Feasibility And Cardiac Safety Of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (Neo) Adjuvant Therapy For Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer,
2015
Zucker School of Medicine at Hofstra/Northwell
Feasibility And Cardiac Safety Of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (Neo) Adjuvant Therapy For Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer, I. E. Krop, T. M. Suter, C. T. Dang, L. Dirix, G. Romieu, C. Zamagni, M. L. Citron, M. Campone, N. Xu, M. Smitt, L. Gianni
Journal Articles
Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) >= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without …
Identification And Characterization Of Distinct Il-17f Expression Patterns And Signaling Pathways In Chronic Lymphocytic Leukemia And Normal B Lymphocytes,
2015
Zucker School of Medicine at Hofstra/Northwell
Identification And Characterization Of Distinct Il-17f Expression Patterns And Signaling Pathways In Chronic Lymphocytic Leukemia And Normal B Lymphocytes, B. Sherry, P. Jain, P. Y. Chiu, L. Leung, S. L. Allen, J. E. Kolitz, K. R. Rai, J. Barrientos, S. Liang, R. Hawtin, N. Chiorazzi
Journal Articles
Chronic lymphocytic leukemia (CLL) is characterized by a progressive accumulation of B lymphocytes. T cell abnormalities are a common feature of CLL and contribute to impaired immune function in these patients. T cells are ineffective in eliminating the leukemic clone and may actually promote tumor growth and survival. Previous work from our laboratory documented elevated circulating levels of IL-17A-producing Th17 cells in CLL patients as compared to healthy age-matched control subjects. These high circulating Th17 levels associated with better prognostic markers and significantly longer overall survival, even among patients whose clones used unmutated IGHVs (U-CLL). Recent studies suggest that Th17 …
Integrating Targeted Drugs With Taxanes And Platinums: Opportunities And Challenges,
2015
Zucker School of Medicine at Hofstra/Northwell
Integrating Targeted Drugs With Taxanes And Platinums: Opportunities And Challenges, D. Kudlowitz, E. Teplinsky, F. Muggia
Journal Articles
In ovarian cancer, multiple attempts to adjust the standard taxane/platinum doublet by adding cytotoxic therapy or varying scheduling, dosage, and delivery have been met with limited success. Alternative methods to improve the grim prognosis of ovarian cancer, including molecular therapies, are currently under investigation. Efforts have been made to study tyrosine kinase inhibitors (including imatinib and pazopanib), Src kinase inhibitors and histone deacetylase inhibitors (HDACi) in combination with taxanes/platinums in order to improve efficacy. Unfortunately, while many pre-clinical and early phase clinical trials argue that the utilization of these molecular targets may enhance survival, only modest benefit has been seen …
Introduction: Moving Beyond Chemotherapy,
2015
Zucker School of Medicine at Hofstra/Northwell
Introduction: Moving Beyond Chemotherapy, F. Muggia, E. Teplinsky
Journal Articles
Epithelial ovarian cancer and related cancers arising in extrauterine Mullerian epithelium are generally chemosensitive—particularly to the platinum drugs, cisplatin and carboplatin, that form the backbone of first-line treatments upon diagnosis even at early stages. Doublets of platinums with paclitaxel have represented the standard-of-care since the late 1990s, with further notable advances taking place by intraperitoneal administration (in Gynecologic Oncology Group studies) after optimal surgical cytoreduction is achieved, and by divided doses of paclitaxel (in a Japanese GOG study). Adding another agent to improve on these results has otherwise proven to be quite challenging. Nevertheless, continued forays into introducing ‘targeted therapies’ …
Long-Term Follow-Up Of Mcl Patients Treated With Single-Agent Ibrutinib: Updated Safety And Efficacy Results,
2015
Zucker School of Medicine at Hofstra/Northwell
Long-Term Follow-Up Of Mcl Patients Treated With Single-Agent Ibrutinib: Updated Safety And Efficacy Results, M. L. Wang, K. A. Blum, P. Martin, A. Goy, R. Auer, B. S. Kahl, W. Jurczak, R. H. Advani, J. C. Barrientos, S. Rule, +14 Additional Authors
Journal Articles
Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of Ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was …
Acute Myeloid Leukemia Ontogeny Is Defined By Distinct Somatic Mutations,
2015
Zucker School of Medicine at Hofstra/Northwell
Acute Myeloid Leukemia Ontogeny Is Defined By Distinct Somatic Mutations, R. C. Lindsley, B. G. Mar, E. Mazzola, P. V. Grauman, S. Shareef, S. L. Allen, A. Pigneux, M. Wetzler, R. K. Stuart, B. L. Ebert, +9 Additional Authors
Journal Articles
Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early …
Successful Pregnancy Outcome In Paroxysmal Nocturnal Hemoglobinuria (Pnh) Following Escalated Eculizumab Dosing To Control Breakthrough Hemolysis,
2015
Zucker School of Medicine at Hofstra/Northwell
Successful Pregnancy Outcome In Paroxysmal Nocturnal Hemoglobinuria (Pnh) Following Escalated Eculizumab Dosing To Control Breakthrough Hemolysis, R. Sharma, A. Keyzner, J. Liu, T. Bradley, S. L. Allen
Journal Articles
Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH) is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.
Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?,
2015
Northwell Health
Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai
Journal Articles
No abstract provided.
Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance),
2015
Zucker School of Medicine at Hofstra/Northwell
Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance), J. A. Ligibel, C. T. Cirrincione, M. Liu, M. Citron, J. N. Ingle, W. Gradishar, S. Martino, W. Sikov, R. Michaelson, W. T. Barry, +6 Additional Authors
Journal Articles
BACKGROUND: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. METHODS: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number …
The Bruton Tyrosine Kinase Inhibitor Ibrutinib With Chemoimmunotherapy In Patients With Chronic Lymphocytic Leukemia,
2015
Zucker School of Medicine at Hofstra/Northwell
The Bruton Tyrosine Kinase Inhibitor Ibrutinib With Chemoimmunotherapy In Patients With Chronic Lymphocytic Leukemia, J. R. Brown, J. C. Barrientos, P. M. Barr, I. W. Flinn, J. A. Burger, A. Tran, F. Clow, D. F. James, K. Rai, S. O'Brien, +2 Additional Authors
Journal Articles
The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naive previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either …
Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide,
2015
Zucker School of Medicine at Hofstra/Northwell
Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide, D. Sanford, F. Lo-Coco, M. A. Sanz, E. Di Bona, S. Coutre, J. K. Altman, M. Wetzler, S. L. Allen, F. Ravandi, H. Kantarjian, J. E. Cortes
Journal Articles
Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m2 /d) during induction and for up to six cycles of consolidation. The …
Management Of Chronic Lymphocytic Leukemia In The Elderly,
2015
Zucker School of Medicine at Hofstra/Northwell
Management Of Chronic Lymphocytic Leukemia In The Elderly, J. C. Barrientos
Journal Articles
No abstract provided.
Management Of Adverse Events Associated With Idelalisib Treatment: Expert Panel Opinion,
2015
Zucker School of Medicine at Hofstra/Northwell
Management Of Adverse Events Associated With Idelalisib Treatment: Expert Panel Opinion, S. E. Coutre, J. C. Barrientos, J. R. Brown, S. De Vos, R. R. Furman, M. J. Keating, D. Li, S. M. O'Brien, J. M. Pagel, A. D. Zelenetz, +3 Additional Authors
Journal Articles
Idelalisib is a first-in-class selective, oral, phosphatidylinositol 3-kinase delta (PI3Kdelta) inhibitor approved for the treatment of several types of blood cancer. Idelalisib has demonstrated significant efficacy and a tolerable safety profile in clinical trials. However, the US prescribing information contains a black box warning for fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation. An expert panel was convened to review the pathology of these treatment-emergent adverse events (TEAEs) to propose key management tools for patients receiving idelalisib therapy. This article provides an overview of idelalisib TEAEs reported in clinical trials, and a summary of the panel's recommendations …
Targeting Mutant Braf In Relapsed Or Refractory Hairy-Cell Leukemia,
2015
Zucker School of Medicine at Hofstra/Northwell
Targeting Mutant Braf In Relapsed Or Refractory Hairy-Cell Leukemia, E. Tiacci, J. H. Park, L. De Carolis, S. S. Chung, A. Broccoli, S. Scott, F. Zaja, S. Devlin, K. R. Rai, M. S. Tallman, +31 Additional Authors
Journal Articles
Background BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues. Methods We conducted two phase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily) - one in Italy and one in the United States. The therapy was administered for a median of 16 weeks in the Italian study and 18 weeks in the U.S. STUDY: Primary end points were …
