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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.

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.

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.

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.MethodsThis study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.OutcomesThe primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.ResultsThirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12–66). The median Expanded Disability Status Scores (EDSS) was 6 (2–7) and patients had failed a median of 4 (2–7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+T regulatory cells, immunosuppressive CD56hinatural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.ConclusionsThe EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.Trial registration numberACTRN12613000339752.

Background: Given the increasing numbers of multiple sclerosis (MS) patients undergoing autologous haematopoietic stem cell transplant (AHSCT) worldwide, and with women of childbearing age overrepresented in the target population, it is increasingly important to review fertility and pregnancy outcomes following AHSCT. Objective: To evaluate the rate of pregnancy and complications post-AHSCT for MS. Method: Retrospective evaluation of the rate of pregnancy and associated complications in a cohort of patients post-AHSCT with BEAM conditioning for MS since 2010 in a tertiary referral centre. Results: In our ongoing Phase 2 trial of AHSCT for MS, 55 patients have undergone AHSCT with 30 females being of childbearing age at time of transplantation. Four pregnancies occurred following AHSCT. Two pregnancies were carried to term. No maternal or neonatal complications were reported in either case. Two pregnancies were not carried to term due to elective terminations. Both of these patients became pregnant unexpectedly 2 years following AHSCT. Of the 21 male patients, one patient has fathered three children since his AHSCT. There were no newborn complications. Conclusions: This is the first report to our knowledge on fertility outcomes in both sexes post-AHSCT for MS. Patients of both sexes should be counselled prior to treatment on infertility and contraceptive use.

Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival.Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis.We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry.A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis.AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

Background Results have been varied regarding the effect of donor age on the outcome of unrelated donor hematopoietic cell transplantation (HCT). Aims This study sought to determine the influence of donor age on adult unrelated donor HCT outcome in Australia. Methods Patients were included in the study if they were aged 16 or above and underwent first allogeneic unrelated donor HCT in Australia for the indications of acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML), chronic myelogenous leukaemia (CML) or myelodysplastic syndromes (MDS) between the years of 2001 and 2014 inclusive. The main outcome measure was overall survival (OS), which was tested against independent variables using univariate Kaplan-Meier methods and multivariate Cox regression. Results A total of 1,158 unrelated donor HCT were represented in the data. Cumulative incidences of engraftment, transplant related mortality (TRM), acute graft-versus-host disease (GvHD), chronic GvHD and relapse were not significantly affected by donor age. OS probability at 5 years post-transplant was 48.3%. In multivariate analysis of OS, year of transplant 2001-2007, recipient age 40 years or greater, poor risk disease, HLA match less than 6/6 and poor performance status at transplant (Karnofsky scale) were independently significant adverse OS risk factors. Donor age was not a significant risk factor for OS in univariate or multivariate analysis. Conclusions The conclusion from this study was that donor age (up to 59 years) did not influence post-transplant outcome among adult unrelated donor HCT performed in Australia for hematologic malignancies. This article is protected by copyright. All rights reserved.

Background Persons living with human immunodeficiency virus (HIV) are at elevated risk of developing the malignant diseases that require allogeneic stem cell transplantation (ASCT). Recent data suggest that these individuals are also at an elevated risk of certain complications post-ASCT. This risk may result from preexisting HIV-related factors affecting dynamics of immune reconstitution post-ASCT. However, to date, there has been little work describing the dynamics of immune reconstitution post-ASCT in persons with HIV and none comparing these data to controls without HIV. Methods We assessed T-cell reconstitution in 6 ASCT with HIV recipients (HIV+ASCT) compared to a control population of 21 ASCT without HIV recipients. In a subset of HIV+ASCT recipients we performed additional flow cytometry profiling of CD8+ T-cell subsets and antigen specificity of reconstituting CD4+ and CD8+ T cells. Results We observe no difference in post-ASCT CD4+ T cells between HIV+ASCT and HIV-negative ASCT recipients, despite much lower pre-ASCT CD4+ T-cell counts in the HIV+ASCT group. In contrast, we observed significantly higher CD8+ T-cell numbers in the HIV+ASCT group post-ASCT. The reconstituting CD8+ T-cells were predominantly CD45RO+, whereas homing markers and antigen specificity of these cells varied between participants. Conclusion This study represents the most extensive characterization of immune-reconstitution post-ASCT in persons with HIV, and the first to our knowledge to compare these data to ASCT controls without HIV. The results indicate that immune reconstitution in this group can be affected by preexisting HIV infection and post-ASCT antigen exposure.

Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapse-free survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P= .002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P = .006), and superior 2-year GRFS (35.5% versus 20.0%, P = .003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials.

Sri Lanka, an island in the Indian Ocean with an area of 62 705 square kilometers, has a population of 21 million people. It is divided into 9 provinces, 25 districts, and 324 divisional secretary areas ([Figure 1][1]). In Sri Lanka, the public sector provides universal free health coverage. The

We conducted a study to analyze and report on indicators of hematopoietic cell transplant (HCT) physician time use and HCT center output measures. HCT centers in Australia and New Zealand (A&NZ) were invited to provide demographic and time use details for physicians participating in HCT patient care (HCT physicians). Resource details for adult and pediatric centers were included. From a total of 46 centers that were invited to participate, completed data were received from 37 centers (80%) representing 185 HCT physicians, with a median age of 48 (range, 33 to 72), of whom 31% were women. Just over half of HCT physicians cited prior work experience in large overseas HCT centers (97, 52%) and over one-third (79, 43%) possessed postgraduate qualifications other than specialist training. Total annual mean HCTs per HCT physician full-time equivalent (FTE) were 14.2 for centers performing both allogeneic and autologous HCT, 6.6 for autologous only centers, and 10.6 for all centers. For all HCT physicians surveyed the mean proportion of time spent on HCT related tasks was 31.7%. In A&NZ, for centers that perform both allografts and autografts, there was a mean of 4.0 allogeneic HCT annually per HCT bed, compared with 2.6 for the United States and 7.1 allogeneic HCT annually per HCT physician FTE (United States, 6.3). Projections of the A&NZ HCT physician workforce indicated that the numbers of HCT physicians are likely to stay within the region of 170 to 190 for the next 10 years, whereas HCT activity will likely continue to climb steadily. Healthcare and government authorities should be prepared to enable and support greater HCT activity in A&NZ in the future.

