bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study on the Relevance of Inducing Apoptosis and Reversal Effect of Nilotinib In Combination with Tet on Multidrug Reststahoe of K562/A02 Cell Line
Authors: Chen Bao-An , Cui Ting-yun , Ding Jia-hua , Gao Chong , Shan Xue-yun , Cheng Jian , Bao Wen , Zhong Yue-jiao , Gao Feng , Xia Guo-hua , Schmitt Anita , Schmitt Michael 
Published: October 2019

Abstract
Abstract 4951

Objective
To investigate the relevance of Inducing apoptosis and reversal effect of nilotinib in combination with Tet on multidrug reststahoe of K562/A02 cell line and its mechanism.

Methods
Methyl-thiazol tetrazolium(MTT) assay is employed to examine the pharmacological effect of Nilotinib or Tet alone on K562/A02 cell line, to calculate the inhibitor concerntration 50(IC50) of daunorubicin(DNR) in K562/A02 cell line and the resistance multiple of DNR to K562/A02 cell line. Flow cytometry(FCM) was employed to comple the effect on the inducing apoptosis of K562/A02. The expression of bax/survivin mRNA was determined by RT-PCR, and the expression of bax/survivin protein was assessed by Western blot.

Results
After 48 h 5 nmol/L nilotinib or 1.0μmoL/L Tet treatment, IC50 of DNR to K562/A02 was 5.71mg/L or 6.52 mg/L respectively;While on combinative treatment, its IC50 decreased to 3.12 mg/L. Nilotinib or Tet alone was able to increase the DNR induced apoptosis rate of K562/A02 cell (P<0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmoL/L nilotinib or 1.0μmoL/L Tet treatment alone, gray—scale vaule of bax mRNA Was 2.90±0.31 or 3.6±0.46, respectively Gwhile on combinative treatment the value increased to 5.9±0.98. The bax protein expression level in K562/A02 cells was 2.1±0.07 or 2.90±0.09 when treated with 5 nmoL/L nilotinib or 1.0μmoL/L Tet alone for 48 h, but on combination treatment, the level increased to 4.8±0.31. After 48 h 5 nmoL/L nilotinib or 1.0μmoL/L Tet treatment alone, gray—scale vaule of survivin mRNA was 0.70±0.01 or 0.55±0.02, respectively;while on combinative treatment the value decreased to 0.35±0.08. The survivin protein expression level in K562/A02 cells was 0.74±0.03or 0.61±0.04 when treated with 5 nmoL/L nilotinib or 1.0μmoL/L Tet alone for 48 h, but on combination treatment, the level decreased to 0.42±0.06.

Conclusion
Nilotinib or Tet alone can pattially reverse drug resistance of K562/A02 cells. There is resistance phenomena of DNR to K562/A02 cells, and Nilotinib or Tet alone alone is able to reserve the resistance of DNR and enhance the inducing apoptasis effect of DNR. The mechanism may be associated with the increase of bax mRNA and protein expression and decrease of survivin mRNA and protein expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination.

Disclosures:
No relevant conflicts of interest to declare.
Multiple Myeloma: Clinical Implications of Cytogenetic Aberrations on Selected Plasma Cells on Conventional Cytogenetics and Interphase Flourescence In Situ Hibridization (FISH)
Authors: Verma Rakesh , Kumar Lalit , Halder Ashutosh , Sharma Atul , Gupta Ritu , Saxena Renu , Chauhan Shyam S , Sinha Subrata 
Published: October 2019

Abstract
Abstract 4987

Purpose:
We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC).

Methods:
Between February 2007 and June 2009, 90 previously untreated patients of MM were enrolled, Patient's median age was 55 years (range, 34 to 75 years) and 67 were males (M: F: 2.9: 1). 24 patients had ISS stage I, stage II-46 & 20 patients had stage III. Purified bone marrow plasma cells, using magnetic activated cell sorter with CD138 micro beads were used. Conventional cytogenetics for numerical chromosomal abnormalities and FISH for deletion 13q14 (RB-1) and 14q32 (IgH) translocations was carried out on these purified plasma cells. 65/90 (72%) patients received therapy; using novel agents, n=54 (thalidomide-dexamethasone (n=50), Lenalidomide-dexamethasone (n=4)) and melphalan, prednisolone and thalidomide (MPT, n=11). Response was evaluated post 4 cycles using EBMT response criteria.

