Hematology Commons^™

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease Or Failed Prior Autologous Transplant In Angioimmunoblastic T-Cell Lymphoma: A Cibmtr Analysis, Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard C. Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah

Internal Medicine Faculty Publications

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 …

Investigational Monoclonal Antibodies In The Treatment Of Multiple Myeloma: A Systematic Review Of Agents Under Clinical Development, Ahmad Iftikhar, Hamza Hassan, Nimra Iftikhar, Adeela Mushtaq, Atif Sohail, Nathaniel Rosko, Rajshekhar Chakraborty, Faryal Razzaq, Sonia Sandeep, Jason Neil Valent, Abraham Sebastian Kanate, Faiz Anwer

Faculty & Staff Scholarship

Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with …

Transcriptional Activation Of The Mir-17-92 Cluster Is Involved In The Growth-Promoting Effects Of Myb In Human Ph-Positive Leukemia Cells., Manuela Spagnuolo, Giulia Regazzo, Marco De Dominici, Andrea Sacconi, Andrea Pelosi, Etleva Korita, Francesco Marchesi, Francesco Pisani, Alessandra Magenta, Valentina Lulli, Iole Cordone, Andrea Mengarelli, Sabrina Strano, Giovanni Blandino, Maria G. Rizzo, Bruno Calabretta

Department of Cancer Biology Faculty Papers

MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL-expressing cells. We investigated whether MYB silencing modulates microRNA expression in Philadelphia-positive (Ph+) leukemia cells and if MYB-regulated microRNAs are important for the "MYB addiction" of these cells. Thirty-five microRNAs were modulated by MYB silencing in lymphoid and erythromyeloid chronic myeloid leukemia-blast crisis BV173 and K562 cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found …

การศึกษาฤทธิ์ของ Fluoxetine ในการยับยั้งการเจริญเติบโตและเหนี่ยวนำการตายแบบ Apoptosis ผ่านวิถี Pi3k/Akt และ Sigma-1 Receptor ใน Leukemic Cell Lines, ชนิชนม์ ชมเชย

Chulalongkorn University Theses and Dissertations (Chula ETD)

Fluoxetine เป็นยากลุ่ม SSRI (selective serotonin reuptake inhibitor) ที่ใช้ในการรักษาโรคซึมเศร้า ยาหลายตัวในกลุ่ม SSRI สามารถจับแบบจำเพาะ sigma-1 receptor แต่ในกรณี fluoxetine จะมีกลไกออกฤทธิ์จำเพาะต่อ serotonin transporter (Ki = 0.81 nM) มากกว่า sigma-1 receptor (Ki = 214–240 nM) หลายงานวิจัยรายงานว่า sigma-1 receptor แสดงออกบนเซลล์มะเร็งหลายชนิด และมีรายงานว่า antagonist สามารถลดการเพิ่มจำนวนและเหนี่ยวนำให้เกิด apoptosis แต่การทำงานร่วมกันระหว่าง fluoxetine กับ sigma-1 receptor ต่อเซลล์มะเร็ง ยังไม่ทราบกลไกการออกฤทธิ์ที่ชัดเจน งานวิจัยนี้มีวัตถุประสงค์เพื่อศึกษาฤทธิ์ของ fluoxetine ในการยับยั้งการแบ่งตัวและเหนี่ยวนำให้เกิด apoptosis ผ่าน sigma-1 receptor ในเซลล์มะเร็งเม็ดเลือดขาว ผลการทดสอบพบว่า fluoxetine สามารถลดเปอร์เซ็นต์การรอดชีวิตของเซลล์ Jurkat และ U937 ได้ โดยมีค่า IC50 เท่ากับ 28 ± 1.4 และ 36 ± 1.6 uM ตามลำดับ เมื่อเซลล์ Jurkat ถูกทดสอบด้วย fluoxetine ตามระดับความเข้มข้นและระยะเวลาที่เพิ่มขึ้น พบว่าfluoxetine สามารถยับยั้งการแบ่งตัวของเซลล์ Jurkat ได้อย่างมีนัยสำคัญทางสถิติ โดยมีกลไกหยุดยั้งวัฎจักรเซลล์ที่ระยะ G2/M และลดการหลั่งไซโตไคน์ IL-2 รวมทั้งเหนี่ยวนำให้เกิด apoptosis โดยการลดการแสดงออกของโปรตีน pro caspase 9 ผ่านการยับยั้งการเกิด phosphorylation ของ AKT ในวิถี PI3K/Akt และ การถูกกระตุ้นของ sigma-1 receptor …

Detection Of Human Plasma Glucose Using A Self-Powered Glucose Biosensor, Gymama Slaughter, Tanmay Kulkarni

Bioelectrics Publications

This work presents the characterization of a self-powered glucose biosensor using individual sequential assays of human plasma glucose obtained from diabetic patients. The self-powered glucose biosensor is exploited to optimize the assay parameters for sensing plasma glucose levels. In particular, the biofuel cell component of the system at pH 7.4, 37 °C generates a power density directly proportional to plasma glucose and exhibited a maximum power density of 0.462 mW·cm⁻² at a cell voltage of 0.213 V in 5 mM plasma glucose. Plasma glucose is further sensed by monitoring the charge/discharge frequency (Hz) of the integrated capacitor functioning as …

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

Operations 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 …

Establishing Hematology And Serum Chemistry Reference Intervals For Wild Hawaiian Monk Seals (Neomonachus Schauinslandi), Angela C. Kaufman, Stacie J. Robinson, Dori L. Borjesson, Michelle Barbieri, Charles L. Littnan

United States Department of Commerce: Staff Publications

Hematology and serum chemistry reference intervals have been previously established for the endangered Hawaiian monk seal (Neomonachus schauinslandi) as an imperative measure for health assessments. Monitoring the health of the wild population depends upon reference intervals that are context specific; hence we developed reference intervals from fresh samples, as opposed to frozen, from wild monk seals. This study builds on the number of parameters from previous efforts by using samples collected between 2004 and 2015 from wild monk seals. Blood samples were analyzed by a single veterinary diagnostic laboratory within 24 hr of collection from apparently healthy, wild …

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 …

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 …

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.

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 …