Anna Johnston

Bisphosphonate guidelines for treatment and prevention of myeloma bone disease

Multiple myeloma (MM) is a haematological malignancy characterised by the clonal proliferation of plasma cells in the bone marrow. More than 80% of patients with MM display evidence of myeloma bone disease (MBD), characterised by the formation of osteolytic lesions throughout the axial and appendicular skeleton. MBD significantly increases the risk of skeletal‐related events such as pathologic fracture, spinal cord compression and hypercalcaemia. MBD is the result of MM plasma cells‐mediated activation of osteoclast activity and suppression of osteoblast activity. Bisphosphonates (BP), pyrophosphate analogues with high bone affinity, are the only pharmacological agents currently recommended for the treatment and prevention of MBD and remain the standard of care. Pamidronate and zoledronic acid are the most commonly used BP to treat MBD. Although generally safe, frequent high doses of BP are associated with adverse events such as renal toxicity and osteonecrosis of the jaw. As such, optimal duration and dosing of BP therapy is required in order to minimise BP‐associated adverse events. The following guidelines provide currently available evidence for the adoption of a tailored approach when using BP for the management of MBD.

Treatment of patients with Waldenström macroglobulinaemia: clinical practice guidelines from the Myeloma Foundation of Australia Medical and Scientific Advisory Group

Waldenström macroglobulinaemia (WM) is an indolent B‐cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM. While treatment of WM has often been considered together with other indolent B cell lymphomas, there are unique aspects of WM management that require specific care. These include the unreliability of IgM and paraprotein measurements in monitoring patients prior to and after treatment, the lack of correlation between disease burden and symptoms and rituximab‐induced IgM flare. Moreover, while bendamustine and rituximab has recently been approved for reimbursed frontline use in WM in Australia, other regimens, including ibrutinib‐ and bortezomib‐based treatments, are not funded, requiring tailoring of treatment to the regional regulatory environment. The Medical and Scientific Advisory Group of the Myeloma Foundation Australia has therefore developed clinical practice guidelines with specific recommendations for the work‐up and therapy of WM to assist Australian clinicians in the management of this disease.

Bortezomib-based antibody depletion for refractory autoimmune hematological diseases

Certain patients with antibody-mediated autoimmune disease exhibit poor responses to conventional immunosuppression, including B-cell depletion with rituximab. Proteasome inhibitors such as bortezomib demonstrate pleiotropic immunomodulatory effects, including direct toxicity to antibody-producing cells. Here, we report preliminary evidence for the efficacy of bortezomib as salvage therapy for refractory autoimmune hematological disease. Thirteen treatment episodes in 10 patients with autoimmune hematological phenomena (autoimmune hemolytic anemia [AIHA; n = 8], acquired hemophilia (n = 1), immune thrombocytopenia (n = 1), and thrombotic thrombocytopenic purpura [TTP; n = 3]) and a median of 5 (range, 3-12) prior lines of therapy demonstrated an overall response rate of 77% (10 of 13) including 38% (5 of 13) complete remissions. The majority of clinical improvements were rapid, correlated with biomarkers of autoantibody reduction, and were associated with an acceptable safety profile. Responses appeared durable following treatment of TTP and acquired hemophilia; AIHA responses were more limited with a pattern of relapse following bortezomib cessation. These data provide proof of concept for the utility of proteasome inhibition as antibody depletion therapy in autoimmune disease.

Little England: nineteenth-century Tasmanian travel writing and settler colonialism

Tasmania was a distinctive location for nineteenth-century travellers, and a regular feature of the rich print culture that emerged from the British Empire. Regularly dubbed a “little England” because of its physical and environmental features, the island provided an early source of imperial ideas about Greater Britain and the spread of the Anglo-Saxon race. This paper traces the emergence of the “little England” trope in travel writing, emphasising the importance of this form for knowledge formation. It argues that the contested and violent history of Tasmania, especially the treatment of Aboriginal people, complicated the trope by making explicit the violence that underpinned British imperial expansion. Debates about the morality of colonisation both in the colonial period, and in recent scholarly publications, reveal the high visibility of Tasmania and the complex inheritances of its colonial past locally and in Britain.

Becoming “Pacific-Minded”: Australian Middlebrow Writers in the 1940s and the Mobility of Texts

The travel writer Frank Clune saw World War II as a turning point in Australia’s consciousness, turning its inhabitants’ attention to the Pacific region. Similarly, the writer Ernestine Hill was delighted to find new American markets for her Australian books in wartime as troops were mobilized across the Pacific theater. In America, as Janice Radway has shown, the sentimental mode of “middlebrow personalism” enabled writers to engage their readers in wider geopolitical affairs. Middlebrow intellectuals, texts, and institutions were crucial in educating Americans about their evolving midcentury relationships with Asia, just as writers such as Clune and Hill educated Australians about the Pacific: a coalition of American and Australian mobilities and imaginaries in middlebrow midcentury print culture. This article examines the multiple ways in which these books and their writers “made Australia” in terms of a regional imaginary that extended across the Pacific during this period.

