bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Rasburicase Effective In Reversing Acute Renal Failure In Patients with Tumor Lyses Syndrome?
Authors: Cherry Mohamad Ali , Srour Samer , Khawandanah Mohamad , Qubaiah Osama , Ghabache Bassam 
Published: October 2019

Abstract
Abstract 4939
Tumor lysis syndrome (TLS) is a potentially life-threatening complication that can occur spontaneously or following treatment of malignant neoplasms, particularly leukemias and lymphomas. TLS can cause acute renal failure (ARF) by precipitation of uric acid (UA) and phosphate crystals in renal tubules. Rasburicase, a recombinant urate oxidase, was proven to be effective in the treatment of TLS and is known to cause an improvement in renal function in a subset of patients with TLS. For the purposes of our analysis ARF was defined as more than 50% increase in creatinine from baseline value or presenting with creatinine more or equal to 2 mg/dl with no previous history of chronic renal failure. To assess the efficacy of Rasburicase in adult patients with documented TLS and ARF in improving or normalizing the creatinine clearance (CrCl), we conducted a retrospective analysis of 53 patients that received Rasburicase for documented TLS. 41 patients fit the inclusion criteria. The median age was 54 yr (26-90), 13 were female. The majority of patients had hematological malignancies (acute leukemia, 11; chronic leukemia, 5; myeloproliferative/myelodysplastic syndromes, 4; lymphoma or myeloma, 10; solid tumor; 11).
Results: On the first day of rasburicase infusion (day 0), median UA, creatinine and CrCl were 11.5 mg/dl (5.1 - 23.7mg/dl), 3.26 mg/dl and 32.5 ml/min (8.0 - 97.8 ml/min) calculated using Cockcroft-Gault equation, respectively. Patients received an average total dose of 0.17 mg/kg (0.06-0.51 mg/kg) of rasburicase in one or two doses. UA levels normalized in 97.3% and 100% of patients by day 2 and 7 respectively. Creatinine levels normalized in 19% and 59.4% by day 2 and 7 respectively. CrCl improved form a median of 32.5 ml/min to 40.5 ml/min and 58 ml/min by day 2 and 7 respectively. A sub analysis for patients with baseline CrCl <30 ml/min (n=17) on day 0 of Rasburicase infusion revealed a similar benefit to those with baseline CrCl >30 ml/min. CrCl improved in this subset of patients from a median of 17 ml/min (8-28.2 ml/min) to 24.5 and 47.4 ml/min on days 2 and 7 respectively. Patients who received a total dose of <0.1mg/kg of rasburicase (n=8) derived similar benefits to those who received 0.2mg/kg or more (n=11).
Conclusion: Rasburicase infusion is effective in improving the creatinine clearance even in patients with advanced renal failure (CrCl<30 ml). Lower doses of Rasburicase are as effective as higher doses, even in patients with advanced renal failure, making the lower dose advisable and cost effective.

Disclosures:
No relevant conflicts of interest to declare.
Synthesis and Reversal Efficacy of Magnetic Nanoparticles Coloaded with Daunorubicin and 5-Bromotetrandrin
Authors: Chen Bao-An , Wang Jun , Cai Xiao-hui , Gao Feng , Cheng Jian , Chen Ping-shen , Zhang Yu , Tang Meng , Ding Jia-hua , Bao Wen 
Published: October 2019

