Hematology Commons^™

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

A Phase 1/2 Study Of The Oral Flt3 Inhibitor Pexidartinib In Relapsed/Refractory Flt3-Itd-Mutant Acute Myeloid Leukemia., Catherine C Smith, Mark J Levis, Olga Frankfurt, John M Pagel, Gail J Roboz, Richard M Stone, Eunice S Wang, Paul L Severson, Brian L West, Mai H Le, Sabine Kayser, Bao Lam, Henry H Hsu, Chao Zhang, Gideon Bollag, Alexander E Perl

Articles, Abstracts, and Reports

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Extra Medullar Granulocytic Sarcoma: A Case Report Of An Exceptional Localization, Bouhani Malek, Sakhri Saida, Jaidane Olfa, Adouni Olfa, Chargui Riadh, Rahal Khaled

Journal of Mind and Medical Sciences

Granulocytic sarcoma is a rare type of tumor composed of extramedullary immature cells. The breast location is very rare; it accounts for less than 8% of cases. The present study reports the case of a 36-year-old female with a medical history of myelodysplastic syndrome. She was referred because of a lump in the left breast. We have diagnosed a case of granulocytic sarcoma of the breast by core biopsy. Histology and immunohistochemistry showed hypercellular smears with immature myeloid cells. The blast cells were myeloperoxidase positive.

The patient underwent a lumpectomy. Five months later, she developed a contralateral recurrence, treated by …

An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya

Faculty, Staff and Students Publications

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, …

Allogeneic Autophagosome-Enriched Composition For The Treatment Of Disease, Traci Hilton, Sandra Aung, Rieneke Van De Ven, Christopher Paustian, Tarsem Moudgil, Christopher Dubay, Christopher Twitty, Hong-Ming Hu, Bernard A Fox

Technology Transfer - Patents

A method is presented for screening cells that produce allogeneic autophagosome enriched compositions able to induce expression of a selective marker on a subpopulation of peripheral blood mononuclear cells, the method comprising contacting a cell with a proteasome inhibitor, contacting the cell with a lysosome inhibitor, harvesting the resulting autophagosomes, determining a molecular signature of the harvested autophagosomes, and selecting cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested autophagosomes. By screening for cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested …

Worldwide Network For Blood And Marrow Transplantation (Wbmt) Recommendations For Establishing A Hematopoietic Stem Cell Transplantation Program In Countries With Limited Resources (Part Ii): Clinical, Technical And Socio-Economic Considerations, M Aljurf, D Weisdorf, S K. Hashmi, A Nassar, E Gluckman, M Mohty, D Rizzo, M Pasquini, M Hamadani, Salman Adil

Section of Haematology/Oncology

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care …

Blood Test Shows High Accuracy In Detecting Stage I Non-Small Cell Lung Cancer., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND: In a previous study (Goebel et. al, Cancer Genomics Proteomics 16:229-244, 2019), we identified 33 biomarkers for an early stage (I-II) Non-Small Cell Lung Cancer (NSCLC) test with 90% accuracy, 80.3% sensitivity, and 95.4% specificity. For the current study, we used a narrowed ensemble of 21 biomarkers while retaining similar accuracy in detecting early stage lung cancer.

METHODS: A multiplex platform, 486 human plasma samples, and 21 biomarkers were used to develop and validate our algorithm which detects early stage NSCLC. The training set consisted of 258 human plasma with 79 Stage I-II NSCLC samples. The 21 biomarkers with …

A Case Of Vancomycin-Induced Immune Thrombocytopenia., K. N. Macdougall, S. Parylo, A. Sokoloff

Journal Articles

Vancomycin-induced immune thrombocytopenia (ITP) is a rare, potentially life-threatening complication from an antibiotic frequently used in medical practice. We report a case of an 81-year-old male with recent removal of an infected right knee prosthesis and insertion of an articulating antibiotic spacer, presenting from rehabilitation for severe thrombocytopenia (1 X 103/µL). The patient's thrombocytopenia was initially falsely attributed to rifampin-induced ITP, a much more common cause of drug-induced thrombocytopenia. Only later, after a second precipitous drop in platelet count, vancomycin was correctly identified as the culprit. The patient's serum was tested for drug-dependent platelet antibodies with and without vancomycin. A …

