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Background: Chemotherapy predisposes people who menstruate to abnormal uterine bleeding that can be life-threatening and may also damage ovaries, resulting in premature menopause. The purpose of this study was to explore the incidence of menstrual history documentation and counseling before, during, and after cancer treatment. Patients and Methods: The medical charts of 137 consecutive females (self-reported) aged 18 to 49 years receiving anticancer treatment at a major tertiary metropolitan hospital in Australia between 2017 and 2020 were reviewed. Data collected included primary diagnosis, stage of cancer, treatment(s) received, rates of remission or progression, documentation of involvement of a specialist gynecologist, reproductive history, menstrual disturbances, menstruation counseling or intervention offered, and diagnosis of early ovarian failure. Results: Only 16.1% of patients had their menstrual history documented at the initial consult, and 49.6% had their menstrual history documented at a subsequent consult with their treating oncologist or hematologist. Most (82.4%) patients with a menstrual history documented experienced menstrual disturbance posttreatment, most commonly amenorrhea (48.0%), followed by menopause or menopause symptoms (20.6%), irregular menstrual bleeding (16.7%), menorrhagia (13.7%), dysmenorrhea (3.9%), and iron deficiency from bleeding (2.9%). Menopause/Menopausal symptoms and iron deficiency were more likely to be treated than other disturbances. Conclusions: Menstruation disturbance is a common side effect of cancer treatment. Menstrual care should be integral to cancer care for people who menstruate, and higher engagement could be achieved through education of medical and allied health staff, information technology systems automating prompts and referral pathways, regular audits to ensure compliance, better alliances between cancer and fertility specialists, and the creation of accessible patient information to promote awareness and facilitate discussion.

Comprehensive clinical characteristics of Australian patients with classical Hodgkin Lymphoma (cHL) have not previously been systematically collected and described. We report real-world data of 498 eligible patients from the first five years of the Lymphoma and Related Diseases Registry (LaRDR), including baseline characteristics, histologic subtype and treatment patterns in first-line therapy. Patient demographics and distribution of histopathological subtypes of cHL are similar to reported international cohorts. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most common therapy for both early and advanced-stage disease, and 48% of patients with early-stage disease received radiotherapy. Treatment patterns are consistent with international guidelines. In comorbid patients ≥ 60 years of age with advanced-stage disease, there is greater variation in treatment. In patients with a recorded response, the objective response rate (ORR) was 96% in early-stage disease, and 88% in advanced-stage disease. Early progression-free survival data suggest Australian patients with cHL have good outcomes, similar to other international studies.

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 (

Acute myeloid leukemia (AML) has an aggressive course and a historically dismal prognosis. For many patients, hematopoietic stem cell transplantation (HSCT) represents the best option for cure, but access, utilization and health inequities on a global scale remain poorly elucidated.To describe patterns of global HSCT use in AML for a better understanding of global access, practices, and unmet needs internationally.Estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease (GBD) 2019 study. HSCT activities were collected from 2009-2016 by the Worldwide Network for Blood and Marrow Transplantation (WBMT) through its member organizations. The primary endpoint was global and regional use (number of HSCT) and utilization of HSCT (number of HSCT/ number of incident cases) for AML. Secondary outcomes included trends from 2009 to 2016 in donor type, stem cell source and remission status at time of HSCT.Global AML incidence has steadily increased, from 102,000 (95% uncertainty interval (UI): 90,200-108,000) in 2009 to 118,000 (104,000-126,000) in 2016 (+16.2%). Over the same period, a +54.9% increase from 9,659 to 14,965 HSCT/year was observed globally, driven by an increase in allogeneic (+64.9%) with a reduction in autologous (-34.9%) HSCT. While the highest numbers of HSCT continue to be performed in high-resource regions, the largest increases were seen in resource-constrained regions [+94.6% in Africa/East Mediterranean Region (AFR/EMR); +34.7% in America-Nord Region (AMR-N)]. HSCT utilization was skewed towards high-resource regions [in 2016: AMR-N 18.4%, Europe (EUR) 17.9%, South-East Asia/Western Pacific Region (SEAR/WPR) 11.7%, America-South Region (AMR-S) 4.5% and AFR/EMR 2.8%]. For patients70 years of age, this difference in utilization was widened; AMR-N had the highest allogeneic utilization rate, increasing from 2009 to 2016 (30.6% to 39.9%) with continued low utilization observed in AFR/EMR (1.7% to 2.9%) and AMR-S (3.5% to 5.4%). Across all regions, total HSCT for AML in 1HSCT remains a central curative treatment modality in AML. Allogeneic HSCT for AML is rising globally but there are marked variations in regional utilization and practices, including types of graft source. Resource-constrained regions have the largest growth in HSCT use, but utilization rates remain low with a predilection for familial related donor sources and are typically offered in CR1. Further studies are necessary to elucidate the reasons, including economic factors, to understand and address these health inequalities and improve discrepancies in use of HSCT as a potentially curative treatment globally.

