Medicine and Health Sciences Commons^™

Enormous, Rapidly Growing Breast Mass., Vivek Verma, Sanjay Muttineni, Rajesh R. Kulkarni, Edibaldo Silva, William W. West, Robert B. Thompson

Journal Articles: Oncology and Hematology

BACKGROUND: Signs and symptoms of a rapidly enlarging breast mass are not only important for all clinicians to recognize and assess, but also are not uncommon occurrences. We describe a similar but unique case that developed into an enormous, 36 cm exophytic mass.

CASE PRESENTATION: A 51-year-old woman with history of psychiatric conditions presented for signs and symptoms of sepsis. It was determined that the source was an enormous 36 cm mass originating from the breast/chest wall. After stabilizing the patient with antibiotics, she underwent successful resection. Surgical margins were positive, and histopathology demonstrated bland spindle cells with stromal overgrowth. …

A Critical Role For Alpha-Synuclein In Development And Function Of T Lymphocytes, Afshin Shameli, Wenbin Xiao, Yan Zheng, Susan Shyu, John Sumodi, Howard J. Meyerson, Clifford V. Harding, Robert W. Maitta

Faculty Scholarship

Alpha-synuclein is highly expressed in the central nervous system and plays an important role in pathogenesis of neurodegenerative disorders such as Parkinson's disease and Lewy body dementia. Previous studies have demonstrated the expression of α-synuclein in hematopoietic elements and peripheral blood mononuclear cells, although its roles in hematopoiesis and adaptive immunity are not studied. Using an α-synuclein knock out (KO) mouse model, we have recently shown that α-synuclein deficiency is associated with a mild defect in late stages of hematopoiesis. More importantly, we demonstrated a marked defect in B lymphocyte development and IgG, but not IgM production in these mice. …

The Paradox Of The Serrated Sickle Erythrocyte: The Importance Of The Red Blood Cell Membrane Topography., Samir K. Ballas, Philippe Connes

Cardeza Foundation for Hematologic Research

Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium.

A Rare Haemoglobin Variant Identified As K Woolwich In A Pakistani Male, Sidra Asad Ali, Natasha Bahadur Ali

Department of Pathology and Laboratory Medicine

Haemoglobin (Hb) K Woolwich is a rare Hb variant which was first described in a family from West Indies and its occurrence was later reported mainly in Black families from many African countries. We report a case of a young male who came for evaluation of anemia. His complete blood count showed hypochromic, microcytic anemia and his serum ferritin was low. Hb electrophoresis done as part of initial workup showed an abnormal band which moved faster than HbA. For further evaluation, Hb analysis by high performance liquid chromatography was subsequently performed and revealed Hb K Woolwich. This is a rare …

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.

Risk Factors Of Pulmonary Hypertension In Brazilian Patients With Sickle Cell Anemia., Clarisse Lopes De Castro Lobo, Emilia Matos Do Nascimento, Renato Abelha, Ana Maria Mach Queiroz, Philippe Connes, Gilberto Perez Cardoso, Samir K. Ballas

Cardeza Foundation for Hematologic Research

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Mary Insana Fisher

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting. When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

Rituximab Maintenance Therapy In Diffuse Large B-Cell Lymphoma: Is Xy The Most Important Variable?, Matthew A. Lunning, James O. Armitage

Journal Articles: Oncology and Hematology

No abstract provided.

Glanzmann's Thrombasthenia: Pathogenesis, Diagnosis, And Current And Emerging Treatment Options, Tia Solh, Ashley Botsford, Melhem Solh

PCOM Scholarly Papers

Glanzmann’s thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa) has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and …

Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Re-Examination Of 30-Day Survival And Relapse Rates In Patients With Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome, Cassiana E. Bittencourt, Jennifer P. Ha, Robert W. Maitta

Faculty Scholarship

Background and Objectives: Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are characterized by microangiopathic hemolytic anemia and thrombocytopenia. Interestingly, markedly different survival rates have been reported despite increases in survivability. We studied TTP-HUS 30-day mortality and relapse rates of patients who received TPE at our institution and compared them to published data. Patients and Methods: Retrospective study analyzed 30-day mortality and relapse rates attributed to TTP-HUS from 01/01/2008 to 12/31/2012 and compared them to comparable literature reporting mortality and survival. Studies describing other etiologies for TPE and different mortality time interval were excluded. Results: Fifty-nine patients were analyzed …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations & Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra

Dissertations & Theses (Open Access)

The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …

Glanzmann’S Thrombasthenia Diagnosed Following Knee Arthroscopy, John Zvijac, Gary Kiebzak