Background Modern antiretroviral therapy (ART) has reduced HIV associated morbidity and mortality, and allowed a similar treatment approach of aggressive lymphomas in PLWH to that of their HIV negative counterparts. Australia is an ethnically diverse country with a low HIV prevalence and an excellent population-wide ART coverage and adherence in PLWH. We aimed to describe the real-world Australian experience in managing PLWH diagnosed with diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL), and compare our treatment approach and outcomes against international data. Methods This was a retrospective, multicenter study conducted by the Australasian Lymphoma Alliance across 6 centers in 5 states. HIV positive patients with biopsy proven BL and DLBCL, diagnosed between 1st January 2009 and 31st December 2019 were identified through each institution's database. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate. Results 44 patients (24 DLBCL, 20 BL) were included in the analysis. The median age was 52 years (range 32-78). The median follow-up was 1.8 years (range 0.1-13.1). 36 (82%) patients presented with advanced stage (III-IV) disease. 28 (64%) were defined as high-risk based on disease specific IPI scoring systems. The mean CD4 count was 334 cells/μL at diagnosis and 10 (23%) patients had a CD4 count of 350 cells/μL and >200 cells/μL respectively. Conclusions A significant proportion of PLWH still present with aggressive lymphoma as an AIDS-defining event prior to HIV diagnosis, despite high levels of health education and healthcare availability. Our results appear equivalent to those for non-HIV patients with acceptable toxicity. Current Australian practice favors treating aggressive lymphomas in PLWH similarly to the HIV negative population, with the addition of concurrent ART. CD4+ T-cell-related immune reconstitution appears to recover within 6 months post-therapy. The OS of this cohort appears similar to the HIV negative population and published cohort studies (Coutinho AIDS 2013, Evens Blood 2019, Alderuccio Blood Adv 2021). Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ku: Genor Biopharma: Consultancy; Antegene: Consultancy; Roche: Consultancy.

