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Background Recent reports suggest genetic polymorphisms influence susceptibility to rituximab-induced late-onset neutropenia ( LON), which in turn may be a predictor of good outcome in B-cell lymphoma. Aims We report the largest study to date assessing FCGR3A- V158F polymorphisms in diffuse large B-cell lymphoma ( DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/ Oncovin (vincristine)/prednisone/rituximab ( CHOP- R). The influence of C1qA- A276G polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to LON and outcome were also examined. Methods 115 DLBCL patients treated with CHOP-R were compared with 105 healthy White people controls with regards to FCGR3A- V158F and C1qA- A276G polymorphisms. LON incidence and event-free and overall survival ( EFS and OS) were analysed for linkage to either polymorphism. Results The FCGR3A- V158F but not the C1qA- A276G polymorphism influenced the risk of developing LON. 50% of FCGR3A-158 V/ V patients experienced LON. In contrast, only 7% V/ F and 2% F/ F experienced LON. The FCGR3A-158 V/ V genotype was associated with LON compared with V/ F ( P = 0.028) and F/ F genotypes ( P = 0.005). Although no patients with either LON or FCGR3A-158 V homozygosity relapsed compared with 33% FCGR3A-158F/ F and 21% non- LON, this did not translate into improved EFS or OS. Conclusions Polymorphic analysis may be a predictive tool to identify those at high risk of LON. Prospective studies are required to establish definitively if LON or FCGR3A-158 V/ V genotype influences outcome. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "High-Dose Cytarabine (24g/2) in Combination With Idarubicin (HiDAC-3) Results in High First Cycle Response With Limited Gastrointestinal Toxicity in Adult Acute Myeloid Leukaemia" in the 2013 issue.

Introduction: Peripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications., Methods and Analysis: A multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure , a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI., Ethics and Dissemination: Ethical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published., Trial Registration Number: ACTRN12619000022167., Competing Interests: Competing interests: Griffith University (AJU's former employer) has received unrestricted research and educational grants to support her research (unrelated from the current project) from 3M, Becton Dickinson and Cardinal Health. Griffith University (DA’s employer) has received consultancy payments for educational lectures based on her research and clinical expertise from 3M and Johnsons and Johnsons. Griffith University (TK’s employer) has received unrestricted research and educational grants from 3M, Becton Dickinson and Medical Specialties Australasia. Griffith University (RMW’s employer) has received unrestricted research and educational grants to support her research (unrelated to current project) from Becton Dickinson. Griffith University (NMM's former employer) has received unrestricted research and educational grants to support her research (unrelated from the current project) from 3M, Becton Dickinson and Cardinal Health. Griffith University (AB's employer) has received consultancy payments from Becton Dickinson (unrelated to the current project). Griffith University (JB’s employer) has received unrestricted research and educational grants to support her research (unrelated to current project) from Becton Dickinson, and Navi Technologies. PM is a member of Myeloma Advisory Boards for Celgene, Janssen, Amgen, Takeda and Amyloidosis Advisory Boards for Pfizer and Caelum. No personal fees have been received for these services. PM’s has received a research grant from Janssen for a clinical trial. PM has accommodation and registration provided by Amgen for attendance at the International Myeloma Workshop in 2019. Griffith University (CMR's former employer) has received unrestricted research and educational grants to support her research (unrelated to the current project) from 3M, Becton Dickinson and Cardinal Health. Other authors have no conflicts of interests to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The public subsidy in Australia of bortezomib (Velcade) for untreated non-transplant multiple myeloma patients was based on the VISTA trial., Aims: To ascertain the health outcomes of bortezomib in 'real world' transplant-ineligible elderly patients, compared to trial data., Methods: Patient and treatment data were extracted from an oncology information system, laboratory information system and medical chart audits for three Queensland public hospitals., Results: We identified 74 patients; the median age was 75 years. Our cohort comprised 47% patients who were International Staging System stage III, 45% at stage II and 8% at stage I. Patients who had comorbidities, such as cardiac disease (41%), pulmonary disease (14%), diabetes (22%), peripheral neuropathy (14%) and other comorbidities (41%) at baseline were included. The common regimens prescribed were VMP, CVD and VD, and most patients (n = 73) received bortezomib on a once-weekly or twice-a-week basis. The overall response rate was 81%. Half (53%) of the patients did not complete their planned therapy due to toxicity (30%), suboptimal response or disease progression (15%), or death on treatment (8%). Overall survival was 40.7 months and progression free survival was 17.7 months., Conclusions: Our patients were older, had worse disease characteristics and more comorbidities than patients in the VISTA trial. While response rates were similar, survival outcomes appeared worse. Bortezomib-based treatment in the real world setting still carries a high risk of toxicity in the elderly population., (© 2020 Royal Australasian College of Physicians.)