Cardiac light chain (AL) amyloidosis is a condition with a very poor prognosis. We report a retrospective analysis comparing the traditional melphalan and dexamethasone protocol with cyclophosphamide, bortezomib and dexamethasone in late-stage cardiac AL amyloidosis. The primary end points were overall survival and haematological response. Both regimens provided meaningful responses in this difficult to treat patient group.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, accounting for 30-40% of lymphoma diagnoses. Though aggressive, cure is achievable in approximately 60% of cases with primary chemo-immunotherapy, 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, CNS 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. This article is protected by copyright. All rights reserved.

This review aims to provide an expert consensus statement to address the role of gene-panel testing in the diagnosis, prognosis and management of adult myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes (MDS/MPN) in Australia. This consensus statement was developed by an expert group, actively involved in gene panel testing in the area of MDS/MPN in Australia. This work was led by the chairs of the MDS (A/Prof A. Enjeti) and MPN (A/Prof D. Ross) working parties of the Australasian Leukaemia and Lymphoma Group (ALLG). The authors were selected after an expression of interest process on the basis of active laboratory involvement in gene panel testing, a specific demonstrated interest in MDS/MPN and/or publication record in this field. The authors were then allocated sections for literature review to identify the specific genes of interest for each MDS/MPN entity. At least two authors reviewed each section and an overarching diagnostic algorithm was developed by a consensus amongst all authors.

Introduction: Pregnancy-associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy-associated gynecological cancer. Material and methods: We conducted a population-based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow-up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. Results: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97–15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25–5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47–6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45–8.31) compared with babies born to women without PAC. Conclusions: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women. Refereed/Peer-reviewed

Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001-2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001-2005 to 58% in 2011-2015 (p 0.001). This was attributed to a reduction in NRM from 35% to 24% (p 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001-2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.

Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between ‘low-grade’ (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of G3BFL cases. With median 5 years follow-up, G3BFL overall (OS; P

Allogeneic hematopoietic; Cell transplantation; Myelofibrosis Trasplante alogénico; Células hematopoyéticas; Mielofibrosis Trasplantament al·logènic; Cèl·lules hematopoètiques; Mielofibrosi Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P

Contains fulltext : 293484.pdf (Publisher’s version ) (Open Access) From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers' performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013-2016. A second phase was delivered in July 2021 covering 2015-2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this 'work in progress', as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems. 01 juni 2023

While ruxolitinib is emerging as the treatment of choice for steroid refractory/dependent chronic graft vs host disease (cGVHD) based on randomized control trial data, there is relatively little real world data published on ruxolitninb for this indication.to evaluate the real world efficacy and safety of ruxolitinib in cGVHD patients who have failed any previous systemic therapy for cGVHD STUDY DESIGN: We retrospectively evaluated the efficacy of ruxolitinib in 115 heavily pre-treated patients with steroid-refractory or dependent chronic GVHD across 5 transplant centres.The majority of the study population had severe chronic GVHD (60%) and received ruxolitinib at the 4Overall, this study demonstrates the therapeutic efficacy of ruxolitinib for cGVHD in a heavily pretreated real-world population.

Refereed/Peer-reviewed Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end-organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for MF transplantation.

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Patients post haematopoietic stem cell transplant or CAR-T cell therapy face significant risk of morbidity and mortality from SARS-CoV19, due to their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learnt much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to optimally manage our patients. This article is protected by copyright. All rights reserved.

ObjectiveTo examine vaccine uptake, hesitancy and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination.DesignCross-sectional survey.SettingTen Australian health services.Participants4683 patients (3560 cancer, 842 diabetes and 281 multiple sclerosis) receiving care at the health services participated in the 42-item survey, between June 30 to October 5, 2021.Main outcome measuresSociodemographic and disease-related characteristics, COVID-19 vaccine uptake, and the scores of three validated scales which measured vaccine hesitancy and vaccine-related beliefs generally and specific to the participants’ disease, including the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale. Multivariable logistic regression was used to determine the associations between scale scores and vaccine uptake.ResultsOf all participants, 81.5% reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas (all pConclusionsDisease-specific concerns impact COVID-19 vaccine-related behaviours and beliefs in people with serious and/or chronic health conditions. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.Trial registrationACTRN12621001467820

Background Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and research. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process.Methods The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre.Results To date more than 4,700 patients have been enrolled from 27 sites. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences.Conclusion Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia and globally.

