Medicine (St Vincent's) - Research Publications

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    Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia
    Odutola, MK ; van Leeuwen, MT ; Turner, J ; Bruinsma, F ; Seymour, JF ; Prince, HM ; Milliken, ST ; Trotman, J ; Verner, E ; Tiley, C ; Roncolato, F ; Underhill, CR ; Opat, SS ; Harvey, M ; Hertzberg, M ; Benke, G ; Giles, GG ; Vajdic, CM (MDPI, 2022-06-01)
    The association between smoking and alcohol consumption and follicular lymphoma (FL) incidence and clinical outcome is uncertain. We conducted a population-based family case-control study (709 cases: 490 controls) in Australia. We assessed lifetime history of smoking and recent alcohol consumption and followed-up cases (median = 83 months). We examined associations with FL risk using unconditional logistic regression and with all-cause and FL-specific mortality of cases using Cox regression. FL risk was associated with ever smoking (OR = 1.38, 95%CI = 1.08-1.74), former smoking (OR = 1.36, 95%CI = 1.05-1.77), smoking initiation before age 17 (OR = 1.47, 95%CI = 1.06-2.05), the highest categories of cigarettes smoked per day (OR = 1.44, 95%CI = 1.04-2.01), smoking duration (OR = 1.53, 95%CI = 1.07-2.18) and pack-years (OR = 1.56, 95%CI = 1.10-2.22). For never smokers, FL risk increased for those exposed indoors to >2 smokers during childhood (OR = 1.84, 95%CI = 1.11-3.04). For cases, current smoking and the highest categories of smoking duration and lifetime cigarette exposure were associated with elevated all-cause mortality. The hazard ratio for current smoking and FL-specific mortality was 2.97 (95%CI = 0.91-9.72). We found no association between recent alcohol consumption and FL risk, all-cause or FL-specific mortality. Our study showed consistent evidence of an association between smoking and increased FL risk and possibly also FL-specific mortality. Strengthening anti-smoking policies and interventions may reduce the population burden of FL.
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    The gamma delta lymphomas: an Australian multi-centre case series
    Harrop, S ; Di Ciaccio, P ; Doo, NW ; Cochrane, T ; Campbell, BA ; Hamad, N ; Dickinson, M ; Van Der Weyden, C ; Prince, HM (AME Publishing Company, 2022-03-01)
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    ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma
    Dhakal, B ; Shah, N ; Kansagra, A ; Kumar, A ; Lonial, S ; Garfall, A ; Cowan, A ; Poudyal, BS ; Costello, C ; Gay, F ; Cook, G ; Quach, H ; Einsele, H ; Schriber, J ; Hou, J ; Costa, L ; Aljurf, M ; Chaudhry, M ; Beksac, M ; Prince, M ; Mohty, M ; Janakiram, M ; Callander, N ; Biran, N ; Malhotra, P ; Otero, PR ; Moreau, P ; Abonour, R ; Iftikhar, R ; Silberman, R ; Mailankody, S ; Gregory, T ; Lin, Y ; Carpenter, P ; Hamadani, M ; Usmani, S ; Kumar, S (ELSEVIER SCIENCE INC, 2022-06-01)
    Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.
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    Alcohol and tobacco use and risk of multiple myeloma: A case‐control study
    Cheah, S ; Bassett, JK ; Bruinsma, FJ ; Cozen, W ; Hopper, JL ; Jayasekara, H ; Joshua, D ; MacInnis, RJ ; Prince, HM ; Vajdic, CM ; Leeuwen, MT ; Doo, NW ; Harrison, SJ ; English, DR ; Giles, GG ; Milne, RL (Wiley, 2022-02)
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    Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data
    Horwitz, SM ; Scarisbrick, JJ ; Dummer, R ; Whittaker, S ; Duvic, M ; Kim, YH ; Quaglino, P ; Zinzani, PL ; Bechter, O ; Eradat, H ; Pinter-Brown, L ; Akilov, OE ; Geskin, L ; Sanches, JA ; Ortiz-Romero, PL ; Weichenthal, M ; Fisher, DC ; Walewski, J ; Trotman, J ; Taylor, K ; Dalle, S ; Stadler, R ; Lisano, J ; Bunn, V ; Little, M ; Prince, HM (ELSEVIER, 2021-12-06)
    The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.
