399 results on '"Andrew Grigg"'
Search Results
2. Evaluation of a safe neutrophil count for cessation of intravenous antibiotics and early hospital discharge in stable, afebrile patients recovering after acute myeloid leukemia therapy or an autograft
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Chih-Chiang Hu, Rakhee Subramanian, and Andrew Grigg
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Cancer Research ,Oncology ,Hematology - Published
- 2023
3. Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study
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Kate Manos, Geoffrey Chong, Colm Keane, Sze-Ting Lee, Charmaine Smith, Leonid Churilov, Joseph McKendrick, William Renwick, Piers Blombery, Melinda Burgess, Niles Elizabeth Nelson, Tineke Fancourt, Joanne Hawking, Wendi Lin, Andrew M. Scott, Allison Barraclough, Joel Wight, Andrew Grigg, Chun Yew Fong, and Eliza A. Hawkes
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Cancer Research ,Oncology ,Hematology - Published
- 2023
4. Augmented ICE in Patients With Poor-Risk Refractory and Relapsed Lymphomas
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Sun Loo, Andrew Lim, Sze Ting Lee, and Andrew Grigg
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Cancer Research ,Oncology ,Hematology - Published
- 2023
5. Fertility recovery after high-dose melphalan containing regimens
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Andrew Grigg and Harini Haran
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Cancer Research ,Oncology ,Hematology - Published
- 2023
6. Challenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma
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Christa Ellen Nath, Andrew Grigg, Sebastian P. A. Rosser, Jane Estell, Elizabeth Newman, Campbell Tiley, Sundra Ramanathan, Shir Jing Ho, Stephen Larsen, John Gibson, Peter Presgrave, Peter John Shaw, and Judith Trotman
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Pharmacology ,Area Under Curve ,Hematopoietic Stem Cell Transplantation ,Humans ,Pharmacology (medical) ,Prospective Studies ,General Medicine ,Middle Aged ,Multiple Myeloma ,Melphalan - Abstract
Aim To evaluate the accuracy of melphalan test dose pharmacokinetic (PK) predictions of the subsequent high dose (HDM) area under the concentration-versus-time curve (AUC) and to identify sources of prediction error (PE). Methods A prospective multicentre PK study was conducted in 40 myeloma patients of median age 60 (range:35–71) years using a 20 mg/m2 test dose administered 1–3 days prior to HDM (predominantly 180 mg/m2). PK data were collected post the test and high doses to compare predicted versus actual AUCs determined using the trapezoidal rule. Test and high dose infusion concentration, volume and duration and the time from preparation to infusion were compared using the paired Wilcoxin rank sign test. The impact of Melphalan administration parameters on PE was evaluated using the Mann–Whitney test. The predictive capacity of a previously published population PK (PopPK) model was also examined. Results Predicted HDM AUC was within 15% of the observed values in only 63% of patients when analysed using the trapezoidal rule and 70% of patients using PopPK. Test dose infusion concentration, volume, duration and time from preparation to infusion were significantly lower than for HDM (p n = 5) was associated with significantly lower PE than administration times of 16–60 min (n = 22), p ± 15%), but the differences were not significant (p = 0.078, 0.228, respectively). Conclusion Test dose PK has the potential to predict subsequent HDM exposure to achieve a target AUC once melphalan administration parameters are optimised to account for stability issues in the formulation.
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- 2022
7. A critical evaluation of the role of iron overload in fatty liver disease
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Monique Fernandez, Julie Lokan, Christopher Leung, and Andrew Grigg
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Metabolic Syndrome ,Iron Overload ,Liver ,Hepatology ,Non-alcoholic Fatty Liver Disease ,Iron ,Ferritins ,Gastroenterology ,Cytokines ,Humans ,Reactive Oxygen Species ,Lipids - Abstract
Nonalcoholic fatty liver disease (NAFLD) has been associated with a condition known as the dysmetabolic iron overload syndrome, but the frequency and severity of iron overload in NAFLD is not well described. There is emerging evidence that mild to moderate excess hepatic iron can aggravate the risk of progression of NAFLD to nonalcoholic steatohepatitis and eventually cirrhosis. Mechanisms are postulated to be via reactive oxygen species, inflammatory cytokines, lipid oxidation, and oxidative stress. The aim of this review is to assess the evidence for true hepatic iron overload in NAFLD, to discuss the pathogenesis by which excess iron may be toxic, and to critically evaluate the studies designed to deplete iron by regular venesection. In brief, the studies are inconclusive due to heterogeneity in eligibility criteria, sample size, randomization, hepatic iron measurement, serial histological endpoints, target ferritin levels, length of venesection, and degree of confounding lifestyle intervention. We propose a trial designed to overcome the limitations of these studies.
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- 2022
8. Ibrutinib for Steroid Refractory Chronic Graft Vs Host Disease - Real World Experience
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Gaurav Sutrave, Tishya Indran, Yatika Jivan, Andrew Hutchison, Nada Hamad, Sui Tan, Duncan Purtill, Andrew Grigg, Siok-Keen Tey, David J. Curtis, David J Gottlieb, and Abir Bhattacharyya
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
9. Early and Deep Molecular Responses Achieved with Frontline Asciminib in Chronic Phase CML - Interim Results from ALLG CML13 Ascend-CML
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David T Yeung, Naranie Shanmuganathan, John Reynolds, Susan Branford, Mannu Walia, Agnes S.M. Yong, Jake Shortt, Kate Burbury, Nicholas Viiala, Ilona Cunningham, David M. Ross, Rosemary Harrup, Matthew Wright, Cecily Forsyth, Alwyn Bernard D'Souza, Robin J Filshie, Peter J. Browett, Steven W Lane, Carolyn Grove, Andrew Grigg, and Timothy Hughes
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
10. Living Long and Well After an Autograft
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Andrew Grigg
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Cancer Research ,Oncology - Published
- 2022
11. Panel-based gene testing in myelodysplastic/myeloproliferative neoplasm overlap syndromes: Australasian Leukaemia and Lymphoma Group (ALLG) consensus statement
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Anoop K. Enjeti, Rishu Agarwal, Piers Blombery, Lynette Chee, Chong Chyn Chua, Andrew Grigg, Nada Hamad, Harry Iland, Steven Lane, Andrew Perkins, Deepak Singhal, Courtney Tate, Ing Soo Tiong, and David M. Ross
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Leukemia ,Myeloproliferative Disorders ,Lymphoma ,Myelodysplastic Syndromes ,Mutation ,Humans ,Myelodysplastic-Myeloproliferative Diseases ,Pathology and Forensic Medicine - Abstract
This review aims to provide an expert consensus statement to address the role of gene-panel testing in the diagnosis, prognosis and management of adult myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes (MDS/MPN) in Australia. This consensus statement was developed by an expert group, actively involved in gene panel testing in the area of MDS/MPN in Australia. This work was led by the chairs of the MDS (A/Prof A. Enjeti) and MPN (A/Prof D. Ross) working parties of the Australasian Leukaemia and Lymphoma Group (ALLG). The authors were selected after an expression of interest process on the basis of active laboratory involvement in gene panel testing, a specific demonstrated interest in MDS/MPN and/or publication record in this field. The authors were then allocated sections for literature review to identify the specific genes of interest for each MDS/MPN entity. At least two authors reviewed each section and an overarching diagnostic algorithm was developed by a consensus amongst all authors.