Australia and New Zealand have achieved excellent community control of COVID‐19 infection. In light of the imminent COVID‐19 vaccination roll out in both countries, representatives of all adult and paediatric allogeneic bone marrow transplant and cellular therapy (TCT) centres as well as representatives from autologous transplant only centres in Australia and New Zealand collaborated with infectious diseases specialists with expertise in TCT on this consensus position statement regarding COVID‐19 vaccination in TCT patients in Australia and New Zealand. It is our recommendation that TCT patients, should have expedited access to high‐efficacy COVID‐19 vaccines given that these patients are at high risk of morbidity and mortality from COVID‐19 infection. We also recommend prioritising vaccination of TCT healthcare workers and household members of TCT patients. Vaccination should not replace other public health measures in TCT patients given the effectiveness of COVID‐19 vaccination in TCT patients is unknown. Furthermore, given the limited available data, prospective collection of safety and efficacy data of COVID‐19 vaccination in this patient group is a priority.

The health and outcomes of long-term survivors after hematopoietic cell transplant (HCT) are areas of evolving interest as short-term transplant outcomes improve. Because recent changes in transplant practice have likely changed the survivor population, we sought to assess the survival of a contemporary cohort of patients who were alive and free of disease 2 years after HCT. Data were extracted from first transplants documented between 2002 and 2011 in the Australasian Bone Marrow Transplant Recipient Registry on patients who received an allogeneic HCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia, chronic myeloid leukemia (CML), non-Hodgkin lymphoma, and myelodysplastic syndromes or an autologous HCT for myeloma or lymphoma. Patients were included if they had survived at least 2 years without disease relapse or progression. Mortality rates were compared with standard Australian and New Zealand populations using relative-survival analysis. A total of 1562 allogeneic and 3822 autologous HCT patients were included, with a median follow-up of 5.6 years. Compared with a matched group of patients from our previous study from 1992 to 2001, the contemporary cohort of allogeneic HCT recipients was older and more likely to receive peripheral blood stem cells and from unrelated donors. Allogeneic HCT for AML increased, wheresa transplants for CML fell from 32% to 8%. Increasing use of reduced-intensity conditioning and unrelated donors was also seen. Long-term survival after allogeneic and autologous HCT were very similar to the previous 1992 to 2001 cohort despite changes in practice over time. Recipients of autologous HCT for myeloma demonstrated substantially lower overall survival than HCT for other indications with no clear plateau. Annual relative survival for survivors of allogeneic HCT was 96% to 99% of the general population but only 89% to 96% of the general population for recipients of autologous HCT. Late deaths were primarily due to nonrelapse causes after allogeneic HCT, but relapse or disease progression remained prominent for recipients of autologous HCT, particularly for myeloma. The management of late HCT effects is important to improve long-term survival of transplant recipients but should be tailored to the risks specific to the primary disease and transplant type. Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization.

Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression-free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8-16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7-37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. INTERPRETATION: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. FUNDING: Karyopharm Therapeutics Inc.

The COVID-19 pandemic has caused major disruption to health systems, with allogeneic haemopoietic cell transplant (alloHCT) services a particularly vulnerable area. Ongoing provision of alloHCT has required dynamic responses at national and local levels. In Australia and New Zealand (ANZ), a high reliance on unrelated donors from overseas registries has posed an additional challenge.To describe the impact of COVID-19 on alloHCT services in ANZ in the first year of the pandemic.Data from the national alloHCT patient and unrelated donor registries were extracted for a 2-year time frame. Comparisons were made between a pre-pandemic period of 1 March 2019 to 29 February 2020 and the corresponding dates during the pandemic, 1 March 2020 to 28 February 2021.There was a 13% decrease in the number of allogeneic transplants, a reversal of steady increases in previous years, with the largest decrease in unrelated donor transplants. Local donors supplied a greater proportion of unrelated stem cell products. With a switch to universal cryopreservation, the time from request of a product to infusion increased by a median of 25.5 days for overseas products and 14 days for local products. There was a significant increase in the number of products collected but not used.A strong public health response and coordinated transplant community activities allowed for safe provision of alloHCT in ANZ; however, our data suggest that the timely delivery of allogeneic transplants was affected by the COVID-19 pandemic. Continued dedicated efforts are required to minimise further impacts.

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL.Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019.We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors.The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT.This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.