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    Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study
    Quaglino, P ; Prince, HM ; Cowan, R ; Vermeer, M ; Papadavid, E ; Bagot, M ; Servitjie, O ; Berti, E ; Guenova, E ; Stadler, R ; Querfeld, C ; Busschots, AM ; Hodak, E ; Patsatsi, A ; Sanches, J ; Maule, M ; Yoo, J ; Kevin, M ; Fava, P ; Ribero, S ; Zocchi, L ; Rubatto, M ; Fierro, MT ; Wehkamp, U ; Marshalko, M ; Mitteldorf, C ; Akilov, O ; Ortiz-Romero, P ; Estrach, T ; Vakeva, L ; Enz, PA ; Wobser, M ; Bayne, M ; Jonak, C ; Rubeta, M ; Forbes, A ; Bates, A ; Battistella, M ; Amel-Kashipaz, R ; Vydianath, B ; Combalia, A ; Georgiou, E ; Hauben, E ; Hong, EK ; Jost, M ; Knobler, R ; Amitay-Laish, I ; Miyashiro, D ; Cury-Martins, J ; Martinez, X ; Muniesa, C ; Prag-Naveh, H ; Stratigos, A ; Nikolaou, V ; Quint, K ; Ram-Wolff, C ; Rieger, K ; Stranzenbach, R ; Szepesi, A ; Alberti-Violetti, S ; Felicity, E ; Cerroni, L ; Kempf, W ; Whittaker, S ; Willemze, R ; Kim, Y ; Scarisbrick, JJ (WILEY, 2021-02-18)
    BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.
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    An Update on the Current Genomic Landscape of Breast Implant-Associated Anaplastic Large Cell Lymphoma
    Harrop, S ; Mehta-Shah, N ; Dsouza, C ; Thompson, E ; Deva, A ; Prince, HM (MDPI, 2021-10-01)
    Breast implant-associated lymphoma (BIA-ALCL) is a rare subtype of anaplastic large-cell lymphoma associated with breast prostheses. Most patients present with a localised periprosthetic effusion and are managed with removal of the implant and surrounding capsule. Less commonly, the lymphoma can form a mass associated with the capsule and rarely can present with disseminated disease. Recent series characterising the genomic landscape of BIA-ALCL have led to insights into the mechanisms of lymphomagenesis. Constitutive JAK/STAT pathway activation has emerged as a likely key component while, more recently, aberrancies in epigenetic regulators have been reported. This review describes the genomic characterisation reported to date and the insight these findings have provided into this rare entity.
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    Antibody interference and response kinetics of isatuximab plus pomalidomide and dexamethasone in multiple myeloma
    Hulin, C ; Beksac, M ; Goodman, HJ ; Spicka, I ; Alegre, A ; Prince, M ; Campana, F ; Finn, G ; Le-Guennec, S ; Mace, S ; Muccio, S ; Tavernier, A ; Rouchon, M-C ; Richardson, PG (SPRINGERNATURE, 2021-10-20)
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    Gram-Negative Bacterial Lipopolysaccharide Promotes Tumor Cell Proliferation in Breast Implant-Associated Anaplastic Large-Cell Lymphoma
    Mempin, M ; Hu, H ; Vickery, K ; Kadin, ME ; Prince, HM ; Kouttab, N ; Morgan, JW ; Adams, WP ; Deva, AK (MDPI, 2021-11-01)
    Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a distinct malignancy associated with textured breast implants. We investigated whether bacteria could trigger the activation and multiplication of BIA-ALCL cells in vitro. BIA-ALCL patient-derived BIA-ALCL tumor cells, BIA-ALCL cell lines, cutaneous ALCL cell lines, an immortal T-cell line (MT-4), and peripheral blood mononuclear cells (PBMC) from BIA-ALCL, capsular contracture, and primary augmentation patients were studied. Cells were subjected to various mitogenic stimulation assays including plant phytohemagglutinin (PHA), Gram-negative bacterial lipopolysaccharide (LPS), Staphylococcal superantigens enterotoxin A (SEA), toxic shock syndrome toxin-1 (TSST-1), or sterilized implant shells. Patient-derived BIA-ALCL tumor cells and BIA-ALCL cell lines showed a unique response to LPS stimulation. This response was dampened significantly in the presence of a Toll-like receptor 4 (TLR4) inhibitor peptide. In contrast, cutaneous ALCL cells, MT-4, and PBMC cells from all patients responded significantly more to PHA, SEA, and TSST-1 than to LPS. Breast implant shells of all surface grades alone did not produce a proliferative response of BIA-ALCL cells, indicating the breast implant does not act as a pro-inflammatory stimulant. These findings indicate a possible novel pathway for LPS to promote BIA-ALCL cell proliferation via a TLR4 receptor-mediated bacterial transformation of T-cells into malignancy.
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    A systematic review on the management of pruritus in patients with cutaneous T-cell lymphoma
    Farrah, G ; Spruijt, O ; McCormack, C ; Buelens, O ; Lazarakis, S ; Prince, M (Ovid Technologies (Wolters Kluwer Health), 2021)