Hematology Commons^™

Selective Lymphadenectomy In Endometrial Cancer: Retrospective Analysis Of Morbidity And Survival Data At A Tertiary Care Centre, Uzma Chishti, Aliya Aziz, Munazza Akhtar, Sana Sheikh

Department of Obstetrics & Gynaecology

Objective: To compare perioperative morbidity and survival data between patients with early-stage endometrial cancer who did or did not undergo selective lymphadenectomy.
Methods: Retrospective analysis of 180 patients with early-stage endometrial carcinoma treated between 1999 and 2008 was performed in Aga Khan University Hospital, Karachi, Pakistan.
Results: Data from 180 patients were analysed. The selective lymphadenectomy group contained 108 women (60%) and the no lymphadenectomy group contained 72 women (40%). The median number of lymph nodes removed was 9. The mean age and extent of disease, as assessed by staging, tumour size, myometrial invasion, and lymphovascular invasion were comparable between …

Dengue Hemorrhagic Fever Complicated By Intercostal Artery Hemorrhage., Syed Ahsan Ali, Sara Ahmed, Mehmood Riaz

Department of Medicine

Hemorrhagic manifestations are fairly common in Dengue hemorrhagic fever and are associated with increased mortality. During last few decades there have been increasing reports of Dengue infection with unusual manifestations. Here we present a case of dengue hemorrhagic fever complicated by spontaneous rupture of an intercostal artery leading to a large hematoma which was treated successfully with angio-embolization. To the authors' knowledge this is a first case of dengue hemorrhagic fever complicated by spontaneous intercostal artery hemorrhage.

Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron

Dartmouth Scholarship

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N=1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total …

Leishmania Donovani Bodies In Bone Marrow, Natasha Ali, Shabneez Hussain

Department of Pathology and Laboratory Medicine

We report a case of a 5-year-old female, resident of Afghanistan, who presented with fever and massive splenomegaly. Bone marrow revealed Leishmania donovani bodies (LD bodies) in macrophages characterized by a kinetoplast and characteristic double dot appearance. She was diagnosed as visceral leishmaniasis which is transmitted by sandflies (Phlebotomus).

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

Late Stages Of Hematopoiesis And B Cell Lymphopoiesis Are Regulated By Α-Synuclein, A Key Player In Parkinson's Disease, Wenbin Xiao, Afshin Shameli, Clifford V. Harding, Howard J. Meyerson, Robert W. Maitta

Faculty Scholarship

α-Synuclein plays a crucial role in Parkinson's disease and dementias defined as synucleinopathies. α-Synuclein is expressed in hematopoietic and immune cells, but its functions in hematopoiesis and immune responses are unknown. We utilized α-synuclein(-/-) (KO) mice to investigate its role in hematopoiesis and B cell lymphopoiesis. We demonstrated hematologic abnormalities including mild anemia, smaller platelets, lymphopenia but relatively normal early hematopoiesis in KO mice compared to wild-type (WT) as measured in hematopoietic stem cells and progenitors of the different cell lineages. However, the absolute number of B220(+)IgM(+) B cells in bone marrow was reduced by 4-fold in KO mice (WT: …

Heterogeneous Red Blood Cell Adhesion And Deformability In Sickle Cell Disease, Yunus Alapan, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

We present a microfluidic approach that allows simultaneous interrogation of RBC properties in physiological flow conditions at a single cell level. With this method, we studied healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs using whole blood samples from twelve subjects. We report that HbS-containing RBCs are heterogeneous in terms of adhesion and deformability in flow.

Quality Of Life In Patients With Thalassemia Major In A Developing Country., Sarah H. Siddiqui, Ruba Ishtiaq, Faiza Sajid, Raihan Sajid

Department of Medicine

Objective: To determine the problems faced by thalassemic patients in their personal, psychological and social life.

Study Design: A cross-sectional multi-centre survey.

Place and Duration of Study: Karachi, Lahore and Quetta Centres of Fatimid Foundation, from October 2009 to October 2010.

Methodology: An indigenously developed Qualifty of Life (QoL) questionnaire modified from SF-36 questionnaire was administered to 101 transfusion dependent subjects suffering from thalassemia major. Variables were analyzed using SPSS version 15 for descriptive statistics.

Results: The mean age of the subjects was 10.5 years ranging from 6 - 21 years. Less than one third of the patients felt that …

Correlational Studies Of Organophosphate Levels And Endocrine Disruption, Immunomodulation, And Altered Glucose Homeostasis In A Human Population Study, Carrie Mckean

Dissertations

Organophosphate (OP) pesticides have become the most widely used insecticides since the removal of organochlorine pesticides (“Ch4 Organophosphate Insecticides.pdf,” n.d.) and are generally the most toxic of all pesticides to vertebrates (Soltaninejad & Abdollahi, 2009). As a result, ongoing research has been aimed at further understanding potential health effects from exposure.

