Scientific Program

Conference Series Ltd invites all the participants across the globe to attend International Conference on Hematology and Oncology Bangkok, Thailand.

Day 2 :

Hematology and Oncology 2017 International Conference Keynote Speaker Ashok Vaid photo
Biography:

Abstract:

Background:Diffuse Large B cell Lymphoma (DLBCL) accounts for approximately 25% of all Non-Hodgkin’s lymphoma (NHL) in the developed world, making it the most common lymphoma. With the diversities in clinical presentation, morphology, molecular and genetic alterations, DLBCL represents a heterogeneous group rather than a single disease entity. Based on the cell-of-origin (COO) concept, gene expression profiling (GEP) has identified two major subtypes of DLBCL with differing prognoses. We aim to study the trends in the clinico-pathological features, prognostic factors and treatment outcomes following standard therapy in Indian population at tertiary care center.

Methods:A prospective study was conducted and all newly diagnosed patients of DLBCL between September 2009 and April 2016 were included. The clinico-pathological features, IPI score, extranodal involvement and stage of disease were recorded using a proforma. All patients received Rituximab based treatment which was modified according to their tolerability. Immunohistochemistry was performed for molecular subtyping.

 Results:We included 189 consecutively diagnosed cases of DLBCL in the study. 52% (n=99) patients were > 60 years and 48% (n=90) < 60 years, the median age being 55 years. Majority were men (63%; n=119) versus women (37%; n=70). Fever (28%), pain abdomen (21%) and painless neck swelling (17%) were the most common presenting symptoms. SVC syndrome and bulky disease were noted in 12 (6.3%) and 10 (5.3%) of patients. 65% (n=123) had nodal predominant disease versus 35% (n=66) with extranodal disease; stomach (12.2%) and skeletal disease (6.3%) being the most common extranodal site. IPI score distribution was as follows: 28% (n=55) with low, 24.5% low intermediate, 22.2% high intermediate and 25.4% with high IPI score. Bone marrow involvement was detected in 20.1% (n=38) by bone marrow biopsy and 13.2% (n=25) by PET CT whole body scan. Stage IV disease was diagnosed in 52% (n=98), 21.2%, stage III 16.9% stage II and 10.1% in stage I. 89.4% were treated with R-CHOP with 92% receiving 6 cycles of chemotherapy. 68.4% achieved complete metabolic response (CMR), 22.7% (n=43) partial response (PR), 1.5% (n=3) progressive disease and 2.1% (n=4) died before completion of chemotherapy course. Better CMR rates were observed in patients < 60 years versus > 60 patients (75.5% {68 out of 90} v/s 53.5% {53 out of 99}; p=0.026). Molecular subtyping was performed in 116 patients with GCB subtype seen in 55.2% (n=64) and ABC in 44.8% (n=52). The CMR rates were seen in 71% (37 of 52 patients) of GCB subtype and 65% (42 out of 22 patients) of ABC subtype (p=0.65).

Conclusions: R-CHOP remains the standard of care for patients with DLBCL. However, literature reports a cure rate of only 60% with standard immuno-chemotherapy cures with 40% eventually dying of the relapsed disease. DLBCL can no longer be considered and treated as one disease. Efforts are in way to improve the standard of care and identify a new biological agent (X) to add on to the R CHOP backbone. It is also imperative to identify those prognostic markers that would identify subset of patients who would benefit from a more aggressive course.

  • Haemostasis & Blood Coagulation/ Genetic Disorders
Speaker
Biography:

Reham Ahmed Rashed  has completed her PhD at the age of 33 years (May, 2008) from Cairo University and postdoctoral studies from National Cancer Institute, cairo university, cairo, Egypt. She is an assistant Professor in the hematology department of National Cancer Institute. Research Objective Focusing: The search and Study on the diagnosis, prognosis and treatment of Different Types of Leukemia and lymphoma with other solid tumours. Approaching this study by applying    Molecular Biology Techniques and bone marrow biopsy with different  immunohistochemical  staining and  has published more than 10 papers in reputed journals to serve the field of interest in research. 

 

Abstract:

Background: Bone marrow biopsies are generally included in the initial staging evaluation of NHL and BM involvement has unique prognostic implication in different histological subgroups of the disease. Flow cytometeric data should always be correlated with BM biopsy finding, immunophenotyping of core biopsy allows parallel morphologic examination and is capable of generating multivariate, quantitative, immunophenotypic data useful in diagnosis of NHL.