Primary central nervous system lymphoma is a clinicopathological disease entity that accounts for 1% of all non-Hodgkin lymphoma (NHL). Advanced patient age, adverse disease biology and complexities of diagnosis and treatment render outcomes markedly inferior to systemic NHL. Despite this, an increasing evidence base, including limited randomised controlled clinical trial data, is informing optimal therapeutic strategies with methotrexate-based induction chemotherapy schedules and intensified consolidation in selected patients. This practice statement represents an evidence-based review of the literature and has been devised to assist healthcare professionals in the diagnosis and management of this disease.

Introduction Post-transplant lymphoproliferative disorders (PTLD) are aggressive lymphomas which occur in solid organ transplant recipients and cause significant mortality. In the era of positron emission tomography (PET) staging and rituximab (R), there is limited real-world data on treatment outcomes and the incidence of graft rejection after reduction in immunosuppression (RIS) has not been well defined. We report real-world outcomes of monomorphic diffuse large B cell lymphoma (DLBCL), the commonest histological subtype of PTLD in which treatment is most likely to be standardised. Methods We conducted a multicentre retrospective study across 11 Australian tertiary referral centres. Inclusion criteria were: (1) age ≥ 18 years with history of solid organ transplant; (2) a diagnosis of monomorphic DLBCL PTLD between January 2004 and December 2017; (3) staging with PET. We examined responses based on treatment: (1) 'R-primary' was defined as patients receiving initial rituximab monotherapy followed by further rituximab monotherapy for patients in remission or R-CHOP chemotherapy for patients with persistent or progressive disease; (2) 'R-chemotherapy' was defined as patients who received rituximab-based chemotherapy at diagnosis. Response assessment was defined according to current international lymphoma criteria (complete metabolic remission (CMR) = Deauville score 1-3). We examined the incidence of clinical and biopsy-proven graft rejection during and after PTLD diagnosis (early Results 91 DLBCL patients were identified. The median follow-up of living patients was 4.7 years (range 0.5-14.5 years). Baseline characteristics for all patients are shown in Table 1. Management approaches: Reduction in immunosuppression (RIS) was used in 88% of patients and rituximab (R) +/- chemotherapy in almost all patients (98%, n=89). Rituximab monotherapy (R-primary) was the first treatment in 24 patients (35%). Of these, 20 had PET restaging after rituximab and 9 patients (45%) achieved CMR and did not require chemotherapy. CMR rate rose to 71% with the subsequent addition of R-CHOP in R-primary non-responders. For patients initially treated with R-CHOP, the CMR rate was 76%. The incidence of graft rejection was 9% for the entire duration of follow up (n=4 biopsy-proven; n=4 clinically suspected) with 3 cases occurring within one year of PTLD diagnosis (Table 2). Survival and Prognostic Factors For the entire cohort, 3-y OS and PFS were 72% and 69%, respectively. There was no significant difference in OS between patients treated with an R-primary vs R-chemotherapy approach (P=0.13). Treatment-related mortality (TRM) was 7% with no significant difference between R-primary and R-chemotherapy approach (p=0.97). Outcomes for patients without CNS involvement (n=68) were comparable to patients with CNS involvement (n=23): 3-y OS 72.5% non-CNS vs 73.1% CNS; (P=0.78) - Figure 1. In multivariate analysis, elevated LDH (HR=3.58, P=0.025 [95% CI 1.17-10.8]) and ECOG ≥2 (HR=3.46, P=0.006 [95% CI 1.43-8.33]) were identified as predictors of worse OS. End of Treatment (EoT) PET imaging A total of 60 patients (66%) had EoT PET. Reasons for not performing an EoT PET (n=31) were: 7 MRI scans for CNS disease, 2 CT scans without PET, 10 patients without imaging (6 PD, 4 TRM), 12 missing data. Achieving CMR at EoT PET was predictive of OS (3-year OS PET negative 92.9% vs PET positive 51.4%; P=0.035) and only 5% of these patients relapsed (Figure 2). Conclusions In one of the largest real-world assessments of monomorphic DLBCL PTLD in the modern era of rituximab and PET imaging our data demonstrate: (1) similar response rate, OS and TRM compared to the PTLD-1 trial (Trappe et al, 2017); (2) the safety and efficacy of an R-primary approach; (3) similar OS for patients with CNS involvement compared to those with systemic lymphoma; (4) lower incidence of graft rejection than previously reported; and (5) achieving CMR at EOT PET is predictive of OS. This demonstrates that RIS and rituximab-based treatment is safe with a low likelihood of graft rejection and effective with a high cure rate for patients achieving CMR. Disclosures Tobin: Gilead: Research Funding. Hamad:Novartis: Honoraria; Abbvie: Honoraria. Talaulikar:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Cheah:Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding; Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria. Lee:Celgene/BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Strasser:Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ispen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mollee:Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees.

