Hematology Commons^™

A Simple Critical Care Provider Transfusion Education Program Reduces Blood Product Use, Ivan Martinez Avalos, Stephen Malkoski, Mellody Descoteaux

View All Washington/Montana GME

Presented at the 2022 Virtual Northwest Medical Research Symposium

Minimal Residual Disease In Multiple Myeloma: Potential For Blood-Based Methods To Monitor Disease, Aisling O'Brien, Fiona O'Halloran, Vitaliy Mykytiv

Department of Biological Sciences Publications

In recent years, the life expectancy of Multiple Myeloma (MM) patients has substantially improved, but this cancer remains incurable with increasing incidence in the developed world. Most MM patients will eventually relapse due to residual drug-resistant cancerous cells that survive treatment, commonly referred to as minimal residual disease (MRD). Methods to improve MRD detection in MM patients are generating considerable interest as a means of monitoring patients' response to treatment. In clinical laboratories, these methods currently require bone marrow aspirates which are invasive and frequently miss detection of localised disease due to the spatial heterogeneity of disease infiltration. By simplifying …

การพัฒนาเทคนิคพีซีอาร์เอชอาร์เอ็มสำหรับตรวจหาการติดเชื้อมาลาเรียในมนุษย์และการกลายพันธุ์ของยีนจีซิกพีดีชนิดเวียงจันทน์และมหิดล, ปวีณ์สุดา รัตนคช

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคมาลาเรียถือเป็นปัญหาด้านสาธารณสุขที่สำคัญ ในปี พ.ศ.2564 องค์กรอนามัยโลกรายงานจำนวนผู้ติดเชื้อมาลาเรียทั่วโลกกว่า 247 ล้านรายและผู้เสียชีวิตกว่า 627,000 ราย ซึ่งมีแนวโน้มเพิ่มสูงขึ้น ส่งผลต่อการควบคุมและการกำจัดโรคมาลาเรีย โดยเฉพาะกลุ่มผู้ป่วยที่ไม่แสดงอาการอาจไม่ได้รับการตรวจวินิจฉัยและการรักษา จึงสามารถเป็นแหล่งสะสมและแพร่กระจายของเชื้อมาลาเรียได้ ในปัจจุบันมีเชื้อพลาสโมเดียมที่ก่อโรคในมนุษย์ 5 สปีสีช์ ได้แก่ P. falciparum, P. vivax, P. malariae, P. ovale และ P. knowlesi ดังนั้นเทคนิคที่มีความไวสูงในการตรวจหาเชื้อมาลาเรียจึงมีความสำคัญมาก นอกจากนี้การรักษาด้วยยาต้านเชื้อมาลาเรีย เช่น ไพรมาควิน อาจส่งผลต่อผู้ที่มีภาวะพร่องเอนไซม์จีซิกพีดีทำให้เกิดภาวะเม็ดเลือดแดงแตกได้ งานวิจัยนี้จึงได้พัฒนาเทคนิคพีซีอาร์เอชอาร์เอ็มสำหรับตรวจหาเชื้อมาลาเรียและการกลายพันธุ์ของยีนจีซิกพีดี รวมทั้งทดสอบปริมาณความหนาแน่นต่ำสุดที่สามารถตรวจพบได้ ความไวและความจำเพาะของเทคนิคที่พัฒนาขึ้นพบว่าสามารถตรวจหาเชื้อมาลาเรียที่มีความหนาแน่นต่ำสุดเท่ากับ 2.354-3.316 copies/µL มีความไวและความจำเพาะในการตรวจหาเชื้อ P. falciparum, P. malariae, P. ovale และ P. knowlesi เท่ากับ 100% และ 100% ตามลำดับ ความไวและความจำเพาะในการตรวจหาเชื้อ P. vivax เท่ากับ 100% และ 99.28% ตามลำดับ สำหรับการตรวจการกลายพันธุ์ของยีนจีซิกพีดีพบว่าสามารถตรวจระบุจีซิกพีดีเวียงจันทน์และจีซิกพีดีมหิดลได้อย่างถูกต้อง ดังนั้นเทคนิคพีซีอาร์เอชอาร์เอ็มที่พัฒนาขึ้นจึงเป็นอีกหนึ่งทางเลือกสำหรับการตรวจเชื้อมาลาเรียและการกลายพันธุ์ของยีนจีซิกพีดี ซึ่งจะเป็นประโยชน์แก่ผู้ป่วยมาลาเรียเพื่อให้ได้รับการรักษาอย่างมีประสิทธิภาพ