Background Patients with secondary acute myeloid leukaemia (sAML), defined as AML that follows a diagnosis of myelodysplastic syndrome or myeloproliferative neoplasm, are known to have a poor prognosis with conventional chemotherapy alone, when compared to de novo AML (dnAML). Allogeneic stem cell transplant offers the best chance of cure due to the often chemo-resistant nature of sAML, although there are limited studies assessing the outcome of allografting in this patient population. The Disease Risk Index (DRI) is a clinical decision tool which assists in determining the balance of transplant risk versus benefit, however validation studies to date have not evaluated the DRI in patients with sAML. Methods A retrospective analysis of 211 patients with dnAML or sAML who underwent allogeneic stem cell transplant between 1 st January 1998 and 31 st July 2015 at St Vincent's Hospital or Royal North Shore Hospital in Sydney Australia, was undertaken. Cases were identified from the Australasian Bone Marrow Transplant Recipient Registry, with additional data collected by medical record review. Overall survival (OS) probability was calculated by the Kaplan-Meier method. Non-relapse mortality (NRM) and relapse incidence (RI) were estimated by cumulative incidence with "death without relapse" and "relapse" as competing risks. A Cox proportional hazards model was used for multivariate regression, with results expressed as hazard ratio (HR) with 95% confidence intervals. Results Of the 211 eligible patients, 63 (30%) had a diagnosis of sAML, compared to 148 with dnAML. Of those with sAML, 74% had antecedent MDS and 26% an MPN. Patients with sAML had an older median age (55 vs 44 years, p3 (p=0.003), and more commonly had at least one cytogenetic abnormality (p=0.026). A myeloablative conditioning regimen was used in 35.3% and 66.0% of s- and dn- AML respectively. Grade II or greater acute graft-versus-host disease (GVHD) occurred in 39.7% of sAML and 29% of dnAML, with chronic GVHD reported in 60.3% and 64.5% respectively. OS at 1 year was 48.5% in sAML and 71.6% in dnAML (HR 1.93 [95%CI 1.32-2.97, p=0.0001]). Multivariate analysis accounting for disease risk index (DRI) as a co-factor identified sAML as an independent adverse risk factor for OS (HR 2.13 [95%CI 1.31-3.45], p=0.002). Compared to dnAML, sAML was associated with higher rates of disease relapse (HR 2.21 [95%CI 1.20-4.05], p=-0.011). Figure 1: Transplant outcomes (A) Overall survival dnAML vs sAML (B) Cumulative incidence of relapse at 1 year dnAML vs sAML Conclusions Patients with sAML experience poorer outcomes following allogeneic stem cell transplant than those with dnAML. Whilst the DRI stratifies AML based on cytogenetic risk and stage, our study identifies sAML as a prognostic marker independent of risk ascribed by the DRI. This has not been reported previously and if replicated, suggests the need for development of an independent prognostic model to capture the adverse risk in the sAML patient cohort. Importantly, despite poor outcomes, the lack of alternate management strategies still makes allogeneic stem cell transplant the only potential curative therapy. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Greenwood: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Background: Pregnant or breastfeeding women are routinely excluded from clinical trials due to fear of teratogenicity and toxicity of therapeutic agents, despite a paucity of evidence to support this practice. In response to the diethylstilbesterol (DES) and thalidomide-induced embryopathy in the mid-20 th century, the US Food and Drug Administration (FDA) released new regulations excluding Women of Child-Bearing Potential (WoCBP) from phase I and II trial participation, followed by an introduction of a new pregnancy category labelling system in 1979. The legacy of these measures is a reliance on accidental exposure pregnancy data rather than rigorous clinical trial efficacy and safety data for medication use in pregnancy and lactation. WoCBP when enrolled in clinical trials are often subjected to prescriptive contraceptive requirements to mitigate the risk of accidental pregnancy, without informed consent for the contraceptive side effects. These barriers to trial participation for WoCBP, particularly in the setting of life-threatening haematological diseases, prevent timely access to therapies only accessible via clinical trial participation. Lymphoma and leukaemia in pregnancy occur with an approximate incidence of 1 in 6000 and 1 in 75,000-100,000 pregnancies respectively. We examined the rates and rationale for exclusion of these patients from clinical trials, as well as contraceptive requirements for WoCBP. Methods: We conducted a cross-sectional observational study of clinical trial protocols recruiting patients with potentially life-threatening haematological malignancies. We searched the clinicaltrials.gov clinical trials database for trial protocols enrolling acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Hodgkin lymphoma (HL) and/or Diffuse Large B Cell lymphoma (DLBCL) between January 2016 and January 2021. Studies were included if they included WoCBP (15-55 years of age). Studies without complete electronic protocol access were excluded. The following data was collected: target disease, study phase, study location, age of patients, whether pregnant or lactating women were excluded (rationale if provided including evidence of teratogenicity), type of contraception and duration mandated and presence or absence of informed consent for contraception. Results: We identified 68 trials for AML, ALL, DLBCL and HL (40%, 26%, 21% and 13% respectively) (Table 1). Most were phase I-II studies (91%) of novel agents (90%) and of note, the majority were of non-chemotherapy agents (83%). The majority (97%) excluded pregnant women and (69%) without providing rationale. Only 2% cited evidence for embryopathy in either human or animal studies. Most studies (84%) explicitly excluded lactating women, of which 85% did not provide justification. Contraception was mandatory in 90% of the protocols, with 47% of these requiring at least two different forms of contraception for the entire study period. These included hormone-based contraception, barrier methods and abstinence. None of the protocols provided informed consent for the potential side effects of the mandated contraceptive methods in the context of the study. Conclusion: The theoretical harm from anti-cancer therapy to the foetus is typically given greater moral precedence than is a pregnant woman's autonomy. Pregnant and lactating women were almost universally excluded from the trials in this study with limited rationale provided. Study protocols frequently mandated contraception without informed consent of its associated risks in the context of the study. This perpetuates the lack of efficacy and safety data in this patient population, and drives a cycle of systematic exclusion, data shortage, and inequity. Pregnant and lactating women with life threatening haematological malignancies with no alternative treatment options should be eligible for clinical trials where this offers potentially life-saving therapy, with appropriate informed consent around the indefinable and potentially harmful effects on their foetus. We propose obligatory rationale for exclusion of pregnant and breastfeeding women in all clinical trials, using safety data from either human or animal studies and contraception informed consent. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background: Chemotherapy is potentially harmful to the developing foetus and there is limited data on the foetal impact of immunotherapy except for rituximab. Therefore determining pregnancy status prior to initiation of chemo- and or immuno-therapy (CIT) should be standard of care. Repeat screening or testing during and after chemotherapy should be considered as women often cannot tell that they are pregnant due to overlapping symptoms of pregnancy, malignancy and treatment. This is of particular importance in women who are not on effective forms of contraception for personal choice or clinical reasons. Clinicians cannot presume that a patient's pregnancy status has been checked, or rely on any assumptions of abstinence, contraception or infertility based on secondary amenorrhoea. While CIT teratogenicity should be part of the informed consent discussion and it is recommended that pregnancy screening occur prior to CIT, there are no specific guidelines on this or on testing during CIT. It is our institutional standard to document consent using a standard tick box form to confirm a discussion of common and uncommon side effects of treatment, long term and life threating complications and impacts on fertility. Teratogenicity, pregnancy implications or contraception are not specified. We performed a retrospective review to evaluate the uptake of pregnancy screening prior to and during first-line CIT as well as an audit of documentation of contraception counselling in haematological and solid-organ malignancies at a large Australian tertiary cancer centre. Methods: We searched our electronic outpatient medical record database for Women of Child Bearing Potential (WoCBP) who were diagnosed with a malignancy and received outpatient based CIT between May 1 2015 and June 12 2020. WoCBP was defined as women 18-55 years of age with no record of menopause or definitive infertility. We captured patient demographics, disease details and CIT regimen. We collected result of any serum or urine b-HCG pregnancy tests done within 90 days prior to or during CIT administration and if positive, the pregnancy outcome. We captured any documentation regarding contraception prior to or during treatment. Results: A total of 415 WoCBP with a median age of 42 years (range 19-51) were included. The majority of women (79.3%) were treated for solid organ malignancies compared to haematological malignancies (20.7%) (Table 1). Only 17.1% were screened for pregnancy prior to its initiation. The average time between screening and CIT initiation was 19.5 days (range 0-90 days). Given the broad range of regimens and taking into consideration teratogenicity potential, CIT was categorised as immunotherapy alone (32.5%), chemotherapy containing an alkylating agent (25.8%) or an antimetabolite (3.9%), combination chemoimmunotherapy (15.2%) and other (22.7%). Rates of pregnancy screening within these categories is represented in Figure 1. One patient with early breast cancer had a positive pregnancy test during her 4 th cycle of adjuvant chemotherapy with paclitaxel, in the emergency department for a presentation of nausea, anorexia, abdominal pain and diarrhoea. The outcome in this case was an early spontaneous miscarriage estimated at 3-4 weeks gestation. This is the only patient who had a pregnancy test beyond the first cycle of CIT. Only 14.8% of patients had documentation of past or present contraception methods. None of the patients had documentation regarding counselling on recommended forms of contraception. Conclusion: A minority of WoCBP received a pregnancy test prior to commencing CIT for haematological or solid organ malignancy, and none intentionally received a test prior to subsequent chemotherapy cycles through the oncology/haematology service. Also none of the women had documented counselling on contraception. These results are concerning because missing a positive pregnancy test puts women at risk of foetal complications, accidental miscarriage, potential bleeding risks and avoidable psychosocial stress. Our results are consistent with the 2 other reports on this topic and are likely generalizable to other cancer centres. This highlights the urgent need for guidelines to increase the rate of pregnancy testing in WoCBP receiving CIT and contraception counselling prior to CIT. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

