Hematology Commons^™

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Frequency And Outcome Of Graft Versus Host Disease After Stem Cell Transplantation: A Six-Year Experience From A Tertiary Care Center In Pakistan, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

Objective: The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan.
Materials and Methods: Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 mu g twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15mg/m(2) on day +1 followed by 10mg/m(2) on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification.
Results: A total of 153 transplants were done from April 2004 to December 2011. Out of these were …

The Use Of Infliximab To Control Recurrent Cytokine Storms In Ebv-Associated Angioimmunoblastic Lymphoma And Hemophagocytic Syndrome, Sameh Gaballa, Emmanuel Besa, Onder Alpdogan

Department of Medical Oncology Faculty Papers

Introduction: Chronic active Epstein-Barr virus infection (CAEBV) has been implicated in several diseases including hemophagocytic lymphohistiocytosis (EBV-HLH) and lymphomas including Angioimmunoblastic T cell lymphoma. The exact mechanism by which EBV infection causes these complications is currently not well understood. EBV-HLH is a syndrome in which T-cells, NK cells and macrophages are aberrantly activated. Cytokine storms play a major role in cellular damage and organ dysfunction. In the event that the body is unable to clear the EBV viremia, dysregulated T, NK cells and macrophages continue to release cytokines leading to the accumulation of lymphohistiocytic infiltrates into organs and organ damage. …

Allogeneic Stem Cell Transplantation In Acute Myeloid Leukemia, Natasha Bahadur Ali, Salman Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients). Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

Sickle Cell Pain: A Critical Reappraisal., Samir K. Ballas, Kalpna Gupta, Patricia Adams-Graves

Department of Medicine Faculty Papers

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute …

Temozolomide For Relapsed Primary Cns Lymphoma., Asif Husain Osmani, Nehal L Masood

Department of Medicine

Primary CNS lymphoma (PCNSL) is an aggressive form of non-Hodgkin's lymphoma that accounts for 3% of all primary brain tumours. No clear risk factors for PCNSL in immunocompetent patients are known. The disease is more common in men and in elderly persons. Patients with AIDS who have low CD4+ counts are at the greatest risk for PCNSL. Virtually all PCNSLs in patients with AIDS express an Epstein-Barr virus (EBV)-related genome. PCNSL is less frequently associated with EBV in patients without AIDS. A 42 years old gentleman diagnosed with primary CNS lymphoma with negative serological test for human immunodeficiency virus was …

Drugs For Preventing Red Blood Cell Dehydration In People With Sickle Cell Disease., Srikanth Nagalla, Samir K Ballas

Department of Medicine Faculty Papers

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials …

Clinical Significance Of Maternal Anti-Cw Antibodies: A Review Of Three Cases And Literature, Shabneez Malik, Bushra Moiz

Department of Pathology and Laboratory Medicine

Anti Cw antibody is a low frequency immunoglobulin (IgG) against red cell antigen- Cw. It is clinically significant and may cause haemolytic disease of the newborn. Due to its low frequency, it is not included in routine antenatal antibody screening panel. The incidence of Anti Cw antibodies has not been reported in our population. Here, we describe the clinical and laboratory spectra of three pregnant women having low titres anti Cw antibodies. Fortunately, haemolytic disease of the newborn was not encountered in any case.

Adjunct Primer For The Use Of National Comprehensive Cancer Network Guidelines For The Surgical Management Of Cutaneous Malignant Melanoma Patients., Edibaldo Silva

Journal Articles: Oncology and Hematology

Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from best practice patterns throughout the country. The study, which analyzed the SEER records of 35,126 stage I to III cutaneous malignant melanoma patients treated from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network (NCCN) therapeutic resection margins occurred in less than 36% of patients. Similarly, considerable variation in the quality of melanoma care in the United States when assessed using 26 quality indicators drawn by a panel of melanoma experts was independently reported. These …

Hemoglobin E Syndromes In Pakistani Population., Bushra Moiz, Amna Nasir, Anila Rashid, Tariq Moatter, Mashhooda Rasool Hashmi

Department of Pathology and Laboratory Medicine

Background:Hemoglobin E is an important hemoglobin variant with a worldwide distribution. A number of hemoglobinopathies have been reported from Pakistan. However a comprehensive description of hemoglobin E syndromes for the country was never made. This study aimed to describe various hemoglobin E disorders based on hematological parameters and chromatography. The sub-aim was to characterize hemoglobin E at molecular level.

