11th International Conference on Hematology & Hematological Oncology November 08-09, 2017 Las Vegas, Nevada, USA

Sikander Ailawadhi has expertise in the field of plasma cell disorders, specifically multiple myeloma and focuses on clinical drug development as well as a special interest in secondary data analysis looking at outcome disparities and healthcare economics. He has accumulated vast experience in the area of disparities in healthcare utilization and outcomes by patient race and ethnicity and how the management, access and effects of therapeutic interventions may be different for various patient subgroups. Several of his research projects focusing on healthcare economics, cost-effectiveness and outcome disparities have been recognized in the form of presentations at national and international meetings as well as peer-reviewed publications.

Background: Cost of cancer care is projected to reach $173 billion by 2020, a 39% increase from 2010. Several factors including psychiatric (psych) comorbidities contribute to this increase. Within the oncology setting, 29-38% of the patients (pts) are reported to have mood disorders and 15% have major depression. Depression alone is associated with increased healthcare utilization in pts with breast, colon, lung and prostate cancers. A 2015 report noted that the presence of at least one psychiatric comorbidity in 300 Leukemia pts was associated with an extra $55,000 per pt in just one year. Similarly, in pts treated with systemic steroids, the incidence of neuropsychiatric disorders can be as high as 75%. However, no such data is available for MM, where more than 90% of pts are treated with steroids, likely increasing risk for mood problems and impacting treatment cost. As such, the aim of our study was to analyze the SEER-Medicare database for healthcare utilization trends and acute cost of care (cost incurred during 6 months after MM diagnosis) in MM pts with or without psych comorbidities.

Methods: Pts diagnosed with MM between 1991-2010 with continuous Medicare coverage (1 year prior to diagnosis-date of death/ end of 2012) were included. Pts were categorized as: MM with any psych disorder (MM+P), MM with depression (MM+D) and MM only. Presence of ≥1 inpatient (ipt) or ≥2 outpatient (opt) ICD9 diagnosis codes were used to assign pts to the psych categories. Within MM+P and MM+D groups were subdivided by presence of psych or depression diagnosis prior to MM (MM+P PRE or MM+D PRE). Medicare claims adjusted for inflation (2013) within the first 6 months (mth)/total MM care were summed by drug and total charges. Univariate and multivariate logistic regression models (adjusted for age, year, sex, race and the Charlson Comorbidity Index; CCI) were performed to determine associations with ipt, opt and any emergency department (ED) charges after MM diagnosis.

Associations between psych conditions prior to MM diagnosis and costs of care after MM diagnosis were assessed using univariate and multivariate proportional odds models.

Results: The study population included 36,007 eligible MM pts with a median follow-up of 1.8 years. 15168 (42%) pts had a psych condition at any time (MM+P), while 9355 (26%) were diagnosed prior to MM diagnosis (MM+P PRE). Depression was present in 8421 pts (23%), 4546 (13%) of those occurring prior to MM diagnosis. In comparison to MM pts, MM+P and MM+D pts tend to be female, White and had a higher CCI (all p<0.001). When compared to MM pts, those with MM+P PRE and MM+D PRE had significantly higher incidence of MM-related complications (hypercalcemia, renal dysfunction, anemia, fractures and dialysis) at the time of or after MM diagnosis and also required increased overall care (all p<0.001). Both, MM+P and MM+D had higher odds of ipt visits (OR 1.48 and 1.41, resp., p<0.001), ED care (OR 1.48 and 1.37, resp., p<0.001) and opt visits (OR 1.25 and 1.22, resp., p<0.001) as compared to MM only pts. Cost of care analysis showed that MM+P and MM+D pts had a significantly higher cost of opt (OR 1.36 and 1.39, resp., p<0.001), ipt (OR 1.49 and 1.54, resp., p<0.001) and total care (OR 1.52 and 1.55, resp., p<0.001) as compared to MM only pts during first 6 mth after MM diagnosis (Figure 1). Total costs of care for MM+P and MM+D were also higher than MM only but the differences were less significant. Cost of care differences existed within first 6 mth of MM diagnosis by pt race as well with

MM+P among Hispanic and Asian pts being more strongly associated with higher costs than Whites and African-Americans (AA) (p<0.001). MM+D had similar trends but not significant after adjustment for multiple comparisons.

Conclusion: Psych comorbidities are associated with significant increase in healthcare utilization and cost of care in MM pts and may contribute to higher MM-related complications. More research is needed to study whether a multidisciplinary approach to identify and manage MM pts with psych conditions may help mitigate these trends.