An Australasian Bone Marrow Transplant Registry (ABMTR) Study of the Trends and Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Hodgkin Lymphoma between 2009-2019: Relapse remains the most common cause of death post transplantation Introduction: Hodgkin Lymphoma (HL) is an eminently curable disease, with 80% of cases achieving cure with first line therapies. There are a subset of patients who relapse and require salvage therapy including autologous stem cell transplant and more recently novel agents such as brentuximab vedotin (BV) and the PD-1 inhibitors. The latter are less toxic and achieve durable responses but are not considered curative for most (LaCasce et al., 2019). In Australia BV and PD-1 inhibitors were approved in December 2013 and September 2017 respectively. Allogeneic HSCT offers a graft vs lymphoma (GVL) effect that may contribute to long term survival in some patients (Peggs et al., 2005). The introduction of reduced intensity conditioning (RIC) has seen improved outcomes with an OS of 67% (59-74%) and Progression Free Survival (PFS)of 45% (35-56%) (Rashidi et al., 2016) Patients and methods: Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic transplant for HL between 2009 and 2019. The Kaplan Meier method was used to calculate OS and PFS with log rank test for comparison. Multivariable Cox proportional hazards models were used to identify associations with OS. We divided the patients into 5 year cohorts to compare transplant outcomes over time. Results: A total of 149 patients from 16 sites in Australia and New Zealand were included. The median age at time of transplant was 31 years (range 19-61) and the majority were male (60%). Seventy-five percent of patients had undergone previous autologous HSCT with data missing for 22%. Median follow up was 75 months (range 4.7-137.1). Forty five percent of patients were in complete remission (CR), 34% in partial remission and 15% relapsed/primary refractory (RR) at the time of HSCT with information missing in 4%. The majority of donors were matched unrelated donors (47%) and sibling donors were used for 37% of patients, haploidentical in 11% and umbilical cord blood in 5%. Reduced intensity conditioning was used in 86% of patients and in vivo T cell depletion with ATG or alemtuzumab was used in 27%. Acute GVHD occurred in 53/149 (30%) of which 31% was grade III-IV. In patients who survived beyond 100 days, the incidence of chronic GVHD was 38%, of which 53% was preceded by some form of aGVHD. Non-relapse mortality (NRM) at 100 days was 8% with 5/12 of these patients dying from aGVHD. Two-year OS and PFS were 75% and 49% respectively. A period effect was not detected with no significant difference in OS (p=0.8) nor PFS (0.2) based on transplant year (figure 1a & 1b). Multivariate analysis of factors associated with OS identified age at transplant of >40 (HR 3.24, 95% CI 1.71-6.15, p The numbers of HSCT performed each year are illustrated in figure 1c, with a larger proportion of patients in CR from 2014 onward. Post-transplant relapse occurred in 38% of patients (figure 1d)with a median time to relapse of 8.5 months (range 0.2 -42). Forty-eight percent (27/56) of patients who relapsed post HSCT were in CR at the time of HSCT. Of those who relapsed, 37% died due to progressive disease with no evidence of chronic GVHD. Relapse was the most common cause of death (37%) Conclusion: Although the rates of HSCT for HL in Australia and New Zealand have not varied over the past decade despite the availability of novel agents, there is a larger proportion of patients in CR prior to transplant. Survival outcomes for HL post HSCT are comparable to those reported internationally. Despite a higher percentage of patients transplanted in CR in later years, relapse post HSCT remains the major cause of death. Further studies to examine strategies to prevent or treat relapse of HL post-allograft are needed. Disclosures Sharplin: Novartis: Other: FUnded to attend Australian Haematology Conference . Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Spencer:AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Celgene, Janssen and Takeda: Speakers Bureau. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad:Abbvie: Honoraria; Novartis: Honoraria.

Introduction Mantle cell lymphoma (MCL) is a mature B lymphoproliferative disorder with a frequently aggressive clinical course. Although the response rates in patients eligible for conventional chemoimmunotherapy are high, relapses are virtually inevitable, with a median overall survival (OS) of three to five years. For some patients allogeneic stem haematopoietic cell transplantation (alloHCT) is a potential therapeutic option. AlloHCT for MCL has been associated with long term overall survival (OS) of around 40%, with high rates of non-relapse mortality (NRM) of 20-40% and relapse rates of 20-30% (Urbano-Ispizua et al., Biol Blood Marrow Transplant 2015;21:1746, Robinson et al., Leukemia 2015;29:464). Whilst there is evidence of a graft-versus-lymphoma effect in MCL, it has not been shown to translate into improved OS. We performed a retrospective national registry study to examine alloHCT practice and outcomes for MCL in Australia and New Zealand in the modern era. Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving an alloHCT for MCL between January 2009 and December 2019. This time range was chosen to capture the era of widespread rituximab use. Survival, relapse and toxicities of alloHCT were investigated, as well as transplant trends over time. Survival was analysed using the Kaplan-Meier method, with comparisons between the transplant periods 2009-2014 and 2015-2019 performed using the log-rank test. Cox proportional hazards regression was performed to determine significant risk factors for transplant outcome. The following risk factors were analysed for impact on outcomes: age, transplant before 2015, previous autologous HCT (autoHCT), remission status at transplant, use of myeloablative conditioning (MAC), haploidentical donor and use of T cell depletion (TCD). Results A total of 86 patients were included in the analysis. The median age was 56 (range 39-71). There was a male predominance with only 12% female patients. At the time of transplant, 51% were in complete remission, 26% had a partial response and 20% had stable or progressive disease (data missing in 3%). Sixty-seven percent had undergone previous autoHCT. The majority of donors were HLA-matched siblings (51%), followed by HLA-matched-unrelated (42%) and haploidentical (7%). Myeloablative conditioning was utilised in 14%, and T-cell depletion (TCD) in 24%. The median times to neutrophil engraftment (>0.5x109/L) and platelet engraftment (>20x109/L) were 16 and 20 days respectively. NRM at 1 and 5 years was 23% (95% confidence interval [95%CI] 10-39%) and 30% (95%CI 15-48%) respectively. The 100-day cumulative incidence of grade II to IV acute GVHD was 29%. The 3-year cumulative incidence of chronic GVHD was 27%. The median duration of follow up was 4.17 years (range 0-9.6 years). Median OS was 4.2 years, with an estimated 5-year OS of 47% (95%CI 35-58%) and 10-year OS of 23% (95%CI 8-43%) (figure 1). Five-year relapse free survival (RFS) was 38% (95%CI 26-50%) (figure 2). The cumulative incidence of relapse (CIR) was 20% at 1 year and 33% at 4 years, with a flattening of the curve after this point (figure 3). On multivariate analysis (MVA), the use of myeloablative conditioning (MAC) was associated with inferior RFS (hazard ratio 2.33; 95%CI 1.05-5.17; p=0.038) and OS (hazard ratio 3.11; 95%CI 1.39-7.00; p=0.006) (figure 4). No risk factors on MVA impacted NRM or CIR. Chronic GVHD was not associated with RFS or CIR. An average of nine alloHCTs were performed each year. There was an increase in the proportion of haploidentical transplants between 2009-2014 and 2015-2019 (4% to 10%). There was no significant change over time in OS, RFS or NRM, or in the use of MAC or TCD. Conclusion There has been no significant change in the rates of alloHCT for MCL in Australia and New Zealand over the past decade. Trends show an increasing utilisation of haploidentical donors. Overall outcomes were comparable to those previously published with favourable OS and durable remissions seen in a subset of patients. MAC was associated with inferior OS and RFS, however the cause for this is unclear given the lack of association with NRM or CIR. Ongoing reporting of alloHCT outcomes in MCL is important given the emerging role of novel therapies, such as Bruton tyrosine kinase inhibitors, bispecific T cells and CAR-T cell therapy. Figure 1 Disclosures Di Ciaccio: Jansen: Honoraria, Other: travel and accomodation grant. Greenwood:MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad:Novartis: Honoraria; Abbvie: Honoraria.