Background Several agents have been investigated for beyond second-line treatment of chronic graft-versus-host disease (GVHD). Ruxolitinib has been recently approved for steroid-refractory acute GVHD, while a prospective randomized study is ongoing to examine its efficacy in steroid-resistant chronic GVHD (cGVHD). The present study evaluated the efficacy of Ruxolitinib in terms of 1) overall response rate (ORR), 2) clinical benefit (CB), 3) dose reduction of corticosteroid exposure, 4) failure-free survival (FFS) and 5) overall survival (OS), in patients heavily pretreated for steroid-resistant cGVHD. Patients and methods A total of 47 patients who developed cGVHD after HCT and treated with Ruxolitinib for cGVHD from March 2016 to April 2020, at three different sites (Princess Margaret Cancer Center, Canada; Vancouver General Hospital, Canada and Saint Vincent Hospital, Australia), were evaluated in the retrospective study. Patients and disease characteristics are as follows: median age 52 years; classical 35 (71%), overlap syndrome 14 (29%). Of note, 27 patients (57.4%) had a previous history of acute GVHD. The ORR and CB were assessed at months 3, 6 and 12, retrospectively. Responses were evaluated according to NIH scoring/staging/response assessment as part of standard clinical practice. CB was assessed considering clinical response as well as steroid dose reduction. For systemic steroid dose reduction, prednisone dose per kg per day was captured prior to Ruxolitinib start, at months 3, 6 and 12. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to treatment. FFS and OS were calculated from the day of starting Ruxolitinib therapy for cGVHD treatment. Results A total of 47 patients had moderate (11/47, 24.4%) to severe (33/47, 73.3%) cGVHD except one who had mild grade cGVHD with a high-risk feature (thrombocytopenia at the time of Ruxolitinib start). The median number of organ involvement was 3 (range 1-7). Over half of patients (63.8%) received Ruxolitinib as 4th line or beyond for cGVHD treatment, while median number of previous lines of therapy was 3 (range 1-9). All 47 patients (100%) had been previously treated with systemic steroids; other previous treatments included ECP therapy (53.2%), Imatinib (29.8%), Ibrutinib (23.4%), Rituximab (21.3%). Ruxolitinib was started at 10-15 mg daily as initial dose, then maintained at 20mg daily in two divided doses on months 3, 6 and 12.With a median follow-up duration of 12 months, ORR was attained in 35.7%, 36.0% and 35.0% at 3, 6 and 12 months, respectively (Figure A). Of note, ORR in patients with sclerotic changes was 56%, and 61.5% in those with lung involvement. Patients resistant to TKI (i.e. Imatinib or Ibrutinib) for cGVHD treatment showed similar ORR compared to those naïve to TKI therapy.The CB was observed in 53.5%, 66.7% and 72.2% at months 3, 6 and 12, respectively (Figure B). Patients resistant to TKI for cGVHD treatment did not show any difference in CB compared to those naïve to TKI therapy.In terms of prednisone dose reduction, by 12 months , half of patients (50.0%) could taper prednisone doses below 0.1mg/kg/day, while the proportion of patients on prednisone dose below 0.1mg/kg/day was 9.3%, 20.0%, 17.4%, and 50.0% at month 0, 3, 6 and 12, respectively (Figure C). The group who achieved CB at 3 months showed a significantly lower dose of prednisone at 12 months (0.078mg/kg/day) compared to those without clinical benefit at 3 months (0.197mg/kg/day; p=0.033; Figure D).Out of 37 patients evaluated, 11 failures (29.7%) were noted, including resistance requiring a switch to other therapy (n=7), NRM (n=2) and intolerance (n=2). The FFS rate at 1 year in the overall population was 68.5% (Figure E). The FFS at 1 year in those having CB at 3 months vs not was 86.5% vs 51.4% (p=0.025).The OS at 1 year was 90.9% (Figure F). The OS at 1 year in those having a CB at 3 months vs not was 100% vs 78.8% (p=0.053). Conclusion: This multicenter retrospective study revealed that Ruxolitinib is an effective treatment option for patients with cGVHD, with good ORR and CB. The achievement of CB in the first 3 months correlated well with steroid dose reduction. It suggests that Ruxolitinib is a feasible GVHD treatment option, even for patients who were heavily pretreated for cGVHD or failed previous TKI drug. Figure 1 Disclosures Hamad: Abbvie: Honoraria; Novartis: Honoraria. OffLabel Disclosure: Ruxolitinib treatment for steroid resistant chronic GVHD