Hematology Commons^™

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

Obstructive Jaundice Due To Pancreatic Involvement As An Initial Presentation Of Adult Acute Lymphoblastic Leukemia., Oreoluwa Oladiran, Ifeanyi Nwosu

Reading Hospital Internal Medicine Residency

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid disorders characterized by monoclonal proliferation and expansion of immature lymphoid cells in the bone marrow, blood, and other organs. It commonly presents with nonspecific symptoms such as lethargy, easy bruising, and weight loss. In this article, we present the case of a 48-year-old male who presented to the hospital with painless jaundice resulting from pancreatic infiltration, initially thought to be due to pancreatic or hepatobiliary malignancy. He was later diagnosed with ALL by lymph node biopsy and peripheral blood flow cytometry immunophenotyping and was transferred to a cancer treatment centre …

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

Cardeza Foundation for Hematologic Research

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. This is an updated version of a previously published review.

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 …

Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, Mmc Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operational Transformation

MANAGEMENT OF O NEGATIVE BLOOD USE

O registered blood cells are the universal donor but it comprises only 7% of the blood supply. As a result, inappropriate use can result in shortages.

At an academic tertiary care medical center, a performance improvement goal was established that O negative blood cells would make up less than 12% of all blood type transfused by the end of their fiscal year.

A root cause analysis established reasons for the use of O negative blood cells. A number of countermeasures were initiated using the plan, do, study, act (PDSA) problem solving model. Using newly …

Ultrastructural Changes In Peripheral Blood Leukocytes In Α-Synuclein Knockout Mice, Hammad Tashkandi, Afshin Shameli, Clifford V. Harding, Robert W. Maitta

Faculty Scholarship

Effects of α-synuclein deficiency on cellular blood components have not been extensively investigated. This study evaluated ultrastructural changes of leukocytes in α-synuclein knockout (KO) mice using electron microscopy (EM). The following ultrastructural characteristics were quantified in leukocytes: mitochondria, primary granules, specific granules (SG), Golgi apparatus (GA), inclusions, rough-endoplasmic reticulum (RER), smooth-endoplasmic reticulum (SER), and cellular projections (CP). EM showed increased numbers or amounts of SG, inclusions, and SER in KO group (5.3 ± 4.5 in WT vs. 14.1 ± 10.3 in KO, p = 0.02; 0.4 ± 0.9 in WT vs. 3.2 ± 2.8 in KO, p = 0.007; and …

Recurrent Autoimmune Hemolytic Anemia In Splenic Marginal Zone Lymphoma., Oreoluwa Oladiran, Rashmi Dhital, Anthony Donato

Reading Hospital Internal Medicine Residency

Autoimmune hemolytic anemia (AIHA) is a condition associated with an extensive differential diagnosis that includes lymphoid malignancies. Although AIHA occurs in about 10-25% of patients with chronic lymphocytic leukemia, it is also reported to occur in all of the other lymphoid subtypes. In this article, we report a case of recurrent AIHA in a 67-year-old woman with two acute episodes of hemolysis separated by 3 years of hematologic remission. Both episodes were severe enough to require blood transfusion, oral steroids, and rituximab. Bone marrow biopsy and immunophenotyping using flow cytometry done during both admissions confirmed the presence of splenic marginal …

Patient Throughput Time In The Emergency Department: Can Obtaining Blood Specimens In A Pre-Hospital Setting Increase Timeliness?, Arielle Rancourt

Interprofessional Research and Innovations Council

Patient Throughput Time in the Emergency Department:

Can Obtaining Blood Specimens in a Pre-hospital Setting Increase Timeliness?

Arielle Rancourt RN

Abstract

The Emergency Department (ED) at Mid Coast Hospital currently follows a practice in obtaining blood specimens in-hospital by emergency department staff; this is done despite the ability of pre-hospital personnel to obtain specimens at the time of intravenous catheter insertions. Our current practice may not be the most effective and timely method. Studies showed that there was no increase in hemolysis of blood specimens drawn by Emergency Medical Services (EMS), and that laboratory results were received quicker when blood …

Α-Synuclein Concentration Increases Over Time In Plasma Supernatant Of Single Donor Platelets, Catherine M. Stefaniuk, Clifford V. Harding, Robert W. Maitta

Faculty Scholarship

OBJECTIVES: In platelets, α-synuclein is important in calcium-dependent granule release. Notably, cells release α-synuclein in setting of cell damage or death. Therefore, we investigated α-synuclein levels in plasma of single donor platelet (SDP) units during storage. METHODS: Aliquots were obtained from same SDP units for 7 days from day of donation. Additionally, randomly sampled SDP units at same storage time points were also assayed by enzyme-linked immunosorbent assay. RESULTS: α-Synuclein in SDP plasma increased continuously over time at each assayed time point. Significant increases were measured on day 3 (11.7 ± 9.6 ng/mL, P = 0.025), day 5 (15.3 ± …