Nova Thomas John has completed her MBBS degree from Kasturba Medical College, Manipal University, Karnataka, India and Internal Medicine residency from University of Illinois Urbana-Champaign, Illinois, USA. She is currently practicing as a Hospitalist Medicine Physician with Starling Physicians Group, P C at Hartford Hospital, Connecticut,

USA, since August 2015.

Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life threatening clinical syndrome characterized by hyperinflammatory cytokine storm due to exaggerated immune response. It may be triggered secondary to infections, malignancies, autoimmune diseases or medications. The following case report demonstrates acute lupus nephritis with initial presentation as HLH called acute

lupus hemophagocytic syndrome. Estimated prevalence of HLH secondary to Systemic Lupus Erythematosus (SLE) is rare between 0.9-4.6%. A 20-year-old African American female presented with progressive myalgia, malaise and recurrent fevers for 3 weeks. Vitals signs were normal except for temperature of 102oF. Her examination was unremarkable except for right posterior cervical

lymphadenopathy. Laboratory data showed pancytopenia, hypertriglyceridemia, hyperferritenemia >17,000, hypoalbuminemia. Urine

24-hour protein was elevated >5000 mg/24 hr. Bone marrow biopsy confirmed HLH and Renal biopsy confirmed Lupus nephritis. With the initiation of immunosuppressive regimen of dexamethasone and mycophenolate mofetil, she improved dramatically with resolution of fevers and normalization of HLH-specific disease markers. This case highlights the diagnostic challenge that may lead to delay in diagnosis of acute lupus hemophagocytic syndrome. Patients presenting with unexplained prolonged fever, cytopenia, abnormal liver function and elevated ferritin levels, should prompt clinicians to perform immunologic testing for SLE in setting of HLH to avoid diagnostic and therapeutic delays.

James Granfortuna is a practicing Hematologist-Oncologist for 30 years. He is currently a full time Faculty Member at the Cone Health Internal Medicine Teaching program, affiliate hospital of the University of North Carolina Chapel Hill Medical Center. His special interests include platelet and clotting disorders in the general population and in pregnancy.

The thrombotic microangiopathies (TMAs), are a complex group of disorders that typically present with a schistocytes hemolytic anemia and associated thrombocytopenia with ensuing microvascular occlusion leading to tissue ischemia and end organ damage. CNS, GI and cardiac microcirculations are frequent targets. Signs and symptoms related to organ dysfunction may evolve over weeks to months and may not be present simultaneously. LDH elevation due to microvascular ischemia is frequently disproportionate to elevation of bilirubin or reticulocyte count. The major thrombotic microangiopathies include TTP, DIC/sepsis and Hemolytic Uremic Syndrome. HUS may be further divided into “typical”, related to Shiga toxin, “atypical”, related to dysregulation or overactivation of complement and secondary, including disorders of pregnancy such as the HELLP syndrome or pre-eclampsia, certain

other infections such as Strep Pneumoniae, auto-immune disorders such as Sjogren’s syndrome, cancer, chemotherapy, or other medications, such as quinine and calcineurin inhibitors. These disorders can provoke direct microvascular damage and present as a thrombotic microangiopathy or act as a trigger for a microangiopathic syndrome in individuals with a genetic predisposition. The level of ADAM-TS 13, Von Willebrand Factor cleaving enzyme, is a key discriminator between TTP and HUS being severely reduced

in TTP but not HUS. Plasma exchange with or without steroids is the mainstay of treatment for TTP. Anti C5 antibody therapy has evolved as an important treatment for a HUS. Although we have gained significant insight into the pathophysiology of many of these disorders, given the complex interplay between genetic factors, acquired factors, the roles of the humoral, cellular and innate immune systems, the inflammatory response and the coagulation system, TMAs remain clinically challenging. This review will focus on a summary of our current knowledge with regard to diagnosis and treatment of TTP and HUS and how they relate to each other and the broader family of TMAs. Three clinical cases will be used to illustrate key points.

David W Scott, PhD is Vice Chair for Research, Department of Medicine, Uniformed Services School of Health Sciences, Bethesda, MD and an alumnus of Antioch College, University of Chicago (MS) and Yale (PhD). Following a fellowship at Oxford University, he held tenured positions at Duke University, University of Rochester and University of Maryland Medical School. He has contributed to over 200 research papers on immunologic tolerance and its application in autoimmune diseases, hemophilia and gene therapy. He is the author of two textbooks, including The Nature of Immunologic Tolerance, he is a recipient of a number of awards, e.g. Distinguished Service Award from the American Association of Immunologists, a Boarhaave Professorship at Leiden University in Holland and the 2009 Scientific Achievement Award from AAPS.

