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Courtney D DiNardo

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https://www.readbyqxmd.com/read/27874212/dorsal-column-myelopathy-after-intrathecal-chemotherapy-for-leukemia
#1
Chelsea C Pinnix, Linda Chi, Elias J Jabbour, Sarah A Milgrom, Grace L Smith, Naval Daver, Naveen Garg, Matthew D Cykowski, Greg Fuller, David Cachia, Carlos Kamiya, Karin Woodman, Courtney Dinardo, Nitin Jain, Tapan M Kadia, Naveen Pemmaraju, Maro Ohanian, Marina Konopleva, Hagop M Kantarjian, Bouthaina S Dabaja
Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used to treat central nervous system malignancies. The mechanisms underlying methotrexate-induced neurotoxicity are unclear but may be related to increased homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking sub-acute combined degeneration, with normal B12 levels, has been documented. We examined treatment and magnetic resonance imaging (MRI) characteristics of 13 patients with leukemia who received intrathecal methotrexate and developed urinary and bowel incontinence, ascending motor weakness, and sensory loss with dorsal column hyper-intensity on MRI between 2000 and 2016...
November 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27806325/inhibiting-glutaminase-in-acute-myeloid-leukemia-metabolic-dependency-of-selected-aml-subtypes
#2
Polina Matre, Juliana Velez, Rodrigo Jacamo, Yuan Qi, Xiaoping Su, Tianyu Cai, Steven M Chan, Alessia Lodi, Shannon R Sweeney, Helen Ma, Richard Eric Davis, Natalia Baran, Torsten Haferlach, Xiaohua Su, Elsa Renee Flores, Doriann Gonzalez, Sergej Konoplev, Ismael Samudio, Courtney DiNardo, Ravi Majeti, Aaron D Schimmer, Weiqun Li, Taotao Wang, Stefano Tiziani, Marina Konopleva
Metabolic reprogramming has been described as a hallmark of transformed cancer cells. In this study, we examined the role of the glutamine (Gln) utilization pathway in acute myeloid leukemia (AML) cell lines and primary AML samples. Our results indicate that a subset of AML cell lines is sensitive to Gln deprivation. Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of Gln to glutamate. One of the two GLS isoenzymes, GLS1 is highly expressed in cancer and encodes two different isoforms: kidney (KGA) and glutaminase C (GAC)...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27673440/buparlisib-a-pi3k-inhibitor-demonstrates-acceptable-tolerability-and-preliminary-activity-in-a-phase-i-trial-of-patients-with-advanced-leukemias
#3
Brittany Knick Ragon, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi, Jorge Cortes, Gautam Borthakur, LaKiesha DeBose, Zhihong Zeng, Heather Schneider, Naveen Pemmaraju, Guillermo Garcia-Manero, Steven Kornblau, William Wierda, Jan Burger, Courtney D DiNardo, Michael Andreeff, Marina Konopleva, Naval Daver
Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day...
September 27, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27602508/differential-impact-of-minimal-residual-disease-negativity-according-to-the-salvage-status-in-patients-with-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia
#4
Elias Jabbour, Nicholas J Short, Jeffrey L Jorgensen, Musa Yilmaz, Farhad Ravandi, Sa A Wang, Deborah A Thomas, Joseph Khoury, Richard E Champlin, Issa Khouri, Partow Kebriaei, Susan M O'Brien, Guillermo Garcia-Manero, Jorge E Cortes, Koji Sasaki, Courtney D Dinardo, Tapan M Kadia, Nitin Jain, Marina Konopleva, Rebecca Garris, Hagop Kantarjian
BACKGROUND: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. METHODS: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission...
September 7, 2016: Cancer
https://www.readbyqxmd.com/read/27520294/efficacy-and-biological-correlates-of-response-in-a-phase-ii-study-of-venetoclax-monotherapy-in-patients-with-acute-myelogenous-leukemia
#5
Marina Konopleva, Daniel A Pollyea, Jalaja Potluri, Brenda Chyla, Leah Hogdal, Todd Busman, Evelyn McKeegan, Ahmed Hamed Salem, Ming Zhu, Justin L Ricker, William Blum, Courtney D DiNardo, Tapan Kadia, Martin Dunbar, Rachel Kirby, Nancy Falotico, Joel Leverson, Rod Humerickhouse, Mack Mabry, Richard Stone, Hagop Kantarjian, Anthony Letai
: We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery)...