Lenalidomide Consolidation Benefits Patients With Cll Receiving Chemoimmunotherapy: Results For Calgb 10404 (Alliance)., John C Byrd, Amy S Ruppert, Nyla A Heerema, Alese E Halvorson, Eva Hoke, Mitchell R Smith, John E Godwin, Stephen Couban, Todd A Fehniger, Michael J Thirman, Martin S Tallman, Frederick R Appelbaum, Richard M Stone, Sue Robinson, Julie E Chang, Sumithra J Mandrekar, Richard A Larson

Articles, Abstracts, and Reports

Prior to novel targeted agents for chronic lymphocytic leukemia (CLL), the best chemoimmunotherapy regimen in patients with non-del(11q) disease was unclear. The role of lenalidomide was also not defined. This phase 2 study randomized 342 untreated patients with non-del(11q) CLL requiring therapy to fludarabine plus rituximab (FR; n = 123), FR plus lenalidomide consolidation (FR+L; n = 109), or FR plus cyclophosphamide (FCR; n = 110) and compared 2-year progression-free survival (PFS) rates of each to the historical control rate with FC (60%). Patients with del(11q) in at least 20% of pretreatment cells continued with FCR (n = 27) or …

Distribution Of Chromosomal Abnormalities Commonly Observed In Adult Acute Myeloid Leukemia In Pakistan As Predictors Of Prognosis, Muhammad Shariq Shaikh, Zeeshan Ansar Ahmed, Mohammad Usman Shaikh, Salman Naseem Adil, Mohammad Khurshid, Tariq Moatter, Anila Rashid, Farheen Karim, Ahmed Raheem, Natasha Ali

Department of Pathology and Laboratory Medicine

Objectives: The heterogenous response to treatment in acute myeloid leukemia (AML) can be attributed largely to the difference in cytogenetic features identified in between cases. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of these patients. The study was conducted to determine the distribution of cytogenetic abnormalities in Pakistani adult patients with AML in order to have insights regarding behavior of the disease.
Methods: A …

Biomimetic Post-Capillary Venule Expansions For Leukocyte Adhesion Studies, Bryan L. Benson, Lucy Li, Jay T. Myers, R. Dixon Dorand, Umut A. Gurkan, Alex Y. Huang

Faculty Scholarship

Leukocyte adhesion and extravasation are maximal near the transition from capillary to post-capillary venule, and are strongly influenced by a confluence of scale-dependent physical effects. Mimicking the scale of physiological vessels using in vitro microfluidic systems allows the capture of these effects on leukocyte adhesion assays, but imposes practical limits on reproducibility and reliable quantification. Here we present a microfluidic platform that provides multiple (54–512) technical replicates within a 15-minute sample collection time, coupled with an automated computer vision analysis pipeline that captures leukocyte adhesion probabilities as a function of shear and extensional stresses. We report that in post-capillary channels …

Multifactorial Aetiology For Non-Uremic Calciphylaxis: A Case Report., Sijan Basnet, Niranjan Tachamo, Rashmi Dhital, Biswaraj Tharu

Reading Hospital Internal Medicine Residency

Calciphylaxis is commonly associated with end-stage renal disease patients on haemodialysis. We present a rare case of calciphylaxis in a non-uremic patient. The diagnosis was made clinically and confirmed with skin biopsy showing calcification of the dermal and subcutaneous tissues in the von Kossa stain. We believe that the combination of uncontrolled diabetes mellitus, a non-functioning paraganglioma and vitamin D deficiency in a susceptible female patient was responsible for causing calciphylaxis in our patient. An index of suspicion should be maintained by clinicians for calciphylaxis even in patients without uremia.

Inherited Bleeding Disorders-Experience Of A Not-For-Profit Organization In Pakistan, Shabneez Hussain, Shahida Baloch, Azra Parvin, Akbar Najmuddin, Farhana Musheer, Mubashra Junaid, Rab Nawaz Memon, Fareeda Bhanbhro, Hayat Ullah, Bushra Moiz

Department of Pathology and Laboratory Medicine

Patient registry is a powerful tool for planning health care and setting groundwork for research. This survey reports a detailed registry of inherited bleeding disorders (IBD) and their management at a not-for-profit organization in a developing country to form the basis for planning development and research. We reviewed medical records of patients with IBD from 8 hemophilia treatment centers of Fatimid Foundation located in various cities. Information collected included sociodemographic data, diagnostic tests, severity of hemophilia A and B, number of bleeding episodes per year, site and frequency of hemarthrosis, and seropositivity for viral diseases. We analyzed 1497 patients from …

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig

Markey Cancer Center Faculty Publications

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.

Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was …

Hematological Changes In Response To A Drastic Increase In Training Volume In Recreational Cyclists, Jessie Axsom

James Madison Undergraduate Research Journal (JMURJ)

Changes in blood volume contribute to improvement in oxygen utilization (VO2max) with chronic endurance exercise training. Although hematological changes resulting from long-term endurance training have been well documented, it has not been well established whether an increased volume of endurance training preferentially affects plasma volume or red blood cell volume. To answer this question, I studied seven female and four male recreational cyclists before and after exposure to drastic increases (632%) in training volume. Following the 10-week training period, the mean hematocrit (Hct) of the 11 subjects who completed the study significantly (p0.05) correlated with the change in self-reported weekly …

Iron Isomaltoside Is Superior To Iron Sucrose In Increasing Hemoglobin In Gynecological Patients With Iron Deficiency Anemia., Richard Derman, Eloy Roman, Gioi N. Smith-Nguyen, Maureen M. Achebe, Lars L. Thomsen, Michael Auerbach

Global Health Articles

No abstract provided.

Structure Determination Of A Bioengineered Human/Porcine Factor Viii For Hemophilia A Treatment, And Improvements To The Human Factor Viii Model, Ian Smith

Graduate Student Symposium

Blood coagulation factor VIII (FVIII), is a non-enzymatic cofactor which plays a crucial role in the formation of a stable blood clot. Absence or deficiency of FVIII results in the blood disorder hemophilia A; with symptoms including internal hemorrhaging and the inability to stop bleeding from open wounds. Treatment of hemophilia A relies on infusions of blood, plasma, or protein concentrates to replace FVIII. Unfortunately, approximately 30% of patients receiving replacement FVIII generate pathologic anti-FVIII inhibitory antibodies, which both reduce the effectiveness of the FVIII therapeutic and increase the severity of hemophilia A symptoms.

We have determined the molecular structure …

Metastatic Breast Cancer Presenting As Painless Jaundice, Daniel S. Wilen Do, Donald J. Mcmahon Do, Brian J. Blair Do, Joanne Kaiser-Smith Do, Darshan B. Roy Md

Rowan-Virtua Research Day

Breast cancer is the most commonly diagnosed cancer in women in the United States. Treatment options are wide-­‐ ranging based on a multitude of factors, including extent of disease and receptor positivity. Following treatment, a relapse-­‐free interval ≥ 2 years carries a more favorable prognosis.

We present a case involving a female with history of breast cancer and relapse-­free interval of 15 years who unfortunately presented with metastatic disease involving the liver, bone, and lymph nodes.

Development Of Novel Dual Inhibitor Of Chemokine Receptor 4 And Mcl-1 Against Multiple Myeloma, Kuntal Bhowmick, Kristy K. Patel, Suman Pathi, Subash Jonnalagadda, Tulin Budak-Alpdogan, Manoj K. Pandey

Rowan-Virtua Research Day

Multiple myeloma (MM) is a neoplastic plasma-cell disorder. This is characterized by clonal proliferation of malignant plasma cells in the bone-marrow (BM) microenvironment, monoclonal protein in blood or urine, and associated organ dysfunction. The treatment options approved by FDA are immune-modulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT). Unfortunately, MM remains uniformly fatal owing to intrinsic or acquired drug resistance and the median survival time is 3 to 5 years. Thus, there is a great need for novel strategies to combat MM.

The intimate relationship of myeloma cells to BM microenvironment is “hallmark of myeloma”. The homing of …

Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi

Dissertations, Masters Theses, Capstones, and Culminating Projects

Sickle cell disease (SCD) is a genetic blood disorder that causes the RBC to become sickle shaped due to a mutation in the β-globin gene encoding the protein hemoglobin. This disease causes reduced oxygen carrying capacity of RBC resulting in painful crisis, hemolytic anemia, and infection susceptibility. SCD affects around 100,000 individuals in USA alone and 14 million people globally. SCD affected individuals have high mortality rates. Early detection and constant monitoring of this disease is essential. The following review focuses on various methodologies that have emerged in the diagnosis of SCD. Also, low cost methods that can be easily …

Patient Attitudes Toward Genetic Testing For Inherited Predispositions To Hematologic Malignancies, Taylor Beecroft

