bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Value of Beta2 Microglobulin, Retinol Binding Protein, Endothelin-1, N Amino ß-d-Glucoaminodase and Cystatin C for the Evaluation Sickle Cell Nephropathy
Authors: Unal Selma , Kotan Caglar , Delibas Ali , Arslankoylu Ali Ertug 
Published: October 2019

Abstract
Abstract 4817

Introduction:
Sickle Cell Anemia (SCA) is a chronic disease characterized by broad clinical manifestations and multi-organ disease. Sickle cell nephropathy is one of the major side effects in the patients with SCA. This study was planned to determine the incidence of renal complications of the patients with SCA and to evaluate the renal complications by using new markers such as ß2 microglobulin, retinol binding protein (RBP), endothelin-1, N amino ß-d-glucoaminodase (NAG) and cystatin C.

Methods:
45 children (mean age 8.4 ± 1.21, range: 1–15 years), 10 adult patients with SCA (mean age:31.4 ± 10.11, range: 16–45 years) and 20 healthy children (mean age:8.45 ± 4.05, range: 1–15 years), 10 healthy adults (mean age: 26.6 ± 8.62, range: 16–45 years) as control groups were included in the study. A detailed history was taken from each child, and a full physical examination was performed. Serum and urine electrolytes, urine analysis, urine culture and renal ultrasonography were performed for all patients. 24 hour urine was collected both in patient and control groups, and GFR was measured. Tubular phosphate reabsorbtion, 24 hour urine protein and calcium excretion, fractional excretion of Na, K, Urea and Cl were calculated from 24 hour urine samples. ß2 microglobulin, endothelin-1 RBP and NAG levels were measured in spot urine samples of patients and controls. Serum cystatin C level was measured in both patient and control groups. ß2 microglobulin, endothelin-1, RBP and cystatin C were measured with micro-elisa method. On the other hand colorimetric assay was used to measure NAG.

Results:
35 patients (63%) had enuresis nocturna, 34 patients (61%) had moderate proteinuria and 9 patient (16%) had poliuria. 26 patients (47%) had past history of urinary tract infection and 3 patients had past history of hematuria. Although all the markers to evaluate tubular functions were in normal ranges, ß2 microglobulin/creatinine ratio was found to be high in 10 patients (18%). GFR measured with creatinine was in normal ranges in all of the patients. Hovewer GFR measured with cystatin-C was low in 3 patients (0.5%). Urine ß2 microglobulin, endothelin-1, RBP, NAG, and serum cystatin-C levels were all in normal ranges both in patient and control groups.

Conclusions:
The commonly observed renal side effects in the patients with SCA are enuresis nocturna, proteinuria and increased tendency to urinary tract infections. It could be suspected that ß2 microglobulin/creatinin ratio and GFR that is calculated by the use of cystatin C could be use in order to evaluate the tubular and glomerular functions in those patients with SCA during the early stages of sickle cell nephropathy. Besides, urine endothelin-1, RBP and NAG levels could not be considered as good markers for determining the sickle cell nephropathy.

Disclosures:
No relevant conflicts of interest to declare.
Distinctive Hematological Abnormalities and GATA1 Mutation Spectra In East Asian Neonates and Children with Down Syndrome
Authors: Kim Hye-Ran , Kim Da-Woon , Baek Hee-Jo , Kook Hoon , Hwang Tai- Ju , Shin Jong-Hee , Suh Soon-Pal , Ryang Dong-Wook , Shin Myung-Geun 
Published: October 2019

Abstract
Abstract 4837

Background:
Many hematological abnormalities have been reported during the neonatal period in infants with Down syndrome (DS). Neonates with DS are predisposed to developing transient abnormal myelopoiesis (TAM) and acute megakaryblastic leukemia (AMKL). However, there is a paucity of data on hematological aberrations and GATA1 gene mutations in neonates with DS in East Asian populations. We therefore investigated the spectrum of hematological abnormalities in infants and children with DS in one such population, and analyzed the frequency and pathophysiological role of GATA1 mutations in DS-TAM and DS-AMKL in this group.