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- 2022
12. Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial
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Meletios A Dimopoulos, Paul G Richardson, Nizar J Bahlis, Sebastian Grosicki, Michele Cavo, Meral Beksaç, Wojciech Legieć, Anna M Liberati, Hartmut Goldschmidt, Andrew Belch, Hila Magen, Alessandra Larocca, Jacob P Laubach, Maria T Petrucci, Donna Reece, Darrell White, María-Victoria Mateos, Ivan Špička, Mihaela Lazaroiu, Jesús Berdeja, Jonathan L Kaufman, Ying-Ming Jou, Alex Ganetsky, Mihaela Popa McKiver, Sagar Lonial, Katja Weisel, Irwindeep Sandhu, Monika Podhorecka, Antonio Palumbo, Adi Shacham-Abulafia, Iuliana Vaxman, Ofer Shpilberg, Britta Besemer, Maurizio Martelli, Roberto Foà, Paolo De Fabritiis, Tommaso Caravita di Toritto, Emanuil Gheorghita, Albert Oriol, Philip Rowlings, Angelucci Emanuele, Angelo M Carella, Massimo Offidani, Joan Bladé, Luis F Casado, Heather Oakervee, Victoria Panelli, Luis Meza, Thomas Kühr, Miguel Granell, Don Benson, Rajesh Nair, Viran Holden, James Reeves, Richard W Eek, Patricia A Walker, John Catalano, András Rosta, Ewa Lech-Marańda, Christy Samaras, Anthony Reiman, Robert Weaver, Peter Acs, Andrew Grigg, Bernard De Prijck, Martha Louzada, Leonard Minuk, Michael Sebag, Martine Klausmann, Manfred Welslau, Andrzej Hellmann, Catalin Danaila, Pamela Becker, William Bensinger, Bruce Porterfield, Manuel Modiano, Stephen M Schultz, Robert Manges, Huey-Shin Cindy Lee, James X Gray, Matthew P Wright, Marie-Christine Vekemans, Aryan Hamed, Zoltán Gasztonyi, Gábor Mikala, Tamás Masszi, Barbara Gamberi, Kazimierz Kuliczkowski, Lidia Usnarska-Zubkiewicz, Enrique Bengoechea, María AE Gutiérrez, Miguel TH García, Jesús San-Miguel, Christoph Driessen, Rajesh Behl, Warren Brenner, Carl Gray, Vincent Hansen, Mehdi Moezi, Hector V Cortes, Charles Yen, Laurent Gressot, Noemi Horvath, James M D'Rozario, Maya Latimer, Maria-Christine Kyrtsonis, Evgeni Chubar, Moshe Mittelman, Luca Baldini, Patrizia Tosi, Angelo Vacca, Wiesław W Jędrzejczak, Tadeusz Robak, Juan J Lahuerta, Jennifer Carney, Franklin Chen, Robert Hirsch, Marco Ruiz, Alvaro Alencar, Madan Jagasia, Samer Kasbari, Philip Kuriakose, Aftab Mahmood, Madhu Chaudhry, Gary Cohen, Stephen Noga, Sch Roa, Andrzej Jakubowiak, Cara Rosenbaum, Michel Delforge, Vanessa Delrieu, Chantal Doyen, Deeren Dries, Hilde Demuynck, Rik Schots, Vladimir Maisnar, Igor W Blau, Heinz A Dürk, Andrea Kerkhoff, Martin Kropff, Markus Munder, Christoph Röllig, Christof Scheid, Argiris S Symeonidis, Árpád Illés, Mark Coyne, Peter O'Gorman, Patrick Hayden, Michael O'Dwyer, Dina Ben-Yehuda, Andrei Braester, Anatoly Nemets, Gilles Lugassy, Yossi Cohen, Naomi Rahimi-Levene, Alberto Bosi, Sara Pezzatti, Fausto Rossini, Enrico M Pogliani, Antonello Pinto, Mieczysław Komarnicki, Gabriela Borsaru, Razvan Stoia, Boris Afanasyev, María A Goñi, Ana V Carboneras, Sarah Ali, S. Eric Rubenstein, Salvador Caputto, Thomas Cosgriff, Suzanne Fanning, Ali Khojasteh, Andrew Liman, Albert Malcolm, Nandagopal Vrindavanam, Ravindranath Patel, Rajesh Belani, Marie Shieh, Keith Stockerl-Goldstein, Charles Strnad, Robert Stuart, Saurabh Chhabra, Luciano Costa, Haresh Jhangiani, Bradley Augustson, Robin Filshie, Amanda Johnston, Mark S Hertzberg, Philippe Mineur, Susan Fox, Rami Kotb, Vi Dao, Richard LeBlanc, Evzen Gregora, Annamaria Brioli, Lars-Olof Mügge, Mathias Hänel, Christian Langer, Eleni Kapsali, Evangelos Briasoulis, Despoina Kyriakou, Izhar Hardan, Netanel A Horowitz, Cangialosi Clotilde, Francesco Fabbiano, Barbara Castagnari, Fabio Ciceri, Gerardo Musuraca, Andrzej Deptała, Janusz Kłoczko, Marius Balea, Ana-Maria Vladareanu, Victor Rossiev, Adrián Alegre, Cristina Encinas, Jorge Gayoso, Thomas Pabst, Neil Rabin, Sherri Arledge, Fernando Cabanillas, Joseph Catlett, Tarek Chidiac, David Clarkson, Madhav Dhodapkar, George Geils, Cyrus MA Khan, Entezam Sahovic, Mohamad Khasawneh, Rajesh Sehgal, Oscar Ballester, Moshe Levy, Joseph Fay, Kiem Liem, Matthew Lunning, Julie Vose, Edward Faber, Donald MacFarlane, Raymond Hohl, Tariq Mahmood, Birbal Bhaskar, Martha Mims, Ira Oliff, Agne Paner, John Maciejewski, Arvinda Padmanabhan, Robert Richard, Amit Sanyal, Gary Schiller, Harry Staszewski, Don Stevens, Christopher Vaughn, Kevin Windsor, Clinical sciences, and Hematology
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Male ,diagnnose ,ELOQUENT-1 ,Hematology ,Antibodies, Monoclonal, Humanized ,elotuzumab ,Dexamethasone ,surgery ,oncology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Multiple Myeloma ,patiens ,Lenalidomide ,transplantation ,Aged - Abstract
BACKGROUND: Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT). METHODS: ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (
- Published
- 2022
13. Disseminated Invasive Mucormycosis Infection Following Autologous Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma
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Edward R. Scheffer Cliff, Gemma Reynolds, and Andrew Grigg
- Abstract
Invasive fungal infections (IFI) are challenging to predict, diagnose and treat, and are associated with a particularly high mortality among patients with hematological malignancies. They are relatively uncommon in patients with lymphoma, compared with those with acute leukemia or undergoing allogeneic transplantation. We present a patient, autografted for recurrent lymphoma, with fever and refractory diarrhea persisting post engraftment, eventually attributable to disseminated mucor infection. This case illustrates the challenge of timely diagnosis and initiation of treatment for IFI in lymphoma patients, who do not routinely receive antifungal prophylaxis, and the importance of aggressive investigation and symptom-directed tissue sampling for evidence of IFI in febrile immunocompromised hosts not responding to broad-spectrum antibiotics.
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- 2023
14. Very late-onset hepatitis B reactivation following chemoimmunotherapy
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Andrew Grigg, Joe Sasadeusz, Kumar Visvanathan, and Edward R Scheffer Cliff
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Hepatitis B virus ,Cancer Research ,medicine.medical_specialty ,Hepatitis B Surface Antigens ,business.industry ,Late onset ,Hematology ,Hepatitis B ,medicine.disease ,Antiviral Agents ,Gastroenterology ,Oncology ,Chemoimmunotherapy ,Internal medicine ,Humans ,Medicine ,Virus Activation ,business - Published
- 2021
15. Optimizing the oral dose of cyclosporine with concomitant posaconazole post stem cell allograft
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Julia McClelland, Eric Wong, and Andrew Grigg
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Cancer Research ,Oncology ,Hematology - Abstract
Cyclosporine is an immunosuppressive agent to prevent acute graft versus host disease (GVHD) in patients undergoing a stem cell allograft. It has a narrow therapeutic range, and its metabolism can be affected by posaconazole, commonly used as antifungal prophylaxis post allograft. There is limited evidence on the optimal oral cyclosporine starting dose in this setting. A delicate balance is required in dose adjustments to avoid toxic levels while maintaining sufficient drug concentrations to prevent GVHD. We undertook a retrospective audit of 28 patients undergoing their first allograft who received posaconazole and commenced on a starting oral cyclosporine dose of 2 mg/kg twice daily. Our key findings were that this starting dose was too high, with all patients experiencing at least one toxicity and an overall low incidence of GVHD.
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- 2022
16. Acute kidney injury in patients receiving high-dose etoposide phosphate as conditioning prior to hematopoietic stem cell transplantation in hematologic malignancies may be associated with elevated body mass index
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Tamasine Stewart, Mark Dowling, Brett Janson, Jim Siderov, Jing Xie, Andrew Grigg, and Amit Khot
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Cancer Research ,Oncology ,Hematology - Published
- 2022
17. Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study
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Andres Forero-Torres, Tatyana Feldman, Christopher Pocock, Andrea Gallamini, John Radford, Joseph Tuscano, Yasuhiro Oki, Andrew M. Evens, Hina Jolin, Anas Younes, Keenan Fenton, Stephen M. Ansell, Joseph M. Connors, Andrew Grigg, Won Seog Kim, Ashish Gautam, Kerry J. Savage, Rachael Liu, and Monika Długosz-Danecka
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Oncology ,medicine.medical_specialty ,Neutropenia ,Dacarbazine ,Vinblastine ,Bleomycin ,chemistry.chemical_compound ,Older patients ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,polycyclic compounds ,medicine ,Humans ,Doxorubicin ,Brentuximab vedotin ,Aged ,Neoplasm Staging ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Peripheral Nervous System Diseases ,Cancer ,Hematology ,medicine.disease ,Hodgkin Disease ,ABVD ,chemistry ,business ,medicine.drug - Abstract
Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs.
