bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Blood Loss and Transfusion Requirement in Patients Undergoing Surgery for Musculoskeletal Tumors
Authors: Thompson Philip A , May Deborah , Choong Peter , McArdle Scott , Gaskell Mary , Powell Gerard , Liew Danny , Cole-Sinclair Merrole Faye 
Published: October 2019

Abstract
Abstract 4384
The management of musculoskeletal tumors has evolved markedly over the past 30 years, with improvements in surgical techniques, staging and chemotherapeutic advances delivering improved survival and functional outcomes, both in the setting of primary malignant bone tumors and in the palliation of tumors metastatic to bone. Advances in surgical technique as well as pre-operative chemotherapy has meant that most patients are now able to undergo limb-sparing surgery. Whilst clearly desirable to improve functional outcome, limb-sparing surgery is however more technically challenging and is associated with greater blood loss than amputation.
There is a paucity of data concerning blood utilization in the setting of major musculoskeletal tumor surgery. We retrospectively analyzed a database containing 1322 consecutive surgeries in 1222 patients over a 14 year timeframe, performed at a quaternary referral center in Melbourne, Australia. The following factors were significantly associated with high blood utilization: Chordomas, sacral and pelvic tumors, lower starting haemoglobin, tumors >5cm in size and high American Society of Anesthesiologists (ASA) score. The ASA score also clearly correlated with 30 day mortality. Pre-operative planning in these patients is critical to ensure adequate blood supply, minimize wastage and optimize the patient's general health prior to surgery. As such, based on modeling from our data, we propose a maximum surgical blood order schedule based on the presence or absence of the above factors.
Allogeneic blood transfusion, while a potentially life-saving intervention, is associated with major complications, including transmission of infectious agents and immunological complications. Longer-term, transfusion has been reported to result in immunomodulation and potentially a higher risk of tumor recurrence. Clearly, minimization of blood loss and avoidance of un-necessary transfusion is desirable. There is also a lack of data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery, especially when compared to similar studies performed in major orthopedic surgery for benign conditions. These would be ideal targets for future randomized studies in the high-risk groups we have identified.

Disclosures:
No relevant conflicts of interest to declare.
CML Shows Characteristic Pattern by Flow Cytometry Analysis of Peripheral Blood
Authors: Scott Kalley , Gorczyca Wojciech 
Published: October 2019

Abstract
Abstract 4430
A total of 75 chronic myeloid leukemia (CML) cases from peripheral blood (40 cases) and bone marrow (BM, 35 cases) with adequate flow cytometry (FC) data, smear, blood cell count, and the presence of t(9;22)/BCR-ABL by fluorescence in-situ hybridization (FISH) studies were analyzed for immunophenotypic pattern. The FC pattern in CML was compared with benign (healthy) controls (blood, 20 cases; BM, 20 cases), blood with reactive neutrophilia (15 cases), myelodysplastic syndrome (BM, 15 cases), and blood with eosinophilia (15 cases). CML showed a characteristic pattern by FC in blood, which can be easily differentiated from reactive neutrophilia or eosinophilia, regardless of WBC count. The identification of distinct population of blasts, basophilia, lack of CD10, CD11b, CD13 and/or CD16 on subset of granulocytes, decreased granularity, and/or aberrant expression of CD56 on granulocytes and monocytes, can be easily identified by routine FC analysis. We suggest using FC analysis of blood as a screening tool for patients with leukocytosis (neutrophilia) with follow-up FISH studies in cases with the phenotypic features suggestive of CML. Patients with confirmed CML diagnosis by FISH will undergo marrow biopsy for differential count including blast and basophil enumeration (to exclude accelerated phase or blast crisis), degree of reticulin fibrosis and cytogenetic studies (for additional chromosomal changes present at diagnosis). This approach, in our opinion, allows to diagnose early (unsuspected) CML and eliminates the need for unnecessary cytogenetic/FISH testing, and especially bone marrow biopsy in patients with reactive leukocytosis or eosinophilia.

