Experiences of cohabiting partners of women diagnosed with cancer during pregnancy: a qualitative study.

PURPOSE: When a pregnant woman is diagnosed with cancer, she faces complex and unique challenges while navigating both obstetric and oncological care. Despite often being the primary support for women diagnosed with cancer during pregnancy (CDP), little is known about the experiences of their partners. We undertook an in-depth exploration of the experiences of partners of women diagnosed with CDP in Australia. METHODS: Semi-structured interviews were conducted with partners of women diagnosed with CDP treated in Australia. Interviews explored partners' inclusion in decision making and communication with health professionals and their own coping experiences. Data were analysed thematically. RESULTS: Data from interviews with 12 male partners (N = 12) of women diagnosed with CDP were analysed. Two unique themes relevant to partners were identified: 'Partners require support to adjust to changing roles and additional burdens' and 'Treating the couple as a team facilitates agency and coping, but partners' needs are placed second by all'. CONCLUSION: Partners of women diagnosed with CDP commonly experience unique stressors and a substantial shift in previously established roles across multiple domains including medical advocacy, household coordination and parenting. Partners' coping is interlinked with how the woman diagnosed with CDP is coping. Inclusion of partners in treatment decisions and communications, and considering partners' wellbeing alongside that of the woman with CDP, is likely to be supportive for partners. In turn, this is likely to enhance the quality of support that women diagnosed with CDP receive from their partners.

Thrombosis in patients with immune thrombocytopenia: incidence, risk, and clinical outcomes.

Background: There is evidence that patients with immune thrombocytopenia (ITP) are at increased risk of thrombosis. However, the association of clinical- and treatment-related factors with thrombosis remains controversial. Objectives: To evaluate the incidence and impact of risk factors for arterial and venous thromboembolism (VTE) in patients with ITP and characterize the clinical features and management of patients. Methods: We performed a retrospective cohort study (January 1, 2011, to October 30, 2022) of adult patients diagnosed with ITP from an Australian tertiary hospital. The incidence rates of thrombosis were calculated in terms of person-years of follow-up. Multiadjusted Cox regression was used to estimate associations. Results: A total of 220 patients with 1365 person-years of follow-up since ITP diagnosis revealed 26 (11.8%) patients with a total of 37 thrombosis events, 29 (78%) VTE and 8 (22%) arterial thromboembolism (ATE). The incidence rate of thrombosis was 2.71 (95% CI, 1.97-3.72) (0.66 [95% CI, 0.33-1.26] for arterial thromboembolism and 2.05 [95% CI, 1.42-2.95] for VTE) per 100 person-years. Mean age and median time to first thrombosis diagnosis was 56 and 2.13 years, respectively. Age, secondary ITP, lines of therapy, thrombosis risk factors, and thrombopoietin receptor agonist therapy were independently associated with thrombosis. Almost all patients (25 of 26, [96%]) had good ITP disease control prior to thrombosis diagnosis, and antithrombotic therapy was deliverable and well tolerated. Conclusion: Diagnosis of thrombosis in patients with ITP, while infrequent, is of clinical significance. We identified from a heterogeneous real-world cohort that older patients with multiply-treated secondary ITP receiving thrombopoietin receptor agonists are at the highest risk.

Efficacy and safety of avatrombopag in combination with immunosuppressive therapy in treatment-naïve and relapsed/refractory severe aplastic anaemia: protocol for the DIAAMOND-Ava-FIRST and DIAAMOND-Ava-NEXT Bayesian Optimal Phase II trials.

INTRODUCTION: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with severe aplastic anaemia (sAA) not eligible or suitable for allogeneic stem cell transplant. While patients respond to IST, few achieve complete responses and a significant proportion are refractory or relapse. The addition of eltrombopag, a thrombopoietin-receptor agonist (TPO-A), to IST has been shown to improve haematological responses in sAA. Avatrombopag is a second-generation TPO-A with potential advantages over eltrombopag. However, to date avatrombopag has not been studied in sAA. METHODS AND ANALYSIS: Investigator-initiated, single-arm registry-based Bayesian Optimal Phase II trial of avatrombopag conducted in two cohorts, patients with untreated sAA (FIRST cohort) and in patients with sAA that has relapsed or is refractory to IST (NEXT cohort). In the FIRST cohort, participants receive IST (equine ATG and ciclosporin) plus avatrombopag from day 1 until day 180 at 60 mg oral daily, with dose adjusted according to platelet count. Participants in the NEXT cohort receive avatrombopag at 60 mg oral daily from day 1 until day 180, with or without additional IST at the discretion of the treating clinician.For each cohort, two primary endpoints (haematological response and acquired clonal evolution) are jointly monitored and the trial reviewed at each interim analysis where a 'go/no-go' decision is made by evaluating the posterior probability of the events of interests. ETHICS AND DISSEMINATION: The trial has received ethics approval (Monash Health RES-18-0000707A). The trial conduct will comply with ICH-GCP and all applicable regulatory requirements. The results of the trial will be submitted to a peer-review journal for publication. TRIAL REGISTRATION NUMBER: ACTRN12619001042134, ACTRN12619001043123.

Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma: Final results of the HOVON 105/ALLG NHL 24 study.

BACKGROUND: Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months. METHODS: One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18-70 years with WHO performance status 0-3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively. RESULTS: For event-free survival, the hazard ratio was 0.85, 95% CI 0.61-1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39-59) and 53% (43-63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term. CONCLUSIONS: Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL.

Sickle cell disease in Australia: a snapshot from the Australian Haemoglobinopathy Registry.

BACKGROUND: Sickle cell disease (SCD) is the most common monogenic disorder worldwide. In deoxygenated conditions, the altered beta chain (haemoglobin S [HbS]) polymerises and distorts the erythrocyte, resulting in pain crises, vasculopathy and end-organ damage. Clinical complications of SCD cause substantial morbidity, and therapy demands expertise and resources. Optimising care for patients and planning resource allocation for the future requires an understanding of the disease in the Australian population. The Australian Haemoglobinopathy Registry (HbR) is a collaborative initiative of specialist centres collating and analysing data on patients with haemoglobin disorders. AIMS: To provide a snapshot of SCD in Australia over a 12-month period based on data from the HbR. METHODS: Patients with a clinically significant sickling disorder across 12 clinical sites were included for analysis. Data include demographic and diagnostic details, as well as details of the clinical management of the condition over a 12-month period. RESULTS: Data on 359 SCD patients demonstrate a shift in the demographic of patients in Australia, with a growing proportion of sub-Saharan African ethnicities associated with the HbSS genotype. Acute and chronic complications are common, and patients require significant outpatient and inpatient support. Prevalence of disease complications and therapeutic trends are in keeping with other high-income countries. CONCLUSIONS: This study provides the first national picture of SCD in Australia, describing the characteristics and needs of SCD patients, elucidating demand for current and novel therapy and facilitating the planning of services for this vulnerable population.

Favourable outcomes with an initial active surveillance strategy for asymptomatic radiation-induced meningiomas in long-term survivors of paediatric and young adult malignancies.

PURPOSE: Radiation-induced meningiomas (RIM) are the most common secondary neoplasm post cranial radiotherapy, yet optimal surveillance and treatment strategies remain contentious. Herein, we report the clinical outcomes and radiological growth rate of RIM, diagnosed in a cohort of survivors undergoing MRI screening, with the objective of informing clinical guidelines and practice. MATERIALS AND METHODS: Long-term survivors of paediatric or young-adult malignancies, diagnosed with RIM between 1990 and 2015, were identified. Absolute (AGR) and relative (RGR) volumetric growth rates were calculated. Rapid growth was defined as AGR > 2 cm3/year or AGR > 1 cm3/year and RGR ≥ 30% RESULTS: Fifty-two patients (87 RIM) were included. Median age at first RIM diagnosis was 33.9 (range,13.8-54.1) years. Seventy-seven (88%) RIM were asymptomatic at detection. Median follow-up time from first RIM detection was 11 (range, 0.6-28) years. Median absolute and relative volumetric growth rates were 0.05 (IQR 0.01-0.11) cm3 and 26 (IQR 7-79) % per year, respectively. Two (3.3%) RIM demonstrated rapid growth. Active surveillance was adopted for 67 (77%) RIM in 40 patients. Neurological sequelae due to RIM progression were reported in 5% of patients on active surveillance. Surgery was performed for 33 RIM (30 patients): 18 (54.5%) at diagnosis and 15 (45.5%) after active surveillance. Histopathology was WHO Grade 1 (85.2%), 2 (11.1%), 3 (3.7%). Following resection, 10-year local recurrence rate was 12%. During follow-up, 19 (37%) survivors developed multiple RIM. CONCLUSIONS: Asymptomatic RIM are typically low-grade tumours which exhibit slow growth. Active surveillance appears to be a safe initial strategy for asymptomatic RIM, associated with a low rate of neurological morbidity.