Patients and Methods:
A total 148 patients with DS were identified from January 2000 to December 2009. Of these, 109 had had blood drawn for a complete blood count (CBC) with differential. There were 37 neonates (°Â4 weeks of age), 55 children (<18 years of age), and 17 adults °Ã 18 years of age) in the study. A comprehensive molecular study of the GATA1 gene was performed using PCR, RT-PCR and direct sequencing for all six exons (7,757 bp) and cDNA sequence of GATA1 gene.

Results:
Thrombocytopenia was most common hematological abnormality (35%) in the neonates. Leukocytosis and polycythemia were each detected in 4 cases (11%). Blasts were identified in the differential count of 6 (16%) neonates. Of the 55 children with DS, 11 (20%) had thrombocytopenia, 10 (18%) had anemia, and 7 (13%) had neutropenia (< 1,500/uL). There were also 4 (7%) cases of AMKL and 2 (4%) cases of acute lymphoblastic leukemia in the children with DS. GATA1 mutations were identified in all of the TAM samples and in 2 of the 3 AMKL samples, but were not detected in the 1 remission sample or the 2 samples from normal DS children.

Conclusions:
East Asian DS neonates showed distinctive hematological abnormalities such as uncommon neutrophilia, relatively common neutropenia, and increased prevalence of TAM compared with reports from Western countries. The GATA1 mutation analysis may offer the potential to accelerate and refine the diagnosis of TAM and AMKL, and to accurately measure the kinetics of the mutant GATA1 clone as a tool for minimal residual disease measurement because virtually all cases of TAM and AMKL harbored this mutation.

Disclosures:
No relevant conflicts of interest to declare.
P53 Abnormality and Prognostic Impact In Leukemia Patients with Complex Chromosomal Abnormalities
Authors: Cao Xiangshan , Zhou Zhaoling 
Published: October 2019

Abstract
Abstract 4847

Objective:
To investigate the prevalence of p53 gene deletion in leukemia patients with complex chromosome abnormalities (CCA) and their relative prognostic impact.

Methods:
The chromosome abnormalities in acute leukemia cases with R banding method, karyotype is named according to international nomenclature ISCN 2005. Interphase fluorescence in situ hybridization (I-FISH) determinations were performed to detect the percentage and frequency of p53 gene deletion in 38 leukemia patients with CCA and 24 patients without CCA. The rate of complete remission (CR) and median survival time (MST) were observed between the two groups in patients with CCA or without CCA.

Results:
(1) Complex karyotype abnormality in the leukemia patients involved in almost all of chromosomes, especially chromosome 17, chromosome 5, and chromosome 7. And the reduction of chromosome number was more common than the increase. (2) The threshold of two green and one red (2G1R) was 7%, the threshold of one green and one red (1G1R) was 4.9%. (3) The percentage of p53 gene deletion was 44.74% in CCA group and 4.16% in non-CCA group (p<0.0001). (4) p53 gene deletions were found in 9 of 10 cases with chromosome 17 abnormalities. The percentage of p53 gene deletion was achieved in 90%. (5) The CR rate was 57.14% and the MST was 31 months in patients with non-CCA compared to 11.76% CR rate and 2 months MST in patients with CCA (p<0.0001).

Conclusion:
The deletion of p53 gene appears to be associated with complex chromosome abnormalities and may play an important role in the prognosis of patients with leukemia

Disclosures:
No relevant conflicts of interest to declare.
Frequency of Citogenetic Abnormalities and the BCR/ABL Fusion Gene In Adult Patients with Acute Lymphoblastic Leukemia (ALL). Multicentric Study From Mexico
Authors: Ignacio Gregorio , Arana Rosa_Maria , Solis Juan_Carlos , Ramos Christian , Gonzalez Mauricio , Perez Oscar , Jimenez Rosa_Maria , Lugo Yolanda , Aguilar Lilia , DeDiego Jope , Guzman Laura , Rozen Etha , Limon Alejandro , Lopez Manuel , Nacho Kevin 
Published: October 2019

Abstract
Abstract 4864
The t(9;22) or BCR/ABL fusion genes occurs in 20–30% of adult patients with ALL overall and its presence leads to worse prognosis for ALL. But there are a few large reports focused on this subtype of adult ALL in México, including its clinical characteristics.