Abstract
Abstract 4945
Owing to serious side effects and multidrug resistance (MDR), systematic chemotherapy is limited in cancer treatment. On the one hand, most of side effects are result from non-selective for target cells of antitumor drugs. On the other hand, the main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). Design and exploitation of novel clinical chemotherapy formulation with dual functional properties of targeted therapy and reversal of drug resistance is a promising approach in tumor therapy. Nanoparticles drug delivery system has been shown to improve cancer therapy by increased drug delivery to target sites because of the enhanced permeability and retention effect (EPR). In the present studies, we developed a new formulation, which magnetic nanoparticles (MNPs) coloaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet), an anticancer drug and a MDR reversal agent, and studied the in vitro antitumor efficacy. The drug encapsulation efficiency of DNR and Br Tet (alone or in combination) in MNPs was 62–83%. The release of DNR and Br Tet from nanoparticles was sustained. The DNR and Br Tet loaded MNPs (DNR-Br Tet-MNPs) are provided with good magnetic responsibility. The drugs in combination incorporated in MNPs displayed well synergistic cytotoxicity in the MDR leukemia K562/A02 cells. Fluorescence intensity of intracellular DNR detection demonstrated that DNR-Br Tet-MNPs could be endocytosed by K562/A02 cells and sustained releasing DNR intracellular. The results of RT-PCR and western blot demonstrated that the expressions of MDR1 mRNA and G-pg of K562/A02 cells are decreased by treated with DNR-Br Tet-MNPs after 48 h. It was concluded that the antitumor efficacy of DNR-Br Tet-MNPs was due to the inhibition of Br Tet to P-gp and reducing the efflux of DNR. Our DNR-Br Tet-MNPs could be of high clinical value in the target treatment of many resistant tumors, such as haematologic malignancies.

Disclosures:
No relevant conflicts of interest to declare.
IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis
Authors: Moscetti Alessandro , Saltarelli Francesca , Bruno Guglielmo , Monarca Bruno , Salerno Gerardo , Corsetti Maria Teresa , Cardelli Patrizia , Ferranti Giovanna , La Verde Giacinto 
Published: October 2019

Abstract
Abstract 5000
AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis.

Disclosures:
No relevant conflicts of interest to declare.
Chemotaxis-Related Factors Are Dysregulated In Bone Marrow Mesenchymal Stem Cells (MSCs) In Multiple Myeloma Patients
Authors: Lu Hua , Hu Huijin , Fei Xiaoming , Li Jianyong 
Published: October 2019

Abstract
Abstract 5010

Abstract Objective:
This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor(HGF), stromal-derived factor-1(SDF-1), Chemokine (C-C motif) ligand 2 (CCL2) and interleukin-8(IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients.

Methods:
The real time quantitative polymerase chain reaction(RQ-PCR)technique was used to detect the mRAN expression levels of HGF, SDF-1, CCL2 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients compared with 9 controls.

Results:
The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with control (P < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with control (P < 0.05). There was no significant difference in the mRNA expression levels of CCL2 and IL-8 between MM and control cohorts (P > 0.05).

Conclusion:
The research suggests that multiple chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysrelugulated in MM patients, which might result from the interplay between MM cell and MSC.

Disclosures:
No relevant conflicts of interest to declare.
Acadesine Inhibits Proliferation and Induces Apoptosis In Multiple Myeloma Cells, and Synergizes with Standard of Care Antimyeloma Agents
Authors: Hernández-García Susana , de Frias Mercè , Campàs Clara , Paiva Bruno , Ocio Enrique M. , Miguel Jesús F. San , Pandiella Atanasio 
Published: October 2019