Disclosures:
No relevant conflicts of interest to declare.
Is There a Benefit of Adding Rituximab to CHOP in the Overall Survival of Patients with B-Cell Non-Hodgkin′s Lymphoma in a Developing Country ?
Authors: Ruiz-Delgado Guillermo J. , Almaguer David Gomez , Tarin-Arzaga Luz C. , Cantú-Rodríguez Olga , Alarcon-Urdaneta Carlos , Rodriguez-Morales Uxmal , Calderon-García Jackeline , Fernandez-Vargas Omar , Montes-Montiel Maryel , Sanchez-Cardenas Monica , Ruiz-Arguelles Guillermo J. 
Published: October 2019

Abstract
Abstract 4892
Rituximab ( R ) has changed the prognosis of patients with non-Hodgkin′s lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 diffuse large B cell lymphoma (DLCL). Patients were treated upfront with either CHOP or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be more clear in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (p NS). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (p =.05). In a multivariate analysis, other variables were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that rituximab produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of rituximab results in a 36 fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Features of Chinese Refractory Cytopenia of Childhood: Lower Overall Survival and Higher Possibillity of Clonal Evolution Than Nsaa Patients
Authors: An Wenbin , Li Zhanqi , Wang Shuchun , Chen Xiaojuan , Yang Wenyu , Guo Ye , Zhang Li , Zhang Peihong , Zhu Xiaofan 
Published: October 2019

Abstract
Abstract 4947

Objective:
To analyze the clinical features and survival time in patients with refractory cytopenia of childhood (RCC), and to develop a new diagnostic scoring system for RCC.

Methods:
The clinical information, laboratory findings at primary diagnosis and survival time in 97 non-severe aplastic anemia (NSAA) children diagnosed in August, 2000 to June, 2006 were analyzed retrospectively. According to the criteria for RCC proposed in the 2008 edition of the World Health Organization classification of hematopoietic and lymphoid tissues, diagnosis of these NSAA patients was reassessed.

Results:
37/97 cases (38. 1%) were reassessed as RCC, 60/97 cases (61. 9%) were still diagnosed as NSAA. There was no significant differences in distribution of age, gender and chromosomal abnormalities, absolute neutrophil count, PLT, MCV, absolute reticulocyte count, the number of cytopenias and duration from onset to starting treatmeat between RCC and NSAA. All patients received the treatment of CsA and androgen. There was no significant differences in distribution of treatment response. The overall survival (OS) of RCC patients was significantly lower than NSAA patients (P=0. 041) in long-term follow-up. The former had 91. 5% of 6-year prospective survival (PS) and the latter had 96. 5% of 6-year PS. At a median follow-up of 93 months (range 6–138), 2 patients reassessed as RCC progressed into AML-M5 and PNH respectively, while no NSAA patient progressed into clonal diseases. There was significant differences in the distribution of HGB<11g/dl at onset and lymphocyte count<3×109/L, dysplastic megakarycytes≥10% (CD41 monoclonal antibogy immunohistochemical staining) and periodic acid schiff (PAS) staining (+) in bone marrow aspirate between RCC and NSAA (P=0. 034, 0. 025, 0. 032, 0. 029). Compared with NSAA, there was significant differences in the distribution of bone marrow cellularity down to 10% of the normal age matched value, dysplastic erythroblastic island, number of erythroblastic mitoses and micromegakaryocytes in bone marrow biopsy of RCC(P< 0. 0001, 0. 0001, 0. 0001, 0. 0001). Using Logistic regression, a new diagnostic scoring model including increased dysplastic erythroblastic island, having micromegakaryocytes in bone marrow biopsy, and lymphocyte count<3×109/L in peripheral blood was developed. By ROC curve analysis, score≥2 points was identified as a cut-off value with sensitivity of 70. 3% and specificity of 95%.

Conclusion:
RCC patients had similar clinical features with NSAA patients but had lower OS and higher possibillity of clonal evolution. This new diagnostic scoring model had significance to differentiate diagnose RCC and NSAA.

Disclosures:
No relevant conflicts of interest to declare.
Array Comparative Genomic Hybridization: Impact in the Assessment of Plasma Cell Myeloma Genetic Profile and Prognosis
Authors: Leon Annette , Sevilla Deborah , Marino Joseph M , Moreno Kenneth D , Obrera Rev , Feldman Liliya , Fan Yan G , Persad Rajendra , Villamil Cesar , Maya Melissa , Mehta Nirav , O'Dea Denise , Kemel Yelena , Mazumder Amitabha , Weisberger James 
Published: October 2019