George Augustus Robinson, the ‘Great Conciliator’: colonial celebrity and its postcolonial aftermath

George Augustus Robinson, the ‘Great Conciliator’, conducted one of the most high profile and subsequently notorious experiments with indigenous people in the nineteenth-century British Empire. His ‘removal’ of Tasmanian Aborigines from the settler-dominated main island was well known at the time: celebrated by many as the most efficacious resolution to frontier conflict, even as it was criticized by (some) liberal commentators. Robinson was acutely aware of himself as an actor on the imperial stage, boasting in his diary on 3 September 1832 that, ‘By taking the whole [group of Aborigines] I gain not only the reward but also celebrity’ (Friendly Mission). As Patrick Brantlinger argues, colonial, American, European and British commentators were acutely interested in the fate of indigenous peoples when they encountered white, Western civilization: the Tasmanian genocide (as it was known) ‘offered a moral and political lesson in how the progress of empire and civilization could be badly botched’. Ideas about Robinson and his ‘mission’ to the Tasmanian Aborigines have circulated in popular culture and art since the 1830s. A variety of mechanisms have kept Robinson in the popular imagination. Benjamin Duterraus portrait of Robinson in ‘The Conciliation’ memorably pictures a soft-faced Briton surrounded by his Aboriginal ‘charges’, but colonial and imperial commentators positioned Robinson equally often within the racial science of high imperialism. Alongside such representations, Robinson and the Tasmanian Aborigines were envisioned by popular newspapers, pamphleteers and writers in the Victorian economys commodification of Empire. These imaginings of Robinson were as vigorous in the imperial centres as in the colonies, and have continued to be so. Twentieth-century authors—from Robert Drewe, to Mudrooroo, to Matthew Kneale, to Stephen Scheding and Nicholas Shakespeare—seem compelled to re-imagine Robinsons story. This paper examines Robinsons colonial celebrity and its postcolonial aftermath through theories of mass media and celebrity.

Reversible pancytopenia caused by severe copper deficiency in a patient with Wilson disease

1 Bone marrow aspirate showing moderate dyserythropoiesis and cytoplasmic vacoulation in erythroid (red arrows) and myeloid precursors (blue arrows) A 26-year-old woman was referred to the haematologist for evaluation of new onset pancytopenia. She was diagnosed with Wilson disease at 13 years of age, when she developed extrapyramidal neurological manifestations, mainly dystonia, ataxia and tremors. Despite copper chelation therapy with zinc sulphate, she had disabilities due to dystonia and became wheelchair bound, requiring high level nursing care. She underwent clinical monitoring with yearly blood tests and her previous full blood counts were consistently normal; however, serum copper values were mildly reduced, consistent with those seen in Wilson disease. Her regular medications were zinc sulphate (200 mg thrice daily), benzhexol, baclofen, diazepam and lactulose. Her nutritional intake was good. Clinical examination revealed fixed posture deformities of upper and lower limbs, bilateral partial KaysereFleischer rings on ocular slitlamp examination, and there were no stigmata of liver disease.

“Our Antipodes”: settler colonial environments in Victorian travel writing

The Australian colonies were popular destinations for mid- to late-nineteenth-century British travellers, celebrated for their modernity and their immense potential for British emigration. Mastering new nineteenth-century technologies of travel, British (and colonial) travellers flooded the antipodean settler colonies, and on return their travel accounts flooded the periodical press and book publishers.

Mrs Milson’s Wordlist: Eliza Hamilton Dunlop and the Intimacy of Linguistic Work

Early colonial linguistic collection reveals the intimate and ongoing negotiations between Indigenous people and their European interlocutors, and provides insight into colonial knowledge production as a shared, cross-cultural process. The poet Eliza Hamilton Dunlop constructed a wordlist from informants in Wollombi, transcribed songs, and published poetry sympathetic to Aboriginal suffering and dispossession from her arrival in New South Wales in 1838. Dunlop’s concerns for Aboriginal people and culture were heightened by her marriage to an agent of the law (David Dunlop was a police magistrate), and the couple were keenly interested in Aboriginal culture, language, and plight on the volatile and violent colonial frontier that surrounded them. The Dunlops had an acquaintance with Reverend Lancelot Threlkeld at the nearby Lake Macquarie Mission, who had shared interests in recording Aboriginal linguistic and cultural knowledge, and in publicising and lamenting colonial violence. This chapter examines Dunlop’s linguistic and other work to reveal the imbrication of language collection, knowledge production, and humanitarian advocacy.

An audit of patients with mature T‐cell non‐Hodgkin lymphoma by transplant status in Tasmania

This retrospective audit of patients diagnosed with mature T‐cell lymphoma across a 10‐year period provides contemporary information on the outcomes and treatment patterns of an Australian cohort. Forty‐two patients diagnosed with mature T‐cell lymphoma were identified from the Tasmanian Cancer Registry and analysed using medical records and simple statistical analysis. The demographics and outcomes of patients in this cohort were comparable to large international studies with treatment patterns in line with the best available evidence.