Comorbidities, Health-Related Quality Of Life, Health-Care Utilization In Older Persons With Hemophilia-Hematology Utilization Group Study Part Vii (Hugs Vii), Randall Curtis, Marilyn Manco-Johnson, Barbara A Konkle, Roshni Kulkarni, Joanne Wu, Judith R Baker, Megan Ullman, Duc Quang Tran, Michael B Nichol

Faculty, Staff and Student Publications

PURPOSE: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40-49 years and ≥50 years.

PATIENTS AND METHODS: The HUGS VII study recruited persons with hemophilia A or B age ≥40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Clinical chart reviews documented hemophilic severity and treatment.

RESULTS: The sample includes 69 males, 65.2% aged ≥50 years, 75.4% with hemophilia A. Individuals ≥50 years were more likely …

Targeting Mcl-1 Dysregulates Cell Metabolism And Leukemia-Stroma Interactions And Resensitizes Acute Myeloid Leukemia To Bcl-2 Inhibition, Bing Z Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Faculty, Staff and Student Publications

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic …

Advancing The Standard: Venetoclax Combined With Intensive Induction And Consolidation Therapy For Acute Myeloid Leukemia, Curtis A Lachowiez, Himachandana Atluri, Courtney D Dinardo

Faculty, Staff and Student Publications

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in combination with the hypomethylating agent azacitidine improved rates of response and measurable residual disease (MRD)-negative remissions in addition to overall survival in the pivotal phase 3 VIALE-A trial compared with azacitidine monotherapy and has since emerged as the current standard of care in older or unfit patients with AML. In younger, fit patients with AML, intensive induction and consolidation chemotherapy (IC) is commonly employed as frontline therapy; however, relapse remains the principal cause of treatment failure …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Complexities And Complications Of Extreme Obesity, Haval Ali, Udit Naik, Michelle Mcdonald, Mohammad Almosa, Karen Horn, Alexis Staines, Louis Maximilian Buja

Faculty, Staff and Student Publications

Obesity is a common chronic disorder and has detrimental long-term consequences if left untreated. Herein, we report a case of a young lady who suffered from morbid obesity and many of its consequences, and we present a literature review of these complications. While the cause of obesity is multifactorial, the genetic component is particularly important in the pathophysiology of marked obesity. Resistance to Leptin is considered one of the main causes of obesity. There is a unique relationship between polycystic ovary syndrome and obesity, as observed in our case. Obesity is associated with cardiovascular and lung diseases such as heart …

Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M. Vose, Matthew A. Lunning, Aliyah R. Sohani, Benjamin J. Chen, Shannon Buckley, Loretta J. Nastoupil, R. Eric Davis, Jason R. Westin, Nathan H. Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J. Rodig, Adnan Mansoor, Michael R. Green

Journal Articles: Oncology and Hematology

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, …

Platelet Micrornas Inhibit Primary Tumor Growth Via Broad Modulation Of Tumor Cell Mrna Expression In Ectopic Pancreatic Cancer In Mice, Jeremy G.T. Wurtzel, Sophia Lazar, Sonali Sikder, Kathy Q Cai, Igor Astsaturov, Andrew S Weyrich, Jesse W Rowley, Lawrence E. Goldfinger

Department of Medicine Faculty Papers

We investigated the contributions of platelet microRNAs (miRNAs) to the rate of growth and regulation of gene expression in primary ectopic tumors using mouse models. We previously identified an inhibitory role for platelets in solid tumor growth, mediated by tumor infiltration of platelet microvesicles (microparticles) which are enriched in platelet-derived miRNAs. To investigate the specific roles of platelet miRNAs in tumor growth models, we implanted pancreatic ductal adenocarcinoma cells as a bolus into mice with megakaryocyte-/platelet-specific depletion of mature miRNAs. We observed an ~50% increase in the rate of growth of ectopic primary tumors in these mice compared to controls …