Abstract
Abstract 4965
Identification of specific chromosomal alterations in plasma cell myeloma (PCM) is essential for the prognosis and treatment of this disease. Although cytogenetic chromosome and fluorescence in situ hybridization (FISH) analyses are techniques currently used for this purpose, incorporation of array comparative genomic hybridization (aCGH) analysis as described in this study, demonstrates the insufficient power of traditional techniques in characterizing the complex and heterogeneous genetic profile of this group of hematological malignancies. In our cohort, aCGH study of 500 diagnosed PCM patients identified clinically significant genomic alterations in 56% of cases compared to 22% and 32% by chromosome and FISH analyses, respectively. Important findings by aCGH include the presence of hyperdiploid chromosome complement (15 > 9 > 5 > 19 > 11 > 3 > 7 > 21 > 6 > 18 >14) in 35% of cases which is associated with a favorable prognosis, as well as adverse prognostic markers such as hypodiploid chromosome complement (13 > Y >14 > 22> 10 >16 >8), gain of genetic material in chromosome 1q (CKS1B, PDZK1, ANP32E) and losses in chromosomes 1p (CDKN2C, FAM46C), 6q (PRDM1), 12p (ETV6, CDKN1B), and 17p (TP53) observed in 25% of patients. Recurrent alterations identified in 9% of cases only by aCGH include extra copies of genes which could be potentially poor prognostic indicators such as IRF4 (6p25. 3, transactivates MYC oncogene), IL-6 (7p15. 3, growth factor), BRAF (7q34, regulating the MAP kinase/ERKs signaling pathway), CYLC2 (9q31. 1, active cyclin in cell cycle progression from G1 to S phase), and genes located in the telomeric region of chromosome Xq. The results obtained in this study demonstrate the superior resolution and detection rate of aCGH technology in understanding the genetic heterogeneity of PCM as well as the importance of incorporating this methodology into current algorithms for the diagnosis and prognosis of plasma cell disorders.

Disclosures:
No relevant conflicts of interest to declare.
Sensitive Detection of Plasma Cells by Integrated Enrichment in-Column Staining and Analysis
Authors: Kühbach Katja , Herber Manuela , Koehler Dorothee , Schmitz Jürgen , Assenmacher Mario 
Published: October 2019

Abstract
Abstract 4968
In Multiple Myeloma immunophenotyping by multiparameter flow cytometry is a well-established method in clinical research to identify, characterize and enumerate neoplastic plasma cells. In addition, recent clinical studies demonstrated prognostic relevance of MRD detection by multiparameter flow analysis. The high applicability of the flow cytometric analysis compared to patient-specific RT-PCR holds the potential to become an important tool in MRD assessment.
For the identification of plasma cells the detection of more than one antigen is required and for an unequivocal discrimination between normal and neoplastic plasma cells the combination with clonality assessment is mandatory. Here we established a combination of five antibodies for surface staining: CD138-PE, CD38-FITC, CD56-APC, CD19-PE-Vio770, CD45-APC-Vio770 and two antibodies for intracellular staining: Anti Igκ-PerCP, Anti Igλ-VioBlue. The combination of fluorochromes for this 7-color panel was optimized for high resolution of the target population.
To minimize variability among flow cytometric data, it is crucial to standardize the various procedures – in particular in clinical settings. Pre-defined antibody panels and simplified sample handling are major factors in the reduction of variability. Furthermore, in order to obtain maximal sensitivity processing of large cell numbers is required, which is a major obstacle for conventional flow cytometers.
Here we demonstrate that magnetic pre-enrichment of CD138+ in combination with a new protocol for in-column intracellular staining for κ/λ light chains of retained plasma cells allows handling of up 108 cells (fig. 1). Together with the optimized antibody panel this approach offers a unique and valuable tool for characterization of rare plasma cells and offers increased sensitivity during MRD assessment. The MACSQuant® Analyzer offers the possibility to combine magnetic pre-enrichment with intracellular staining and flow cytometric analysis. This minimizes manual handling steps and reduces cell loss due to omission of centrifugation steps usually required for intracellular staining procedures.
The approach of combined cell enrichment, in-column intracellular staining and usage of standardized antibody panels on the MACSQuant Analyzer provides an automated workflow, which is highly suitable for routine detection and characterization of rare plasma cells.
Figure 1 Figure 1.

Disclosures:
Kühbach: MiltenyiBiotec GmbH: Employment. Herber:Miltenyi Biotec GmbH: Employment. Koehler:Miltenyi Biotec GmbH: Employment. Schmitz:Miltenyi Biotec GmbH: Employment. Assenmacher:Miltenyi Biotec GmbH: Employment.
Expression and Clinical Significance of Notch1 On the Membrane of Bone Marrow CD38+CD138+Plasma Cells in the Patients with Multiple Myeloma
Authors: Fu Rong , Zhao Yiran , Shao Zonghong , Wang Honglei , Zhang Tian , Li Lijuan , Liu Hui 
Published: October 2019

Abstract
Abstract 4981

Objective:
To investigate the expression of bone marrow CD38+CD138+, CD38+CD138-plasma cells and the expression of Notch1 on the membrane of them in the patients with multiple myeloma(MM), and explore the importance of Notch signaling pathway in the formation and progression of MM further.