Aim:  To evaluate the role of flow cytometric immunophenotyping (FCI) of lymphoma biopsy samples next to immunohistochemistry and histopathology for better diagnosis and characterization among Egyptian patients.

Subjects and methods: 60 B-NHL patients stage IV, diagnosed after histopathological examination of lymph node biopsy or Fine needle aspiration (FNA) of other primary site and staged according to Ann Arbor system. Clonality assessment was established using Flow cytometric (FCM) immunophenotypic analysis of BMA and biopsy after obtaining single cell suspensions by mechanical disaggregation, with a restricted panel of (CD45, CD20, CD3, CD19, anti Kappa and anti Lambda) using (BD FACSscan 4 color flowcytomtery). In addition to Histopathology of paraffin- embedded BM trephine biopsy with immunohistochemical (IHC) staining   for morphological BM evaluation and clonality assessment.

Results: FCI analysis of BMB samples showed 24/60 cases  (40%) positive for infiltration by B- monoclonal lymphocytes with light chain restriction and 36/60 (60%) negative cases, while BMA positive in only 16.7%, negative in 76.7%, and 6.7% dry tap with difficult FCM analysis. FCI of core biopsy versus histopathological assessment and light chain expression and restriction detection by IHC revealed concordance rates of (63.6 % and 85%) and discordance rates of (36.4% and 15%). Clonality assessment and light chain expression detection revealed a kappa value of 0.708 for IHC versus FCM with concordance of 85% and discordance 15%. 

Conclusion: Our results showed fair agreement level for IHC and FCM of BMB, yet FCM is faster, specific and has a more definite role in detection of monoclonality of NHL, so accurate assessment of hematolymphoid neoplasms requires an integrated multiparameter approach. Although morphologic histopathologic examination remains the mainstay of initial assessment, immunophenotypic analysis of core biopsy is essential to determine the pattern of differentiation and detect minimal disease when morphology is inconclusive. Fnally, an integrated approach using multimodality technologies is a must with identifying the strengths, weaknesses, and limitations to be an efficient and cost-effective method for better assessment.

Speaker
Biography:

Murugan A K completed his PhD from the Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan and Postdoctoral studies from Hoshi University, Tokyo, Japan and The Johns Hopkins University School of Medicine, Baltimore, USA. Currently, he is a Scientist in the Department of Molecular Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia. He has published more than 35 papers in reputed journals and holds a patent for identification of novel ALK mutations in anaplastic thyroid cancer. His research focuses on molecular biology of head and neck squamous cell carcinoma and thyroid cancer identifying molecular therapeutic targets and biomarkers. He has been serving as Reviewer in Thyroid, PLOS One, Oncogene, Cancer Research, Tumor Biology, Endocrine Related Cancer, Oral Oncology, etc.

 

Abstract:

PI3Ks are heterodimeric lipid kinases that regulate cellular activities such as proliferation, survival, motility and morphology through the second messenger PIP3. Studies have reported that the P110α (PIK3CA), the catalytic subunit of PI3-kinase is somatically mutated in human cancers. Here, we found PIK3CA mutations in 29.4% of head and neck squamous cell carcinoma cell lines, 10.5% of Indian, 11.7% of Japanese (unpublished data) and no mutation in Vietnamese tumors. Functional analysis of these mutations including a novel insertion mutation in Indian tumor showed increased PI3 kinase activities, followed by growth factor-independent proliferation, changes in morphology, a higher rate of cell migration and invasion. Our findings suggest that PIK3CA mutations in HNSCC are likely to be oncogenic and may significantly contribute to HNSCC carcinogenesis and pave an attractive target for therapeutic prevention.

As there were no mutations found in PIK3CA of Vietnamese oral cancers, we hypothesized that the RAS could be more likely activated as an upstream effector of PI3K. We, therefore, sequenced the exons 1 and 2 of H-RAS. The RAS mutations were detected in 10 of 56 tumors (18%) suggesting that RAS is an important member in the PI3K/Akt signaling and could play an important role in the tumorigenesis of oral carcinoma. SWAP-70 is a PIP3 binding protein involved in actin rearrangement, especially in membrane ruffling. Mouse embryo fibroblast (MEFs) deficient in SWAP-70 show impaired membrane ruffling and fail to grow on soft agar after transformation by v-Src. Here, we show that MEFs transformed by v-Src-expressing SWAP-70 are highly invasive. MEFs expressing SWAP-70 or v-Src alone were far less invasive, suggesting that both proteins were required for the cells to be invasive.