The aim of this dissertation research project is to investigate and characterize correlations of OP body burden with human health effects. This research involves an investigation into three pertinent areas concerning OP exposure: thyroid disruption, altered hematology biomarkers, and alterations of glucose homeostasis. Data under investigation come exclusively from …

Response To Imatinib Mesylate In Patients With Early Chronic Phase Chronic Myeloid Leukemia And Derivative Chromosome 9 Deletion Or Clonal Evolution, Mohammad Usman Shaikh, Tariq Moatter, Naveen Naz Syed, Natasha Bahadur Ali, Salman Adil

Department of Pathology and Laboratory Medicine

Objectives: The significance of clonal evolution and derivative chromosome 9 in Philadelphia-positive CML is not fully characterized and studies have yielded conflicting results. After working on emergence of clonal evolution from our region, we continued to find out the response of Imatinib Mesylate on such cases of CML treated in our center.
Materials and methods: We conducted a cross sectional, prospective analysis on response of Imatinib Mesylate on patients with Philadelphia positive chronic myeloid leukemia with clonal evolution treated from period of September 2007 till 2010. Patients were grouped on basis of cytogenetic analysis performed by conventional cytogenetic and fluorescence …

Steady Increment Of Immature Platelet Fraction Is Suppressed By Irradiation In Single-Donor Platelet Components During Storage, Hong Hong, Wenbin Xiao, Robert W. Maitta

Faculty Scholarship

Circulating immature platelet fraction (IPF) reflects real-time thrombopoiesis and correlates with platelet recovery from thrombocytopenic presentations. To understand the dynamics of IPF in platelet transfusions, we quantified the %-IPF in single-donor platelet components (SDP) during prolonged storage. %-IPF significantly increased from baseline by day 5 post-donation. Absolute IPF counts (A-IPC) had similar significant increments. However, gamma-irradiation suppressed the increments of %-IPF and A-IPC by >50%. Ultrastructural analysis of SDP units at day 10 showed well preserved morphology of immature platelets. Our findings suggest that IPF might actively expand ex-vivo and may have a longer shelf life than their mature counterparts. …

Phase 2 Trial Of Cpx-351, A Fixed 5:1 Molar Ratio Of Cytarabine/Daunorubicin, Vs Cytarabine/Daunorubicin In Older Adults With Untreated Aml, J. E. Lancet, J. E. Cortes, D. E. Hogge, M. S. Tallman, T. J. Kovacsovics, L. E. Damon, R. Komrokji, S. R. Solomon, J. E. Kolitz, E. J. Feldman, +3 Additional Authors

Journal Articles

CPX-351 is a liposomal formulation of cytarabine: daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2: 1 to first-line CPX-351 or 713 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission 1 incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs …

Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors

Journal Articles

DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall …

Prognostic Gene Mutations And Distinct Gene- And Microrna-Expression Signatures In Acute Myeloid Leukemia With A Sole Trisomy 8, H. Becker, K. Maharry, K. Mrozek, S. Volinia, A. K. Eisfeld, M. D. Radmacher, J. Kohlschmidt, K. H. Metzeler, J. E. Kolitz, C. D. Bloomfield, +14 Additional Authors

Journal Articles

No abstract provided.

Recombinant Interleukin-2 In Patients Aged Younger Than 60 Years With Acute Myeloid Leukemia In First Complete Remission, J. E. Kolitz, S. L. George, D. M. Benson, K. Maharry, G. Marcucci, R. Vij, B. L. Powell, S. L. Allen, D. J. Deangelo, Oncology Alliance Clinical Trials, +8 Additional Authors

Journal Articles

BACKGROUNDRecombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells. METHODSIn the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily …

Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors

Journal Articles

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL.

Effect Of Age On The Pharmacokinetics Of Busulfan In Patients Undergoing Hematopoietic Cell Transplantation; An Alliance Study (Calgb 10503, 19808, And 100103), J. H. Beumer, K. Owzar, L. D. Lewis, C. Jiang, J. L. Holleran, S. M. Christner, W. Blum, S. Devine, J. E. Kolitz, M. J. Egorin, +5 Additional Authors

Journal Articles

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (> 60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability. AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC-MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight …

Epigenetics Meets Genetics In Acute Myeloid Leukemia: Clinical Impact Of A Novel Seven-Gene Score, G. Marcucci, P. Yan, K. Maharry, D. Frankhouser, D. Nicolet, K. H. Metzeler, J. Kohlschmidt, K. Mrozek, J. E. Kolitz, C. D. Bloomfield, +21 Additional Authors

Journal Articles

Purpose Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML. Methods Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older ( 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and …

Lenalidomide And Rituximab For The Initial Treatment Of Patients With Chronic Lymphocytic Leukemia: A Multicenter Clinical-Translational Study From The Chronic Lymphocytic Leukemia Research Consortium, D. F. James, L. Werner, J. R. Brown, W. G. Wierda, J. C. Barrientos, J. E. Castro, A. Greaves, A. J. Johnson, K. R. Rai, T. J. Kipps, +2 Additional Authors

Journal Articles

Purpose Lenalidomide is an immunomodulatory agent with therapeutic activity in chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted synergistically with rituximab. The CLL Research Consortium initiated a phase II study to evaluate this combination in treatmentnaive patients. Patients and Methods Lenalidomide was initiated at 2.5 mg/day and was escalated based on treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was continued for seven cycles. Patients received allopurinol and aspirin for prophylaxis. Results Sixty-nine patients enrolled onto one of two age-specific …

Ighv1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React With Hiv-1 And Hepatitis C Virus Antigens As Well As Intestinal Commensal Bacteria, K. K. Hwang, A. M. Trama, D. M. Kozink, S. L. Allen, K. R. Rai, R. Catera, X. J. Yan, C. C. Chu, N. Chiorazzi, B. F. Haynes, +12 Additional Authors

Journal Articles

IGHV1-B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG(1) antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and …