Objective.
(1) To know the frequency of chromosome Ph-positive or BCR/ABL by cytogenetic and RT-PCR studies; (2) to evaluate the clinical prognostic factors and the correlation with cytogenetic abnormalities.

Methods.
In the present report, we study of 104 adults with ALL de novo from seven different hospitals from Mexico, between November 2008 – June 2010. All patients were de novo and were subjected to karyotyping in bone marrow and RT-PCR from BCR/ABL at diagnosis.

Results.
From 104 ALL adults included 47(45%) males and 57(54.8%) females, with age range 17–73 years (mean= 33.81 years). The most frequent subtype FAB were L2 (87%) an L1 (13%) with immunophenotype by LAL-B 95%, and 4.8% bilinear. Blood counts were very low, mean hemoglobin 7.8 g/dL (SD+ 2.61), platelet 67,266 × mm3 (SD 79,627), and leukocytic 37,815 × mm3 (SD 60,905). The grown of liver, spleen and adenomegaly was only 40.4%. 19 (18.26%) karyotypes was not useful. Eigthfive informative karyotypes were subdivided into 6(7%) t(9;22); 49(57.6%) normal; 14(16.5%) hyperdiploid; 2(1.9%) hypodiploid; 2(1.9%) poliploid; and 5(5.8%) rearr(12). Chromosomes 9,11,12 and 3 were the most frequently envolved by structural rearrangements. The frequencies of the BCR/ABL studied with RT-PCR (minor and major break point region); only 4 cases was not useful, then 20/100 was positive; only 2/20 (10%) with the b2a2/b3a2 transcript of the P210BCR/ABL; the rest 90% with e1a2+ of the P190BCR/ABL.

Conclusion:
The frequency reported for BCR/ABL positive (20%) in Mexican adults with ALL is in concordant with worldwide; but only by RT-PCR. The karyotype has low sensitivity by detection of the t(9;2) but is useful by identify others anormalities in karyotype. We don't have correlation between clinical and cytogenetic characteristics.

Disclosures:
No relevant conflicts of interest to declare.
Invasive Mould Infections (IMI) In Acute Leukemia Patients on Chemotherapy - Can We Win the Battle?
Authors: Wong Gee Chuan , Tan Ban Hock 
Published: October 2019