All Publications

A 41-year-old man with an unremarkable medical history presented with a painful knee after a sports injury. He was diagnosed with a medial meniscal tear. Symptoms did not abate after 6 months of physical therapy, and he underwent arthroscopic partial medial meniscectomy. A week after beginning physical therapy he experienced a knee effusion, decreased ROM, and inability to flex his quadriceps. His knee was aspirated. Blood tests were ordered and his complete blood count, liver functions tests, and INR/PTT were normal. The patient had recurrent effusions requiring three additional joint aspirations. Ten weeks after the initial surgery, the patient underwent …

C-Anca Positive Necrotizing Crescentic Glomerulonephritis With Linear Immunoglobulin Staining, Akshita Mehta

GW Research Days 2015

Necrotizing crescentic glomerulonephritis is found in anti-glomerular basement membrane (GBM) disease (Type 1), immune complex (Type 2) deposition and anti-neutrophil cytoplasmic (ANCA)-related disease (Type 3).

ANCA positive glomerulonephritis is typically characterized on renal biopsy as pauci-immune, with mild or absent glomerular staining for immunoglobulin, or complement staining by immunofluorescence.

Rare cases of concomitant p-ANCA plus linear immunofluorescence pattern staining have been discussed, however none with prior association with c-ANCA.

We report a case of systemic c-ANCA pulmonary-renal syndrome with anti-GBM-disease-typical linear staining on renal biopsy immunofluorescence.

A Very Rare Cause Of Pancytopenia., Talal Alzahrani, Dana Kay, Kelly Zhang, Linda Lesky

GW Research Days 2015

INTRODUCTION:

Levetiracetam (Keppra) is a pyrrolidone derivative and acts as an anti-epileptic medication by modulating neurotransmitter release. Pancytopenia is a very rare adverse effect caused by levetiracetam. There are fewer than four case reports in the medical literature discussing the association between levetiracetam and pancytopenia. The pathogenesis behind this relationship is unclear. Therefore, this case will serve to spread awareness of a rare cause of pancytopenia and to hypothesize how this medication causes pancytopenia.

CASE REPORT:

A brain MRI of a 79-year-old female with a medical history of hypertension, Type II diabetes, and CVA revealed a right temporoparietal mass. She …

Emerging Drugs For Sickle Cell Anemia., Priya C Singh, Samir K. Ballas

Cardeza Foundation for Hematologic Research

INTRODUCTION: The search for effective therapeutic interventions for sickle cell disease (SCD) has been an ongoing endeavor for over 50 years. During this period, only hydroxyurea (HU), which received US FDA approval in February 1998, was identified as an effective therapeutic agent in preventing or ameliorating the frequency of vaso-occlusive crises, acute chest syndrome and the need for blood transfusion. Approximately 25% of patients with sickle cell anemia (SCA), however, do not respond to HU and some patients experiencing serious side effects of this chemotherapeutic agent. Nevertheless, the success of HU opened the sluice gates to identify other effective drug …

The Effect Of Caffeine On Cisplatin-Induced Apoptosis Of Lung Cancer Cells, Gan Wang, Vanitha Bhoopalan, David Wang, Le Wang, Xiaoxin Xu

Institute for Environmental Health Sciences

Background: Cisplatin is an important DNA-damaging anticancer drug that has been used to treat many cancer types. However, the effectiveness of cisplatin treatment diminishes quickly as cancer cells develop resistance to the drug, which eventually results in treatment failure. Caffeine is an ingredient contained in many food sources. Caffeine can inhibit activities of both ATM and ATR, two important protein kinases involved in DNA damage-induced cell cycle arrest and apoptosis. The effect of caffeine on cisplatin-based cancer treatment is not well known.

Methods: Caspase-3 activation and cell growth inhibition assays were used to determine the effect of caffeine …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Harold L. Merriman

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting. When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

Morphine For The Treatment Of Pain In Sickle Cell Disease., Mihir Gupta, Lilian Msambichaka, Samir K. Ballas, Kalpna Gupta

Cardeza Foundation for Hematologic Research

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. …

Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel

Journal Articles: Oncology and Hematology

No abstract provided.