- Published
- 2021
18. Germline Missense Variants in SH2B3 Underpin Platelet Count Variation and Inherited MPN
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Liesl Butler, Christine Lee, Graham William Magor, Rhiannon Morris, Michael Tallack, Charlene Lam, Adam Ivey, Jane Lin, Zihao Deng, Andrew Grigg, Jane Mason, Malaika Perchard, Helen Weston, Nik Cummings, Andrew Brooks, Jeffrey J Babon, Andrew J Murphy, Jessica M Salmon, and Andrew Charles Perkins
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. Toxicity associated with high-dose intravenous methotrexate for hematological malignancies
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Joel Wight, Matthew Ku, Melissa Garwood, Duncan Carradice, Masa Lasica, Louise Keamy, Eliza A. Hawkes, and Andrew Grigg
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Cancer Research ,Methotrexate ,Oncology ,Drug-Related Side Effects and Adverse Reactions ,Hematologic Neoplasms ,Australia ,Humans ,Hematology ,Renal Insufficiency ,Kidney ,Retrospective Studies - Abstract
Intravenous high-dose methotrexate (HD-MTX) is a critical chemotherapeutic agent in hematological malignancies, however, data are lacking on how to predict and prevent toxicities such as kidney injury. We retrospectively analyzed 539 episodes of HD-MTX (≥1 g/m
- Published
- 2022
20. Genomics analysis of leukaemia predisposition in X‐linked agammaglobulinaemia
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Andrew Grigg, Keishiro Amano, Masahiro Hirayama, Osamu Ohara, Akihiro Hoshino, Hirokazu Kanegane, Tomohiro Morio, Julian J. Bosco, Masatoshi Takagi, Takuya Naruto, Akira Nishimura, Masahiro Migita, Shotaro Iwamoto, Menno C. van Zelm, and Satoshi Miyamoto
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Genetics ,Acute megakaryoblastic leukemia ,biology ,medicine ,biology.protein ,Bruton's tyrosine kinase ,X-linked agammaglobulinemia ,Genomics ,X linked agammaglobulinaemia ,Hematology ,medicine.disease - Published
- 2021
21. Routine Blood Tests in Asymptomatic Patients With Indolent Lymphoma Have Limited Ability to Detect Clinically Significant Disease Progression
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Andrew Grigg, Zoe Loh, Joanna Chan, Geoffrey Chong, Tania Cushion, Gurjot Gill, Matthew Whybird, Eliza A Hawkes, Steven Cheema, and Oliver Piercey
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Adolescent ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Hematologic Tests ,Hematology ,Oncology (nursing) ,business.industry ,Lymphoma, Non-Hodgkin ,Health Policy ,Disease progression ,Australia ,Cancer ,Retrospective cohort study ,medicine.disease ,Lymphoma ,Indolent lymphoma ,030104 developmental biology ,Clinical research ,030220 oncology & carcinogenesis ,Disease Progression ,Neoplasm Recurrence, Local ,medicine.symptom ,business - Abstract
PURPOSE: Patients with indolent non-Hodgkin lymphoma (iNHL) undergo regular active surveillance in between treatment periods to detect disease relapse or progression. As part of surveillance, international guidelines recommend regular routine blood testing, which is based on consensus rather than evidence of utility. METHODS: We conducted a retrospective analysis of all patients older than age 16 years diagnosed with grade 1-3A follicular or marginal zone lymphoma between 2008 and 2017 from 2 Australian cancer centers to assess the utility of full blood examination, lactate dehydrogenase, and β2-microglobulin in detecting progression events, defined as either disease relapse or progression of disease. RESULTS: One hundred eighty patients attended 1,757 outpatient appointments (median follow-up, 36 months). Routine blood tests (RBTs) were performed before 83% of appointments. Seventy-four progression events occurred in 62 patients. Only 2 events (3%) were detected by RBTs alone, both of which occurred in treatment-naïve patients who subsequently developed symptoms within 3 weeks. The remainder of progression events were suspected clinically (88%) or detected by imaging (9%). RBT results were frequently abnormal in asymptomatic patients (19%), with abnormal results leading to either additional investigations or an increased surveillance frequency in 8% of cases. The overall sensitivity and positive predictive value of abnormal RBT results in detecting progression events were 39% and 9%, respectively. CONCLUSION: RBTs have poor performance characteristics and rarely detect clinically significant disease progression or relapse in asymptomatic patients with iNHL.
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- 2020
22. Recommendation for TP53 mutation testing in newly diagnosed mantle cell lymphoma: a statement from working groups sponsored by the Victorian Comprehensive Cancer Centre
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Constantine S. Tam, Gareth P. Gregory, Matthew Ku, Shaun Fleming, Sasanka M. Handunnetti, Denise Lee, Patricia Walker, Andrew Perkins, Thomas E. Lew, Shreerang Sirdesai, Chong Chyn Chua, Michael Gilbertson, Masa Lasica, Mary Ann Anderson, William Renwick, Andrew Grigg, Sush Patil, Stephen Opat, Adam Friebe, Rachel Cooke, Jasper De Boer, Andrew Spencer, David Ritchie, Rishu Agarwal, and Piers Blombery
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Adult ,Mutation ,Internal Medicine ,Humans ,Lymphoma, Mantle-Cell ,Tumor Suppressor Protein p53 ,Prognosis - Published
- 2022
23. Stability of Al-substituted jarosite in the presence of Fe(II)
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Andrew Grigg, Luiza Notini, Ralf Kaegi, Laurel ThomasArrigo, and Ruben Kretzschmar
- Abstract
Jarosite is a ferric iron sulfate mineral [(KFe3(SO4)2(OH)6] that is commonly formed in acidic environments that are rich in iron and sulfate, such as acid-sulfate soils or acid mine drainage. The stability of jarosite is important because the mineral contains embodied acidity and may scavenge trace elements by sorption and co-precipitation. Although stable under high Eh and low pH conditions, previous studies have shown that jarosite is prone to transformation by hydrolysis at circumneutral pH, or may undergo Fe(II)-catalysed transformation where ferrous ions are present [1-3]. Jarosite may be exposed to Fe(II) at circumneutral pH in reducing environments, such as in flooded acid-sulfate soils [2]. Jarosite is a member of the alunite supergroup and forms a solid solution series with alunite by substitution of Al for Fe. However, the effect of Al substitution on the stability of jarosite in the presence of Fe(II) has not previously been investigated. Here, we performed batch experiments using samples of a synthetic jarosite without aluminium substitution, and synthetic jarosite containing 7.3% Al-for-Fe substitution. Mineral samples were reacted with 0.5 mM and 5 mM Fe(II) at pH 7.1 (50 mM MOPS buffer) for up to 24 hours. Rietveld analysis of X-ray diffraction patterns was used to quantify mineral transformations and to determine the crystallinity of, and Al substitution in, product phases. Complete transformation of jarosite to mixtures of ferrihydrite, goethite and lepidocrocite occurred within several hours for all jarosite samples and Fe(II) treatments. The 10-fold increase in Fe(II) concentration resulted in a 50% increase in jarosite transformation rate, and pure jarosite transformed 110% to 280% faster than Al-substituted jarosite. The transformation products of Al-substituted jarosite contained a smaller proportion of lepidocrocite than the products of pure jarosite transformation, and the unit cell size of the lepidocrocite that initially formed from Al-substituted jarosite indicates that Al was substituted into the structure. These results demonstrate that structural Al can stabilise jarosite against transformation, which has implications for understanding the longevity of jarosite, and its importance to trace element cycling, in reducing environments.1. Welch, S. A., et al. (2008) Chem. Geol. 254: pp. 73-862. Karimian, N., et al. (2017) Environ. Sci. Technol. 51: pp. 4259-42683. Whitworth, A. J., et al. (2020) Chem. Geol. 554
- Published
- 2022
24. Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy
- Author
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Árpád Illés, Andres Forero-Torres, Sergey Alekseev, Anas Younes, Valeria Buccheri, Keenan Fenton, Pier Luigi Zinzani, Joseph M. Connors, Anna Sureda, Andrea Gallamini, Rachael Liu, Lena Specht, Jan Walewski, Ashish Gautam, Andrew Grigg, Tae Min Kim, Graham P. Collins, Indra Purevjal, David J. Straus, Straus D., Collins G., Walewski J., Zinzani P.L., Grigg A., Sureda A., Illes A., Kim T.M., Alekseev S., Specht L., Buccheri V., Younes A., Connors J., Forero-Torres A., Fenton K., Gautam A., Purevjal I., Liu R., and Gallamini A.
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Newly diagnosed ,Vinblastine ,03 medical and health sciences ,0302 clinical medicine ,brentuximab vedotin ,primary prophylaxis ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Doxorubicin ,In patient ,Stage (cooking) ,Brentuximab vedotin ,frontline therapy ,Brentuximab Vedotin ,Chemotherapy ,business.industry ,growth factor ,Hematology ,Hodgkin Disease ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,business ,030215 immunology ,medicine.drug - Abstract
We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40–1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD.