Relative survival (RS) in myeloma has improved in younger but not older patients (≥80 years) with treatment advances. Whether place of residence or socioeconomic status (SES) affect RS is unknown. We used the Queensland cancer registry to calculate the five-year RS of myeloma patients diagnosed between 1982 and 2014. This period was divided into three eras: (1) 1982-1995 chemotherapy alone; (2) 1996-2007 autologous stem cell transplantation; (3) 2008-2014 novel agents (proteasome inhibitors and IMIDs). 6025 patients were diagnosed from 1982 to 2014. RS improved across eras: (1) 30% vs. (2) 43% vs. (3) 53% ( p  < .001 (2) vs. (1); p  < .001 (3) vs. (2)). RS improved across all age groups, including patients ≥80 years. Patients with disadvantaged SES (39% vs. affluent 46%; p  < .001) and rural patients (40% vs. urban 45%; p  < .001) had an inferior RS. RS has improved across all ages with treatment advances.

Purpose: Understanding the immunobiology of the 15% to 30% of patients with follicular lymphoma (FL) who experience progression of disease within 24 months (POD24) remains a priority. Solid tumors with low levels of intratumoral immune infiltration have inferior outcomes. It is unknown whether a similar relationship exists between POD24 in FL., Patients and Methods: Digital gene expression using a custom code set-five immune effector, six immune checkpoint, one macrophage molecules-was applied to a discovery cohort of patients with early- and advanced-stage FL (n = 132). T-cell receptor repertoire analysis, flow cytometry, multispectral immunofluorescence, and next-generation sequencing were performed. The immune infiltration profile was validated in two independent cohorts of patients with advanced-stage FL requiring systemic treatment (n = 138, rituximab plus cyclophosphamide, vincristine, prednisone; n = 45, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), with the latter selected to permit comparison of patients experiencing a POD24 event with those having no progression at 5 years or more., Results: Immune molecules showed distinct clustering, characterized by either high or low expression regardless of categorization as an immune effector, immune checkpoint, or macrophage molecule. Low programmed death-ligand 2 (PD-L2) was the most sensitive/specific marker to segregate patients with adverse outcomes; therefore, PD-L2 expression was chosen to distinguish immune infiltration HI (ie, high PD-L2) FL biopsies from immune infiltration LO (ie, low PD-L2) tumors. Immune infiltration HI tissues were highly infiltrated with macrophages and expanded populations of T-cell clones. Of note, the immune infiltration LO subset of patients with FL was enriched for POD24 events (odds ratio [OR], 4.32; c-statistic, 0.81; P = .001), validated in the independent cohorts (rituximab plus cyclophosphamide, vincristine, prednisone: OR, 2.95; c-statistic, 0.75; P = .011; and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: OR, 7.09; c-statistic, 0.88; P = .011). Mutations were equally proportioned across tissues, which indicated that degree of immune infiltration is capturing aspects of FL biology distinct from its mutational profile., Conclusion: Assessment of immune-infiltration by PD-L2 expression is a promising tool with which to help identify patients who are at risk for POD24.