Methods:

This was a hospital based study conducted prospectively for a period of one year extending from January 1 to December 31, 2008. EDTA blood samples were analyzed for completed blood counts and hemoglobin variants through automated hematology analyzer and …

Phase I Study Of Bosutinib, A Src/Abl Tyrosine Kinase Inhibitor, Administered To Patients With Advanced Solid Tumors, Adil Daud, Smitha Krishnamurthi, Mansoor Saleh, Barbara Gitlitz, Mitesh Borad, Philip Gold, Elena Chiorean, Gregory Springett, Richat Abbas, Shefali Agarwal

Haematology and Oncology, East Africa

Purpose: Bosutinib, a potent ATP-competitive, quinolinecarbonitrile Src/Abl kinase inhibitor, was tested in this first-in-human phase I trial in patients with advanced solid tumor malignancies.

Patients and Methods: This trial was conducted in 2 parts. In part 1 (dose escalation), increasing oral bosutinib doses were administered using a 3 + 3 design. In part 2 (dose expansion), approximately 30 patients each with refractory colorectal, pancreas, or non–small cell lung cancer were treated at the recommended phase II dose (RP2D). Primary efficacy endpoints for part 2 were median progression-free survival (colorectal and non–small cell lung) and median overall survival (pancreas).

Results: In …

Acute Myeloid Leukaemia In Children: Experience At A Tertiary Care Facility Of Pakistan, Zehra Fadoo, Naureen Mushtaq, Saima Alvi, Muhammad Ali

Department of Paediatrics and Child Health

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan.

Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review.

Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of > 100,000 was seen in 19% …

Newer Agents In Antiplatelet Therapy: A Review., Jennifer Yeung, Michael Holinstat

Cardeza Foundation for Hematologic Research

Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use …

Regulation Of Platelet Exoctosis And Its Role In Diseases, Rania A. Al Hawas

Theses and Dissertations--Health and Clinical Sciences

In addition to their role in hemostasis, platelets appear to contribute to vascular inflammatory diseases. Platelets achieve this through the secretion of various prothrombotic and pro-inflammatory molecules. Platelet secretion is mediated by integral membrane proteins called Soluble NSF Attachment protein REceptors (SNAREs). SNAREs come from both granule/vesicle membranes (v-SNAREs) and target membranes (t-SNAREs) to form a trans-bilayer complex that promotes membrane fusion and subsequent granule cargo release. The work described in this dissertation dissects various, yet related aspects of platelet secretion in both physiological relevant and pathological circumstances.

Atherosclerosis is a leading cause of death in the westernized countries and …

Utility Of Fdg Pet-Ct Scan In Determining Pathological Response To Neo-Adjuvant Chemo-Radiation Therapy In Non-Small Cell Lung Cancer (Nsclc), Eliot L. Friedman Md, Michael F. Szwerc Md, Robert Kruklitis Md, Michael J. Weiss Mph, Robert Rienzo Md, Wen Young Md

Department of Medicine

No abstract provided.

Effects Of Arterial Strain And Stress In The Prediction Of Restenosis Risk: Computer Modeling Of Stent Trials, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose — In-stenting restenosis is one of the major complications after stenting. Clinical trials of various stent designs have reported different restenosis rates. However, quantitative correlation between stent features and restenosis statistics is scant. In this work, it is hypothesized that stress concentrations on arterial wall caused artery injury, which initiates restenosis. The goal is to assess the correlation between stent-induced arterial stress and strain and the documented restenosis rates.

Methods — Six commercially available stents, including balloon-expandable stents and self-expanding stents, were virtually implanted into the arteries through finite element method. The resulted peak Von Mises stress, principal stress, …

Phase Iii Study Of Doxorubicin/Cyclophosphamide With Concomitant Versus Sequential Docetaxel As Adjuvant Treatment In Patients With Human Epidermal Growth Factor Receptor 2–Normal, Node-Positive Breast Cancer: Bcirg-005 Trial, Wolfgang Eiermann, Tadeusz Pienkowski, John Crown, Saeed Sadeghi, Miguel Martin, Arlene Chan, Mansoor Saleh, Sandeep Sehdev, Louise Provencher, Vladimir Semiglazov

Haematology and Oncology, East Africa

Purpose: Anthracyclines, taxanes, and alkylating agents are among the most active agents in treatment of adjuvant breast cancer (BC), but the optimal schedule for their administration is unknown. We performed an adjuvant trial to compare the sequential regimen of doxorubicin with cyclophosphamide (AC) followed by docetaxel (ie, AC>T) with the combination regimen of TAC.