Results:
Metaphases could be obtained on CC in 53/90 patients (58%); with numerical abnormalities in 21: hyperdiploid -16 & hypodiploid in 5. Del 13q14 and t (14q32) by FISH was present in 51 (56%) and 75 (83%) patients, respectively. t (14q32) was present more in patients with ISS-III (p<.008). Presence of del13q14 correlated with BM plasma cells >40% (P<.007) and Hb ≤9.2G/dl (p=.06). Following therapy, 49/65 patients (75.2%) achieved significant response (CR+VGPR+PR). Patients aged ≤55 years (P = 0.07), those with ISS- I (P <0.05), IgG-kappa (P<0.04) and with absence of del13q14 (P = 0.04) responded better. The median overall survival (OS) has not reached yet, median event-free survival (EFS) is 33 months (95% CI 18–48). Estimated OS and EFS at 2 years is 77% and 50 %, respectively. Durie Salmon stage IIIB (HR 3.6) and response to therapy (HR 7.8) were significant predictors of OS. For EFS - del13q14 (HR 2.7, P <0.036), response to therapy (HR 2.7,P<0.01) and use of novel agents (HR 3.1, (P<0.008) were important predictors.

Conclusion:
Chromosomal abnormalities including IgH translocations and del13q14 with numerical chromosomal abnormalities are common in MM patients at diagnosis and can predict the treatment outcome and survival.

Disclosures:
No relevant conflicts of interest to declare.
African-American Multiple Myeloma Patients Exhibit Less Bone Disease Compared to Other Racial/Ethnic Groups
Authors: Dean Eric W. , Ziv Elad 
Published: October 2019

Abstract
Abstract 4994

Background:
Bone destruction remains one of the major complications in Multiple Myeloma (MM) leading to morbidity and mortality. African-Americans have a higher incidence of MM but exhibit longer survivals compared to Caucasians. We analyzed bone involvement in a cohort of patients with MM to determine if non African American (non AA) vs. African American (AA) race predicts the presence and severity of bone disease at presentation.

Methods:
Clinical data was gathered on 197 (176 non AA and 21 AA) MM patients at the University of California, San Francisco. Each patient had a skeletal survey at diagnosis and identified as having 0 lytic lesions, 1–2 lytic lesions or 3 or more lytic lesions. The presence of compression fractures was also documented for each patient as was age and sex.

Results:
The presence of compression fractures strongly correlated with the number of lytic lesions in both the non AA and AA groups, with no compression fractures observed in the patients with zero lytic lesions (p<0.001). Among the AA group, there were fewer (6 of 15) patients with compression fractures compared with patients from the non AA group (92 of 161) (p=0.02). There was also a trend towards fewer lytic lesions among the AA group (p=0.053). No significant difference was observed between the extent of bone disease and age or sex between the two groups.

Conclusions:
Within this cohort of patients, there is a significantly lower rate of compression fractures among African-Americans. These data supports the idea that African-American patients present with less bone disease which confers a survival advantage compared to other racial/ethnic groups.

Disclosures:
No relevant conflicts of interest to declare.
A Review of Multiple Myeloma Patients on Dialysis Treated with High Cutoff Hemodialysis
Authors: Podymow Tiina , Alam Ahsan , Vasilevsky Murray , Beauchemin Roch , Shustik Chaim , Sebag Michael 
Published: October 2019

Abstract
Abstract 5002

Background:
Kidney failure is a major cause of morbidity in patients with Multiple Myeloma (MM). While up to half of MM patients can be shown to have renal impairment, 10% will become dialysis dependent. The main mechanism of kidney failure is cast nephropathy, which is linked to high amounts of circulating free light chains. A proposed strategy to prevent this outcome is the use of extended high cutoff (HCO) dialysis. An ongoing randomized controlled trial is testing the Gambro HCO1100 filter. Here we report the use of another dialyzer (Bellco Phylther), which has a smaller pore size than the Gambro filter, but which may prove to be as effective and is less costly.

Methods:
We present three patients with symptomatic MM, elevated κ or λ serum free light chains (>500mg/L), biopsy confirmed cast nephropathy, and kidney failure (estimated GFR <15ml/min/1.73 m2) requiring dialysis. In all patients, dialysis consisted of 10 hemodiafiltration dialysis sessions in the first two weeks and three times a week thereafter using a high flux Bellco Phylther HF22SD dialyzer (Bellco, Modena, Italy). All patients received concurrent chemotherapy: bortezomib 1.3mg/m2 IV and dexamethasone 40mg po on days 1, 4, 8 and 11 of a 21 day cycle and liposomal doxorubicin at 30mg/m2 on day 4 of every cycle. Serum free light chains were determined pre- and immediately post-dialysis using a nephelometric immunoassay (FREELITE, The Binding Site, Birmingham UK).