Published studies on the epidemiology of amyloidosis have relied on death certificate data for case ascertainment. We estimated the incidence and mortality burden of amyloidosis among residents of the Australian state, Queensland, aged ≥20 years for the years 1999-2013 based on case ascertainment from histopathology reports. Information systems for participating laboratories were scrutinised to identify histopathology reports that documented a diagnosis of amyloidosis. Case mortality status was determined via linkage to the National Death Index. A total of 447 cases of amyloidosis were identified, with a median age at diagnosis of 66 years. A plasma cell dyscrasia was identified in 72% of patients who had paraprotein studies performed. The estimated incidence for Queenslanders aged ≥20 years was 12·1 cases per million person years. The median survival was 2·45 years. Age at diagnosis, presence of a paraprotein, earlier year of diagnosis, and inner regional location of residence (compared with residence in a major city) were independently associated with reduced survival. Our data confirms previously reported incidence data for amyloidosis of approximately 10 cases per million patient years and indicates that survival for Queensland patients with amyloidosis is improving, though it remains poor for the elderly and patients with AL amyloidosis., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To evaluate relative survival of patients in Queensland with different lymphoma subtypes; to determine whether outcomes have improved with recent changes in treatment; to evaluate relative survival according to place of residence and socio-economic status., Design: Retrospective population-based study; analysis of data from the Oncology Analysis System, an online reporting tool for cancer incidence and outcomes in Queensland., Participants: Patients over 15 years of age diagnosed with lymphoma in Queensland during 1993-2012., Main Outcome Measures: Relative survival by lymphoma subtype; influence of place of residence and socio-economic status, age group, sex, year of diagnosis (in 5-year bands), and Pharmaceutical Benefits Scheme funding of rituximab for treating B-cell lymphomas on relative survival., Results: 9509 people (56% men) were diagnosed with lymphoma during 1993-2012. Five-year relative survival improved significantly between 1993-1997 and 2008-2012 for patients with diffuse large B-cell lymphoma (47%; 95% CI, 42-51% v 64%; 95% CI, 61-67%) or follicular lymphoma (62%; 95% CI, 57-66% v 88%; 95% CI, 85-90%; each P < 0.001). Rituximab became available for treating these subtypes during 2003-2006. There was no change in relative survival for patients with Hodgkin lymphoma (81%; 95% CI, 76-85% v 80%; 95% CI, 75-84%; P = 0.22). The only statistically significant difference according to place of residence or socio-economic status was inferior relative survival for rural residents with diffuse large B-cell lymphoma (hazard ratio, 1.14; 95% CI, 1.01-1.28)., Conclusion: Relative survival for patients with B-cell non-Hodgkin lymphoma improved significantly with the introduction of rituximab as first-line therapy in Australia.

Background: Thrombotic events in essential thrombocythaemia (ET) are difficult to predict with current risk stratification based on age and prior history of thrombosis., Aims: We aimed to assess the predictive value of the JAK2 V617F mutation (JAK2) and spontaneous erythroid colony (SEC) growth for the development of thrombotic events post diagnosis in patients with ET., Methods: Consecutive patients with ET were retrospectively identified, and clinical and laboratory correlates were evaluated. Thrombotic events were categorized according to their occurrence at or prior to diagnosis (prior thrombosis), and any time post diagnosis of ET (subsequent thrombosis). JAK2 analysis was performed by allele-specific PCR on whole blood or bone marrow., Results: A total of 62 patients was identified, median age 63 years; 67% (41/61) JAK2-positive and 47% (25/53) SEC-positive. Median follow-up was 33 months (range, 1 to 137). JAK2-positive patients showed a trend to increased prior thrombosis (27% vs 5%, P= 0.08), and a significant increase in the development of subsequent thrombosis (5-year event rate 31% vs 6%, P= 0.04), which persisted when stratified for a history of prior thrombosis (P= 0.04). Survival was not affected by JAK2 status. The SEC assay predicted an increased rate of baseline thrombosis (16% vs 0%, P= 0.04), but was not found to be predictive of any subsequent thrombotic events., Conclusions: Patients with ET who are JAK2-positive by whole blood allele-specific PCR appear to be at increased risk of thrombotic complications, which is independent of a prior history of thrombosis., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)