Abstract
Abstract 4871
Aim: To determine risk factors for, and clinical features of, invasive mould infections in patients with acute leukemia on chemotherapy.
Methods: A matched case control study where acute leukemia patients on chemotherapy were identified and clinical data pertaining to their disease, clinical course, IMI characteristics and treatment outcomes were evaluated. This was conducted in a tertiary hospital from 1 January 2004 to 31st March 2007.
Results: All acute leukemia patients on chemotherapy receive itraconazole prophylaxis. Nineteen cases of invasive mould infections (IMI) were found in the period, giving an incidence of 11.2%, using only patients undergoing curative chemotherapy as denominator. The incidence in patients receiving the first cycle of chemotherapy was 8.9%; in patients receiving subsequent cycles of chemotherapy was 4%. Thirteen cases were proven by EORTC/MSG criteria, 8 of them by histology without positive cultures. There were 3 proven cases of fusariosis, and 1 each of aspergillosis and nodulisporiosis. Cases were more likely than controls to have had an absolute neutropenia for at least 14 days in the chemotherapy episode in which the IMI was diagnosed (p=0.045), to have been bacteremic prior to the diagnosis of IMI (p=0.045), and to have had fever not responding to a carbapenem (p=0.016). They also had a longer length of stay (51.8 vs 27.2 days, p=0.01). The use of itraconazole as anti-fungal prophylaxis was not less common in cases than controls. Common clinical features noted in cases included fever not responding to a carbapenem (84.7%), cough (42.1%), a rise in alkaline phosphatase (36.9%), breathlessness (26.3%), and hemoptysis (21.1%). A pleural effusion was noted on CXR or CT chest in 52.8% of cases, and a characteristic CT thorax in 47.4% of cases. Sixty-eight percent of cases received amphotericin (conventional or lipid preparation) as part of a febrile neutropenia protocol, though only 15.8% received this agent when an IMI was considered. Clinical improvement was attributed to an increase in ANC in 26.3% of cases, and to the introduction of voriconazole in 10.5%. The next cycle of chemotherapy was delayed for 2 – 4 weeks in 15.8% of cases, and for >4 weeks in 31/6% of cases. Three patients (15.8%) died within three months of IMI diagnosis, 47.4% survived >1 year.
Conclusions: Anti-fungal prophylaxis with itraconazole did not reduce the likelihood of IMI and this should be changed. Absolute neutropenia is a risk factor for IMI in patients with acute leukemia. Fever not responding to carbapenems and a rise in ALP may be considered as red flags for clinicians to consider the possibility of an IMI and institute prompt treatment.

Disclosures:
No relevant conflicts of interest to declare.
Essential Role of γδT Cells In Naturally Acquired Immunity to Falciparum Malaria
Authors: Kanda-Taniguchi Tomoyo , Mannoor Kaiissar Md. , Li Changchun , Watanabe Norihiro , Yamahira Akie , Phompida Samlane , Narita Miwako , Watanabe Hisami , Takahashi Masuhiro 
Published: October 2019

Abstract
Abstract 4877
It is important to understand the mechanisms of naturally acquired immunity to malaria for the development of effective malaria vaccines. We have demonstrated that γδT cells expanded in the peripheral blood of the falciparum malaria patients in Thailand but did not expand in patients living in malaria endemic areas of Laos. However, the percentage of Vγ9-T cells, a γδT cell subset, increased in the Laos patients. The levels of naturally acquired antibodies to crude P. falciparum (Pf) antigens also increased with an age dependent manner in individuals living in endemic areas of Laos. In this study, we further investigated the role of Vγ9-T cells in naturally acquired immunity to the falciparum malaria. The peripheral blood lymphocytes (PBLs) and plasma obtained from hospitalized uncomplicated falciparum malaria patients (UMPs) and severe falciparum malaria patients (SMPs) in Thailand and from non-hospitalized UMPs living in endemic areas of Laos were analyzed. The plasma levels of IL-10, which is anti-inflammatory cytokine and associated with antibody production from B cells, were elevated in both hospitalized and non-hospitalized falciparum malaria patients. There was a correlation between the levels of IL-10 and the percentage of Vγ9-T cells in γδT cells. IL-10 and Pf specific antibodies were detected only in culture supernatant of PBLs from non-hospitalized UMPs in the presence of IL-2 for 2 wks. These results indicate that Vγ9-T cells may contribute to acquiring natural immunity to malaria.

Disclosures:
No relevant conflicts of interest to declare.
Rituximab Plus CHOP Given Every 15 Days with GM-CSF (sargramostim) In Patients Withnewly Diagnosed Diffuse Large B-Cell Lymphoma
Authors: Tulpule Anil , Berman Nancy , Ahmed Nazish , Boswell William , El-Masry Mary , Chaudhary Preet 
Published: October 2019

Abstract
Abstract 4886

Background:
The R-CHOP regimen administered every three weeks has become the standard of care for treatment of patients with diffuse large B-cell lymphomas. Previous studies have not shown an advantage of dose dense (cycles given every 2 weeks) R-CHOP therapy. Granulocyte-macrophage colony stimulating factor (GM-CSF), in addition to stimulating hematopoetic recovery augments dendritic cell numbers and promotes antigen presentation, induces immune recognition of tumor cells, causes antibody dependent cytotoxicity, and upregulates activity of rituximab. In a Phase II study, we analyze the efficacy and tolerability of R-CHOP given every 15 days with GM-CSF administered on days 3 through 13 of each cycle.