- Published
- 2020
25. Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience
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Loretta J. Nastoupil, Nada Hamad, John Casey, Chan Yoon Cheah, Andrew Grigg, Collin K. Chin, Peter Wood, Kate Manos, Eliza A Hawkes, Maher K. Gandhi, Katharine L Lewis, Shir Jing Ho, Bryan Do, Julie Crawford, and Samar Issa
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Lymphoma ,Central nervous system ,Disease-Free Survival ,Central Nervous System Neoplasms ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Dexamethasone ,Aged ,Aged, 80 and over ,Hematology ,business.industry ,Adenine ,Cancer ,Middle Aged ,medicine.disease ,Survival Rate ,Clinical trial ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,Female ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression-free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8-16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.
- Published
- 2020
26. Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low‐intensity chemotherapy in acute myeloid leukaemia
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Nicola E. Potter, Manohursingh Runglall, Adam Ivey, Anthony P. Schwarer, Kavita Raj, Phillip C. Nguyen, Nigel H. Russell, Chun Yew Fong, Annie‐Louise Latif, Andrew H. Wei, Tse-Chieh Teh, Andrew Grigg, Nicholas James Cummings, Ing Soo Tiong, Richard Dillon, and David Taussig
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,NPM1 ,Neoplasm, Residual ,Myeloid ,medicine.medical_treatment ,Azacitidine ,Short Report ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Short Reports ,AML ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sulfonamides ,Chemotherapy ,venetoclax ,Venetoclax ,business.industry ,Nuclear Proteins ,Haematological Malignancy ‐ Clinical ,Hematology ,Middle Aged ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Neoplasm Proteins ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,MRD ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Mutation ,Cytarabine ,Female ,business ,Nucleophosmin ,030215 immunology ,medicine.drug - Abstract
Summary Based on promising results in older adults with acute myeloid leukaemia (AML), we treated patients with NPM1 mut measurable residual disease (MRD) using off‐label venetoclax in combination with low‐dose cytarabine or azacitidine. Twelve consecutive patients were retrospectively identified, including five with molecular persistence and seven with molecular relapse/progression. All patients with molecular persistence achieved durable molecular complete remission (CRMRD‐) without transplantation. Six of seven patients with molecular relapse/progression achieved CRMRD‐ after 1–2 cycles of venetoclax. This paper highlights the promising efficacy of venetoclax‐based therapy to reduce the relapse risk in patients with persistent or rising NPM1 mut MRD.
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- 2020
27. High rate of durable remissions post autologous stem cell transplantation for core-binding factor acute myeloid leukaemia in second complete remission
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Humphrey Pullon, Andrew Spencer, Julie Crawford, Andrew Grigg, Matthew J Rees, Hock Choong Lai, Frank Alvaro, Sam Milliken, Duncan Purtill, and Peter Browett
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High rate ,Transplantation ,business.industry ,Core Binding Factors ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Hematology ,Core binding factor acute myeloid leukaemia ,Transplantation, Autologous ,Leukemia, Myeloid, Acute ,Autologous stem-cell transplantation ,Cancer research ,Humans ,Medicine ,business ,Stem Cell Transplantation - Published
- 2020
28. New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation
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Ashish Bajel, Julian Lindsay, David Gottlieb, Monica A. Slavin, Michelle K Yong, Andrew Grigg, David Ritchie, Jen Kok, and William D. Rawlinson
- Subjects
Ganciclovir ,medicine.medical_specialty ,T-Lymphocytes ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,030204 cardiovascular system & hematology ,Antiviral Agents ,03 medical and health sciences ,Letermovir ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,business.industry ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Maribavir ,Valganciclovir ,medicine.disease ,Transplantation ,Cytomegalovirus Infections ,business ,Viral load ,medicine.drug - Abstract
Cytomegalovirus (CMV) viraemia continues to be a frequent complication in the post-haemopoietic stem cell transplantation period despite a low incidence of CMV end-organ disease. Several significant advances in the understanding and management of CMV infection have occurred in the last few years including improved diagnostics, monitoring of CMV immunity, availability of novel anti-CMV drugs, and emerging use of immunotherapies including CMV-specific T-cell infusions. In addition to reviewing these advances we also explore some of the more practical prescribing issues of the older and newer CMV drugs including cost, toxicity and drug interactions to help clinicians navigate this new era of CMV management.
- Published
- 2020
29. Nurse-initiated pre-prescribed antibiotic orders to facilitate prompt and appropriate antibiotic administration in febrile neutropenia
- Author
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Andrew Grigg, Jason A Trubiano, Carl M. J. Kirkpatrick, Samuel E Grigg, Karen F Urbancic, Steven T Walker, and Emma Cohen
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Male ,medicine.drug_class ,Antibiotics ,Drug Prescriptions ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Clinical pathway ,Nursing ,law ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Aged ,Febrile Neutropenia ,Retrospective Studies ,Septic shock ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Intensive care unit ,Anti-Bacterial Agents ,Hospitalization ,Intensive Care Units ,Oncology ,030220 oncology & carcinogenesis ,Administration, Intravenous ,Female ,business ,Febrile neutropenia ,Cohort study - Abstract
To assess the impact of a pathway allowing nurse initiation of first dose intravenous (IV) antibiotics on time to antibiotic administration (TTA) in adult inpatients with febrile neutropenia (FN).This study evaluated the impact on TTA of a clinical pathway (November 2017 to April 2018) allowing nurse initiation of pre-prescribed antibiotics in adult haematology patients with FN, compared with a prior cohort (November 2016 to April 2017) in which antibiotics were only prescribed and administered after medical review. The primary endpoint for comparison was TTA, calculated as the time between the first recorded fever and IV antibiotic administration. Secondary endpoints included appropriateness of initial antibiotic choice, 30-day all-cause mortality and admission to intensive care unit (ICU).Forty-seven eligible FN episodes in 40 patients and 61 episodes in 52 patients were evaluated in the pre- and post-implementation groups, respectively. Baseline characteristics were comparable between groups. Median (IQR) TTA, in the pre-implementation group [66 min (40-100 min)] was significantly prolonged versus post-implementation group [29 min (20-41 min); p 0.001]. A significantly higher proportion of episodes were administered appropriate initial antibiotics in the post-versus pre-implementation groups (100% vs. 89%, p = 0.03). There was no significant change in 30-day all-cause mortality (0% vs. 5%, p = 0.3) or ICU admission within 48 h of fever (0% vs. 2%, p 0.99) between pre- and post-implementation groups, respectively.A pathway allowing nurse initiation of pre-prescribed antibiotic orders for FN significantly reduced TTA from first recorded fever and increased the proportion of appropriate initial antibiotic choices without significantly impacting on patient outcomes.
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- 2020
30. The impact of G-CSF alone vs G-CSF and cyclophosphamide mobilisation on autograft immune cell content in multiple myeloma
- Author
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Matthew J. Rees, Ashish Panigrahi, Simon J. Harrison, Andrew Spencer, Tiffany Khong, Simon Gibbs, Jay Hocking, Andrew Grigg, and Daniela Zantomio
- Subjects
Transplantation ,Granulocyte Colony-Stimulating Factor ,Hematopoietic Stem Cell Transplantation ,Humans ,Antigens, CD34 ,Hematology ,Autografts ,Multiple Myeloma ,Cyclophosphamide ,Hematopoietic Stem Cell Mobilization - Published
- 2022
31. Initial conditions can have long-term effects on plant species diversity in jarrah forest restored after bauxite mining
- Author
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MI Daws, Andrew Grigg, Cameron Blackburn, J Barker, Rachel Standish, and Mark Tibbett
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- 2022
32. Treatment practice and outcomes in FLT3-mutant acute myeloid leukemia in the pre-midostaurin era: a real-world experience from Australian tertiary hospitals
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Anthony P. Schwarer, Mark Droogleever, Stephen B. Ting, Chong Chyn Chua, Ing Soo Tiong, Jasmine Singh, Chun Y Fong, Lan Zhang, Andrew Grigg, Andrew H. Wei, and Andrew Lim
- Subjects
Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Myeloid leukemia ,Hematology ,Intensive chemotherapy ,Clinical trial ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Oncology ,chemistry ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Treatment practice ,medicine ,Generalizability theory ,Midostaurin ,Intensive care medicine ,education ,business ,030215 immunology ,Patient factors - Abstract
Recent regulatory approval of midostaurin, a FLT3 targeting small molecular inhibitor, will likely lead to increased use of midostaurin in combination with intensive chemotherapy for patients with FLT3-mutant AML. Translation of clinical trial results into everyday practice has its challenges. This study compared the relevance of the trial population and practices studied in the midostaurin registration study (RATIFY) with real-world practice in terms of patient factors, chemotherapy, mutation-specific frequencies and clinical outcomes among patients with FLT3-mutant AML in the pre-midostaurin era (2010-2015) in Australia. We observed substantial diversity of chemotherapy regimens used in the community and limitations of the generalizability of eligibility criteria used in RATIFY (such as age and hyperleukocytosis). This study provides real-world historical data that may be used for comparison with future trial cohorts incorporating FLT3 inhibitors into the management of FLT3-mutant AML and highlights the inherent difficulties in translating clinical trial data into routine practice.