Results:
We observed significant (>50%) and rapid reductions in sFLCs. These reductions were sustained at 3 months in all cases, likely because of effective anti-myeloma treatment. Two of the three patients had recovery of kidney function and remain dialysis-independent at least 6 months after cessation of dialysis. Interestingly, the only patient that did not recover kidney function was also found to have tubulointerstitial disease on renal biopsy in addition to cast nephropathy.

Conclusions:
The HCO Bellco Phylther dialyzer appears effective in the rapid reduction of sFLCs in light chain MM patients with cast nephropathy requiring dialysis and concurrent anti-myeloma drug therapy. While the numbers are small, our review suggests that patients with uncomplicated MM cast nephropathy may benefit from aggressive hemodiafiltration with this HCO membrane. This dialysis membrane and protocol are worth considering for further study in patients with MM cast nephropathy.

Disclosures:
No relevant conflicts of interest to declare.
MARROW of Essential Thrombocythemia PATIENTS IS ENRICHED IN Effector Memory CD4+ and CD4+CD25++ Lymphocytes as Compared to BLOOD
Authors: Sedzimirska Mariola , Drabczak-Skrzypek Daria , Lange Andrzej 
Published: October 2019

Abstract
Abstract 5058
The role of T cells residing in the marrow is poorly understood. However, some literature data suggest that the presence of CD8+ lymphocytes in the marrow plays a role in keeping the tumor cells in a dormant state. In chronic myeloid leukemia a significant role of lymphocytes in controlling the malignant clones is well documented. The aim of this study was to define whether there is a specific enrichment of some CD4+ lymphocytes subpopulations in the marrows of newly diagnosed patents with essential thrombocythemia (ET).
Seven patients (F/M: 6/1, age 28–72 - median 6 yrs) with ET diagnosed according to the WHO criteria were studied. They had platelets 425–809 ×10∧3/ul (median 676 × 10∧3), NAP 74–138 score (median 112 score), 6 of them were positive for JAK 2 V617F mutation (heterozygotes). Marrow cellularity was from 18 – 64 ×10∧3/ul (median 44 × 10∧3/ul) Cytological evaluation revealed normal differentiation of erythroid and myeloid lineages, in contrast an increased number of megakaryocytes often enlarged, hyperlobulated and in clusters was seen in all patients. Trephine biopsy revealed activation of megakaryopoiesis with enlarged numerous megakaryocytes with normal representation of other lineages and a lack of an increase in the reticulin fibers. Lymphocytes in the marrows were in proportions from 4.5 – 15,7% (median 10,6%) what resulted with lymphocytosis from 2640/ul to 19405/ul (median 5645/ul). The whole populations of marrow and blood cells were labeled for a purpose of this study with the use CD4, CD25, CD45RO and CCR7 MoAb (Becton Dickinson, San Jose, CA, USA) followed by detection and analysis with the use of flow cytometry (FACS Calibur, Becton Dickinson) equipped with PCLysis programe.
We found:Proportions of lymphocytes in the marrows were rather in a normal value range but in numbers they prevailed over blood lymphocytes (2640-19405/ul, median 5645/ul vs 1300–3100/ul, median 1800/ul, p= 0,003 Wilcoxon Test for pairs),Among T cells subpopulations effector/memory CD4+ lymphocytes CD45RO+, CCR7-) were significantly higher in numbers in the marrows of ET patients as compared to blood (744-3241/ul, median 1126/ul vs 406–2437/ul, median 592/ul, p=0,04 Wilcoxon Test for pairs). There was no difference when numbers of naïve (CD45Ro-, CCR7+) and central memory (CD45RO+, CCR7+) CD4+ lymphocytes were analyzed.The marrows of ET patients had higher numbers of CD4+CD25++ lymphocytes as compared to blood (8,1-40,7/ul, median 11,4/ul vs 1,2-14,8/ul, median 7,3/ul; p=0,02 Wilcoxon Test for pairs).
It appeared that in ET patients there was a selective enrichment of marrow lymphocyte populations in CD4+EM cells and CD4+CD25++ lymphocytes what strongly suggests the presence of active immune response in the marrows affected by this myeloproliferative disorder.