Background The treatment landscape for chronic lymphocytic leukaemia (CLL) has significantly changed over the past decade with the advent of targeted therapies. Subsequent improvement in remission rates has been seen in all patient groups, however patients with high-risk genetic features (del17p, TP53 mutation) continue to have poorer outcomes. In such patients, and in multiply relapsed/refractory standard risk patients, allogeneic stem cell transplantation remains a viable management option despite the associated morbidity and mortality. The aim of this study was to examine trends in allogeneic stem cell transplantation for CLL in Australia and New Zealand over the past decade, and to identify predictive factors for overall survival (OS) and progression free survival (PFS). Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic stem cell transplantation for CLL, in the absence of Richter's transformation, between January 2009 and December 2018. Transplant outcomes were compared between 2 time periods, 2009-2013 and 2014-2018 using log rank test for survival and Gray's test for cumulative incidence curves. Cox regression analysis was performed to identify factors predictive of survival. Medians are reported with ranges, hazard ratios (HR) and cumulative incidence with 95% confidence intervals (CI). Results A total of 153 patients (75% males) were included. Median age at transplantation was 55 years (range 23-69) with a median time from diagnosis to transplantation of 5.7 years (range 100days - 24.7years). Most patients received reduced intensity or non-myeloablative conditioning (84.3%, n=129) and did not receive T cell depleting therapy (73%, n=94). The median follow up was 5.9 years (range 0.8-11years). Median time to neutrophil engraftment was 16 days (range 6-49) and median time to platelet engraftment was 18 days (range 1-69). At 100 days following transplantation the cumulative incidence of graft failure was 3.9%, CMV reactivation 41% (95% CI 31-50%) and CMV disease 3.2% (95% CI 1-8%). Acute graft versus host disease (aGVHD) grade II-IV occurred in 39% (95% CI 29-49%) of patients and grade III-IV in 17% (95% CI 9-25%). The cumulative incidence of chronic GVHD (cGVHD) was 65% (95% CI 53-76%) at 5 years; extensive cGVHD occurred in 77% of patients with cGVHD. Median OS was 4.3 years (95% CI 3.6-not reached) and PFS was 2.6 years (95% CI 1.7-3.9). The most common contributors to mortality were infection (43%), GVHD (40%) and persistent disease or relapse (24%). In a multivariate analysis active disease at time of transplantation was associated with a worse OS (HR 2.16, 1.01-4.63), however, age, matched sibling donor, myeloablative conditioning and the use of T cell depleting therapies did not have a significant impact. The use of myeloablative conditioning was associated with improved PFS (HR 1.85, 1.1-3.1) in a univariate analysis but lost significance in multivariate analysis. Ninety-seven patients underwent transplantation between 2009-2013 and 56 patients between 2014-2018. There was no statistical difference in patient age, performance status, donor or disease status at transplantation between the groups. Myeloablative conditioning was used in 18.6% and 8.9% (p=0.197), and T cell depleting therapy in 25% and 31% (p=0.58), for the 2009-2013 and 2014-2018 periods respectively. There was a significant improvement in 5-year non-relapse mortality (NRM) from 41.5% (31-52%) to 23.4% (13-29%; p=0.04). Five year OS (46% vs 56%), PFS (36% vs 46%) and relapse rates (21% vs 31%) were not statistically different. Cumulative incidence of both acute and chronic GVHD was reduced in the later cohort; aGVHD 51% (95% CI 34-65%) vs 29% (95% CI 16-43%; p=0.03), cGVHD 76% (95% CI 57-88%) vs 53% (36-66%; p=0.02). Kaplan-meier and cumulative incidence curves for these outcomes are presented in figure 1. Conclusion The number of allogeneic stem cell transplantations performed for CLL has reduced over the past decade in Australasia. There has been an improvement in NRM and incidence of GVHD, however OS and PFS have not significantly changed. This may reflect improved GVHD prophylaxis and management, or advances in supportive care. Further analysis of impact of high-risk genetic factors at transplantation is pending at the time of abstract submission. Figure Disclosures Spencer: Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tam:AbbVie: Honoraria, Research Funding; BeiGene: Honoraria; Janssen: Honoraria, Research Funding. Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Hamad:Novartis: Honoraria; Abbvie: Honoraria.