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- 2019
33. Safe administration of obinutuzumab to rituximab-intolerant patients
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Kate Manos and Andrew Grigg
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,Antibodies, Monoclonal, Humanized ,chemistry.chemical_compound ,chemistry ,Obinutuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Rituximab ,business ,Administration (government) ,medicine.drug - Published
- 2021
34. Results of a Phase 2, Randomized, Double-Blind Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)
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Michael Murray, Devendra K Hiwase, Glen A Kennedy, Nichloas Murphy, Stephen B. Ting, Ashish Bajel, Paula Marlton, Ing Soo Tiong, Harry J. Iland, Simon He, Mark J. Levis, Sam Yuen, Andrew W. Roberts, Joanna Leadbetter, Campbell Tiley, Natasha S Anstee, Meaghan Wall, Tristan Rawling, Gavin Cull, Kirk Morris, Andrew Grigg, Uyen Nguyen, Maya Latimer, Doen Ming Ong, Sundra Ravanathan, John Taper, Anthony P. Schwarer, Uwe Hahn, James D'Rozario, Ian Bilmon, Andrew H. Wei, Sun Loo, Anoop K Enjeti, and Emma Verner
- Subjects
Oncology ,Sorafenib ,medicine.medical_specialty ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Intensive chemotherapy ,Placebo ,Biochemistry ,Double blind study ,Internal medicine ,medicine ,business ,Flt3 itd ,medicine.drug - Abstract
Introduction Midostaurin is the only approved FLT3 inhibitor for combination with intensive induction and consolidation chemotherapy in newly diagnosed patients with FLT3 mutant AML. The FLT3 inhibitor, sorafenib, was investigated in the randomized SORAML trial (Röllig, Lancet Onc 2015), in combination with intensive chemotherapy (IC) for newly diagnosed adults with AML Methods The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized phase 2 study [ACTRN12611001112954] in 99 adults aged 18-65 years with newly diagnosed FLT3-ITD positive (allelic ratio (AR) ≥0.05) AML to determine whether addition of SOR to IC would improve event-free survival (EFS). The study was powered to identify a 25% increase in 2-year EFS with SOR. Patients 18-55 yrs received induction with IDAC-3 (idarubicin [IDA] 12 mg/m2 D1-3 and ara-C 1.5 g/m2 BD D1,3,5,7); patients 56-65 received 7+3 (IDA 12 mg/m2 D1-3 and ara-C 100 mg/m2 D1-7 IVI). Patients were randomized 2:1 to SOR or PBO 400 mg BD on days 4-10 of induction and each consolidation cycle. Due to the pharmacokinetic interaction between SOR and azoles, antifungal prophylaxis during induction was with AmBisome 5 mg/kg IV twice weekly. For consolidation, patients 18-55 yrs received 2 cycles of IcE (IDA 9 mg/m2 D1-2, ara-C 100 mg/m2 D1-5 IVI and etoposide 75 mg/m2 D1-5), those 56-65 yrs received 2 cycles of IDAC-2 (IDA 12 mg/m2 D1-2 and ara-C 1g/m2 BD D1,3,5). Maintenance was with SOR/PBO 400 mg bd days 1-28 for 12 cycles. Allogeneic HCT (allo-HCT) was at investigator discretion. SOR/PBO was not continued post allo-HCT. The primary endpoint was EFS without censoring for allo-HCT with events defined as failure to achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi), relapse or death. Pre-specified secondary endpoints included overall response rate (ORR) defined as CR and CRi, tolerability, EFS according to FLT3-ITD AR < or ≥ 0.7 and impact of randomization on allograft outcome. Results Between Jan 2013-May 2018, 18 centers randomized 99 patients to induction with either SOR (n=65) or PBO (n=33); one patient later found to be FLT3-ITD negative was excluded. Patient characteristics are shown in Table 1. Treatment arms were balanced apart from fewer patients in the SOR arm with NPM1 mutant AML. Deliverability of therapy was comparable, with commencement of consolidation in 78% and 79% and maintenance therapy in 32% and 27% in the SOR and PBO arms, respectively. The overall response rate (ORR) was high in both arms; 91% in the SOR (CR 80%, CRi 11%) and 94% in the PBO (CR 70%, CRi 24%) arm. In the SOR arm, 5% achieved partial remission, went off study and were deemed treatment failures. With a median overall follow-up of 25 mo, there was no significant difference in EFS (HR 0.87 95% CI 0.50-1.49; P=0.61)(Fig A) or OS (HR 0.70 95% CI 0.38-1.29; P=0.26)(Fig. B), nor in a sensitivity analysis with censoring at HCT. 2 yr EFS was 47.9% (SOR) vs 45.4% (PBO) and 2-year OS 66.8% (SOR) vs 56.4% (PBO). Hematopoietic cell transplant (HCT) in CR1 was performed in 62% and 58% in the SOR and PBO arms, respectively. For patients in CR1, 2 yr OS post-HCT was 78.5% (SOR) vs 54.2% (PBO)(Fig C). Suggestive of an on-target effect against FLT3-ITD, the impact of SOR on OS appeared greater for patients with higher FLT3-ITD AR ≥0.7 (Fig. D) (Table 2). Only one early death (within 30 days) was recorded in each treatment arm. The frequency of grade 3-4 adverse events (AEs) were similar between the two arms, apart from palmar-plantar rash, reported as drug-related in 15.4% and 6.1% pts in the SOR and PBO arms, respectively. Correlative studies will be reported in a companion abstract. Conclusions SOR did not improve EFS when combined with intensive chemotherapy in adults with newly diagnosed FLT3-ITD AML. Although not powered for significance, SOR showed a trend for improved OS among patients with higher FLT3-ITD AR or receiving HCT in CR1. Further exploration of more potent FLT3 inhibitors in the pre- and post-allograft setting are warranted for patients with newly diagnosed FLT3 mutant AML. Acknowledgements: The ALLG AMLM16 trial was funded through an Australian Government NHMRC grant and a research grant from the Leukaemia Foundation of Australia. Bayer supplied sorafenib and Gilead AmBisome. Disclosures Wei: Roche: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Astra Zeneca: Honoraria, Research Funding; Janssen: Honoraria; Macrogenics: Honoraria. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; Bayer: Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Verner:Janssen Cilag Pty Ltd.: Research Funding. Hahn:Roche: Honoraria; Astra Zeneca: Honoraria. Hiwase:Novartis Australia: Research Funding. Anstee:Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:FujiFilm: Honoraria, Research Funding; Amgen: Honoraria; Daiichi-Sankyo: Honoraria; Menarini: Honoraria; Astellas: Honoraria, Research Funding. Bajel:Abbvie: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria. Roberts:Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties; Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding. OffLabel Disclosure: Sorafenib for FLT3-ITD AML
- Published
- 2020
35. The Impact of Sorafenib on Phospho-FLT3 Inhibition and FLT3-ITD MRD after Chemotherapy: Correlative Studies from the Phase 2 Randomized Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)
- Author
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Michael Murray, Paula Marlton, Andrew Grigg, Andrew W. Roberts, Sarah MacRaild, Tristan Rawling, James D'Rozario, Giovanna Pomilio, Adam Ivey, Anthony P. Schwarer, Glen A Kennedy, Mark J. Levis, Doen Ming Ong, Anoop K Enjeti, Ian Bilmon, Andrew H. Wei, and Natasha S Anstee
- Subjects
Sorafenib ,Chemotherapy ,medicine.medical_specialty ,Venetoclax ,business.industry ,medicine.medical_treatment ,Immunology ,Myeloid leukemia ,Consolidation Chemotherapy ,Cell Biology ,Hematology ,Placebo ,Biochemistry ,law.invention ,chemistry.chemical_compound ,Maintenance therapy ,Randomized controlled trial ,chemistry ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Introduction The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized trial (AMLM16) combining the FLT3 inhibitor sorafenib (SOR) or placebo (PBO) with intensive induction and consolidation chemotherapy, followed by 12 months of maintenance therapy in patients with FLT3-ITD mutant AML. The clinical results of the AMLM16 study are detailed in a companion abstract co-submitted to ASH 2020. We hypothesized that the optimal time to administer sorafenib would be d4-10 of induction in order to limit overlap with anthracyclines on d1-3 and to avoid high FLT3 ligand (FLT3L) levels beyond d10, which could abrogate FLT3 on-target activity and diminish the therapeutic index. Key objectives of the correlative studies were to correlate in vivo SOR activity on suppression of FLT3 phosphorylation (P-FLT3) using the plasma inhibitory assay (PIA) with relapse risk and to assess for the presence of FLT3-ITD measurable residual disease (MRD) after therapy. Methods Patients aged 18-65 years with newly diagnosed AML (excluding APML) were enrolled to a National Blood Cancer Registry; those with a FLT3-ITD mutant: wild-type