Romidepsin In Peripheral And Cutaneous T-Cell Lymphoma: Mechanistic Implications From Clinical And Correlative Data, S. E. Bates, R. Eisch, A. Ling, D. Rosing, M. Turner, S. Pittaluga, H. M. Prince, M. H. Kirschbaum, S. L. Allen, R. L. Piekarz, +15 Additional Authors

Journal Articles

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients …

Therapeutic Potential Of New B Cell-Targeted Agents In The Treatment Of Elderly And Unfit Patients With Chronic Lymphocytic Leukemia, K. R. Rai

Journal Articles

Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients >= 65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential …

Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide, D. Sanford, F. Lo-Coco, M. A. Sanz, E. Di Bona, S. Coutre, J. K. Altman, M. Wetzler, S. L. Allen, F. Ravandi, H. Kantarjian, J. E. Cortes

Journal Articles

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m2 /d) during induction and for up to six cycles of consolidation. The …

Management Of Chronic Lymphocytic Leukemia In The Elderly, J. C. Barrientos

Journal Articles

No abstract provided.

Phase Ii, Multicenter, Randomized Trial Of Cpx-351 (Cytarabine: Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adults With First Relapse Aml, J. E. Cortes, S. L. Goldberg, E. J. Feldman, D. A. Rizzeri, D. E. Hogge, M. Larson, A. Pigneux, C. Recher, G. Schiller, J. E. Kolitz, +3 Additional Authors

Journal Articles

BACKGROUNDCPX-351 is a liposome-encapsulated fixed-molar-ratio formulation of cytarabine and daunorubicin that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. METHODSThis phase II study randomized 125 patients 2:1 to CPX-351 or investigators' choice of first salvage chemotherapy. Patients with acute myeloid leukemia (AML) in first relapse after initial Complete Remission (CR) lasting 1 month were stratified per the European Prognostic Index (EPI) into favorable, intermediate, and poor-risk groups based on duration of first CR, cytogenetics, age, and transplant history. Control salvage treatment was usually based on cytarabine and anthracycline, often with 1 or more additional agents. Survival at 1 year …

Feasibility And Cardiac Safety Of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (Neo) Adjuvant Therapy For Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer, I. E. Krop, T. M. Suter, C. T. Dang, L. Dirix, G. Romieu, C. Zamagni, M. L. Citron, M. Campone, N. Xu, M. Smitt, L. Gianni

Journal Articles

Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) >= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without …

Identification And Characterization Of Distinct Il-17f Expression Patterns And Signaling Pathways In Chronic Lymphocytic Leukemia And Normal B Lymphocytes, B. Sherry, P. Jain, P. Y. Chiu, L. Leung, S. L. Allen, J. E. Kolitz, K. R. Rai, J. Barrientos, S. Liang, R. Hawtin, N. Chiorazzi

Journal Articles

Chronic lymphocytic leukemia (CLL) is characterized by a progressive accumulation of B lymphocytes. T cell abnormalities are a common feature of CLL and contribute to impaired immune function in these patients. T cells are ineffective in eliminating the leukemic clone and may actually promote tumor growth and survival. Previous work from our laboratory documented elevated circulating levels of IL-17A-producing Th17 cells in CLL patients as compared to healthy age-matched control subjects. These high circulating Th17 levels associated with better prognostic markers and significantly longer overall survival, even among patients whose clones used unmutated IGHVs (U-CLL). Recent studies suggest that Th17 …

Integrating Targeted Drugs With Taxanes And Platinums: Opportunities And Challenges, D. Kudlowitz, E. Teplinsky, F. Muggia

Journal Articles

In ovarian cancer, multiple attempts to adjust the standard taxane/platinum doublet by adding cytotoxic therapy or varying scheduling, dosage, and delivery have been met with limited success. Alternative methods to improve the grim prognosis of ovarian cancer, including molecular therapies, are currently under investigation. Efforts have been made to study tyrosine kinase inhibitors (including imatinib and pazopanib), Src kinase inhibitors and histone deacetylase inhibitors (HDACi) in combination with taxanes/platinums in order to improve efficacy. Unfortunately, while many pre-clinical and early phase clinical trials argue that the utilization of these molecular targets may enhance survival, only modest benefit has been seen …

Introduction: Moving Beyond Chemotherapy, F. Muggia, E. Teplinsky

Journal Articles

Epithelial ovarian cancer and related cancers arising in extrauterine Mullerian epithelium are generally chemosensitive—particularly to the platinum drugs, cisplatin and carboplatin, that form the backbone of first-line treatments upon diagnosis even at early stages. Doublets of platinums with paclitaxel have represented the standard-of-care since the late 1990s, with further notable advances taking place by intraperitoneal administration (in Gynecologic Oncology Group studies) after optimal surgical cytoreduction is achieved, and by divided doses of paclitaxel (in a Japanese GOG study). Adding another agent to improve on these results has otherwise proven to be quite challenging. Nevertheless, continued forays into introducing ‘targeted therapies’ …