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Courtney D DiNardo

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
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
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
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
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
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...
2016: International Journal of Molecular Sciences
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
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
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
Maliha Khan, Courtney D DiNardo
No abstract text is available yet for this article.
February 2016: Future Oncology
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
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
Courtney D DiNardo
No abstract text is available yet for this article.
September 3, 2015: Blood
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
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
Courtney D DiNardo, Farhad Ravandi
No abstract text is available yet for this article.
2015: Leukemia & Lymphoma
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
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
Courtney D DiNardo, Jorge E Cortes
INTRODUCTION: Acute myelogenous leukemia (AML) is a genetically heterogeneous disease. Yet current therapy has changed little over the decades and includes the nucleoside analog cytarabine in combination with an anthracycline as primary therapy. With this approach, durable cures occur in the minority of patients. With the recent improved scientific understanding of the underlying genetic and epigenetic aberrations in AML, there is now the potential of individualized and targeted therapeutic approaches for the curative treatment of AML...
January 2015: Expert Opinion on Pharmacotherapy
Guilin Tang, Courtney DiNardo, Liping Zhang, Farhad Ravandi, Joseph D Khoury, Yang O Huh, Tariq Muzzafar, L Jeffrey Medeiros, Sa A Wang, Carlos E Bueso-Ramos
MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in AML/MDS remains poorly characterized. Here, we report a series of 21 patients with myeloid neoplasms associated with MLL gene amplification from 1 institution. This series included 13 men and 8 women, with a median age of 64 years. Eleven patients presented as AML with myelodysplasia-related changes, 6 as therapy-related AML, and 4 as therapy-related MDS...
January 2015: Human Pathology
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