allelic ratio (AR) ≥ 0.05 were eligible for enrolment to the AMLM16 study. Patients were randomized 2:1 to SOR or PBO 400mg orally bd on d4-10 of induction and each consolidation cycle in combination with intensive chemotherapy and for 12 months as maintenance monotherapy. Serum FLT3-L levels were measured by ELISA, SOR and its metabolites by mass spectrometry. SOR mediated inhibition of FLT3 was measured in serum samples using the PIA as previously described (Levis, Blood 2006) in which P-FLT3 inhibition to ≤15% baseline is defined as response. Quantitation of FLT3-ITD levels by NGS was performed at study screening and after each induction and consolidation chemotherapy cycle. Quantitation was by amplicon-based sequencing which detected ITDs >6 bp with a sensitivity of 0.001%: levels below and above this were termed measurable residual disease (MRD) negative and positive respectively. Prepared libraries were sequenced (Illumina) using 150 bp paired-end reads with a minimum coverage of 400,000 reads. Bioinformatics analysis was performed using getITD (Blätte, Leukemia, 2019). Results 98 evaluable patients were randomized to induction with either SOR (n=65) or PBO (n=33) with a FLT3-ITD AR ranging from 0.05 to 8.4. FLT3-ITD AR was ≥ 0.5 or ≥ 0.7 in 48% and 29%, respectively. During induction, FLT3-L levels increased by an average of 150-fold from d4 to d10 and a further 1.6-fold to d15, with a return to baseline by d28. Serial plasma samples to assess PIA were available for 63 patients (Fig A). Response to ≤15% on d10 (relative to d4) was observed in 88% of SOR patients, compared with 4.5% receiving PBO. The relapse risk was 32% and 62% among PIA responders and non-responders, respectively (Fig A). Among patients with PIA response to ≤15% by d10 (the last day of SOR/PBO), only 8.3% had evidence of a sustained PIA response by d15. Reduction of FLT3-ITD to undetectable levels (VAF We compared the relationship between inhibition of P-FLT3 on d10 and bone marrow FLT3-ITD MRD after induction with relapse risk (Fig D, E). In the SOR arm, if P-FLT3 was not reduced to ≤15%, all patients had persistent FLT3-ITD MRD after induction and the relapse risk was 80% (Fig D). In contrast, if P-FLT3 inhibition was ≤15% and FLT3-ITD MRD not detected, the relapse risk was only 20%. In the PBO arm after induction, persistent and undetectable FLT3-ITD MRD (VAF Conclusions These studies demonstrate that in vivo SOR inhibited P-FLT3 to ≤15% during induction in the majority of cases and was associated with reduced relapse risk. Persistent FLT3-ITD MRD post-induction was associated with a high relapse risk in both treatment arms. For patients receiving SOR, failure to reduce P-FLT3 response to ≤15% was associated with a high risk of persistent FLT3-ITD MRD and clinical relapse. Disclosures Anstee: Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Research Funding. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Bayer: Speakers Bureau; Sanofi: Speakers Bureau. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Roberts:Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding; Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties. Wei:Astra Zeneca: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Roche: Honoraria; Macrogenics: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria. OffLabel Disclosure: Sorafenib for FLT3-ITD AML
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- 2020
36. BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY IN ADOLESCENTS AND YOUNG ADULTS (AYAS) WITH STAGE III OR IV HODGKIN LYMPHOMA: A SUBGROUP ANALYSIS FROM THE PHASE 3 ECHELON‐1 STUDY
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Ann S. LaCasce, Nancy L. Bartlett, Kerry J. Savage, David J. Straus, Harry H. Miao, Andrew Grigg, Howland E. Crosswell, Pier Luigi Zinzani, Graham P. Collins, Keenan Fenton, Cassie Dong, and Michelle A. Fanale
- Subjects
Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Subgroup analysis ,Hematology ,General Medicine ,humanities ,Young age ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Hodgkin lymphoma ,Young adult ,Stage (cooking) ,business ,Brentuximab vedotin ,medicine.drug ,Rare disease - Abstract
7528 Background: Hodgkin lymphoma (HL) is a rare disease that commonly occurs in adolescents and young adults (AYAs) which is typically defined as 15 to 39 years. Given their young age at presentation, key factors in treatment selection include a high cure rate and limiting long-term toxicities. Brentuximab vedotin (Adcetris®; A) is a CD30-directed ADC approved in combination with doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD) for adults with previously untreated stage III/IV cHL based on results from the phase 3 ECHELON-1 trial. Recent 5-year data demonstrated a significantly improved PFS per investigator (INV) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.69; 95% CI, 0.54–0.9; P = 0.003) (Straus 2020). Here we describe key efficacy and safety results for AYA pts enrolled in ECHELON-1. Methods: ECHELON-1 (N = 1334) is a global, open-label, multicenter, randomized trial of pts with previously untreated stage III/IV cHL. A total of 771 AYAs (57.8%) received either A+AVD (n = 396) or ABVD (n = 375) with a PET scan after cycle 2 (PET2). An analysis of PFS (time from randomization to progression or death from any cause) per INV was conducted. Results: After a median follow-up of 60.7 months (95% CI, 60.4-61.0), there was a 36% reduction in the risk of progression or death in AYAs receiving A+AVD vs ABVD (HR 0.64; 95% CI, 0.45-0.92; P = 0.013) with a 5-year PFS of 86.3% vs 79.4%, respectively, similar to the ITT population. The PFS benefit of A+AVD vs ABVD was independent of PET2 status; PET2 positivity (Deauville 4-5) was 6% and 8%, respectively. On the A+AVD arm, 81 AYAs (20%) had at least 1 subsequent anticancer therapy vs 96 AYAs (26%) on the ABVD arm; 26 AYAs (7%) received subsequent high dose chemotherapy and autologous stem cell transplant vs 32 AYAs (9%) on the A+AVD and ABVD arms, respectively. Resolution or improvement of peripheral neuropathy (PN) were similar in both arms; 224 AYAs (88%) on the A+AVD had resolution or improvement of PN vs 133 AYAs (89%) on the ABVD arm. Ongoing PN was predominantly Gr 1 (62%) and Gr 2 (26%), with 8 AYAs (13%) on the A+AVD arm and 1 AYA (5%) on the ABVD arm reporting ongoing Gr 3 PN. Finally, 7 AYAs (1.8%) and 5 AYAs (1.4%) on the A+AVD and ABVD arms, respectively, reported a secondary malignancy. Subsequent pregnancies were reported in female pts (44 A+AVD; 26 ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths were reported. All but 1 pt in each arm was < 40. Conclusions: Consistent with the ITT population, AYAs treated with A+AVD compared to ABVD had a durable PFS benefit at this significant 5-year milestone. No impact on the rate of secondary malignancies and a numerically greater number of pregnancies were observed, outcomes of interest to AYAs. Additionally, the majority of PN events improved or resolved over time. A+AVD should be considered a treatment option for AYAs with stage III/IV cHL. Clinical trial information: NCT01712490.
- Published
- 2021
37. IMMUNE PRIMING WITH NIVOLUMAB FOLLOWED BY NIVOLUMAB & RITUXIMAB IN 1 ST LINE TREATMENT OF FOLLICULAR LYMPHOMA: THE PHASE 2 1 ST FLOR STUDY
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S. T. Lee, Rishu Agarwal, Kate Manos, David Ritchie, Colm Keane, C. Smith, Eliza A Hawkes, K. Houdyk, Allison Barraclough, Rachel Koldej, G. Chong, Andrew Grigg, T. Fancourt, Leonid Churilov, Michael Gilbertson, and J. Hawking
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Follicular lymphoma ,Priming (immunology) ,Flor ,Hematology ,General Medicine ,Immunotherapy ,medicine.disease ,Immune system ,Internal medicine ,medicine ,Indolent Non-Hodgkin Lymphoma ,Rituximab ,Nivolumab ,business ,medicine.drug - Published
- 2021
38. Nivolumab induces dynamic alterations in CD8 T-cell function and TIM-3 expression when used to treat relapsed acute myeloid leukemia after allogeneic stem cell transplantation
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Eric Wong, David Ritchie, Joanne E. Davis, Jeff Szer, Andrew Grigg, and Rachel Koldej
- Subjects
Cancer Research ,Myeloid ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Transplantation ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Cytotoxic T cell ,Stem cell ,Nivolumab ,business ,030215 immunology - Abstract
Trial registration: ClinicalTrials.gov identifier: NCT03146468.Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (alloSCT) is a major cause of mortali...