Patients and Methods: Women with node-positive, human epidermal growth factor receptor 2–nonamplified, operable BC were stratified by number of axillary nodes and hormone receptor status and were randomly assigned to adjuvant chemotherapy with six cycles of TAC (75/50/500 mg/m2 every 3 weeks) or four cycles …

Transfection Of Human Platelets With Short Interfering Rna., Wei Hong, Altaf A Kondkar, Srikanth Nagalla, Wolfgang Bergmeier, Ying Jin, Jay Herman, Paul Bray

Cardeza Foundation for Hematologic Research

Platelets contain mRNAs and are capable of translating mRNA into protein, and it has been previously demonstrated that platelets increase their levels of integrin β3 overtime while in blood bank storage conditions. We are unaware of prior attempts to introduce nucleic acids into platelets. Considering the potential clinical and research utility of manipulating platelet gene expression, we tested whether small interfering RNAs (siRNAs) could be transfected into normal human platelets. Multiple conditions were tested, including lipofectamine versus electroporation, different amounts of siRNA, the effect of different buffers and the presence of plasma during transfection, and the time for optimal siRNA …

Randomized Phase Iii Trial Of Paclitaxel/Carboplatin With Or Without Pf-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment For Advanced Non–Small-Cell Lung Cancer, Vera Hirsh, Luis Paz-Ares, Michael Boyer, Rafael Rosell, Gary Middleton, Wilfried Eberhardt, Aleksandra Szczesna, Pavel Reiterer, Mansoor Saleh, Oscar Arrieta

Haematology and Oncology, East Africa

Purpose: This phase III study examined efficacy of the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m2 and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS).

Results: Baseline demographics …

Sunitinib Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel For First-Line Treatment Of Patients With Advanced Breast Cancer: A Phase Iii, Randomized, Open-Label Trial, Nicholas Robert, Mansoor Saleh, Devchand Paul, Daniele Generali, Laurent Gressot, Mehmet Copur, Adam Brufsky, Susan Minton, Jeffrey Giguere, John W. Smith Ii

Haematology and Oncology, East Africa

Introduction: A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2− advanced breast cancer.

Patients and Methods: Patients with HER2− advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m2 every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks.

Results: The trial was terminated early …

Septic Shock: Current Management And New Therapeutic Frontiers, R. Phillip Dellinger, Md

Division of Pulmonary, Allergy, and Critical Care Medicine Presentations and Grand Rounds

No audio is available for this presentation.

Dr. R. Phillip Dellinger is a Professor of Medicine who holds a faculty appointment in the Division of Pulmonary and Critical Care Medicine at the Robert Wood Johnson School of Medicine, University of Medicine and Dentistry of New Jersey. He is also the Vice-Chair, Department of Medicine and the Director, Medical/Surgical/Cardiovascular Surgical Intensive Care Unit at the Cooper Medical Center in Camden New Jersey. In 2006-2007, he was selected as South Jersey Top Docs by South Jersey Magazine. Dr. Dellinger's interests are in the treatment and outcomes of septic shock.

Incidence And Impact Of Baseline Electrolyte Abnormalities In Patients Admitted With Chemotherapy Induced Febrile Neutropenia., Asim Jamal Shaikh, Samira Ahmed Bawany, Nehal Masood, Ausaf Ahmed Khan, Ahmed Nadeem Abbasi, Syed Najeeb Niamutullah, Adnan Zaidi, Salman Adil, Shiyam Kumar

Section of Haematology/Oncology

Background: Febrile neutropenia (FN) and myelosupression remain a challenging oncologic medical emergency and dose limiting toxicity associated with chemotherapy for cancers. Various factors are known to affect the outcomes for Patients diagnosed with FN. Electrolyte abnormalities have commonly been observed, but the real incidence and their impact has been only scarcely studied in literature. Methods: This was a prospective, observational study. A total of two hundred and fifteen (215) Patients admitted between January 2007 and August 2008 were included. Analysis of data was made using SPSS version16.0. Toxicity profile was graded according to CTC version 3.0. Results: Almost equal number …