Abstract
Abstract 5023
Multiple myeloma (MM) is a malignancy characterized by the accumulation of plasma cells. The disease represents the second most common hematologic malignancy and remains incurable, despite recent advances in its treatment. Therefore, studies to develop new therapies are still necessary, particularly in patients with bad prognostic factors, such as 17p deleted/p53 mutated patients. In this study we describe the preclinical activity of 5-Aminoimidazole-4-carboxamide-1–4-ribofuranoside (AICAR or acadesine) in multiple myeloma. Acadesine is an analog of AMP that is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy changes.
Acadesine induces apoptosis in different cell types including CLL, mantle cell lymphoma (MCL) and splenic marginal zone B-cell lymphoma (SMZL) cells and tumor cell lines, without affecting primary T lymphocytes. Thus, acadesine is a promising drug for the treatment of B-cell neoplasms. A clinical phase I/II study of acadesine is currently being performed in CLL patients.
We studied the effects of acadesine on the MTT metabolization of several multiple myeloma cell lines (MM1S, MM1R, RPMI-8266, RPMI-LR5, U266, U266-LR7, U266 Dox4, MM144, MGG, SJR, OPM-2, NCIH-929). Acadesine inhibited MM cell growth and induced apoptosis, with IC50 values in the micromolar range, and independently of the p53 mutational status.
Cancer treatment, including myeloma, is generally based on combinations of drugs with different mechanisms of action. Thus, we studied the effect of acadesine in double combinations with drugs used in myeloma therapy, such as dexamethasone, melphalan, doxorubicin, bortezomib, and lenalidomide. Analyses of these data using the Chou and Talalay method indicated that acadesine was synergistic with dexamethasone (CI values of 0.60), and particularly with lenalidomide (CI values of 0.42). These promising results with double combinations promoted the investigation of triple combinations in the MM1S cell line. Triple combination of acadesine plus dexamethasone plus lenalidomide or bortezomib notably improved the efficacy of the respective double combinations, being the combination of acadesine plus lenalidomide plus dexamethasone especially efficient.
Further studies to determinate the mechanism of action, and in vivo studies in MM1S xenograph are ongoing.

Disclosures:
de Frias: Advancell: Employment. Campàs:Advancell: Employment.
Analysis of the JAK2 Gene cDNA Full-Length In One Chinese Familial Myeloproliferative Disorders
Authors: Feng Ru , Hao Lixia , Zhang Yongmin , Wei Yongqiang , Huang Fen , Yin Changxin 
Published: October 2019

Abstract
Abstract 5056

Introduction:
JAK2V617F point mutation have been confirmed to be one of the major molecular mechanism of BCR/ABL negative myeloproliferative disorders(MPD). Besides, some other gene mutations such as JAK2 exon12, MPL W515L/K, c-mpl and EPOR have extended the scope of the research in this field. Most of the MPD patients are sporadic and there are seldom reports in Chinese familial MPD. 2008 ASH metting we have reported in a Chinese family of MPD's findings, the two brothers in our hospital diagnosis for MPD (one is a PV, another is ET), then we investigated the 15 members of the family. We discovered that there were three male members carried the JAK2V617F mutation in this family, including the two MPD patients and their father, which affected in two generations. All the family members were confirmed as BCR/ABL, MPL W515L/K, c-mpl, and EPOR negative. Subsequently, in order to understand the existence of family members in addition to the gene JAK2 V617F mutation, the existence of JAK2 gene mutations in other parts of the? if other mutations in existence and the high incidence of family members of MPD? We focus on the cDNA full-length of JAK2 gene to provide some theory basis on the pathogenesis in MPD.

Methods:
A total of 15 family members were enrolled in our study, including 2 brothers of MPD patients (the older one was thrombocythemia (ET), and another is polycythemia vera (PV)) and the other members in the same family. The mRNA of mononuclear cells from peripheral blood sample was extracted according to the manufacturer's instruction (TAKARA). RT-PCR and DNA sequencing have been used to analyze the cDNA full-length of the JAK2 gene.

Results:
All of the samples can be analyzed for JAK2 cDNA full-length. 3 members carried the JAK2V617F mutation (1849G®T) in this family, including the two MPD patients and their father. And the older brother was homozygous mutation and the other two were heterozygous mutation. All of the 15 samples were JAK2 exon12 gene mutation negative. 2 persons who were the male ET patient's children had a heterozygous mutation (380G®A) in JAK2 exon 3, caused a glycine-to-asparticacid substitution at position 127. Besides, 13 persons had 489C®T mutation in exon 4 and 14 persons had 2490G→A mutation in exon 17 in this family, But they were both same-sense mutation.