Introduction Plasmablastic lymphoma (PBL) is a rare, aggressive large cell lymphoma, first described in 1997. PBL is strongly associated with immunodeficient states, such as HIV infection and solid organ transplantation, but up to one third of cases are reported to occur in immunocompetent patients. The pathogenesis of PBL is incompletely understood, though the oncogenic impact of EBV, in particular in the context of dysregulated immune surveillance, together with acquired abnormalities in the MYC pathway appear to play key roles in many cases. Plasma cell markers such as CD138 and CD38 are typically positive, as well as CD30 in a significant subset. Classical B cell markers such as CD20, CD19 and PAX5 are typically absent. The literature on clinical outcomes in PBL is generally limited to small, single-centre case series. Reports describe an aggressive disease of poor prognosis, with median survival of 8 to 15 months, with one series reporting a longer median survival of 32 months. Methods We retrospectively identified patients diagnosed with PBL between 1999 and 2019 from 16 sites across Australia, the United Kingdom and Canada. Patients aged ≥18 years with confirmed tissue diagnosis of PBL at their local treating centre were included. Factors associated with overall survival (OS) were analysed using Cox regression, stratified by site to account for heterogeneity across sites. Risk time for mortality began on the date of diagnosis and ended on the date of death. Patients who were alive, lost to follow-up or transferred to another centre for care, were censored on the date of last follow-up. Risk factors analysed included age, year of diagnosis, HIV status, MYC rearrangement status, CD30 status, lactate dehydrogenase level, disease stage by Lugano consensus criteria, and bone marrow involvement. Results We identified 197 patients with PBL (Table 1). The median age at diagnosis was 55 years (range 18-95) and there was a male predominance (69%). 37% of patients were HIV positive, 56% were HIV negative and 7% were either not tested or had missing results. Other immunosuppressive risk factors included solid organ transplant, allogeneic stem cell transplant (SCT), and immunosuppressive medication. No immunodeficient state was detected in 44%. Fifty per cent of patients were stage IV at diagnosis. Fifty-four per cent were staged using PET/CT. The median follow-up time from diagnosis was 1.36 years, with the longest follow up out to 18.4 years. There were 87 deaths (44%). For patients receiving first-line treatment with curative intent, the rate of complete remission was 57% (103 of 181 patients). Most patients (53%) received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy as first line, and 27% treatment of higher intensity than CHOP. Rituximab was administered to 20% and 10% were exposed to proteasome inhibitors as part of first line therapy. Five percent of patients underwent autologous SCT in first remission, and a further 5% after first relapse or later. The median survival time was 4.8 years, with a 5-year OS of 49% and 10-year OS of 45% (figure 1). In multivariate analysis the only adverse factors associated with OS were bone marrow involvement and stage IV disease. Patients without bone marrow involvement at diagnosis had improved OS, compared to those who did (hazard ratio (HR) 0.36, 95%CI 0.18-0.72, p=0.004) (figure 2). There was an increasing trend for mortality with higher disease stages (p-trend=0.002). The median survival was 14.1 years for stage I, 10.7 years for stage II, 5.1 years for stage III and 1.2 years for stage IV. However, only stage IV disease was independently associated with inferior OS in multivariate analysis (HR 2.93, 95%CI 1.43-6.00, p=0.003) (figure 3). OS did not change depending upon year of diagnosis. Conclusion We report a multinational retrospective cohort of patients diagnosed with PBL and to our knowledge the largest single series of PBL to date. OS was longer than previously published data, particularly in patients with early-stage disease. However, patients with stage IV disease and baseline bone marrow involvement had inferior OS. HIV infection did not affect outcome. These findings suggest that baseline bone marrow biopsy and PET staging are useful prognostic tools. There is also an ongoing need for the evaluation of the predictive value of PET imaging and novel agents in PBL, especially in higher-risk disease. Disclosures Di Ciaccio: Jansen: Honoraria, Other: travel and accomodation grant. Cwynarski:Takeda: Consultancy, Other: Conference/travel support; Roche: Consultancy, Other: Conference/travel support. Burton:Celgene: Honoraria; Leeds Teaching Hospitals NHS Trust: Current Employment; Takeda: Honoraria, Other: Travel Support; BMS: Honoraria; Roche: Honoraria, Other: Travel Support. Kuruvilla:Antengene: Honoraria; Janssen: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Merck: Consultancy, Honoraria; Celgene Corporation: Honoraria; Amgen: Honoraria; TG Therapeutics: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Bristol-Myers Squibb Company: Consultancy. McKay:Greater Glasgow and Clyde Health Board: Current Employment; Roche, Gilead, Takeda, Janssen: Other: For lectures etc; Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau. Linton:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Conference/travel support; Roche: Consultancy, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Patents & Royalties; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Hartley-Taylor: Honoraria; The Christie NHS Foundation Trust and The University of Manchester: Current Employment. Manos:Bristol-Myers Squibb: Other: Conference sponsorship. Hamad:Abbvie: Honoraria; Novartis: Honoraria.

BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments. METHODS: In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18. FINDINGS: Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p

Introduction A majority of patients with diffuse large B cell lymphoma (DLBCL) will be cured with frontline chemoimmunotherapy, however a significant number of patients will relapse. Although autologous haematopoietic stem cell transplantation (autoHCT) may lead to sustained survival in some relapsing patients, long term survival with relapsed DLBCL is approximately 25% (Larouche et al., J Clin Oncol 2010;28(12):2094). Allogeneic HCT (alloHCT) is a potential treatment strategy in some DLBCL patients with relapsed disease. We performed a retrospective national registry study to examine alloHCT practice and outcomes for DLBCL in Australia and New Zealand in the modern era. Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving an alloHCT for DLBCL between January 2009 and December 2019. Survival was analysed using the Kaplan-Meier method, with comparisons between the transplant periods 2009-2014 and 2015-2019 performed using the log-rank test. Both univariate and Cox proportional hazards regression were performed to determine significant risk factors for transplant outcome. The following risk factors were analysed for impact on outcomes: age, transplant before 2015, previous autoHCT, remission status at transplant, use of myeloablative conditioning (MAC), haploidentical donor (HD) and use of T cell depletion (TCD). Results A total of 154 patients were included in the analysis. The median age was 52 years (range 19-71) and 68% were male. Disease status at transplant was complete remission (CR) in 49%, partial response in 31% and stable or progressive disease in 17% (missing data in 3%). Fifty-five per cent had undergone a previous autoHCT. Approximately equal proportions of donors were HLA-matched siblings or matched unrelated (45% and 46% respectively) and 9% were HDs. MAC was utilised in 26%, and TCD in 24% (alemtuzumab in 3%, anti-thymocyte globulin in 21%) (data missing in 12%). The median times to neutrophil engraftment and platelet engraftment were 16 and 18 days respectively. Non-relapse mortality (NRM) at 1-year and 5-years was 20% (95%CI 7-30%) and 26% (95%CI: 13-38%). The 100-day cumulative incidence of grade II to IV acute graft versus host disease was 15% (95%CI 5-31%). The 3-year cumulative incidence of chronic graft versus host disease (cGVHD) was 56% (95%CI 46-65%) (figure 1). The median duration of follow up for the cohort was 3.98 years (range 0-9.64 years). Median overall survival (OS) post-transplant was 4.01 years, with 5-year OS of 47% (95%CI 38-56%) and 10-year OS of 40% (95%CI 26-54%) (figure 2). The 5-year relapse free survival (RFS) was 45% (95%CI 26-50%) (figure 3). The cumulative incidence of relapse (CIR) was 21% at 1 year and 32% at four years, however relapses were not seen after this point, suggesting a subpopulation with durable remissions (figure 4). On univariate analysis, TCD was associated with both reduced incidence of cGVHD (HR 0.35 95%CI 0.19-0.66, p=0.012) and increased NRM (HR 2.10 95%CI 0.88-4.99 p=0.043). These associations were maintained on multivariate analysis (MVA) (HR 0.29 95%CI 0.16-0.76, p=0.011; HR 2.19 95%CI 1.02-4.70, p=0.045) (figures 5, 6). TCD did not impact on RFS. The vast majority of TCD was given in unrelated donor alloHCTs. CR at time of transplant was associated with improved RFS on univariate analysis (HR 1.65 95%CI 1.04-2.64, p=0.034), however this association was not seen on MVA. No other analysed risk factors impacted OS, RFS, NRM, CIR or GVHD rates on either univariate or MVA. An average of 14 alloHCTs were performed each year, with a trend towards increasing annual numbers over time. There was a significant increase in the proportion of haploidentical transplants between 2009 and 2019 (p=0.003), though total numbers were low (n=14). There was no significant change over time for the use of MAC, TCD, nor in OS, RFS or NRM. Conclusion There has been an increase in the rates of alloHCT with HDs for DLBCL in Australia and New Zealand over the past decade. Survival and relapse rates are relatively favourable compared to the published literature, with sustained remissions observed (5 and 10-year OS of 47% and 40% respectively). TCD is associated with reduced cGVHD rates, as well as increased NRM. Ongoing reporting of alloHCT outcomes in DLBCL is important given the emerging role of novel therapies such as bispecific monoclonal antibodies and chimeric antigen receptor T cell therapy. Figure 1 Disclosures Di Ciaccio: Jansen: Honoraria, Other: travel and accomodation grant. Greenwood:Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Spencer:Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy. Arthur:Royal North Shore Hospital: Current Employment. Hamad:Novartis: Honoraria; Abbvie: Honoraria.