Mutations Associated With A 17-Gene Leukemia Stem Cell Score And The Score’S Prognostic Relevance In The Context Of The European Leukemianet Classification Of Acute Myeloid Leukemia, M. Bill, D. Nicolet, J. Kohlschmidt, C. J. Walker, K. Mrózek, A. K. Eisfeld, D. Papaioannou, X. Rong-Mullins, J. E. Kolitz, C. D. Bloomfield, +8 Additional Authors

Journal Articles

© 2020 Ferrata Storti Foundation. Leukemia stem cells (LSC) are more resistant to standard chemotherapy and their persistence during remission can cause relapse, which is still one of the major clinical challenges in the treatment of acute myeloid leukemia (AML). A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients’ outcomes. We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with de novo AML, and studied associations of the 17-gene LSC …

Advances In Targeted Therapy For Acute Myeloid Leukemia., Jifeng Yu, Peter Y Z Jiang, Hao Sun, Xia Zhang, Zhongxing Jiang, Yingmei Li, Yongping Song

Articles, Abstracts, and Reports

Acute myeloid leukemia (AML) is a clonal malignancy characterized by genetic heterogeneity due to recurrent gene mutations. Treatment with cytotoxic chemotherapy has been the standard of care for more than half of a century. Although much progress has been made toward improving treatment related mortality rate in the past few decades, long term overall survival has stagnated. Exciting developments of gene mutation-targeted therapeutic agents are now changing the landscape in AML treatment. New agents offer more clinical options for patients and also confer a more promising outcome. Since Midostaurin, a FLT3 inhibitor, was first approved by US FDA in 2017 …

The Impact Of Age On Survival In Cll Patients Receiving Ibrutinib As Initial Therapy., Chaitra Ujjani, Anthony Mato, Brian T Hill, John N Allan, Frederick Lansigan, Ryan Jacobs, Alan Skarbnik, Hande Tuncer, John M Pagel, Danielle Brander, Bruce Cheson, Paul Barr, Lindsey E Roeker, Jeffrey Pu, Nirav N Shah, Andre Goy, Stephen J Schuster, Nicole Lamanna, Alison Sehgal, Constantine S Tam, Mazyar Shadman

Articles, Abstracts, and Reports

Introduction: Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to 70 years of age.

Methods: Therefore, we conducted a retrospective analysis to investigate whether ibrutinib was associated with a greater mortality in older patients outside of a clinical trial setting. This multicenter analysis was performed by investigators at 20 academic and community practices.

Results: Amongst the 391 patients …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Secretion Of A Heparin-Like Anticoagulant (Hlac) In Plasma Cell Neoplasia, Kevin J. Hess Do, Joseph Moran Do, Rachel Kinney Do

Department of Medicine

No abstract provided.

Factors Influencing Family Burden In Pediatric Hematology/Oncology Encounters, Hannah R. Abrams, Hayden S. Leeds, Heidi V. Russell, Melody B. Hellsten

Journal of Patient-Centered Research and Reviews

Purpose: Caring for a child with cancer or hematologic disease places unique stress on a family unit. Families’ subjective experience of this care-related burden mediates the relationship between cost and health-related outcomes. While financial costs are well described for families of pediatric hematology/oncology patients, it is unclear how cost and other factors each contribute to families’ overall experience of care-related burden. This study identifies and groups the challenges that families report and describes their association with overall reported burden.

Methods: This mixed-methods analysis of a cross-sectional single-center study was conducted via structured, self-administered questionnaire provided to inpatient and outpatient caregivers …

Granuloma Whorls, Farrukh Zia, Natasha Bahadur Ali

Section of Haematology/Oncology

What is the significance of bone marrow examination in presence of peripheral cytopenias? It is still regarded as a mandatory investigation to diagnose hematological disorders. In this case, bone marrow trephine was initially done as a diagnosis of exclusion for ITP, whereas it revealed multiple granulomas suggesting mycobacterium tuberculosis infection.