- Published
- 2019
39. Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms
- Author
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Andrew C. Perkins, David M. Ross, Andrew Grigg, Kate Burbury, Nathalie C. Cook, Cecily Forsyth, Wai Hoong Chan, Steven W. Lane, Forsyth, Cecily J, Chan, Wai-Hoong, Grigg, Andrew P, Cook, Nathalie C, Lane, Steven W, Burbury, Kate L, Perkins, Andrew C, and Ross, David M
- Subjects
Pegylated interferon α ,Disease ,030204 cardiovascular system & hematology ,myeloproliferative neoplasms ,Polyethylene Glycols ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Pregnancy ,Pegylated interferon ,IFN treatment for MPNs ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Myelofibrosis ,Myeloproliferative neoplasm ,Myeloproliferative Disorders ,business.industry ,Australia ,Interferon-alpha ,Cancer ,medicine.disease ,Thrombosis ,pegylated IFN ,Treatment Outcome ,Hematologic Neoplasms ,Immunology ,Disease Progression ,Female ,business ,medicine.drug - Abstract
The classical myeloproliferative neoplasms (MPN) are uncommon clonal haematopoietic malignancies characterised by excessive production of mature blood cells. Clinically they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance, and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon‐α (IFN) but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side effects. The pegylated form of IFN is a long‐acting preparation which is better tolerated and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPNs, suggest criteria for patient selection in each of these diseases, and discuss strategies to manage the side effects of pegylated IFN. Refereed/Peer-reviewed
- Published
- 2019
40. Screening and Prophylaxis to Prevent Hepatitis B Reactivation
- Author
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Marion G. Peters, Joe Sasadeusz, Seng Lee Lim, Andrew Grigg, Peter Hughes, Monica A. Slavin, Geoff McColl, Joseph Doyle, James A Rickard, Kumar Visvanathan, Sue-Anne McLachlan, Peter De Cruz, Michaela Lucas, Vijaya Sundararajan, Nicholas A. Shackel, Robert G. Gish, and Alexander J. Thompson
- Subjects
Oncology ,medicine.medical_specialty ,Cost effectiveness ,Hepatitis C virus ,medicine.medical_treatment ,medicine.disease_cause ,Organ transplantation ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Immunity ,Internal medicine ,Medicine ,In patient ,Mass screening ,Hepatitis B virus ,Hepatitis ,Hepatology ,business.industry ,Immunosuppression ,Immunotherapy ,Entecavir ,Hepatitis C ,Hepatitis B ,Acquired immune system ,medicine.disease ,Transplantation ,030220 oncology & carcinogenesis ,Immunology ,Rituximab ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.
- Published
- 2019
41. Comprehensive geriatric assessment is useful in an elderly Australian population with diffuse large B‐cell lymphoma receiving rituximab‐chemotherapy combinations
- Author
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Bianca Devitt, Chan Yoon Cheah, Doen Ming Ong, Zoe Loh, Eliza A Hawkes, Geoffrey Chong, Grace Gard, Huayi Ellen Huang, Michael Ashby, Zi Y Ng, Andrew Grigg, Yee Shuen Chong, and Allison Mo
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Frail Elderly ,medicine.medical_treatment ,Risk Assessment ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Activities of Daily Living ,Antineoplastic Combined Chemotherapy Protocols ,Severity of illness ,medicine ,Humans ,Prospective cohort study ,Geriatric Assessment ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,business.industry ,Hazard ratio ,Australia ,Retrospective cohort study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.
- Published
- 2019
42. Is there a role for proton pump inhibitor prophylaxis in haematology patients?
- Author
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Emma Leitinger, Lisa Hui, and Andrew Grigg
- Subjects
medicine.medical_specialty ,Gastrointestinal bleeding ,medicine.drug_class ,medicine.medical_treatment ,Proton-pump inhibitor ,Inappropriate Prescribing ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outpatients ,Internal Medicine ,medicine ,Mucositis ,Humans ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Intensive care medicine ,Adverse effect ,Glucocorticoids ,Inpatients ,Chemotherapy ,Hematology ,business.industry ,Australia ,Proton Pump Inhibitors ,medicine.disease ,Hematologic Diseases ,Practice Guidelines as Topic ,Drug Therapy, Combination ,Gastrointestinal Hemorrhage ,business - Abstract
While proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy-induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14-month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.
- Published
- 2019
43. The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia
- Author
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Lucy C. Fox, Rebecca Cleary, Kate Burbury, Amy Holmes, David T Yeung, Olga Motorna, Rosemary Harrup, Kah Lok Chan, Katherine D Cummins, Anthony P. Schwarer, Jake Shortt, Andrew McQuillan, Maciek Tatarczuch, Sumita Ratnasingam, Ben Costello, Andrew Grigg, Adrian G. Minson, Shaun Fleming, Asma Ashraf, Cecily Forsyth, Wei Hsun Hsu, and Faye Putt
- Subjects
Adult ,Male ,medicine.medical_specialty ,law.invention ,Safety-Based Drug Withdrawals ,Pharmacotherapy ,Randomized controlled trial ,law ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,Vascular Diseases ,Adverse effect ,Protein Kinase Inhibitors ,Aged ,Dyslipidemias ,Retrospective Studies ,Aged, 80 and over ,Myeloid Neoplasia ,business.industry ,Incidence (epidemiology) ,Age Factors ,Australia ,Myeloid leukemia ,Imatinib ,Retrospective cohort study ,Hematology ,Middle Aged ,Pyrimidines ,Nilotinib ,Female ,business ,medicine.drug - Abstract
Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P = .022) and dyslipidemia (P = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.
- Published
- 2019
44. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study
- Author
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Monique C. Minnema, Margaret A. Shipp, Stephen M. Ansell, Nishitha Reddy, Scott J. Rodig, Jonathon B. Cohen, Selda Samakoglu, Kazunobu Kato, Margaretha G.M. Roemer, Sarit Assouline, Philippe Armand, Anne Sumbul, Michelle Poon, Peter Johnson, Azra H. Ligon, Manish Sharma, John M. Timmerman, and Andrew Grigg
- Subjects
Male ,Oncology ,Diffuse/drug therapy ,Cancer Research ,Time Factors ,Lymphoma ,Programmed Cell Death 1 Receptor ,Phases of clinical research ,Transplantation, Autologous/adverse effects ,Clinical Trial, Phase II ,Antineoplastic Agents, Immunological ,immune system diseases ,hemic and lymphatic diseases ,Immunological/adverse effects ,80 and over ,Treatment Failure ,Non-U.S. Gov't ,Aged, 80 and over ,Research Support, Non-U.S. Gov't ,Programmed Cell Death 1 Receptor/antagonists & inhibitors ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,ORIGINAL REPORTS ,Middle Aged ,Clinical Trial ,Progression-Free Survival ,Phase II ,Multicenter Study ,Nivolumab ,Lymphoma, Large B-Cell, Diffuse/drug therapy ,Disease Progression ,Female ,Lymphoma, Large B-Cell, Diffuse ,Chromosomes, Human, Pair 9 ,Human ,Pair 9 ,Antineoplastic Agents, Immunological/adverse effects ,Adult ,medicine.medical_specialty ,Autologous/adverse effects ,Antineoplastic Agents ,Research Support ,Transplantation, Autologous ,Chromosomes ,N.I.H ,Young Adult ,Research Support, N.I.H., Extramural ,Refractory ,Internal medicine ,Large B-Cell ,Journal Article ,medicine ,Humans ,Autologous transplantation ,Progression-free survival ,Hematopoietic Stem Cell Transplantation/adverse effects ,Aged ,Transplantation ,business.industry ,Extramural ,Nivolumab/adverse effects ,medicine.disease ,business ,Diffuse large B-cell lymphoma - Abstract
Purpose Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. Methods In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. Results Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. Conclusion Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
- Published
- 2019
45. Next generation restoration metrics: Using soil eDNA bacterial community data to measure trajectories towards rehabilitation targets
- Author
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Craig Liddicoat, Siegfried L. Krauss, Andrew Bissett, Ryan J. Borrett, Luisa C. Ducki, Shawn D. Peddle, Paul Bullock, Mark P. Dobrowolski, Andrew Grigg, Mark Tibbett, and Martin F. Breed
- Subjects
Benchmarking ,Soil ,Environmental Engineering ,Bacteria ,Microbiota ,General Medicine ,Management, Monitoring, Policy and Law ,Waste Management and Disposal ,Soil Microbiology - Abstract
In post-mining rehabilitation, successful mine closure planning requires specific, measurable, achievable, relevant and time-bound (SMART) completion criteria, such as returning ecological communities to match a target level of similarity to reference sites. Soil microbiota are fundamentally linked to the restoration of degraded ecosystems, helping to underpin ecological functions and plant communities. High-throughput sequencing of soil eDNA to characterise these communities offers promise to help monitor and predict ecological progress towards reference states. Here we demonstrate a novel methodology for monitoring and evaluating ecological restoration using three long-term (>25 year) case study post-mining rehabilitation soil eDNA-based bacterial community datasets. Specifically, we developed rehabilitation trajectory assessments based on similarity to reference data from restoration chronosequence datasets. Recognising that numerous alternative options for microbiota data processing have potential to influence these assessments, we comprehensively examined the influence of standard versus compositional data analyses, different ecological distance measures, sequence grouping approaches, eliminating rare taxa, and the potential for excessive spatial autocorrelation to impact on results. Our approach reduces the complexity of information that often overwhelms ecologically-relevant patterns in microbiota studies, and enables prediction of recovery time, with explicit inclusion of uncertainty in assessments. We offer a step change in the development of quantitative microbiota-based SMART metrics for measuring rehabilitation success. Our approach may also have wider applications where restorative processes facilitate the shift of microbiota towards reference states.