Dissertations & Theses (Open Access)

Although inherited predispositions to hematologic malignancies have previously been considered extremely rare, approximately 12 causative genes have been implicated in the last decade. Since individuals diagnosed with leukemia have not historically been considered for evaluation of inherited predispositions, genetic testing is underperformed in this population. This study used focus group discussions to explore the attitudes, motivations, and barriers to genetic testing for 23 patients with leukemia. Participants generally exhibited a positive regard for the utility of genetic testing, and were primarily motivated by concern for their family and a sense of altruism toward all leukemia patients. While drawbacks and barriers …

Sorafenib-Induced Tumor Lysis Syndrome In A Patient With Metastatic Hepatocellular Carcinoma., Sardar Zakariya Imam, Mohammad Faizan Zahid, Muhammad Asad Maqbool

Medical College Documents

Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with meta-static hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following ini-tiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1–2 weeks while being treated

No Risk Reduction For Plasmodium Vivax Malaria In Sickle Cell Disease, Bushra Moiz, Ayesha Majeed Memon

Department of Pathology and Laboratory Medicine

Hemoglobin S is known to protect against uncomplicated Plasmodium falciparum malaria. However, there is paucity of the literature regarding interaction of HbS and other malaria species. Usually, P. vivax malaria is a relapsing condition, and without radical cure with primaquine, recurrence may be observed even with hemoglobin S.

Adequacy Of Platelet Counting By Automated Haematology Analyzers: An Insight On Current Methodologies, Muhammad Shariq Shaikh, Noor Rahman Khan, Zeeshan Ansar Ahmed

Department of Pathology and Laboratory Medicine

No abstract provided.

Comorbidities In Aging Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with …

Sickle Cell Disease: Classification Of Clinical Complications And Approaches To Preventive And Therapeutic Management., Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is an inherited disorder of hemoglobin structure that has no established cure in adult patients. Cure has been achieved in selected children with sickle cell anemia (SCA) using allogeneic bone marrow transplantation or cord blood transplantation. SCD is essentially a triumvirate of (1) pain syndromes, (2) anemia and its sequelae and (3) organ failure, including infection. Pain, however, is the hallmark of SCD and dominates its clinical picture throughout the life of the patients. The prevalence of these complications varies with age from infancy through adult life. However, pain, infections and anemia requiring blood transfusion occur …

Blood Rheological Abnormalities In Sickle Cell Anemia., Philippe Connes, Céline Renoux, Marc Romana, Manouk Abkarian, Philippe Joly, Cyril Martin, Marie-Dominique Hardy-Dessources, Samir K. Ballas

Department of Medicine Faculty Papers

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different …

Cough, Hemoptysis And Hair Expectoration: An Intrapulmonary Teratoma, Shanila Ahmed, Habib Kibzai, Talha Shahzad, Saulat Fatimi, Madiha Bilal L Qureshi

Section of Haematology/Oncology

Teratomas can be found in different organs of the body and may involve gonads, saccrococcygeal region, mediastinum and other sites. Intrathoracic teratomas always occur in mediastinum and less often arise within the lung. As teratomas mostly involve sex organs (gonads), they rarely occur as extra-gonadal tumors accounting for only 3% of all the cases and very small percentage of such tumors occur in mediastinum.We reported an interesting case of middle aged male who presented to us with symptoms of cough, hemoptysis and trichoptysis (hair expectoration).We found that patient had intrapulmonary teratoma that was initially being treated as case of pulmonary …

Cold Agglutinins In Peripheral Blood With Atypical Cells With An Owl-Eye Appearance In Bone Trephine, Ayesha Majeed Memon, Farheen Karim

Department of Pathology and Laboratory Medicine

Autoimmune hemolytic anemia (AIHA) is a form of hemolytic anemia in which red cells lysis occurs due to presence of an autoantibody. Association of AIHA is well known with lymphoproliferative disorders, especially with non-Hodgkin's lymphoma. However, AIHA in association with Hodgkin's lymphoma is seen occasionally. Of the AIHA associated with Hodgkin's lymphoma, most are of warm type or mixed type. Cold AIHA, as seen in our case, is very rare in Hodgkin's lymphoma.

Clinical Audit To Assess Delays In Chemotherapy Administration At Daycare Oncology Center At A Tertiary Care Hospital In Karachi, Pakistan, Arifa Aziz, Zarka Samoon, Mohammad Khurshid, Afsheen Feroz, Nadia Ayoub, Safia Awan, Madhia Beg

Section of Haematology/Oncology

Aim: There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays.

Materials and Methods: The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the …