Disclosures:
No relevant conflicts of interest to declare.
Waldeyer's Ring Marginal Zone B-Cell Lymphoma: Which Is Their Clinical and Prognostic Feature, Nodal or Extranodal?
Authors: Oh Sung Yong , Kim Won Seog , Kim Jin Seok , Kim Seok Jin , Lee Suee , Suh Cheolwon , Lee Dae Ho , Lee Soon il , Kang Hye Jin , Choi Chul Won , Jeong Seong Hyun , Park Jinny , Song Moo-Kon , Kim Hyo Jung , Kwon Jung Hye , Kwak Jae-Yong , Bae Sung Hwa , Park Byeong-Bae 
Published: October 2019

Abstract
Abstract 5084

Background:
Waldeyer's ring (WR) is circular band of lymphoid tissue located at the opening of the respiratory and digestive tract. There is controversy as to whether WR should be considered as a nodal or extranodal site. In this study, we conducted retrospective analyses of WR involving MZLs (WR-MZLs) to identify their clinical features, treatment, prognosis- favor nodal or extranodal. And we want to get additional information about specific organ relationship between WR-MZL and other MALT sites.

Patients and Methods:
From 1987 to 2010, 124 patients who were histologically confirmed as a MZL arising from head and neck (H&N) area was including WR (47 patients) were reviewed. Primary orbit and ocular adnexa MZL patient was excluded this data collection.

Results:
The male/female ratio of the 47 patients was 23 to 24. The median age was 53 years (range, 17–77). The commonly involving sites were tonsil (53.2%) followed by nasopharyn (40.4%). Fourteen patients (29.7%) were accompanied with extra-WR area MALT site- gastrointestinal tract (14.9%), ocular and adnexa (12.8%). Ann Arbor stage I/II disease was present in 50% (23 out of 46). Thirty-nine patients were categorized into the low/low-intermediate risk group (84.8%) according to International Prognostic Index (IPI). Complete and partial remissions were achieved in 18 (78.3%) and 2 (8.7%) of the 23 stage I/II patients. In 23 patients with stage III/IV, CR and PR were achieved in 15 (65.2%) and 4 (17.4%), respectively. The median progression-free survival (PFS) was 3.6 years (95% CI, 2.4–4.8 years). The estimated 5-year overall survival (OS) was 88%. Compared with H&N MALT site MZLs, WR-MZLs were significantly poor in PFS and OS (P=0.005 and P=0.007).

Conclusion:
WR-MZLs were also an indolent disease like general MZL. But, WR-MZL patients presented with more advanced stage and poorer survivals than other site H&N MZL patients. Therefore, even though WR has been considered histologically extranodal MALT organ, clinically it is closer to nodal MZL.

Disclosures:
No relevant conflicts of interest to declare.
Associations of Aberrant T Cell Antigen Expression on B Cells of Diffuse Large B Cell Lymphoma Patients with Their Background and Prognosis
Authors: Suzuki Yuhko , Yoshida Tsutomu , Kimura Hirokazu , Ohsaka Manabu , Miyazaki Koji , Danbara Mikio , Horie Ryouichi , Satoh Yuhichi , Higashihara Masaaki 
Published: October 2019

Abstract
Abstract 5088

Aim:
With the exception of CD5, the clinical implications of aberrant T-cell antigen expression on B cells in diffuse large B cell lymphoma (DLBCL) have not been well studied. The present retrospective study aimed to determine associations between T cell antigen expression and patients′ characteristics and prognosis
Patients, Material and Methods: 249 cases with B-cell lymphoma (BCL) newly-diagnosed in our Institute between January 2002 and August 2009 were biopsied and also analyzed by flow cytometry. Biopsy specimens were fixed in formalin, stained with Hematoxylin-Eosin, and also immunostained. Histological subtypes were defined according to the World Health Organization Classification Version 3. Flow cytometric (F/C) analysis was performed following standard methods.
The aberrant expression of one or more T cell surface antigens on B cells (CD2, 3, 4, 7, 8) was assessed. Statistical analysis was conducted to seek associations between aberrant positive and negative cases and patients′ background laboratory data, and prognosis.
This study was approved by the Ethics Committee of Kitasato University School of Medicine.

Results:
150 DLBCL, 68 Follicular lymphoma (FL), 17 Marginal zone lymphoma (MZL), 6 MCL and 4 CLL patients were tested. Of the DLBCL cases, 12 (8%) showed aberrant T cell antigen expression with 4, 1, 5, 1 and 1 patients′ B cells positive for CD2, CD4, CD7, CD8 and CD7 + 8 respectively. Aberrant expression among the FL, MCL, MZL and CLL cases was seen in 0, 1, 1 and 1 patient, respectively.
Among the DLBCL patients, T antigen-negative cases tended to have higher WBC counts and greater CD20 expression by F/C analysis. No statistically significant associations with gender, age, IPI, clinical stage, laboratory data, expression of CD5 and other markers, ABC/GCB, or karyotype were observed between the positive and negative groups.
96 of the 150 DLBCL patients received rituximab-chemotherapy. Again, there were no statistically significant differences between the two groups in overall survival and response to treatment.