October 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27469452/clinical-significance-of-newly-emerged-isolated-del-20q-in-patients-following-cytotoxic-therapies
#6
C Cameron Yin, Jie Peng, Yu Li, Rashmi K Shamanna, Tariq Muzzafar, Courtney DiNardo, Joseph D Khoury, Shaoying Li, L Jeffrey Medeiros, Sa A Wang, Guilin Tang
No abstract text is available yet for this article.
August 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27355333/targeting-isocitrate-dehydrogenase-idh-in-cancer
#7
Takeo Fujii, Muhammad Rizwan Khawaja, Courtney D DiNardo, Johnique T Atkins, Filip Janku
Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG...
May 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27248996/hereditary-predispositions-to-myelodysplastic-syndrome
#8
REVIEW
Sarah A Bannon, Courtney D DiNardo
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e...
May 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27245312/evidence-for-clinical-differentiation-and-differentiation-syndrome-in-patients-with-acute-myeloid-leukemia-and-idh1-mutations-treated-with-the-targeted-mutant-idh1-inhibitor-ag-120
#9
K C Birendra, Courtney D DiNardo
BACKGROUND: Cancer-associated isocitrate dehydrogenase (IDH) mutations block normal cellular differentiation via production of the oncometabolite, R-2-hydroxyglutarate. In patients with acute myeloid leukemia (AML) receiving targeted mutant IDH inhibitor therapy, neutrophil recovery within the setting of clinical differentiation syndrome (DS) has been anecdotally described. PATIENTS AND METHODS: We describe 3 patients who developed clinically apparent DS during monotherapy with the mutant IDH1 inhibitor, AG-120, for relapsed/refractory AML...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27210295/evaluation-of-patients-and-families-with-concern-for-predispositions-to-hematologic-malignancies-within-the-hereditary-hematologic-malignancy-clinic-hhmc
#10
Courtney D DiNardo, Sarah A Bannon, Mark Routbort, Anna Franklin, Maureen Mork, Mary Armanios, Emily M Mace, Jordan S Orange, Meselle Jeff-Eke, Jane E Churpek, Koichi Takahashi, Jeffrey L Jorgensen, Guillermo Garcia-Manero, Steve Kornblau, Alison Bertuch, Hannah Cheung, Kapil Bhalla, Andrew Futreal, Lucy A Godley, Keyur P Patel
INTRODUCTION: Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. PATIENTS AND METHODS: From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC)...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/26799610/interactions-and-relevance-of-blast-percentage-and-treatment-strategy-among-younger-and-older-patients-with-acute-myeloid-leukemia-aml-and-myelodysplastic-syndrome-mds
#11
Courtney D DiNardo, Guillermo Garcia-Manero, Sherry Pierce, Aziz Nazha, Carlos Bueso-Ramos, Elias Jabbour, Farhad Ravandi, Jorge Cortes, Hagop Kantarjian
Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20-29% blasts classified as refractory anemia with excess blasts in transformation (RAEB-T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment-naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014...
February 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/26768493/great-expectations-in-acute-myeloid-leukemia
#12
Maliha Khan, Courtney D DiNardo
No abstract text is available yet for this article.
February 2016: Future Oncology
https://www.readbyqxmd.com/read/26687423/sequential-azacitidine-and-lenalidomide-in-patients-with-high-risk-myelodysplastic-syndromes-and-acute-myeloid-leukaemia-a-single-arm-phase-1-2-study
#13
Courtney D DiNardo, Naval Daver, Elias Jabbour, Tapan Kadia, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Hui Yang, Sherry Pierce, William Wierda, Carlos Bueso-Ramos, Keyur P Patel, Jorge E Cortes, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero
BACKGROUND: The standard of care for myelodysplastic syndromes is hypomethylating agents such as azacitidine. However, responses to azacitidine are generally temporary, and outcomes after hypomethylating agent failure are dismal. Therefore, the development of more effective treatments is crucial to improve outcomes in patients with myelodysplastic syndromes. We aimed to assess azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia...