Conclusion:
It is necessary to do routine analysis of blood and other related inspection for MPD patient's family members, so as to make diagnosis earlier. However, we are not sure that the sequencing results are unique to all the familial MPD and need to be confirmed by more cases. We still do not determine the current discovery point mutations have biological significance, still need to be further explored.

Disclosures:
No relevant conflicts of interest to declare.
Long-Term Follow-up of Rituximab and Infusional Cyclophosphamide, Doxorubicin, and Etoposide (CDE) In Combination with HAART In HIV-Related Non-Hodgkin's Lymphomas (NHL)
Authors: Spina Michele , Jaeger Ulrich , Sparano Joseph A , Talamini Renato , Rossi Giuseppe , Vaccher Emanuela , Tirelli Umberto 
Published: October 2019

Abstract
Abstract 5072

Background:
The combination of Rituximab plus chemotherapy (CT) is more effective than CT alone in the treatment of high grade NHL. Objective: To report the long-term follow-up of CDE plus Rituximab in HIV-NHL.

Methods:
In June 1998, we started a phase II study using infusional CDE (Cyclophosphamide 187.5 mg/m2/day, Doxorubicin 12.5 mg/m2/day and Etoposide 60 mg/m2/day) administered by continuous intravenous infusion for 4 days every 4 weeks and Rituximab 375 mg/m2 i.v. on day 1. HAART was given concomitantly with CT.

Results:
Seventy-four patients (pts) have been enrolled. The median CD4+ cell count was 161 (range 3–691) and the median Performance Status was 1 (range 0–3). Diffuse large B-cell NHL was diagnosed in 72% of pts and Burkitt in 28%. Seventy per cent of pts had advanced stage (III-IV) disease and 57% of pts had an age-adjusted international prognostic index >2. Fifty-two out of 74 pts (70%) achieved a complete remission (CR), 4/74 (5%) had a partial remission and 18 pts progressed. With a median follow-up of 61 months, only 17% of CRs have relapsed and 41/74 pts are alive. The overall survival, disease free survival and time to treatment failure (TTF) at 5 years were 56%, 81% and 52%, respectively. Four cases of secondary tumors have been observed. No case of late pulmonary or cardiac toxicity has been reported.

Conclusions:
The combination of Rituximab and CDE in HIV-NHL treated concomitantly with HAART is very active. CR rate (70%) and TTF at 5 years (52%) are comparable to those observed in high grade NHL of the general population. Our data confirm that in HAART era a high proportion of HIV-NHL can be cured.

Disclosures:
No relevant conflicts of interest to declare.
Flow Cytometric Immunophenotypic Analysis of Cerebrospinal Fluid Cells In Hematological Malignancies
Authors: Ciriello Maria Matilde , Calcagno Lara , Callegari Tiziana , Gatto Simona , Primon Valeria , Arfini Carlo , Levis Alessandro 
Published: October 2019

Abstract
Abstract 5094

Background.
Leptomeningeal involvement is an adverse complication of haematological malignancies, acute leukemias and lymphomas. The diagnostic gold standard to identify cerebrospinal fluid (CSF) involvement is conventional cytological analysis, technique characterized by low sensitivity and specificity. Recent papers make evidence that the efficiency of CSF involvement detection could improve by use of Flow Cytometry (FCM) immunophenotypic analysis of CSF samples. We describe the FCM method used in our hospital and we compare the results with cytological findings.

Methods.
CSF samples should be processed immediately, within 1 hour after collection to avoid cell's deterioration; in B Non Hodglin Lymphomas (B-NHL) we use two steps FCM approach, in four color staining (FITC/PE/PerCP/APC). The first step was two tubes: kappa/lambda/CD45/CD19 and CD5/CD20/CD45/CD3 or CD3/CD20/CD45/CD10 on the basis of a previous know immunophenotype or not. If a pathological population is identified, we complete immunophenotype characterization with a second step, using antibody panels suitable for the suspected malignancy. In case of suspected meningeal relapse of Acute Leukemia we use a monoclonal antibody combination select for Minimal Residual Disease.