Building on Chimeric Antigen Receptor (CAR) therapy for cancer, we have created and expanded human “natural” regulatory T cells (Tregs), as well as cytotoxic T cells that are rendered specific by expression of either T-cell receptor (TCR), single chain Fv (scFv) V regions or a novel CAR derivative, called B-cell antibody receptors (BAR). These specific Tregs demonstrate potent suppression of T-cell and B-cell responses in two disease models, MS and hemophilia, in vitro and in vivo. These cells are stable, specific and potent. Engineered BAR cytotoxic cells have also been generated that can directly target and kill specific B cells. Our results are a platform to generate T cells that can be used to block adverse immune responses. Translation into large animals and clinical trials are planned.

Knox Van Dyke is a Professor of Biochemistry and Molecular Pharmacology at West Virginia University Medical School with 50 years of research experience. He completed his PhD in Biochemistry in the Edward A Doisy–Nobel Prize Department at Saint Louis University in 1966. He did Post-doctoral studies in the Department of Pharmacology at West Virginia University Medical School. During this time, he developed the first effective drug screening system for antimalarial drugs while screening over 10,000 drugs. Mefloquine and halofantrine were recognized by this screening system and were further developed by Walter Reed and various companies as patented drugs. He first solved the problem of black lung disease and silicosis by demonstrating that coal dust per se is not particularly toxic to human cells compared to silica and that silica is not particularly toxic alone but it is contaminated with calcium. He recognized that urate in the blood protects against peroxynitrite generating chronic diseases. He has recognized that many chronic diseases like cancer, arthritis, diabetes and heart diseases etc., are caused by excessive peroxynitrite or its derivatives. He has over 300 publications and 150 patents.

Toxic dusts like coal and silica, present a confusing picture regarding toxicity when inhaled into the lung. Why should such dusts be inherently inflammatory and/or toxic both in the short and particularly in the long term? Since these dusts create at first acute and then chronic diseases- are there important ways to treat these diseases once they have begun their inevitable course. Mine dusts are a complex mixture of different compositions of dust but almost all coal dust contains both the dust from coal (carbon) and rock dust (silica). We have found that the silica has a major contaminant since X-ray microanalysis indicates two clear peaks –one for SiO2(-2) and one for Ca+2. We dripped a slurry of silica powder into lungs of rats under anesthesia. Twenty-four hours post silica exposure- luminescence- from the lavage cells were assayed using L-012 and the peroxynitrite-based light was 10-fold higher which could be completely inhibited by dexamethasone. In the treated silica animal, the nitric oxide production increased 10-fold without dexamethasone-steroid. After 6 weeks, the luminescence was increased 1000-fold. But, then the steroid had no effect

because induction of nitric oxide synthase had already occurred. Steroids are not effective for chronic diseases, since the epigenetic deacetylation mechanism used by steroids is damaged by excessive peroxynitrite. This same scenario occurs in humans if a person has inhaled silica, the acute disease can be controlled using chronic steroids but if they are withdrawn, the patient will die. The development into the chronic state must be stopped to preserve life.

Tomas Kozak has completed his MD from Charles University in Prague and later Post-doctoral studies from Masaryk University in Brno. He is Professor at the Department of Internal Medicine and Haematology at the 3rd Faculty of Medicine, Charles University in Prague, Czech Republic. He has published more than 90 papers in reputed journals as Author, Co-author or Senior Author and has been serving as an Editorial Board Member of repute.

We analysed data of 40 patients with SM, focusing on markers that could be sensitive to support the diagnosis of SM and that might distinguish indolent and aggressive course of the disease. We looked at C-KIT mutation detection in both bone marrow and peripheral blood and we ańalyzed the tryptase level. Median age of patients at the time of diagnosis was 53 (25-84) years, 45%

of patiens were males. Indolent SM (ISM) was diagnosed in majority of patiens: 29 (72%), aggressive SM (ASM) in 9 (23%) patients and in 2 patients was established SM-AHN (ET and AML). All patiens were treated with long term antiallergic profylaxis with both H1 and H2 blockers, 19 patients started specific first line treatment for SM with interferon- alfa (13) or cladribin (5). Three patiens died, 2 for ASM progression, 1 for SM-AHN (AML). Presence of C-KIT D816V mutation by PCR was analysed in 31 patients in bone marrow (BM) and/or peripheral blood (PB). In 27 patients, the mutation was examined in bone marrow, 22 (81%) of them were positive. In 12 patients, the c-kit mutation was examined in peripheral blood, only 4 of them were positive (33%). The c-kit mutation was analysed in 8 patients in both BM and PB, 5 of them (63%) were positive in BM and negative in PB at the same time. We analysed difference of tryptase level in ISM and compared it to the ASM. Median tryptase level in ISM was 37, 1 (6, 03-200) μg/l, in ASM 200 (58-200) μg/l respectively.