Discussion:
1) CD2 and CD7 are relatively common among aberrant T cell antigen- positive DLBCL. 2) No statistically significant differences were observed between the two groups in terms of background and prognosis. 3) Both CD8-positive DLBCL patients experienced a very aggressive clinical course and rapidly succumbed to their disease. CD8-positive DLBCL cases may in general have poorer survival. 4) Further analysis will be necessary to confirm these results.

Disclosures:
No relevant conflicts of interest to declare.
Rare Splenic Intravascular Diffuse Large B-Cell Lymphoma with Massive Hypersplenism and Concomitant Minor Liver Infiltration and Supra-Mesenteric Nodes.
Authors: De Salvo Dalila , Salas-Auvert Rodolfo J , De Salvo Cardullo Luigi 
Published: October 2019

Abstract
Abstract 5101
We report a 23 yr female patient which relates beginning of current illness three months prior diagnosis; characterized with increased abdominal volume, concomitant active hemorrhagic manifestations consisting of ecchymosis and petechiae. Upon clinical, bone marrow biopsy, immunohistochemistry and subsequent surgery, case corresponded to Diffuse Large B-Cells Lymphoma(DLBCL) of splenic intravascular origin. Organ weight and size after splenectomy 2.53 Kg size 30×22×10 cm). Microscopic diagnosis description corresponds with presence of monomorphic lymphoid cells with predominance of small neoplasic lymphoid cells with small round nucleus, granular chromatin and small nucleolus accompanied with eventual cytoplasmic membrane irregularities. Presence of reactive plasmocytes and sever splenic congestion. The unusual case reported corresponds to an invasive lymphoma of splenic vascular origin. By our knowledge this is the first case register in Venezuela.

Disclosures:
No relevant conflicts of interest to declare.
Folic Acid Food Fortification and Incidence of Anemia In General Population
Authors: Bansal Goldy , Fernandez Gloria 
Published: October 2019

Abstract
Abstract 5140

Introduction:
Folic acid (FA) deficiency is considered one of the important causes of anemia and of neural tube defects in infants. In 1996 FDA issued a regulation that by 1998 all enriched grain products contain 140 mg of folic acid per 100 grams. This process began in 1996 and was essentially completed by mid-1997. This program intended to increase folic acid intake among women of childbearing age has decreased the incidence of pregnancies affected by neural tube defects. This has also led to a decrease in incidence of FA as a cause of anemia. In 2000 we reported the impact of folate food fortification in our community hospital. In 1994 to 1996, of 4403 patients sample tested 60 were found to be folate deficient. From 1997 to 1999 only 3 of 6326 patients tested were folate deficient. The first patient was 73 year old and had severe CHF and COPD, the second patient was 62 year old alcoholic admitted with delirium tremens, and third patient was 90 year old with dysphagia who required PEG replacement. All three appeared to have stopped eating in the days prior to admission. On the basis of this experience in our community hospital we concluded at that time that folate food fortification has largely eliminated FA deficiency and that the routine determination of FA as part of anemia work up in this era is not indicated. We now report our continuing experience from 2003 to 2006.

Methods:
We studied retrospectively the patients who presented in our community hospital with anemia and folate level ordered as a part of anemia work up. Serum folate levels were measured using Bayer Center Chemiluminescent Assay. Serum FA level <1.1 mg/ml is considered indicative of deficiency. We evaluated 1861 patients from year January'2003 to May'2006. We also assessed the cost effectiveness of ordering this test routinely as part of anemia workup.

Results:
Among the 1861 patients, we did not find any patient who had folate level of less than 1.1, which is the lower limit for folate level in our laboratory. Medicare cost for serum folate level test for our institute is $20.54 (code 82746) and phlebotomy cost for one test is $3.00 (code 36418). Total cost for this test for one patient is $23.54. Total health cost for these tests in 3 years and five months was $43807.94.

Conclusion:
Our results which are similar to our previous report suggest that food fortification and possibly also vitamin supplementation has substantially improved blood folate levels and has largely eliminated folic acid deficiency as a cause of anemia in the population that we tested. Routine folate level determination in the workup of anemia is not cost effective and may be best limited in patients who are malnourished as in patients with poor nutrition status, malabsorption, alcoholics and psychiatric disorders.

Disclosures:
No relevant conflicts of interest to declare.