Methods:
Thirty-three MM patients and 15 healthy controls were enrolled in this study. The expression of bone marrow CD38+CD138+, CD38+CD138-plasma cells and the expression of Notch1 on the membrane of them were analyzed by flow cytometry. The expression of Notch1 mRNA of bone marrow mononuclear cells were analyzed by RT-PCR.

Results:
The ratio of CD38+CD138+ plasma cells from 24 newly diagnosed MM patients was (51. 50%±12. 48%) which was significantly higher than CD38+CD138- plasma cells of MM patients (42. 88%±11. 41%)(P=0. 016)and controls 20. 13%±5. 8(P=0. 000). The expression of CD38+CD138+ plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow(r=0. 546, p=0. 006), serum level of lactate dehydrogenase(LDH)(r=0. 567, p=0. 004), and β2-MG(r=0. 431, p=0. 035). The ratio of Notch1 on the membrane of CD38+CD138+ plasma cells of MM patients was (60. 21%±25. 06%) which was significantly higher than those of CD38+CD138- plasma cells of MM patients 39. 84%±18. 94%(P=0. 000)and controls (38. 34%±19. 39%)(P=0. 004). There was no statistical difference between the two latter groups(P>0. 05). The expression of Notch1 on CD38+CD138+ plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there brone marrow(r=0. 914, p=0. 000), serum level of lactate dehydrogenase(LDH) (r=0. 604, p=0. 002), and β2-MG(r=0. 455, p=0. 026). The ratio of Notch1 on the membrane of CD38+CD138+ plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notch1 on CD38+CD138+ plasma cells from 17 MM patients who received VD chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy(r=0. 842, p=0. 000). The expression of Notch1 mRNA of bone marrow mononuclear from 10 MM patients was (0. 8252±0. 4079) which was significantly higher than those of controls (0. 3759±0. 0813)(p=0. 032).

Conclusion:
Notch1 over expressed on CD38+CD138+ plasma cells with relation to the effects of early VD therapy and long term outcome of MM.

Disclosures:
No relevant conflicts of interest to declare.
Tumor Antigens and T Cell Subpopulations: Is There Correlation Between These Two Possible Targets for Immunotherapy in Multiple Myeloma?
Authors: Braga Walter Moises Tobias , Silva Bruna Raphaeli , de Carvalho Fabricio , Alves Veruska Lia Fook , Colleoni Gisele Wally Braga 
Published: October 2019

Abstract
Abstract 4985

Introdution:
Cancer/Testis Antigens (CTAs) are a promising class of tumor antigens that have a limited expression in somatic tissues (testis, fetal ovary, and placental cells). CTAs are attractive targets for immunotherapy in cancer because the gonads are immune privileged organs and anti-CTA immune response can be tumor-specific. Recently, the importance of microenvironment for development and maintenance of many types of malignancies has been demonstrated. Multiple myeloma (MM) offers a good model to study tumor/microenvironment interactions because it involves a series of genetic alterations and changes in bone marrow microenvironment, favoring the tumor growth and failure of local immune control. A detailed analysis of the balance between Tregs and Th17 lymphocytes seems necessary to design more effective and less toxic types of immunotherapy in myeloma which is still an incurable malignancy.

Aims:
The present study aims to characterize and correlate expression of genes related to tumor cells (CTAs) and genes related to antitumoral control (Treg and Th17 lymphocytes) in patients with MM.

Matherial and Methods:
Forty-six bone marrow samples from newly diagnosed MM patients were analyzed. MAGE-C1/CT-7, MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE expression were analyzed by conventional RT-PCR. CTLA4 and RORyt were used to evaluate Treg and Th17 subpopulations, respectively, by quantitative PCR (qPCR). The analysis of the possible correlation between the expression of CTLA4 and RORyt and MAGE-C1/CT7, MAGEA3/6, NY-ESO, LAGE-1 and GAGE were made using median comparison expression of the first two genes with the positive or negative expression of the CTAs, using the Mann-Whitney test.