Biography:

Ayishah Choudhary is doing her MPhil from Universirsty of Health Sceinces, Lahore, Pakistan. Currently, she is also working as Demostarator at University of Lahore Pakistan. She has completed her MBBS from Liaquat University of Health Sciences, Jamshoroo, Pakistan. Recently, she has completed her Certificate of Medical Teaching from University of Health Sciences in collabration with University of Liverpool, UK.

Abstract:

Background: Childhood obesity is often related to cardiovascular diseases and accompanied by a dysregulation of coagulation and fibrinolytic systems. Obesity have been found to be associated with increased levels of Factor VII, Fibrinogen, Plasminogen activator inhibitor (PAI-1) and PAI-1 gene (-675bp 4G/5G) polymorphism. Therefore, we investigated the hemostatic parameters i.e. factor VII, fibrinogen, plasminogen activator inhibitor and PAI-1 4G/5G gene polymorphism in childhood obesity.

Methods: In this cross-sectional study, 42 obese (mean age, 8.91±2.56) and 42 healthy weight (mean age, 9.27±2.29) children, classified by Body Mass Index (BMI) were recruited. They were assessed for anthropometric measures. Factor VII levels were determined by chromogenic assay, fibrinogen levels were determined by clotting method of Clauss and PAI-1 levels in plasma were determined by Colorimetric Assay. PAI-1 4G/5G polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism.

Results: BMI, waist and hip circumference (p<0.001) were significantly higher in obese children. Plasma factor VII level, fibrinogen were significantly higher in obese group as compared to other group (p<0.001). Plasma PAI-1 in obese (mean 32±16) is higher than non-obese (mean 26±16) but statistically not significant. The allele frequency of 4G (obese 0.66% and non-obese 0.34%, odds ratio 0.385, p value-<0.001) was significantly higher. The genotype frequency of 4G/4G in obese 15% and in non-obese 2%, 4G/5G in obese was 5% and non-obese is 37% and 5G/5G in obese was 5% and non-obese is 37%.

Conclusion: The results suggest that obesity may play role in regulation of hemostatic factors. Even in childhood, obesity is associated with unfavorable concentration of hemostatic factors that are in turn implicated in cardiovascular morbidity and mortality later in life.

Biography:

Patrick Van Dreden is a Head of Clinical Research Department and Prospective Research Manager at Diagnostics Stago. He has Degree of Hemostasis study: Pathogenesis and pharmacology of thrombosis. He is an International Member of Society of Haemostasis and Thrombosis, Member of the European Thrombosis Research Organization, Member of the Mediterranean League against Thromboembolic Diseases, Member of the American Society of Hematology and Member of International Academy of Clinical and Applied Thrombosis/Hemostasis.

Abstract:

Backround: Multiple myeloma (MM) and the associated immunomodulatory (IMiD)treatments are associated with risk of vascular complications. Thrombin generation (TG) assessment reflects the equilibrium between procoagulant and anticoagulant activities in the plasma.

Aim: We conducted a multicenter study to explore the relationship between stages of MM and alterations of thrombin generation profile.

Methods: Patients with MM (n=129) were recruited from July 2014 to December 2016 and stratified to the following groups: 44 newly diagnosed treatment-naïve patients (ND), 33 patients receiving IMiDs (IM), 45 in complete remission (CR) and 7 patients in partial remission on IMiDs (PR/IM). Patients on anticoagulant treatment were excluded from the study. The control group (CG) consisted of 30 healthy age and sex-matched individuals. Samples of platelet-poor plasma (PPP) were assessed for thrombin generation (TG) with the TF 5pM PPP-Reagent® on Calibrated Automated Thrombogram (Stago, France). The upper and lower normal limits (LNL and UNL) were calculated by the mean±2 SD.

Results: Patients with ongoing MM (ND, IM, PR/IM) had significantly lower Peak, ETP and MRI as compared to the CG. In contrast, patients in CR had Peak, ETP, MRI values similar to the CG. Patients with PR had lower ETP and MRI values as compared to the CR group (Table 1). In ND 8% had TG >UNL and 20% had TGUNL and 57% had TGUNL and 33% had TGUNL and 14% had TG

Conclusion: Patients with active MM showed attenuated TG which was enhanced in the presence of IMiD treatment. Complete remission was associated with normalization of TG. The unexpected decrease of TG in patients with active MM and its normalization when the disease is in a remission might indicate that this test reflects vascular aggression which is followed by release of thrombomodulin, heparin cofactor II, sEPCR and TFPI.