January 2015: Lancet Haematology
https://www.readbyqxmd.com/read/26432046/combination-of-hyper-cvad-with-ponatinib-as-first-line-therapy-for-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukaemia-a-single-centre-phase-2-study
#14
Elias Jabbour, Hagop Kantarjian, Farhad Ravandi, Deborah Thomas, Xuelin Huang, Stefan Faderl, Naveen Pemmaraju, Naval Daver, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, C Cameron Yin, Joseph D Khoury, Jeffrey Jorgensen, Zeev Estrov, Zachary Bohannan, Marina Konopleva, Tapan Kadia, Nitin Jain, Courtney DiNardo, William Wierda, Vicky Jeanis, Susan O'Brien
BACKGROUND: Combination of chemotherapy with a tyrosine-kinase inhibitor is effective in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia. Ponatinib is a more potent BCR-ABL1 inhibitor than all other tyrosine-kinase inhibitors and selectively suppresses the resistant T315I clones. We examined the activity and safety of combining chemotherapy with ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia in this continuing phase 2 trial...
November 2015: Lancet Oncology
https://www.readbyqxmd.com/read/26337351/getting-a-handle-on-hereditary-cebpa-mutations
#15
COMMENT
Courtney D DiNardo
No abstract text is available yet for this article.
September 3, 2015: Blood
https://www.readbyqxmd.com/read/26141213/jumping-translocations-in-myeloid-malignancies-associated-with-treatment-resistance-and-poor-survival
#16
David Sanford, Courtney D DiNardo, Guilin Tang, Jorge E Cortes, Srdan Verstovsek, Elias Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero
BACKGROUND: Jumping translocations (JT) are uncommon cytogenetic abnormalities involving nonreciprocal translocations of a single donor chromosome onto 2 or more chromosomes. The clinical characteristics and prognosis of JTs in patients with myeloid malignancies are not well described. MATERIALS AND METHODS: We searched our cytogenetic database from 2003 to 2014 to identify cases of myeloid malignancies associated with a JT. These cases were cross-referenced with our clinical databases to determine patient characteristics, response to treatment and overall survival...
September 2015: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/26044451/clinical-significance-of-newly-emerged-isolated-del-20q-in-patients-following-cytotoxic-therapies
#17
C Cameron Yin, Jie Peng, Yu Li, Rashmi K Shamanna, Tariq Muzzafar, Courtney DiNardo, Joseph D Khoury, Shaoying Li, L Jeffrey Medeiros, Sa A Wang, Guilin Tang
Deletion 20q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(20q) in patients following cytotoxic therapies raises concerns for an emerging therapy-related myeloid neoplasm. In this study, we identified 92 patients who acquired isolated del(20q) in their bone marrow following cytotoxic therapies for malignant neoplasms. Seventy-six patients showed interstitial and sixteen patients showed terminal 20q deletion. The median interval from prior cytotoxic therapies to detection of del(20q) was 58 months (range, 5-213 months)...
August 2015: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/26037522/time-to-revise-the-revised-international-prognostic-scoring-system
#18
COMMENT
Courtney D DiNardo, Farhad Ravandi
No abstract text is available yet for this article.
2015: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26016821/characteristics-clinical-outcome-and-prognostic-significance-of-idh-mutations-in-aml
#19
Courtney D DiNardo, Farhad Ravandi, Sam Agresta, Marina Konopleva, Koichi Takahashi, Tapan Kadia, Mark Routbort, Keyur P Patel, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian
The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92)...
August 2015: American Journal of Hematology
https://www.readbyqxmd.com/read/25612675/runx3-promoter-hypermethylation-is-frequent-in-leukaemia-cell-lines-and-associated-with-acute-myeloid-leukaemia-inv-16-subtype
#20
Marcos R H Estécio, Sirisha Maddipoti, Carlos Bueso-Ramos, Courtney D DiNardo, Hui Yang, Yue Wei, Kimie Kondo, Zhihong Fang, William Stevenson, Kun-Sang Chang, Sherry A Pierce, Zachary Bohannan, Gautam Borthakur, Hagop Kantarjian, Guillermo Garcia-Manero
Correlative and functional studies support the involvement of the RUNX gene family in haematological malignancies. To elucidate the role of epigenetics in RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23 leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1 and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly variable among patient samples, with clear association to cytogenetic status...
May 2015: British Journal of Haematology
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