- Published
- 2022
46. The real-world tolerability and efficacy of asparaginase in adults aged 40 years and older with Philadelphia-negative acute lymphoblastic leukemia
- Author
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Simon Wu, Christian E Bryant, Andrew Grigg, Ing Soo Tiong, Mridula Mokoonlall, Anthony P. Schwarer, Caroline Dix, James D'Rozario, and Matthew J Rees
- Subjects
Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Asparaginase ,Lymphoblastic Leukemia ,Antineoplastic Agents ,chemistry.chemical_compound ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Philadelphia Chromosome ,Philadelphia negative ,Adult all ,business.industry ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Tolerability ,chemistry ,Feature (computer vision) ,Acute Disease ,business - Abstract
Pediatric-inspired acute lymphoblastic leukemia (ALL) regimens are increasingly used in adult ALL [1]. These protocols universally feature asparaginase (ASP), a bacterial enzyme which deprives ALL ...
- Published
- 2021
47. Case Report: Confirmation by Metagenomic Sequencing of Visceral Leishmaniasis in an Immunosuppressed Returned Traveler
- Author
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Nicole Isles, Torsten Seemann, Eloise Williams, Jason C Kwong, Trevor J. Kilpatrick, Benjamin P Howden, Marcel Leroi, and Andrew Grigg
- Subjects
Male ,030231 tropical medicine ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Bone Marrow ,Virology ,medicine ,Humans ,Leishmania infantum ,Travel ,biology ,business.industry ,Leishmaniasis ,Articles ,Middle Aged ,biology.organism_classification ,medicine.disease ,Leishmania ,Fingolimod ,Pancytopenia ,Infectious Diseases ,Visceral leishmaniasis ,medicine.anatomical_structure ,Italy ,Metagenomics ,Immunology ,Leishmaniasis, Visceral ,Parasitology ,Bone marrow ,business ,medicine.drug - Abstract
There has been increased interest in using metagenomic next-generation sequencing as an unbiased approach for diagnosing infectious diseases. We describe a 61-year-old man on fingolimod therapy for multiple sclerosis with an extensive travel history who presented with 7 months of fevers, night sweats, and weight loss. Peripheral blood tests showed pancytopenia and abnormal acute phase reactants. A bone marrow aspirate showed the presence of numerous intracellular and extracellular amastigotes consistent with visceral leishmaniasis (VL). Metagenomic sequencing of the bone marrow aspirate confirmed Leishmania infantum, a species widely reported in the Mediterranean region. This correlated with acquisition of VL infection during the patient's most recent epidemiological exposure in southern Italy 12 months prior. This case demonstrates the potential application of metagenomic sequencing for identification and speciation of Leishmania in cases of VL; however, further assessment is required using other more readily obtained clinical samples such as blood.
- Published
- 2020
48. Optimal oral cyclosporin dosing with concomitant posaconazole post allogeneic stem cell transplantation
- Author
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Charlotte F. M. Hughes, Andrew Grigg, and Danielle H Robinson
- Subjects
musculoskeletal diseases ,Cancer Research ,Posaconazole ,Antifungal Agents ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Dosing ,Drug toxicity ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Triazoles ,Transplantation ,Oncology ,Mycoses ,030220 oncology & carcinogenesis ,Concomitant ,Cyclosporine ,Stem cell ,business ,human activities ,030215 immunology ,medicine.drug - Abstract
Cyclosporin is an immunosuppressive agent in allogeneic hematopoietic stem cell transplantation and its metabolism is strongly affected by concomitant drugs, including posaconazole which is now extensively used as anti-fungal prophylaxis post-allograft. We undertook a retrospective audit of 29 patients undergoing their first allograft who were receiving posaconazole at the time of transition from intravenous to oral cyclosporin. This group had a median initial oral cyclosporin dose of 2.58 mg/kg bd (range 1.75-3.95) and high incidence of cyclosporin-related toxicity was noted, requiring significant dose reductions such that by day 60 the media dose was 1.60 mg/kg bd (range 0.86-3.33). We subsequently amended our dosing protocol and analyzed a further 20 patients specifying an initial oral cyclosporin dose of 2.25 mg/kg bd and found this had little impact on toxicity or requirement for dose reductions. Starting doses of no greater than 2 mg/kg bd appear optimal to prevent toxicity in allograft recipients receiving concomitant posaconazole.
- Published
- 2020
49. Follicular Lymphoma Evaluation Index (FLEX): A new clinical prognostic model that is superior to existing risk scores for predicting progression-free survival and early treatment failure after frontline immunochemotherapy
- Author
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Wolfgang Hiddemann, Carla Casulo, Federico Mattiello, Robert Marcus, Andrea Knapp, Christopher R. Bolen, Michael Herold, John F Seymour, Farheen Mir, Andrew Grigg, and Tina Nielsen
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Follicular lymphoma ,Models, Biological ,Disease-Free Survival ,law.invention ,International Prognostic Index ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,Medicine ,FLEX ,Humans ,Progression-free survival ,Treatment Failure ,Survival rate ,Lymphoma, Follicular ,Research Articles ,Aged ,business.industry ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,humanities ,Progression-Free Survival ,Clinical trial ,Survival Rate ,Editorial‐commentaries ,Cohort ,Commentary ,Female ,Immunotherapy ,business ,Research Article ,Follow-Up Studies - Abstract
Patients with advanced‐stage follicular lymphoma (FL) who progress early after receiving first‐line therapy have poor overall survival (OS). Currently applied clinical prognostic models such as FL International Prognostic Index [FLIPI], FLIPI‐2 and PRIMA‐Prognostic Index [PRIMA‐PI] have suboptimal sensitivity and specificity to predict this poor prognosis subgroup. The primary objective was to develop a novel prognostic model, the FL Evaluation Index (FLEX) score, to identify high‐risk patients and compare its performance with FLIPI, FLIPI‐2 and PRIMA‐PI. Progression‐free survival (PFS) after first‐line immunochemotherapy was the key endpoint, while OS and progression of disease within 24 months (POD24) were also assessed. The model, which includes nine clinical variables, was developed using a cohort of patients with previously untreated advanced‐stage FL from the phase 3 GALLIUM trial ({"type":"clinical-trial","attrs":{"text":"NCT01332968","term_id":"NCT01332968"}}NCT01332968). The performance of the model was validated using data from the SABRINA trial ({"type":"clinical-trial","attrs":{"text":"NCT01200758","term_id":"NCT01200758"}}NCT01200758). In GALLIUM (n = 1004; 127 with and 877 without POD24), FLEX increased the intergroup (low‐risk/high‐risk) difference in 2‐year and 3‐year PFS rates and demonstrated superior intergroup differences in 2‐year and 3‐year OS rates compared with FLIPI, FLIPI‐2 and PRIMA‐PI. Sensitivity for a high‐risk score to predict POD24 was 60% using FLEX compared with 53% for FLIPI and FLIPI‐2, and 69% for PRIMA‐PI, while specificity was 68% for FLEX compared with 58% for FLIPI, 59% for FLIPI‐2 and 48% for PRIMA‐PI. The prognostic value of FLEX in SABRINA was similar to FLIPI. Therefore, FLEX appears to perform better than existing prognostic models in previously untreated FL, in particular for the newer treatment regimens.
- Published
- 2020
50. Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients
- Author
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Eliza A Hawkes, Sam E Grigg, Andrew Grigg, Ortis Estacio, Patrick Date, Douglas F Johnson, and Zoe Loh
- Subjects
Adult ,Male ,Microbiological Techniques ,medicine.medical_specialty ,Adolescent ,Urinalysis ,Urinary system ,Urine ,Asymptomatic ,Tazobactam ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Chemotherapy-Induced Febrile Neutropenia ,Aged ,Febrile Neutropenia ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,Diagnostic Tests, Routine ,business.industry ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Female ,Gentamicin ,medicine.symptom ,business ,Febrile neutropenia ,Piperacillin ,medicine.drug - Abstract
There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. All haematology inpatients over a 5-year period (2011–2015) were retrospectively reviewed for episodes of FN (neutrophil count 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed ‘asymptomatic’), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 105 colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised. Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p
- Published
- 2018
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