Biography:

Patrick Van Dreden is a Head of Clinical Research Department and Prospective Research Manager at Diagnostics Stago. He has Degree of Hemostasis study: Pathogenesis and pharmacology of thrombosis. He is an International Member of Society of Haemostasis and Thrombosis, Member of the European Thrombosis Research Organization, Member of the Mediterranean League against Thromboembolic Diseases, Member of the American Society of Hematology and Member of International Academy of Clinical and Applied Thrombosis/Hemostasis.

Abstract:

Introduction: The hypercoagulable state of malignancy occurs due to the ability of tumor cells to activate the coagulation system. The prominent role is attributed to exposure of tissue factor (TF) and procoagulant phospholipids (PPL) by the tumor cell. We recently showed that contact of human plasma with pancreas adenocarcinoma cells (BXPC3) or breast cancer cells (MCF7) enhances thrombin generation (TG). We demonstrated that the procoagulant activity of the cancer cells alone was not sufficient to induce hypercoagulability  We analyzed the specific procoagulant role of microparticles (MVs) originate from the cancer cells and we estimated their association with cancer cells for cancer induced hypercoagulability
Methods: BXCP3 and MCF7 cells were culturedin 96-well plates.Primary human umbilical vein cells (HUVEC) were used as normal control experiment. The CAT® assay (Stago France) was used to study TG of normal platelet poor plasma added in wells carrying (a) cancer cells, (b) cancer cells in presence of their respectively isolated MVs, or (c) MVs alone.TF activity (TFa) of cells and MVs was assessed with a specific clotting assay. 
Results: The TFa were found in abundant amounts BXPC3 cells, and BXPC3 MVs compared to MCF7 cells and MCF7 MVs. The HUVEC cells and HUVEC MVs showed TF activity comparable to a normal pool. Analytical data of TG are depicted in Table 1

 

 

Thrombin generation on cells ± MVs with MP reagent in Normal Pool plasma ( no TF/PPL 4µM)

Pool

HUVEC

BXPC3

MCF7

HUVEC +MVs

BXPC3

+MVs

MCF7

+MVs

Pool +MVs(BXPC3)

Pool +MVs(MCF7)

Lag-time (min)

8.9±1.6

7.7±0.9

4.8±0.6

7.5±0.7

7.9±0.9

1.2±0.5

5.1±0.7

2.2±0.6

6.1±0.4

tt-Peak (min)

14.6±1.3

12.1±0.9

5.7±0.8

9.3±1.0

11.7±0.9

2.6±0.6

6.9±1.1

3.3±0.4

8.2±0.8

Peak

(nM)

136±11

150±11

220±12

179±11

166±10

410±12

220±10

380±14

210±11

MRI (nM/min)

24±9

35±10

244±13

99±12

45±10

294±11

120±12

247±14

100±13

 Table1: Thrombin generation on cells in presence and absence of MVs in normal pool Plasma


Conclusions: This experiment showed that hypercoagulability induced by cancer cells is the resultant of the combination of the procoagulant properties of cancer cells with procoagulant elements of the plasma microenvironment. To the best of our knowledge, the present study showed for the first time that the inherent procoagulant properties of cancer cells are not sufficient to induce hypercoagulability and documents that procoagulant elements of the microenvironment, namely MVs are necessary elements for cancer induced hypercoagulability. 

Biography:

Swarali Tadwalkar has completed her Master’s in Public Health (MPH) from University of South Florida, Tampa in 2015. She has an extensive experience in primary and secondary healthcare research stemming from projects in digital health, health policy and management, and health economics and outcomes research (HEOR). Swarali currently works with Decision Resources Group (DRG) as an Associate Epidemiologist with the epidemiology team and develops epidemiological populations forecasts for different infectious and non-communicable diseases with particular interests in the oncology space.

Abstract:

Objective: estimate the global incidence and prevalence of Chronic Myeloid Leukemia (CML) by world regions over the next ten years using a multi-factorial forecast model.