Methods:
All patients were treated with Rituximab, 375 mg/m2; Cyclophosphamide, 750 mg/m2; Doxorubicin, 50 mg/m2; Vincristine, 1.4 mg/m2, all given IV on day 1; oral prednisone 100 mg given orally on days 1–5 and subcutaneous GM-CSF, 250 mg/m2 on days 3–13. Chemotherapy cycles were repeated every 15 days.

Results:
In this mid-study evaluation, thus far 36 patients with a median age of 53 (range 22–81) have been accrued. All patients were previously untreated and had CD20+ diffuse large B cell lymphoma. 26 (72%) patients had stage III (8) or IV (18) disease. Thirteen (36%) patients had bone marrow involvement. Twenty eight (77%) had elevated serum LDH levels, and 16 (44%) patients had an intermediate or high risk IPI score. Toxicities have been primarily hematologic with transient grade 3 or 4 neutropenia in 27 (74%) patients; grade 3 anemia in 6 (16%) patients; and grade 3 or 4 thrombocytopenia in 4 (11%) patients. In addition, 4 patients experienced neutropenic fever. Non-hematologic side effects of note were grade 3 mucositis/stomatitis in 2 patients; grade 3(n=1) and grade 4 (n=1) cardiac dysfunction in 2 patients. IgG, IgA, IgM levels were all decreased after 2 cycles of chemotherapy. Further cycles did not affect immunoglobulin levels. Of the 34 patients evaluable for response, 24 (71%) achieved complete remission, 7 (21%) achieved partial remission, 1 (3%) had stable disease, and 2 (6%) had progression of disease.

Conclusion:
The mid study evaluation confirms that R-CHOP given every 15 days with GM-CSF (sargramostim) administered on days 3 through 13 of each cycle provides promising response rates with tolerable toxicity.

Disclosures:
Tulpule: Genzyme, I am the PI on this study funded by Genzyme.: Research Funding.
Carfilzomib (CFZ): A Novel Proteasome Inhibitor That Induces Cell Cycle Arrest and Cell Death In Rituximab-Chemotherapy Resistant Lymphoma and Potentiates the Anti-Tumor Activity of Chemotherapeutic Agents
Authors: Gu Juan , Hernandez-Ilizaliturri Francisco J. , Kaufman Gregory P. , Mavis Cory , Czuczman Myron S. 
Published: October 2019

Abstract
Abstract 4908
Rituximab-chemotherapy relapsed/refractory B-cell lymphomas represent an emerging clinical challenge that underlies the need to develop alternative therapeutic strategies. Targeting the ubiquitin-proteasome system using bortezomib (BTZ) has resulted in significant anti-tumor activity and potentiates the effects of chemotherapy/biologic agents in multiple myeloma, and to a lesser degree, B-cell lymphoma. CFZ is as a novel proteasome inhibitor which is selective and structurally distinct from BTZ. In an attempt to characterize the biological activity of CFZ, we evaluated its anti-tumor activity in several lymphoma pre-clinical models. Rituximab-chemotherapy sensitive cell lines (RSCL), rituximab-chemotherapy resistant cell lines (RRCL), as well as primary tumor cells derived from patients with de novo or relapsed/refractory B-cell lymphoma, were exposed to escalating doses of CFZ or BTZ (1-7.5nM) alone or in combination with doxorubicin, paclitaxel, or gemcitabine for 24, 48 and 72hours. Cell viability was determined by cell titer glow luminescent assay and cell cycle was analyzed by FASCan DNA methodology. Patient-derived lymphoma cells were isolated from fresh biopsy tissue via negative selection using magnetic beads. Western blots were performed using cell lysates from CFZ, BTZ or control-treated cells to detect PARP-cleavage and/or changes in Bcl-2 family members. CFZ was more active than BTZ and exhibited dose-dependent and time-dependent cytotoxicity against RSCL, RRCL, and primary tumor cells. We found a 10-fold concentration difference between CFZ and BTZ activity. In vitro exposure of RRCL or RSCL to CFZ resulted in G2/M phase cell cycle arrest. In addition, CFZ exposure resulted in the up-regulation of Bak and Noxa levels and subsequent PARP cleavage in RRCL. Finally, CFZ demonstrated the ability to overcome resistance to chemotherapy in RRCL and potentiated the anti-tumor activity of paclitaxel and gemcitabine in B-cell lymphoma cell lines. In summary, our data strongly suggest that CFZ is a novel and potent proteasome inhibitor which is able to: overcome resistance to some conventional chemotherapeutic agents, upregulate proapoptotic proteins to enhance cell death, and induce G2/M cell cycle arrest in lymphoma cells. Our preclinical data supports future clinical evaluation of CFZ in patients with refractory B-cell lymphoma. (Supported by USPHS grant R01 CA136907-01A1 from the National Cancer Institute).