The clinical features, management and outcomes of lymphoma in pregnancy: A multicentre study by the Australasian Lymphoma Alliance.

Lymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; however, the evidence regarding this clinical scenario is limited. We conducted a multicentre retrospective observational study reporting on the features, management, and outcomes of LIP in patients diagnosed between January 2009 and December 2020 at 16 sites in Australia and New Zealand for the first time. We included diagnoses occurring either during pregnancy or within the first 12 months following delivery. A total of 73 patients were included, 41 diagnosed antenatally (AN cohort) and 32 postnatally (PN cohort). The most common diagnoses were Hodgkin lymphoma (HL; 40 patients), diffuse large B-cell lymphoma (DLBCL; 11) and primary mediastinal B-cell lymphoma (PMBCL; six). At a median follow up of 2.37 years, the 2- and 5-year overall survival (OS) for patients with HL were 91% and 82%. For the combined DLBCL and PMBCL group, the 2-year OS was 92%. Standard curative chemotherapy regimens were successfully delivered to 64% of women in the AN cohort; however, counselling regarding future fertility and termination of pregnancy were suboptimal, and a standardised approach to staging lacking. Neonatal outcomes were generally favourable. We present a large multicentre cohort of LIP reflecting contemporary practice and identify areas in need of ongoing research.

Capturing the lived experiences of women with lymphoma in pregnancy: a qualitative study.

Lymphoma in pregnancy is a rare and challenging diagnosis that complicates ∼1:6000 pregnancies; posing a series of unique therapeutic, social, and ethical challenges to the patient, her family, and the medical professionals involved. These difficulties are compounded by the paucity of real-world data on the management of LIP, and a lack of relevant support systems for women in this setting. We conducted a retrospective multicenter qualitative study, interviewing women aged ≥18 years of age diagnosed with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) during pregnancy or within 12 months postpartum, between 1 January 2009 and 31 December 2020 from 13 Australasian sites. Semi-structured telephone interviews were conducted, recorded, and analyzed using QSR Int NVivo 12 Pro (March 2020, USA) to quantify salient themes. Of the 32 women interviewed, 20 (63%) were diagnosed during pregnancy (16, 34, and 13% in the 1st, 2nd, and 3rd trimesters, respectively), while 12 (37%) were diagnosed post-partum. Women recalled that their chief concerns at diagnosis were the welfare of their child (n = 13, 41%) and a fear of dying (n = 9, 28%). Perceived diagnostic delay attributed to pregnancy was reported by 41% of participants. Other key themes were communication, educational materials, psychosocial supports, and oncofertility issues. To our knowledge this is the first report capturing the lived experiences of survivors of lymphoma during pregnancy, affording a unique opportunity to consider the management, psychosocial supports, and delivery of care to meet the needs of these women.What is the NEW aspect of your work? To our knowledge, this is the first report capturing and analyzing the healthcare experiences of survivors of Lymphoma in Pregnancy (LIP).What is the CENTRAL finding of your work? Women valued clear and empathic communication, provision of tailored educational materials, access to psychosocial supports (particularly childcare and financial supports), and timely oncofertility management in their healthcare journey.What is (or could be) the SPECIFIC clinical relevance of your work? Women's personal accounts of positive and negative experiences of LIP care provide insights into their specific concerns and needs which can shape healthcare policy and development of a specific framework for managing and supporting patients with LIP (and other cancers).

Proinflammatory microenvironment promotes lymphoma progression in mice with high megakaryocyte and TPO levels.

Platelets have been shown to enhance the survival of lymphoma cell lines. However, it remains unclear whether they play a role in lymphoma. Here, we investigated the potential role of platelets and/or megakaryocytes in the progression of Eµ-myc lymphoma. Eµ-myc tumor cells were transplanted into recipient wild-type (WT) control, Mpl-/-, or TpoTg mice, which exhibited normal, low, and high platelet and megakaryocyte counts, respectively. TpoTg mice that underwent transplantation exhibited enhanced lymphoma progression with increased white blood cell (WBC) counts, spleen and lymph node weights, and enhanced liver infiltration when compared with WT mice. Conversely, tumor-bearing Mpl-/- mice had reduced WBC counts, lymph node weights, and less liver infiltration than WT mice. Using an Mpl-deficient thrombocytopenic immunocompromised mouse model, our results were confirmed using the human non-Hodgkin lymphoma GRANTA cell line. Although we found that platelets and platelet-released molecules supported Eµ-myc tumor cell survival in vitro, pharmacological inhibition of platelet function or anticoagulation in WT mice transplanted with Eµ-myc did not improve disease outcome. Furthermore, transient platelet depletion or sustained Bcl-xL-dependent thrombocytopenia did not alter lymphoma progression. Cytokine analysis of the bone marrow fluid microenvironment revealed increased levels of the proinflammatory molecule interleukin 1 in TpoTg mice, whereas these levels were lower in Mpl-/- mice. Moreover, RNA sequencing of blood-resident Eµ-myc lymphoma cells from TpoTg and WT mice after tumor transplantation revealed the upregulation of hallmark gene sets associated with an inflammatory response in TpoTg mice. We propose that the proinflammatory microenvironment in TpoTg mice promotes lymphoma progression.

Did new treatments contribute to a decrease in melanoma deaths?

Melanoma is one of the most common cancers diagnosed in New Zealand, and New Zealand has one of the highest rates of melanoma incidence and mortality in the world. Monitoring by Environmental Health Intelligence NZ (EHINZ) has found a recent sharp decline in melanoma mortality rates in New Zealand. Since 2014 and 2015 (with 376 and 378 melanoma deaths, respectively), melanoma deaths have declined to 362 deaths in 2016, 308 deaths in 2017, and 296 deaths in 2018. We believe that two new PD-1 inhibitor drug treatments introduced in New Zealand in 2016-nivolumab (Opdivo, BMS) and pembrolizumab (Keytruda, MSD)-may have contributed to this decrease in melanoma mortality. Other factors are unlikely to have had such a major effect, with the drop unlikely due to random variation, and no major changes in melanoma registrations or melanoma thickness at diagnosis over the past decade. While our monitoring of the time trend is descriptive only, and cannot attribute causality, it does suggest a recent decrease in melanoma mortality rates at the population level. These national-level statistics reflect both what might be expected in the New Zealand situation with the introduction of PD-1 inhibitor treatments, based on clinical trials, and what oncologists are seeing at an individual level. Further studies could investigate this observational finding, to confirm whether PD-1 inhibitor drug treatments are having an impact on melanoma mortality and survival rates in New Zealand.

Ibrutinib protects T cells in patients with CLL from proliferation-induced senescence.

BACKGROUND: The development of Bruton's tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukaemia (CLL) has provided a highly effective and relatively non-toxic alternative to conventional chemotherapy. Some studies have shown that BTKi can also lead to improvements in T cell immunity in patients despite in vitro analyses suggesting an immunosuppressive effect of BTKi on T cell function. METHODS: In this study, we examined both the in vitro effect and long-term in vivo effect of two clinically available BTKi, ibrutinib and zanubrutinib. Additional in vitro assessments were undertaken for a third BTKi, acalabrutinib. Immune subset phenotyping, cytokine secretion, T cell degranulation and proliferation assays were performed on peripheral blood mononuclear cells isolated from untreated CLL patients, and CLL patients on long-term (> 12 months) BTKi treatment. RESULTS: Similar to prior studies we observed that long-term BTKi treatment normalises lymphocyte subset frequency and reduces PD-1 expression on T cells. We also observed that T cells from patients taken prior to BTKi therapy showed an abnormal hyper-proliferation pattern typical of senescent T cells, which was normalised by long-term BTKi treatment. Furthermore, BTKi therapy resulted in reduced expression of the T cell exhaustion markers PD-1, TIM3 and LAG3 in late generations of T cells undergoing proliferation. CONCLUSIONS: Collectively, these findings indicate that there are critical differences between the in vitro effects of BTKi on T cell function and the effects derived from long-term BTKi exposure in vivo. Overall long-term exposure to BTKi, and particularly ibrutinib, resulted in improved T cell fitness in part due to suppressing the abnormal hyper-proliferation of CLL T cells and the associated development of T cell senescence.

Social Vulnerability Indicators for Flooding in Aotearoa New Zealand.

Social vulnerability indicators are a valuable tool for understanding which population groups are more vulnerable to experiencing negative impacts from disasters, and where these groups live, to inform disaster risk management activities. While many approaches have been used to measure social vulnerability to natural hazards, there is no single method or universally agreed approach. This paper proposes a novel approach to developing social vulnerability indicators, using the example of flooding in Aotearoa New Zealand. A conceptual framework was developed to guide selection of the social vulnerability indicators, based on previous frameworks (including the MOVE framework), consideration of climate change, and a holistic view of health and wellbeing. Using this framework, ten dimensions relating to social vulnerability were identified: exposure; children; older adults; health and disability status; money to cope with crises/losses; social connectedness; knowledge, skills and awareness of natural hazards; safe, secure and healthy housing; food and water to cope with shortage; and decision making and participation. For each dimension, key indicators were identified and implemented, mostly using national Census population data. After development, the indicators were assessed by end users using a case study of Porirua City, New Zealand, then implemented for the whole of New Zealand. These indicators will provide useful data about social vulnerability to floods in New Zealand, and these methods could potentially be adapted for other jurisdictions and other natural hazards, including those relating to climate change.

Cancer during pregnancy: A qualitative study of healthcare experiences of Australian women.

OBJECTIVES: To identify features enhancing the quality of healthcare experiences for women with gestational cancer, and explore the impact of the heterogeneous Australian healthcare system on those experiences. METHODS: Semi-structured, qualitative interviews were conducted with women diagnosed with any cancer during pregnancy in the last five years. Recruitment occurred during 2018-2019 via social media and professional, clinical and community networks. Questions related to women's experiences of their healthcare, wellbeing and psychosocial needs. Interviews were analysed thematically. RESULTS: Study participants (n = 23) received treatment in the private sector (n = 10), public sector (n = 8), or both (n = 5). Five interview themes were found: Control over healthcare; Trust in clinicians, hospitals and systems; Coordination of care; An uncommon diagnosis; Holistic, future-oriented care. Women were most likely to have had a positive healthcare experience when (a)care was well-coordinated and adjusted to meet their unique needs/challenges, and (b)women perceived their care went beyond their immediate medical needs and encompassed future psychosocial wellbeing, including preparation for postpartum challenges. CONCLUSION: Existing 'usual care' in the public and/or private sector for both the pregnancy and the cancer is insufficient to meet these women's needs. Prioritising psychological wellbeing including psychosocial needs, and communication and planning around fertility and postnatal challenges are essential for this population.

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.

Open-Label, phase 2 study of blinatumomab as second salvage therapy in adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.

The phase 2 portion of this open-label phase 2/3 study assessed the efficacy and safety of blinatumomab as second salvage for aggressive relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL) following platinum-based first salvage chemotherapy. Forty-one patients with aggressive disease (32% relapsed; 68% refractory) enrolled and received stepwise blinatumomab (9-28-112 µg/day) in a 70-day cycle 1 and an optional 28-day cycle 2; 19 (46%) completed cycle 1 and 3 (7%) completed cycle 2. The overall response rate after 12 weeks was 37%, including 9 (22%) complete metabolic responses. Eight (20%) patients (all responders) subsequently received stem cell transplants. Grade ≥3 adverse events were reported in 29 (71%) patients. Grade 3 cytokine release syndrome occurred in one patient. Grade 3 neurologic events occurred in 10 (24%) patients; all resolved. Blinatumomab monotherapy appears effective as second salvage therapy in patients with r/r aggressive B-NHL. Trial registration: NCT02910063.

Maternal breast cancer and communicating with children: A qualitative exploration of what resources mothers want and what health professionals provide.

OBJECTIVE: To explore the communication and resource needs of mothers diagnosed with breast cancer treated with curative intent in communicating with their young children and to identify gaps in the resources and support provided to these women. METHODS: Data were collected via semi-structured telephone interviews from 13 mothers who were diagnosed with breast cancer while parenting a young child (age 3-12 years), and 10 health professionals in Victoria, Australia. Data were analysed qualitatively using the Framework Method. RESULTS AND CONCLUSION: Mothers and health professionals prioritised communication with children about the cancer diagnosis; however, health professionals and mothers differed in their views of parents' communication needs both in terms of the nature of the support/information needed and the delivery of this support/information. Mothers wanted easily accessible resources that were both instructive and practical. Mothers also emphasised quality over quantity of support. Health professionals were mostly aware of mothers' needs, however, emphasised less instructive support and information. This study highlights the need for improved coordination and tailoring of psychosocial resources and supports for these parents and families communicating about a cancer diagnosis with their young children.