Phase Ii Double-Blind Placebo-Controlled Randomized Study Of Armodafinil For Brain Radiation-Induced Fatigue,
2015
Zucker School of Medicine at Hofstra/Northwell
Phase Ii Double-Blind Placebo-Controlled Randomized Study Of Armodafinil For Brain Radiation-Induced Fatigue, B. R. Page, E. G. Shaw, L. Lu, D. Bryant, D. Grisell, G. J. Lesser, D. C. Monitto, M. J. Naughton, S. R. Savona, M. D. Chan, +3 Additional Authors
Journal Articles
BACKGROUND: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. METHODS: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. RESULTS: From September 20, 2010, to October 20, 2012, 54 participants …
Egfr And Her2: Is There A Role In Ovarian Cancer?,
2015
Zucker School of Medicine at Hofstra/Northwell
Egfr And Her2: Is There A Role In Ovarian Cancer?, E. Teplinsky, F. Muggia
Journal Articles
Advanced ovarian cancer carries a grim prognosis and development of targeted therapies to improve outcomes has become an active area of research in this disease. The epidermal growth factor receptor (EGFR) and HER2/neu have shown to be overexpressed in ovarian cancer and there have been several clinical trials evaluating anti-EGFR and HER2 therapies in ovarian cancer. Unfortunately, the drugs have shown minimal efficacy and more recent work has now focused on identifying mechanisms of resistance and alternative ways of targeting these pathways. This review will discuss the currently published trials with anti-EGFR and HER2 agents in ovarian cancer and the …
In Support Of A Patient-Driven Initiative And Petition To Lower The High Price Of Cancer Drugs,
2015
Zucker School of Medicine at Hofstra/Northwell
In Support Of A Patient-Driven Initiative And Petition To Lower The High Price Of Cancer Drugs, A. Tefferi, K. Rai, A. I. Schafer, C. Schiffer, M. A. Sekeres, L. L. Siu, F. M. Stewart, M. Thompson, J. M. Vose, P. H. Wiernik, +109 Additional Authors
Journal Articles
No abstract provided.
Absolute Reticulocyte Count Acts As A Surrogate For Fetal Hemoglobin In Infants And Children With Sickle Cell Anemia.,
2015
George Washington University
Absolute Reticulocyte Count Acts As A Surrogate For Fetal Hemoglobin In Infants And Children With Sickle Cell Anemia., Emily Riehm Meier, Colleen Byrnes, Maxine Weissman, Y Terry Lee, Jeffery L Miller
Pediatrics Faculty Publications
Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were …
Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis.,
2015
University of Arizona
Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel
Journal Articles: Oncology and Hematology
No abstract provided.
Hiv Prevalence In Blood Donors And Recipients In Pakistan: A Meta-Analysis And Analysis Of Blood-Bank Data,
2015
Aga Khan University
Hiv Prevalence In Blood Donors And Recipients In Pakistan: A Meta-Analysis And Analysis Of Blood-Bank Data, Bushra Moiz, Barkat Ali, Muhammad Hasnain Chatha, Ahmed Raheem, Hasan Abbas Zaheer
Department of Pathology and Laboratory Medicine
Background:
The first instances of HIV-antibody detection in donated blood in Pakistan were reported in 1988. Since then, documentation of HIV in blood donors and of rates of transmission via transfusion has been limited. Previously assumed to have a low prevalence, HIV is an increasing health concern in Pakistan. Since there is no national, centralized blood-banking system, there are no reliable data on which to base estimated risks of transfusion-associated HIV infection. This study was therefore conducted to estimate the prevalence of HIV in blood donors and recipients in Pakistan between 1988 and 2012.
Methods:
Meta-analyses were undertaken of reported …
