50.6% and 71.6% respectively at 100ug/ml bortezomib for 48hr.when 150ng/ml bortezomib incubated with leukemia cells for 24 hours, The protein expression of PI3K and p-Akt were lowest.

Conclusion:
Bortezomib could inhibit SHI-1 cells proliferation and induce leukemia cells apoptosis, and could down-regulate the expression of PI3K and p-Akt significantly, this might be the one of mechanisms that bortezomib induce SHI-1 cells apoptosis, we presume that bortezomib inhibit proliferation of acute myelogenous leukemia cells through effect of PI3K/Akt signaling pathways.

Disclosures:
No relevant conflicts of interest to declare.
Increased Use of Direct Thrombin Inhibitor Argatroban In Hospitalized Patients
Authors: Jain Amit , Smit Kristen , Manchanda Naveen 
Published: October 2019

Abstract
Abstract 4398
Heparin Associated Thrombocytopenia (HAT) is associated with profound thrombo-embolic complications and Heparin substitutes are widely used as prophylactic and sometimes as therapeutic anticoagulants. Argatroban is one of several Direct Thrombin Inhibitors (DTI) used in these patients. We observed over the past several years that there was increasing use of Argatroban in hospitalized patients without a suspicion or diagnosis of HAT. In order to determine the extent and indications for use of Argatroban at our university hospital we analyzed medical records of all patients who had received this drug over a three-year period.
Of the 60 individual patients who received Argatroban over a one year period, most of them received this drug once during their hospitalization and few received it multiple times over several hospitalizations. Seven of these patients (11.6%) received this drug for non-HAT related diagnoses. The following indications were provided for use of this agent:
1. Recurrent VTE on therapeutic Enoxaparin/Fondaparinux in patients with cancer: 3
2. Recurrent VTE on therapeutic Enoxaparin/Fondaparinux: 1
3. Anti-thrombin deficiency: 2
4. Heparin allergy: 1
Outcomes:
1. Cancer associated DVT: One survived, one died of progressive thrombosis; one lost to follow-up
2. Recurrent VTE on Enoxaparin/Fondaparinux: currently off Argatroban
3. Patients with AT deficiency and Heparin allergy are off anticoagulants.
Argatroban, a DTI, is a drug with a narrow therapeutic index and is licensed for use in patients known or suspected to have HAT. Recently, it has found increasing use as an anticoagulant considered to have increased efficacy as compared to Enoxaparin and Fondaparinux. While accepted as an alternate to UFH in several instances, it is considered less effective in situation involving Cardiopulmonary bypass. However, whether it is a better agent to treat patients with or without cancer who have recurrent or progressive VTE and have failed conventional anticoagulants needs to be investigated further.

Disclosures:
No relevant conflicts of interest to declare.