Methods: using a critically appraised set of country-specific cancer registries, CML incidence was estimated for 45 countries, representing approximately 90% of the world population in 2017. Measures of economic development across countries such as gross domestic product (GDP) were considered as key indicators for access to healthcare and the adoption of potentially leukemogenic dietary patterns and lifestyles. Observed correlations between GDP, CML risk, and survival were used to trend CML incidence over the next ten years. CML survival was trended using an attenuated function of the historical trend, representing the continuing optimization of Tyrosine Kinase Inhibitor-based treatment. Prevalence was estimated as a cumulative incidence over preceding twenty years with adjustments for disease-specific and competing-cause mortality for each year. To estimate incident and prevalent CML globally, aggregate estimates for each region were divided by the proportion of countries in that region for which direct estimates were made using the methods described above.

Results: the incidence of CML in Africa, Latin America, lower-income Asia Pacific countries, high-income Asia Pacific countries, Europe, and North America is 0.4, 0.7, 0.7, 1.2, 1.4, and 2 cases per 100,000/ year. The prevalence of CML in Africa, Latin America, lower-income Asia Pacific countries, high-income Asia Pacific countries, Europe, and North America is 3, 5, 6, 10, 11, and 15 cases per 100,000 in 2017. Latin America is expected to see the highest growth in prevalent cases over the next ten years: 36% by 2027.

Conclusion: the incidence and prevalence of CML is expected to increase globally. Improvements in the survival of CML patients will result in 20 thousand additional cases surviving by 2027 worldwide. 

Speaker
Biography:

Ghulam Mustafa, age 29 years old from the department of Haematology University of Health Sciences Lahore, Pakistan. I have completed my M. Phil MLS in the subject of Haematology in 2016 and previously I had done my graduation in the subject of Medical Lab Technology in 2011. Regarding my job experiences; Recently, I am working as a Medical Lab Technologist from August 2009 to present date in the department of Haematology, Ittefaq Hospital Trust Lahore, Pakistan. I am also giving my services as a “Lab Manager” from August 2016 to present date in the department of Haematology of University of Health Sciences Lahore, Pakistan. I am actively involved in research project designing and synopsis and thesis writing. Regarding my research work experiences; I have done my research work on the titled “Single Nucleotide Polymorphism of P2RY12 and CYP3A5 Genes in Clopidogrel Resistant Ischemic Heart Disease Patients” which was a Higher Education Commission funded project. I did my research work on 250 patients and present this work in an Annual Conference of Pakistan Society of Haematology held at Expo Center, Karachi Pakistan on May 5-6, 2016. Currently, I have published one paper with titled “Fine mapping of chromosome 9 locus associated with congenital cataract” in an international Ophthalmology journal (IF=0.95) while five further papers are in pipeline for publications.

Abstract:

Background: Antiplatelet therapy with clopidogrel is generally used to decrease the risk of ischemic heart disease. Environmental and genetic factors including SNPs in CYP3A5 and P2RY12 genes are attributed for this inter-individual variation in response to drug.

Objective: To examine the role of CYP3A5 rs776746 and P2RY12 rs2046934 polymorphisms in clopidogrel resistance in IHD patients.

Methods: A total of 237 IHD patients were recruited who had received 75mg clopidogrel for more than 07 days. Platelet aggregation studies were performed on Innovance® PFA-200 system. The rs776746 and rs2046934 polymorphism were determined by PCR-RFLP.

Results: Out of selected IHD cases, 85.7% were clopidogrel responders and 14.3% were non- responders. Genotype for CYP3A5 responder, 5.4% were homozygous (*1/*1), 89.7% were heterozygous (*1/*3) and 4.9% were homozygous (*3/*3). Non-responders CYP3A5 indicated that 8.8% were homozygous (*1/*1), 64.7% were heterozygous (*1/*3) and 26.5% were homozygous (*3/*3). The allele frequencies difference among responders and non-responders were highly significant (p<0.05). P2RY12 genotypes with clopidogrel responder patients showed that 78.3% were TT alleles, 19.7% were CT alleles and 2.0% were for CC alleles. Similarly, non-responder patients showed 91.2% were with TT alleles, 8.8% were CT alleles and no patient were with CC alleles. So, these frequencies difference in alleles among clopidogrel responder and non-responder P2RY12 patients were not statistically significant (p>0.05).

Conclusion: The allele CYP3A5*3/*3 showed a significant association with clopidogrel resistance whereas, P2RY12 did not show association with clopidogrel resistance in studied samples.