Safety And Efficacy Of Bendamustine In The Conditioning Regimen For Autologous Stem Cell Transplantation In Patients With Relapsed/Refractory Lymphoma, Munira Moosajee, Samad Jehangir, Sobia Sawani, Tariq Muhammed, N. Ali, Usman Shaikh, Salman Adil

Section of Haematology/Oncology

Background: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas.
Methods: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT.
Results: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's …

Blood Film Says It All! Rare Case Of Congenital Ttp Misdiagnosed As Itp, Ayesha Majeed Memon, Natasha Ali

Department of Pathology and Laboratory Medicine

We report a case of a 16-year-old female who presented with bleeding diathesis. Peripheral blood film examination was consistent with microangiopathic hemolytic anemia with 7% fragmented red blood cells. The ADAMTS13 level was 40 ng/ml (reference range: 630-850 ng/ml). She responded to plasma exchange therapy and methylprednisolone and was discharged in a stable condition.

Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell

School of Medicine Faculty Publications

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. METHODS: In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro …

Acalabrutinib Monotherapy In Patients With Chronic Lymphocytic Leukemia Who Are Intolerant To Ibrutinib., Farrukh T Awan, Anna Schuh, Jennifer R Brown, Richard R Furman, John M Pagel, Peter Hillmen, Deborah M Stephens, Jennifer Woyach, Elena Bibikova, Prista Charuworn, Melanie M Frigault, Ahmed Hamdy, Raquel Izumi, Bolan Linghu, Priti Patel, Min Hui Wang, John C Byrd

Articles, Abstracts, and Reports

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation. Acalabrutinib is a potent, covalent BTK inhibitor with greater selectivity than ibrutinib. We evaluated the safety and efficacy of 100 mg of acalabrutinib twice daily or 200 mg once daily in patients with CLL who discontinued ibrutinib because of intolerance as determined by the investigators. Among 33 treated patients (61% men; median age, 64 years; range, 50-82 years), median duration of prior ibrutinib treatment was 11.6 months (range, 1-62 months); median time from ibrutinib discontinuation …

Rare Sarcomatoid Carcinoma Of The Liver In A Patient With No History Of Hepatocellular Carcinoma: A Case Report, Kevat B. Patel, Rita H. Hawarny, Elizabeth Saunders, Marc Hettlinger, Niru Nahar

Marshall Journal of Medicine

Sarcomatoid carcinoma is a rare malignant tumor of unknown pathogenesis characterized by poorly differentiated carcinoma tissue containing sarcoma-like differentiation of either spindle or giant cell and rarely occurs in the gastrointestinal tract and hepatobiliary-pancreatic system.¹ Primary hepatic sarcomatoid carcinoma accounts for only 0.2 % of primary malignant liver tumors, and 1.8% of all surgically resected hepatocellular carcinomas.² The majority of hepatic sarcomatoid carcinoma cases appear to occur simultaneously with hepatocellular or cholangiocellular carcinoma.³ The preferred treatment for hepatic sarcomatoid carcinoma is surgical resection and the overall prognosis is poor.⁴ This case depicts a 62-year-old female whom …

Extended Infusions Of Meropenem For Febrile Neutropenia, Daniel J. Przybylski, Pharmd, David J. Reeves, Pharmd, Bcop

BU Well

Background: Neutropenic fever is an oncologic emergency that requires quick intervention with anti-pseudomonal beta-lactam antibiotics, such as meropenem. Previous literature suggests that extended infusions of beta-lactam antibiotics may improve clinical outcomes. To date, there are 3 prior studies utilizing an extended infusion beta-lactam in this population; however, there is only one previous study investigating the use of extended infusion meropenem in patients with febrile neutropenia.

Objective: To describe the outcomes of eight patients receiving extended infusions of meropenem for the treatment of febrile neutropenia.

Methods: A retrospective chart review was completed including adult patients admitted to a community teaching hospital …

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 …

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 ( …

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 …

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 …

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

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.