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation Of Monocytes And Reduces Il-1Β Secretion By Urate Crystal Stimulated Gout Pbmcs, Sandy Elsayed, Gregory D. Jay, Ralph Cabezas, Marwa Qadri, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Objectives

To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods

Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU …

Inhibition Of Nadph Oxidase Blocks Netosis And Reduces Thrombosis In Heparin-Induced Thrombocytopenia, Halina H L Leung, Jose Perdomo, Zohra Ahmadi, Feng Yan, Steven E. Mckenzie, Beng H Chong

Department of Medicine Faculty Papers

Heparin-induced thrombocytopenia (HIT) is associated with severe and potentially lethal thrombotic complications. NETosis was recently shown to be an important driver of thrombosis in HIT. We investigated the role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their contributions to thrombus development in HIT. We showed that neutrophil activation by HIT immune complexes induced ROS-dependent NETosis. Analysis of thrombi formed in a microfluidics system showed ROS production in both platelets and neutrophils, and abundant neutrophil extracellular traps (NETs) and ROS distributed throughout the clot. Neutrophil-targeted ROS inhibition was sufficient to block HIT-induced NETosis …

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Central Line Associated Bloodstream Infection Caused By Kodamaea Ohmeri In A Young Child, Amier Haidar, Farhana Khaja, Brian Simms, Amr Issam Elgehiny, Tracy Omoegbele, Nikita Khetan

Faculty, Staff and Student Publications

INTRODUCTION:

CASE REPORT: The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as

CONCLUSIONS: This case report further acknowledges …

Vte And Anticoagulation In Menstruating Women, Ida Micaily, Bethany T. Samuelson Bannow

Department of Medicine Faculty Papers

Women of childbearing potential have a high prevalence of venous thromboembolism (VTE) due to high estrogen states, such as pregnancy and the use of estrogen-containing contraceptives. Abnormal uterine bleeding (AUB) affects up to two-thirds of menstruating women on anticoagulation (AC), and can severely impair a woman's quality of life. Rates of heavy menstrual bleeding (HMB) and other forms of AUB including inter-menstrual and postmenopausal bleeding are consistently underreported in the original clinical trials utilizing AC. VTE can occur at any time in a woman's life, and the aim of this review article is to discuss the current landscape of literature …

Predicting Risk Factors For Thromboembolic Complications In Patients With Sickle Cell Anaemia - Lessons Learned For Prophylaxis, Salam Alkindi, Anwaar R Al-Ghadani, Samah R Al-Zeheimi, Said Y Alkindi, Naglaa Fawaz, Samir K. Ballas, Anil V Pathare

Cardeza Foundation for Hematologic Research

Objective: To assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality.

Methods: This retrospective case-control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio).

Results: A total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with …

Thrombosis With Thrombocytopenia Syndrome After Administration Of Azd1222 Or Ad26.Cov2.S Vaccine For Covid-19: A Systematic Review, Usama Waqar, Shaheer Ahmed, Syed M H Ali Gardezi, Muhammad Sarmad Tahir, Zain Ul Abidin, Ali Hussain, Natasha Bahadur Ali, Syed Faisal Mahmood

Medical College Documents

Background: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS.
Methods: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes.
Findings: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered …

Editorial: Thrombotic Microangiopathies, Diagnostic And Therapeutic Advances, Robert W. Maitta, Hollie M. Reeves

Faculty Scholarship

Thrombotic microangiopathies (TMAs) as a disease group represent a diagnostic and clinical challenge to practitioners. Presentations, which at times have overlapping symptomatology or have undetermined etiologies, emphasize the need for a constant reassessment of what is known about this disease group in order to determine not only how to best treat patients but also to develop targeted approaches to test for a given etiology. Likewise, in those instances when excluding diagnoses is the only available option, timely adjustment of therapy due to lack of therapeutic response needs to be achieved in the most efficient way. It is with this in …

Outcomes Of Patients With Double/Triple Expressor Diffuse Large B-Cell Lymphoma (Dlbcl) Treated With R-Da-Epoch/R-Chop: A Single-Center Experience, Kanta Devi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly …