Improving disease-specific survival for patients with Sezary syndrome in the modern era of systemic therapies.

Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5-year disease-specific survival (DSS) less than one-third in historical cohorts. However, newer therapies and combinations are associated with impressive time-to-next-treatment (TTNT), particularly allogeneic stem-cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long-term survival exceeded historical reports with 5-year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5-year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5-year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations.

Marginal zone lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance.

Marginal zone lymphomas (MZLs) are a rare, indolent group of non-Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa-associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy. The heterogeneous presentation and relapsing course present the clinician with several diagnostic and therapeutic challenges. This position statement presents evidence-based recommendations in the setting of Australia and New Zealand.

Diagnosis, management and follow-up of follicular lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype, accounting for 15-20% of all lymphoma diagnoses. Although typically slow-growing and responsive to frontline therapies, advanced-stage FL remains incurable with current treatments and typically follows a chronic relapsing/remitting course with increasingly shorter responses to subsequent lines of therapy. Outcomes are highly variable; some patients experience prolonged first remissions that may approximate a 'functional cure'. By contrast, a significant minority of patients experience disease progression shortly after frontline treatment resulting in high rates of lymphoma-related mortality. Reflecting on the heterogeneous natural history of FL, clinical practice varies widely, particularly in controversial areas, including appropriate disease staging, selection of management strategies and duration of clinical follow-up. This position statement presents an evidence-based synthesis of the literature for application in Australasian practice.

The Drug Overdose Epidemic in the U.S.-Mexico Border Region: Shifts, Progression, and Community Characteristics.

OBJECTIVE: Previous studies show the reach of the current drug overdose epidemic into the U.S.-Mexico border region, albeit with a unique border-specific wave pattern compared to national waves and a delayed onset of fentanyl involvement (Wave I: 2002-2011, Wave II: 2012-2016, and Wave III: since 2017). The objective of this study is to examine the community predictors and the progression of overdose deaths across the U.S-Mexico border-specific epidemic waves. METHOD: Descriptive epidemiological profile of border communities across the unfolding of the opioid epidemic, integrated data from the CDC-WONDER multiple causes of death data set, the CDC SVI, Uniform Crime Report, and the Behavioral Risk Factor Surveillance System. Using spatially adjusted Bayes rates by border-specific epidemic waves, we provide a descriptive profile of the spatial unfolding of the drug overdose epidemic. Negative binomial regression models assessed community predictors of overdose deaths across waves. RESULTS: Spatial analysis identified moderate to steep increases in drug overdose deaths over the three waves along the border. The impact and unfolding of the epidemic in the U.S.-Mexico border region were not uniform and affecting communities with differing severity and timing. Our study also finds support for social vulnerability and community violence as predictors of overdose deaths over the current wave of the epidemic. CONCLUSION: Findings suggest that more disadvantaged U.S.-Mexico border communities may encounter increasing rates of overdose death over the coming years. Interventions need to target not only the supply side but also the underlying social root causes for sustainable overdose prevention.

Are dynamic or fixed FDG-PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing autologous haematopoietic stem cell transplantation?

Positron emission tomography (PET) response assessment using the Deauville score has prognostic utility in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem-cell transplantation (ASCT). Improved predictive methods are required to identify patients with poor outcomes who may be better considered for other salvage options. We investigated the prognostic value of mean tumour volume (MTV) and maximum standardised uptake value (SUVmax) at pre-salvage and pre-ASCT time-points, and the quantitative changes between scans (∆MTV and ∆SUVmax). One hundred and twenty-five patients with R/R DLBCL underwent salvage immunochemotherapy and ASCT: 80 patients had pre-salvage PET and 90 had pre-ASCT PET available. With a median follow-up of 5.6 years, 5-year progression-free survival (PFS) and overall survival (OS) were 52% and 65%, respectively. For patients with PET-positive residual disease after salvage therapy, pre-ASCT MTV was a significant negative prognosticator for PFS (HR 1.19 per 100 ml, p < 0.001) and OS (HR 1.78 per 100 ml, p < 0.001). Similarly, pre-ASCT SUVmax was negatively associated with PFS (HR 1.08, p < 0.001) and OS (HR 1.08, p < 0.001). Notably, pre-salvage MTV and SUVmax and ∆MTV and ∆SUVmax were not associated with PFS or OS. In conclusion, pre-ASCT MTV and SUVmax appear to be of greater predictive value than the degree of response. Potential application may exist for PET-directed management of R/R DLBCL patients.

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.

Advances in neonatal cell therapies: Proceedings of the First Neonatal Cell Therapies Symposium (2022).

Despite considerable advances, there is a need to improve the outcomes of newborn infants, especially related to prematurity, encephalopathy and other conditions. In principle, cell therapies have the potential to protect, repair, or sometimes regenerate vital tissues; and improve or sustain organ function. In this review, we present highlights from the First Neonatal Cell Therapies Symposium (2022). Cells tested in preclinical and clinical studies include mesenchymal stromal cells from various sources, umbilical cord blood and cord tissue derived cells, and placental tissue and membrane derived cells. Overall, most preclinical studies suggest potential for benefit, but many of the cells tested were not adequately defined, and the optimal cell type, timing, frequency, cell dose or the most effective protocols for the targeted conditions is not known. There is as yet no clinical evidence for benefit, but several early phase clinical trials are now assessing safety in newborn babies. We discuss parental perspectives on their involvement in these trials, and lessons learnt from previous translational work of promising neonatal therapies. Finally, we make a call to the many research groups around the world working in this exciting yet complex field, to work together to make substantial and timely progress to address the knowledge gaps and move the field forward. IMPACT: Survival of preterm and sick newborn infants is improving, but they continue to be at high risk of many systemic and organ-specific complications. Cell therapies show promising results in preclinical models of various neonatal conditions and early phase clinical trials have been completed or underway. Progress on the potential utility of cell therapies for neonatal conditions, parental perspectives and translational aspects are discussed in this paper.

CD30-positive lymphoproliferative disorders-An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre.

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.

Diagnosis, management and follow up of peripheral T-cell lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance.

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared with aggressive B-cell lymphomas. However, such outcomes are heavily dependent on subtype. Although anthracycline-based regimens such as cyclophosphamide, doxorubicin, vincristine and prednisone remain the standard first-line treatment for most aggressive PTCL, there are important variations including incorporation of novel agents, use of radiotherapy and judicious consideration of stem cell transplantation. Relapsed or refractory disease represents a significant area of unmet need where chemotherapy intensification has limited efficacy and novel agents such as brentuximab vedotin and pralatrexate provide additional opportunities for attainment of remission and potential stem cell transplant. In the future, pre-therapy prognostic biomarkers including genomic characterisation, may aid in risk stratification and help guide initial patient management to improve survival. There is an urgent need to understand better the pathogenesis of PTCL to facilitate novel drug combinatorial approaches to improve survival. This position statement represents an evidence-based synthesis of the literature for application in Australian and New Zealand practice.

Diffuse large B-cell lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, accounting for 30-40% of lymphoma diagnoses. Although aggressive, cure is achievable in approximately 60% of cases with primary chemoimmunotherapy, and in a further substantial minority by salvage therapy and autologous stem cell transplantation. Despite promising activity in early phase clinical trials, no intensified or novel treatment regimen has improved outcomes over R-CHOP21 in randomised studies. However, there remain several areas of controversy including the most appropriate prognostic markers, central nervous system prophylaxis and the optimal treatment for patients with high-risk disease. This position statement presents an evidence-based synthesis of the literature for application in Australasian practice.

Prolonged survival with the early use of a novel extracorporeal photopheresis regimen in patients with Sézary syndrome.

Extracorporeal photopheresis (ECP) has demonstrated therapeutic benefit in patients with Sézary syndrome (SS) and erythrodermic mycosis fungoides (e-MF). To examine the efficacy of ECP in the modern era of novel therapies, we conducted a retrospective analysis of 65 patients with a diagnosis of SS or e-MF with blood involvement who were treated with ECP at our institute. Overall survival (OS), time to next treatment (TTNT), and skin response rate (RR) were used as the study end points to determine patient outcome. The median follow-up from diagnosis was 48 months (range 1-225 months), with a median predicted OS of 120 months. The majority (88%) of patients commenced ECP at treatment lines 1 to 3, either as a monotherapy or in conjunction with other systemic agents. The use of ECP monotherapy resulted in a significantly longer median TTNT when compared with interferon-α (P = .0067), histone deacetylase inhibitors (P = .0003), novel immunotherapy agents (P = .028), low-dose methotrexate (P < .0001), and chemotherapy (P < .0001). In particular, early commencement of ECP at treatment lines 1 to 3 yielded a TTNT of 47 months. The results of our study support the utilization of ECP for SS/e-MF, and we recommend that ECP should be considered as early as possible in the treatment paradigm for these patients.

Assessment and management of newly diagnosed classical Hodgkin lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

The management of Hodgkin lymphoma (HL) has undergone significant changes in recent years. Due to the predilection of HL to affect younger patients, balancing cure and treatment-related morbidity is a constant source of concern for physicians and patients alike. Positron emission tomography adapted therapy has been developed for both early and advanced stage HL to try and improve the outcome of treatment, while minimising toxicities. The aim of this review is to digest the plethora of studies recently conducted and provide some clear, evidence-based practice statements to simplify the management of HL.

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement.

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).

Australian and New Zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the COVID-19 pandemic.

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.

Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB) negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

Maintenance of agricultural drains alters physical habitat, but not macroinvertebrate assemblages exploited by fishes.

The effects of drain maintenance on fish habitat and benthic macroinvertebrate assemblages (fish prey) were investigated for eight agricultural drains in southwestern Ontario, Canada. Our investigation employed a replicated Before-After-Control-Impact (BACI) design where each maintained section of a drain was paired with an unmaintained section downstream and an unmaintained section on a nearby reference drain of similar size and position in the watershed. Seven variables characterizing physical habitat features important to fishes and three variables characterizing the taxonomic abundance, densities, and relative densities of benthic macroinvertebrates were measured before drain maintenance and 10-12 times over 2 years following maintenance. Pulse responses were detected for three habitat variables quantifying vegetative cover: percent vegetation on the bank, percent in-stream vegetation, and percent cover. All three variables returned to pre-maintenance levels within two years of maintenance. No consistent changes were observed in the remaining habitat features or in the richness and densities of benthic invertebrate assemblages following drain maintenance. Our findings suggest that key features of fish habitat, structural properties and food availability, are resistant to drain maintenance.

Early and Intensive Dietary Counseling in Lung Cancer Patients Receiving (Chemo)Radiotherapy-A Pilot Randomized Controlled Trial.

Malnutrition is prevalent in patients undergoing (chemo)radiotherapy (RT) for lung cancer. This pilot study tested the feasibility and acceptability of delivering an intensive nutrition intervention for lung cancer patients receiving RT. Twenty-four patients with lung cancer were randomized to receive the intervention which employed a care pathway to guide intensive dietary counseling from pretreatment until 6-wk posttreatment or usual care. Nutritional, fatigue, and functional outcomes were assessed using valid and reliable questionnaires before randomization, at the start and end of RT and 1- and 3-mo post-RT. Consent rate was 57% with an overall attrition of 37%. Subject compliance with the completion of study questionnaires was 100%. A clinically important mean difference indicated greater overall satisfaction with nutritional care in the intervention group (5.00, interquartile range [IQR] 4.50-5.00; 4.00, IQR 4.00-4.00). Clinically important differences favoring the intervention were observed for weight (3.0 kg; 95% confidence interval [CI] -0.8, 6.8), fat-free mass (0.6 kg; 95% CI -2.1, 3.3), physical well-being (2.1; 95% CI -2.3, 6.5), and functional well-being (5.1; 95% CI 1.6, 8.6), but all 95% CIs were wide and most included zero. Recruitment feasibility and acceptability of the intervention were demonstrated, which suggest larger trials using an intensive nutrition intervention would be achievable.

Multidisciplinary lung cancer meetings: improving the practice of radiation oncology and facing future challenges.

Clinical guidelines widely recognize the importance of multidisciplinary meetings (MDM) in the optimal care of lung cancer patients. The published literature suggest that dedicated Lung Cancer MDM lead to increased treatment utilization rates and improved survival outcomes for patients with lung cancer. For radiation oncologists, Lung Cancer MDM have been proven to support evidence-based practice and improve the utilization of radiotherapy. Lung Cancer MDM also allow for education and promotion of specialty radiotherapy services. The fast pace of modern medicine is also presenting new challenges for the multidisciplinary lung cancer team, and technological advances are likely to lead to new changes in the structure of traditional Lung Cancer MDM.