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    Plasmablastic Richter transformation as a resistance mechanism for chronic lymphocytic leukaemia treated with BCR signalling inhibitors
    Chan, K-L ; Blombery, P ; Jones, K ; Lade, S ; Carney, D ; Tran, H ; Seymour, JF ; Tam, CS (WILEY, 2017-04)
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    Oseltamivir Resistance in Adult Oncology and Hematology Patients Infected with Pandemic (H1N1) 2009 Virus, Australia
    Tramontana, AR ; George, B ; Hurt, AC ; Doyle, JS ; Langan, K ; Reid, AB ; Harper, JM ; Thursky, K ; Worth, LJ ; Dwyer, DE ; Morrissey, CO ; Johnson, PDR ; Buising, KL ; Harrison, SJ ; Seymour, JF ; Ferguson, PE ; Wang, B ; Denholm, JT ; Cheng, AC ; Slavin, M (CENTERS DISEASE CONTROL, 2010-07)
    We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
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    A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma
    Cheah, CY ; Herbert, KE ; O'Rourke, K ; Kennedy, GA ; George, A ; Fedele, PL ; Gilbertson, M ; Tan, SY ; Ritchie, DS ; Opat, SS ; Prince, HM ; Dickinson, M ; Burbury, K ; Wolf, M ; Januszewicz, EH ; Tam, CS ; Westerman, DA ; Carney, DA ; Harrison, SJ ; Seymour, JF (NATURE PUBLISHING GROUP, 2014-09-09)
    BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
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    Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia
    Kenealy, M ; Hertzberg, M ; Benson, W ; Taylor, K ; Cunningham, I ; Stevenson, W ; Hiwase, D ; Eek, R ; Zantomio, D ; Jong, S ; Wall, M ; Blombery, P ; Gerber, T ; Debrincat, M ; Zannino, D ; Seymour, JF (FERRATA STORTI FOUNDATION, 2019-03-31)
    Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chronic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% azacitidine arm and 54% lenalidomide+azacitidine arm (P=0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalidomide+azacitidine (P=0.14). There was no difference in progression- free or overall survival between the arms (each P>0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at www.anzc-tr.org.au as ACTRN12610000271000.
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    The Use of Optimal Treatment for DLBCL Is Improving in All Age Groups and Is a Key Factor in Overall Survival, but Non-Clinical Factors Influence Treatment
    Wong Doo, N ; White, VM ; Martin, K ; Bassett, JK ; Prince, HM ; Harrison, SJ ; Jefford, M ; Winship, I ; Millar, JL ; Milne, RL ; Seymour, JF ; Giles, GG (MDPI, 2019-06-26)
    INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma for which a cure is usually the therapeutic goal of optimal treatment. Using a large population-based cohort we sought to examine the factors associated with optimal DLBCL treatment and survival. METHODS: DLBCL cases were identified through the population-based Victorian Cancer Registry, capturing new diagnoses for two time periods: 2008-2009 and 2012-2013. Treatment was pre-emptively classified as 'optimal' or 'suboptimal', according to compliance with current treatment guidelines. Univariable and multivariable logistic regression models were fitted to determine factors associated with treatment and survival. RESULTS: Altogether, 1442 DLBCL cases were included. Based on multivariable analysis, delivery of optimal treatment was less likely for those aged ≥80 years (p < 0.001), women (p = 0.012), those with medical comorbidity (p < 0.001), those treated in a non-metropolitan hospital (p = 0.02) and those who were ex-smokers (p = 0.02). Delivery of optimal treatment increased between 2008-2009 and the 2012-2013 (from 60% to 79%, p < 0.001). Delivery of optimal treatment was independently associated with a lower risk of death (hazard ratio (HR) = 0.60 (95% confidence interval (CI) 0.45-0.81), p = 0.001). CONCLUSION: Delivery of optimal treatment for DLBCL is associated with hospital location and category, highlighting possible demographic variation in treatment patterns. Together with an increase in the proportion of patients receiving optimal treatment in the more recent time period, this suggests that treatment decisions in DLBCL may be subject to non-clinical influences, which may have implications when evaluating equity of treatment access. The positive association with survival emphasizes the importance of delivering optimal treatment in DLBCL.
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    Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients
    Guy, SD ; Tramontana, AR ; Worth, LJ ; Lau, E ; Hicks, RJ ; Seymour, JF ; Thursky, KA ; Slavin, MA (SPRINGER, 2012-08)
    PURPOSE: Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. METHODS: Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38°C and neutrophil count <500 cells/μl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. RESULTS: The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/μl (range 0-730 cells/μl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as "true positives" by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). CONCLUSION: This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required.