Results:
The CTA more frequently expressed in MM was MAGEC1/CT7 (66%). Expression MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE were, respectively: 40%, 23%, 32% and 30%. RORyt presented hipoexpression in 41% of the cases and CTLA4 presented overexpression in 70% of MM cases. The correlation analyses between all the CTAs and the CTLA4 or RORyt did not show any significant result (p> 0. 05).

Conclusion:
We found overexpression of a Treg subpopulation related gene (CTLA4) and hipoexpression of Th17 (RORyt), indicating possible imbalance of T lymphocytes in the tumoral microenvironment. However, it was not possible to establish a correlation between the expression of the most frequently expressed CTAs in MM with Treg and Th17 cells′related genes expression. It suggests that the expression of these genes does not seem to occur in a coordinate manner and its importance as therapeutical target in MM must occur by an independent way (Supported by Fapesp 2010/17668-6).

Disclosures:
No relevant conflicts of interest to declare.
Clinical Significance of Serum Free Light Chain Test in the First Onset of Multiple Myeloma
Authors: Hong Pan , Meng Xiaojian , He Jingsong , Wu Wenjun , Li Yi , Han Xiaoyan , Zheng Gaofeng , Zhao Yi , He Donghua , Shi Jimin , Xie Wanzhuo , Zhang Jie , Ye Xiujin , Huang He , Cai Zhen 
Published: October 2019

Abstract
Abstract 4999

Objective:
Clinical significance of serum free light chain (sFLC) test in the diagnosis, efficacy evaluation, prognosis judgment of first onset of multiple myeloma (MM).

Method:
Medical records of 39 cases of first-onset MM were gathered in our hospital from 1/2010 to 2/2012, including 25 male and 14 female patients with the median age being 63 years old. sFLC-kappa and sFLC-lambda were determined by immune turbidimetric assay, sFLC-kappa/lambda were calculated and the results were compared with that of immunofixation electrophoresis (IFE) as well as serum protein electrophoresis (SPE) for sensitivity assessment. All patients were treated with chemotherapy followed by sFLC detection and efficacy assessment. Patients with a sFLC results higher than median were marked as high-sFLC, the rest were marked as low-sFLC, and survival analysis were made comparing the two groups.

Results:
Of the 39 first-onset MM patients, 38 were detected as sFLC- kappa/lambda positive, that's a sensitivity of 97. 4%, higher than IFE (79. 5%), SPE (53. 8%), and uPE (38. 5%). As condition improves after treatment, sFLC gradually decline and sFLC- kappa/lambda level falls back to normal. Evaluation of efficacy by sFLC results has an accuracy of 77. 27%, significantly higher than that of corresponding M protein test£̈ P=0. 009£©. Follow-up survival analysis showed that the OS time and TTP time of low-sFLC group are significantly higher than those of high-sFLC group (P=0. 037, 0. 009 respectively).

Conclusion:
sFLC detection is a highly sensitive quantitative method, can help the diagnosis of MM, gives a quicker assessment of treatment efficacy, and can predict disease recurrence. When it's the first onset, sFLC level can also roughly forecast the prognosis.

Disclosures:
No relevant conflicts of interest to declare.
MiR-15a, Mir-16-1 and Mir-17-92 Cluster Expression Are Linked to Poor Prognosis in Multiple Myeloma
Authors: Lijuan Chen , Gao Xiao , Run Zhang , Xiaoyan Qu , Sensen Zhang 
Published: October 2019

Abstract
Abstract 5000
Multiple myeloma (MM) is characterized by a profound genomic instability of potential prognostic relevance. Loss of chromosome 13, observed in almost half of patients, negatively affects prognosis. MiR-15a, miR16-1 and miR-17-92 cluster, located on 13q, play important roles in the regulation of cell proliferation, differentiation and apoptosis. Therefore, we investigated a possible correlation of miRNA expression with chromosome 13 deletions (del(13)) and prognosis. We measured the expression of miR-15a, miR16-1 in 70 newly diagnosed MM patients and miR-17-92 cluster in 85 newly diagnosed MM patients by quantitative real-time PCR analyses. MiR-15a, miR-16-1 and miR-17 -92 cluster expression levels are independent of the del(13). High levels of miR-15a, miR-16-1, miR-17, miR-20a and miR-92-1 are associated with shorter progression-free survival (PFS), suggesting poor prognosis. Our data suggest that the expression of specific miRNAs may be contributed to MM prognosis.

Disclosures:
No relevant conflicts of interest to declare.