The Nurse's Knowledge Of Blood Conservation As A Part Of Blood Management, Lindsey Putnam Austin

Nursing Theses and Capstone Projects

Medicine has historically regarded blood transfusion as an integral component of major surgery or illness. However, clinical studies have shown that allogeneic blood transfusions are associated with increased morbidity and decreased survival. Knowledge of this research and the concepts of blood conservation so as to avoid unnecessary blood transfusions is needed in order to deliver holistic care and serve as patient advocate. This knowledge reaches every specialty of nursing care.

This study of the nurse's knowledge of blood conservation as a part of blood management utilizes The Conservation Model developed by Myra E. Levine in 1973. Levine's work is a …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

Eltrombopag For Management Of Chronic Immune Thrombocytopenia (Raise): A 6-Month, Randomised, Phase 3 Study, Gregory Cheng, Mansoor Saleh, Claus Marcher, Sandra Vasey, Bhabita Mayer, Manuel Aivado, Michael Arning, Nicole Stone, James Bussel

Haematology and Oncology, East Africa

Background: Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period.

Methods: We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months’ duration who had baseline platelet counts lower than 30 000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a …

Pemetrexed With Or Without Matuzumab As Second-Line Treatment For Patients With Stage Iiib/Iv Non-Small Cell Lung Cancer, Joan Schiller, Joachim Von Pawel, Philipp Schütt, Rafat Ansari, Michael Bijoy Thomas, Mansoor Saleh, Robert D. Mccroskey, Wolfgang Pfeife, Thomas Marsland, Goetz Kloecker

Haematology and Oncology, East Africa

Introduction: This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer.

Methods: Patients received pemetrexed 500 mg/m2 every 3 weeks either alone (n = 50) or in combination with matuzumab at either 800 mg weekly (n = 51) or 1600 mg every 3 weeks (n = 47). The primary end point was objective response, as assessed by an independent review committee.

Results: Tumor EGFR expression was detected in 87% of randomized patients. The objective response rate …

Phase Iii, Randomized, Double-Blind, Placebo-Controlled Evaluation Of Pregabalin For Alleviating Hot Flashes, N07c1, Charles L. Loprinzi, Rui Qin, Ernie P. Baclueva, Donald J. Jurgens

Articles

PURPOSE:

Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes.

PATIENTS AND METHODS:

A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 …

Rhnull: A Rare Blood Group Phenotype, Adnan Qureshi, Muhammad Salman, Bushra Moiz

Section of Internal Medicine

Rhnull phenotype is a rare blood group characterized by the lack of expression of all Rh antigens (D, C, c, E and e) on the red cells. The phenotype is further classified into the regulator and amorph type based on underlying genetic defect. The clinical significance of its recognition is that such patients suffer from Rhnull syndrome associated with osmotically fragile red cells called stomatocytes with subsequent chronic haemolytic anaemia of varying degree. Another importance is that such subjects readily form alloantibodies on exposure to Rh antigens. We report herein rare Rhaull phenotype in a young pregnant female which was …

Acute Lymphoblastic Leukemia Subsequent To Temozolomide Use In A 26-Year-Old Man: A Case Report., Asim Jamal Shaikh, Nehal Masood

Section of Haematology/Oncology

Introduction: We report the development of acute lymphoblastic leukemia in a Patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported. Case Presentation: A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide. Conclusion: Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, …

Proteomic Analysis Of Plasma Exosomes Reveals That Kappa:Lambda Ratio Predicts Severe Acute Graft-Versus-Host Disease, Joseph Alge

MUSC Theses and Dissertations

Background: Acute Graft-Versus-Host disease (acute GVH D) is an often fatal, inflammatory multi-organ disease driven by T cell alloreactivity directed toward host tissues. One of the chief obstacles to improving outcomes of acute GVHD patients is timely diagnosis. Currently, acute GVHD is diagnosed clinically, once the symptoms are fully manifested. However, it is clear that important immunologic events occur prior to the occurrence of symptoms. A biomarker that could predict disease during the asymptomatic period could improve patient outcomes by allowing for earlier intensification of immunosuppressant therapy. Exosomes are an attractive target for acute GVHD biomarker discovery. They contain a …