Results.
Between 2006 and 2009 we studied by FCM analysis 53 CSF samples of 36 patients. 7 CSF of 29 B-NHL newly diagnosed resulted positive at FCM analysis (24,1%), 1 CSF of 7 Acute Leukemias shows disease relapse. The conventional cytology was positive only in 1 case of B-NHL.

Conclusion.
Our study confirms that immunophenotypic flow cytometric analysis of CSF cells markedly improves sensitivity to identify CSF involvement in haematological malignancies.

Disclosures:
No relevant conflicts of interest to declare.
Acute T Cell Lymphoma/Leukemia (ATL) Cases for Notch1 and FoxP3 Expression and the Clinical Implications
Authors: Yan Wang Chun 
Published: October 2019

Abstract
Abstract 5096
[Abstract] Objective To investigate acute T cell lymphoma/leukemia (ATL) cases for Notch1 and FoxP3 expression and the clinical implications.

Methods
The expressions of Notch1 and FoxP3 in lymphoma and bone marrow specimens from 22 cases of ATL were studied by immunohistochemical analysis. The expressions of Notch1 and FoxP3 were analyzed by Image-ProPlus 6.0 and shown in integral optical density (IOD) (X±S).

Results
The neoplastic T cells of 90.91% of cases expressed FoxP3 and 72.73% of cases expressed Notch1, and 63.64% of patients had Notch1 and FoxP3 co-expression. IOD of FoxP3 and Notch1 were 13.57±11.38 and 8.42±3.48, respectively. The comparison of their IOD had no statistical significance (P=0.055).

Conclusion
The expressions of Notch1 and FoxP3 were high in ATL, which may be associated with the clinical outcome of ATL.

Disclosures:
No relevant conflicts of interest to declare.
Patients with Systemic Lupus Erythematosus (SLE) Having Developed Malignant Lymphomas. Continuing Complete Remission of Lymphoma Following Chemotherapy, but Not of SLE
Authors: Rossi Edoardo , Catania Gioacchino , Carella A. M. Michele , Marmont Alberto 
Published: October 2019

Abstract
Abstract 5098

Intoduction:
The development of malignant lymphomas, generally of the non-Hodgkin type (NHL), and with a preference to diffuse large cell B lymphomas (DLCBL), in systemic lupus erythematosus (SLE), has been proven and analyzed in an exhaustive recent literature. The combination of germline and somatic mutations, persistent immune overstimulation and the impairment of immune surveillance facilitated by immunosuppressive drugs, is thought to be at the origin of the increased lymphoma genesis. However the treatment and course of such affected patients is less known, and prognosis is generally estimated as poor. Materials: Out of 258 patients with complete/incomplete lupus and secondary antiphospholipid syndrome (APS) seen and treated at the institutional Day Hospital between 1982 and 2009, 6 developed lymphomas (4 DLCBL, 1 Hodgkin's and 1 indolent lymphocytic lymphoma).

Results:
The first 5 patients were treated with chemotherapy and achieved continuous complete remissions (CCR) with a follow-up comprised between 18 and 172 months. One patient achieved complete remission (CR) of both diseases. In the other 4 lupus serology (ANA, APA) persisted, with occasional lupus flares and vascular complications.

Conclusion:
While eradication of the last cancer stem cell is tantamount to cure in neoplastic disease, persistent autoantigenic overstimulation may contribute to the refractoriness of autoimmunity. The implications of these results for the increasing utilization of hematopoietic stem cell transplantation for severe autoimmune diseases (SADS), with lupus as a paradigm, are extensively discussed elsewhere (1).
(1) Rossi E, Catania G, Grassia L, and Marmont AM. Patients with systemic lupus erythematosus (SLE) having developed malignant lymphomas. Continuing complete remission of lymphoma following high-dose chemotherapy, but not of SLE. (submitted for publication)

Disclosures:
No relevant conflicts of interest to declare.