Disclosures:
No relevant conflicts of interest to declare.
Effect of Denileukin Diftitox on Pruritus and Other Skin-Related Symptoms Vs Placebo In Patients with Cutaneous T-Cell Lymphoma
Authors: Pinter-Brown Lauren , Kozlovski Anna 
Published: October 2019

Abstract
Abstract 4922

Introduction.
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin's lymphomas (NHLs) that develop primarily in the skin but may progress to involve lymph nodes, blood, and visceral organs. CTCL is characterized by skin patches, plaques, tumors, and erythroderma. Pruritus is frequently associated with skin lesions in CTCL and may be severe. Some treatments have been noted to produce improvements in pruritus that appears to be independent of the response rate. Denileukin diftitox (DD, Ontak), a recombinant fusion protein targeting IL-2-receptor-expressing T lymphocytes, has demonstrated a significant effect on overall response rate with minimal immunosuppression in patients with CD25 assay-positive CTCL. For this post-hoc analysis, we used data from a randomized, double-blind, placebo-controlled, phase III clinical trial to assess the effect of DD on pruritus and overall skin condition in patients with CTCL.

Patients and methods.
Patients with CD25 assay-positive, stage Ia to III CTCL were randomized to receive 9 μg/kg/d DD (n=45), 18 μg/kg/d DD (n=55), or placebo (n=45). Study medications were administered on the first 5 days of a 21-day cycle for up to 8 cycles. Four grading scales were used to assess clinical signs and symptoms (Table 1).

Results.
Higher percentages of DD-treated patients experienced clinically significant improvements in skin-related symptoms than did patients on placebo during treatment and follow-up (Table 2). The differences between the proportions of patients in the placebo group experiencing clinically significant improvement and the proportions of those in the 18 μg/kg/d and combined DD dose groups were statistically significant for all 4 assessments. Substantially more DD-treated patients had ≥20% and ≥50% improvement in pruritus (relative to baseline) at any time than those receiving placebo; improvements were maintained for ≥6 weeks. The global skin score improvement and pruritus score improvement in both high dose and low dose groups were significantly correlated, with higher correlation in high dose group compared to low dose group (p=0.0004 vs p=0.0381). There is no correlation in placebo group for the two scores (p=0.3798). Improvement in pruritis was to some extent independent of response, as demonstrated by the proportion of agreement between tumor response and significant pruritus improvement (27% and 19% for high dose and low dose, respectively, in DD groups), based on Kappa concordance coefficient.

Conclusion.
Patients treated with DD, particularly at the 18-μg/kg/d dose, were more likely to experience clinically significant improvements in pruritus and other skin-related symptoms than were patients receiving placebo. DD was observed to improve pruritus independent of response.

Disclosures:
Kozlovski: Eisai Inc.: Employment.