Nabusige Jean Brenda Gesa is a dedicated scholar of Hematology and Oncology, passionate about healthcare advancement in Uganda and proficient in at least 3 languages, including English and Mandarin Chinese. She received her Bachelors’ degree in Biomedical Laboratory Technology from Makerere University, Kampala and a Master of Medicine in Clinical Laboratory Diagnostics at Beihua University, China (2017). She also acquired diagnostic laboratory experience at St. Raphael of St. Francis Hospital, Nsambya in Kampala and Jilin Central Hospital, China. Her research interests include environmental pollutants in relation to hematological malignancies and hematological cancer research; diagnostics and therapeutics.

APL is the most curable form of AML due to its sensitivity to ATRA, but challenges due to the threat of DIC at diagnosis and drug toxicity of combination therapies during treatment, still remain. The aim of this study was to generate information on a newly selected group of ssDNA aptamer candidates and build a potential aptamer library, for future use and reference in improving diagnostic and therapeutic efficacy in APL management. This study involved the amplification of 7 highly specific ssDNA sequences of 39-40bp each flanked by an 18bp primer sequence on both 5’ and 3’ ends. DNA was cloned into DH5α cells and ssDNA obtained by affinity chromatography, purified and quantified by spectrophotometry. Cell binding affinity assays were conducted with APL HL-60 cells at room temperature, with incubation at 37 0c. Results were quantified by spectrophotometry. Quality and yield of PCR amplified DNA was dependent on concentration of plasmid template in the PCR mix and the number of cycles employed. It was realized that DNA purification using Phenol-chloroform was most effective when plasmid templates used were freshly extracted and hadn’t been subjected to prolonged storage. Of the 7 DNA sequences tested, sequences 135, 57 and 2 were observed to have the highest affinities and 59, the lowest. Sequences 135 and 2, on statistical analysis demonstrated the highest affinities and are deemed ideal candidates for further investigation in the development of effective aptamers and other tools for timely diagnosis and effective management of APL. We suggested that further research be done.

Erhabor Osaro is a Professor of Hematology, Blood Transfusion Medicine and Laboratory Total Quality Management. He has received his PhD in Immuno-Hematology from the Rivers State University of Science and Technology in Port Harcourt, Nigeria. He is also an Alumni of University of Greenwich in the United Kingdom and Francis Tuttle College of Technology in Oklahoma, USA. Currently, he is a Professor in Usmanu Danfodiyo University, Sokoto, Nigeria, where he teaches best practices in hematology, blood transfusion science and laboratory total quality management. He has more than 200 published articles in both local and international journals, 5 scientific books and 5 chapters of scientific books. He is on the Editorial Board of several reputable local and international journals and Editor-in-Chief of the renowned Sokoto Journal of Medical Laboratory Science. He is an expert reviewer to several international scientific journals. He has recently bagged the Specialist Certificate in Blood Transfusion Science Practice (SCTSP) from the British Blood Transfusion Society in the United Kingdom. He is a recipient of several awards and honors including the Margaret Kenwright Award from the British Blood Transfusion Society (BBTS). He is the President of Board of Directors of Nelon Medical Limited, UK.

Hypertension is a major public health problem that adversely affects the health status of individuals, families and communities. L-arginine levels of a total of 90 consecutively- recruited hypertensive subjects and 50 age-matched non-hypertensive controls were studied. Plasma from subjects and control participants were analyzed for L-arginine. The mean values of L-arginine level were significantly lower among the hypertensive subjects 174.33±78.31 μmol/L, compared to those of the 50 non-hypertensive controls 237.82±261.16 μmol/L (p=0.04). There was no statistically significant difference in the L-arginine levels of hypertensive subjects based on gender, age and ethnicity (p=0.87, 0.23 and 0.57), respectively. The L-arginine level was significantly higher among married hypertensive subjects (181.71±78.17 μmol/L) compared to single or unmarried subjects 130.62±65.99 μmol/L (p=0.03). The mean value of L-arginine level was significantly higher among hypertensive subjects with mild blood pressure 187.63±77.93 μmol/L, compared to those with high blood pressure 156.93±76.31 μmol/L. The difference however was not statistically significant (p=0.05). The findings from this study confirm that the level of L-arginine is lower among hypertensive subjects compared to non-hypertensive controls. Age, gender and ethnicity did not have a significant effect on the L-arginine levels of hypertensive subjects. L-arginine level was significantly lower among single hypertensive patient and those with markedly raised blood pressure. It is recommended that L-arginine supplement be prescribed to hypertensive patient as a prophylactic measure. There is need to enlighten hypertensive patients in the area on the need to maintain a balanced diet containing sufficient level of L-arginine.