Over the past 40 years a global discourse on population obesity has emerged, with moral outrage surrounding the rise in childhood obesity during this time. Women are portrayed as predominantly to blame for the intergenerational transmission of obesity, due to gender norms emphasising maternal responsibility during early-life events. Through a structured review of recent studies exploring epigenetic and social mechanisms of obesity risk transmission, we argue that the role of the father in influencing the obesity risk of children during early life is underappreciated. Paternal actions, embedded within a structural network of the social determinants of health, operate both pre-conception to induce epigenetic changes to the spermatozoa and during the gestational period to influence developmental programming. Paternal contributions influenced by social structures including poor diet and stress influence the subsequent metabolic functioning of the child. An examination of epigenetic pathways, operating at the nexus of genomics and human behaviour, sheds new light on shared parental responsibility for the intergenerational origins of obesity. These emergent findings call into question the effectiveness of early-life obesity interventions that focus exclusively on the mother. More broadly, an examination of the epigenetics of obesity reveals a two-way dynamic between social processes and genomic health information. On the one hand, epigenetic pathways could be an explanatory link between the social determinants of health and physiological outcomes such as obesity. Conversely, a critical appraisal of how this emerging epigenetics knowledge is debated and employed can highlight the very processes that reinforce existing gender disparities in the social determinants of health framework. Ultimately this critical appraisal could lead to a reconfiguration of research and health services agendas, towards more equitable responsibilities across genders for preventing obesity.

In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).

Introduction The COVID-19 pandemic has had drastic effects on healthcare provision across Australia and the world. Rural hematology patients who may rely on visiting medical officers from larger cities or long distance travel for reviews are particularly vulnerable to having their treatment affected by the recent changes to healthcare delivery given severe travel restrictions. The Griffith Hematology/Oncology Unit is based in Griffith Base Hospital, a regional hospital in New South Wales, Australia. It is serviced by consultant hematologists from St Vincent's Hospital at the capital city of Sydney, Australia, who visit fortnightly to run hematology outreach clinics and supervise chemotherapy delivery. Griffith is located 575km from Sydney and has an estimated population of over 26,000(1). The COVID-19 pandemic imposed significant travel restrictions, such that visiting haematologists have been unable to travel to continue in-person clinics since April 2020. This has led to the exclusive reliance on telemedicine (telehealth and telephone reviews) and remote chemotherapy delivery supervision. Having an electronic health record (EHR) containing all relevant patient information which is remotely accessible to treating physicians has been integral to the continuity of comprehensive specialist cancer care in this rural setting via telemedicine. Methods The previously reported shared EHR between Griffith and St Vincent's Hospital, Sydney was used to review the impact of COVID-19 on service delivery in Griffith(2). All rural patient information was accessible from the metropolitan location including comprehensive documentation of a patient's clinical findings, routine observations, diagnostic pathology and radiology results, and details of treatment at the Griffith site. Remote chemotherapy prescribing and telemedicine notes were documented through the EHR. Results The number of new referrals, follow ups and total patients over the four months prior to the COVID-19 related changes (December 2019 to March 2020) and the four months following (April to July 2020) were compared. From April 2020 onwards, the Griffith clinic patients underwent reviews via telemedicine or telephone with no in-person reviews able to be conducted in Griffith due to the travel restrictions. The number of new referrals, follows up visits and the total number of patients seen following the change to telemedicine had all increased with no reduction in service delivery seen (Table 1). The total number of patient reviews was 167 visits over the four months prior to the change, which increased to 186 reviews after the travel restrictions were applied. Despite the travel restrictions, the hematology outreach services to Griffith were maintained through telemedicine reviews in a similar manner to the metropolitan service. Griffith rural hematology patients continue to undergo regular telemedicine reviews with monitoring of laboratory and imaging results through the EHR, receiving the same level of care as metropolitan patients. Chemotherapy is still able to be prescribed, adjusted and reviewed from the Sydney location for all patients. The total number of chemotherapy treatment cycles delivered in Griffith only slightly decreased despite the changes to service provision, which was attributed to normal variation in patients requiring treatment over 2020 (Table 2). 32 chemotherapy treatment cycles were delivered prior to the change compared to 26 cycles following, for the primary indications of lymphoma and myeloma. Conclusion In recent months, the centralised EHR has proven critical in minimising clinical service disruptions caused by the COVID-19 pandemic by facilitating telemedicine links and remote patient management. We demonstrate how the shared EHR has been integral to the continuation of complex rural patient management during the COVID-19 pandemic due to the availability of remotely accessible patient information and chemotherapy prescribing. No significant change in clinical service activity was seen following the drastic travel restrictions due to the pandemic. Given these travel restrictions are expected to continue, it is encouraging that the shared EHR will allow rural Griffith patients continued access to appropriate specialist hematology care over the coming months. This work demonstrates how an EHR is fundamental to the sustainability of vital cancer services for rural communities. Disclosures Hamad: Abbvie: Honoraria; Novartis: Honoraria.

Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients.Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors.The incidence of PTLD was 7.59% in heart-lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (1 year post-transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p0.001) and serum albumin30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p0.001). Five-year overall survival was 29%.This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Introduction Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. Methods CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers. The study included 70 control samples, 63 samples with CLL or atypical CLL phenotype, 6 MCL samples, and 40 samples of other mature B cell neoplasms. Results All CLL samples were positive for CD200, whereas MCL samples were dim or negative for CD200. Of the CLL samples, 7 were atypical by conventional flow cytometry, with Matutes scores ≤3. These cases were tested for evidence of a t(11;14) translocation, characteristic of MCL, and all were negative, consistent with their classification as atypical CLL. All these atypical CLL samples were strongly positive for CD200. Conclusion CD200 proved to be a useful marker for differentiation between CLL and MCL by flow cytometry. In particular, CD200 was useful in distinguishing CLL samples with atypical immunophenotypes from MCL.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. Methods: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4+ T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4+ T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. Results: All patients have been in continued remission for 4–6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir–related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. Conclusions: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.

Background Patients with hematologic malignancies treated with anticancer immunosuppressive therapies (ITs) are at increased risk of herpes zoster (HZ). In a previous report of this phase 3, observer-blind, multicenter trial (NCT01767467), the adjuvanted recombinant zoster vaccine (RZV) was shown to be immunogenic and well-tolerated in ≥18 years of age patients with hematologic malignancies who completed or were undergoing anticancer IT.1 Here we report end-of-study results from the same trial. Methods Participants were randomized 1:1 to receive 2 doses of RZV or placebo (PL) 1–2 months apart, either ≥10 days before or after a cancer therapy cycle, or 10 days to 6 months after cancer therapy ended. Humoral and cell-mediated immune (CMI) responses were evaluated at 1 month and 12 months post-dose 2 (month 2 and month 13, respectively). Confirmatory objectives were to evaluate humoral response rate to RZV and to compare humoral immune responses to RZV and PL at month 2 excluding either subjects with chronic lymphocytic leukemia and non-Hodgkin B-cell lymphoma (NHBCL), or only those with NHBCL. Efficacy against HZ was explored in a post-hoc analysis of confirmed HZ cases. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Results Of the 562 (RZV: 283, PL: 279) treated participants, 415 (RZV: 217, PL: 198)/310 (RZV: 168, PL: 142) were included in the according-to-protocol (ATP) cohort for humoral immunogenicity/immune persistence. The ATP sub-cohort for CMI included 132 (RZV: 69, PL: 63) participants at month 2 and 100 (RZV: 54, PL: 46) at month 13. All confirmatory immunogenicity objectives were met (Table 1). RZV efficacy against HZ, assessed post-hoc, was 87.2% (Table 2). RZV was more reactogenic than PL. The occurrence of unsolicited AEs, SAEs, and pIMDs was similar between the study groups (Table 3). Conclusion RZV induced robust humoral and cellular immune responses and showed an effect in the reduction of HZ incidence in patients with hematologic malignancies who completed or were undergoing anticancer IT. No safety concerns were identified. Reference 1. Oostvogels et al. IDWeek2017, abs 1344. Funding. GlaxoSmithKline Biologicals SA. Disclosures A. F. Dagnew, GSK: Employee and Shareholder, Salary. J. Murphy, GSK: Investigator, Research support. S. A. McNeil, GSK group of companies: Grant Investigator, Research grant and Research support. B. Salaun, GSK group of companies: Employee and Shareholder, Salary. E. Di Paolo, GSK group of companies: Employee, Salary. L. Campora, GSK group of companies: Employee and Shareholder, Salary. M. López-Fauqued, GSK group of companies: Employee, Salary. M. El Idrissi, GSK group of companies: Employee, Salary. A. Schuind, GSK: Employee, Salary. T. C. Heineman, GSK group of companies: Consultant, Employee and Shareholder, Consulting fee and Salary. P. Van Den Steen, GSK: Employee and Shareholder, Restricted shares and Salary. L. Oostvogels, GSK: Employee, Salary and Stock and stock options.

Background: Rural Australian oncology patients are known to have inferior mortality rates compared to metropolitan patients, possibly related to access to appropriate healthcare services and treatments. Replacement of paper-based chemotherapy charting with electronic systems improves the safety of chemotherapy administration through reduced prescribing and administrative errors. Aims: To integrate the electronic healthcare delivery systems at a metropolitan hospital and a rural outreach haematology clinic to facilitate streamlined and safe rural outpatient care. Method: The MOSAIQ v2.64 [Elekta] system utilized at St Vincent's Hospital, Sydney, was introduced at a linked rural outreach haematology clinic in Griffith, a city in the Riverina region of New South Wales. MOSAIQ is a comprehensive practice management system incorporating all relevant patient results and notes along with administrative capabilities. The two systems were consolidated into one with patient information accessible from both sites. Results: The electronic systems were successfully linked between the two sites in October 2017. As of November 2018 there were 497 patients registered with the service with the breakdown of diagnoses shown in Figure 1, with lymphoma found to be the most common haematological diagnosis. Tracking of service activity over time including clinic appointments and patient numbers is now possible, with increases in both seen since implementation. Nine chemotherapy regimen types encompassing 2174 overall treatments were delivered at the service over the fifteen months since implementation, the most common being R-CHOP [Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] followed by azacitidine. The linked system has improved streamlined care during patient transitions between the two hospitals with enhanced continuity of documentation and management. Chemotherapy prescribing has transitioned to electronic at the Griffith site and is guided by inbuilt, pharmacist-reviewed protocols allowing for safer and flexible prescribing remotely which has standardized management of haematology patients across both hospitals. Conclusion: Our study provides a novel example of the successful implementation of a centralised electronic healthcare record and chemotherapy prescribing system in a haematology setting shared between a metropolitan service and a rural outreach hospital clinic. This has positive implications for the safety and efficiency of healthcare delivery at the rural site applicable to all linked rural clinics, as well as allowing data collection to assist future planning of the service. Disclosures No relevant conflicts of interest to declare.

Aim: Although allogeneic stem cell transplant (alloSCT) remains the only curative option for myelofibrosis, novel therapeutic agents, the application of new prognostic scoring systems and the emergence of molecular genetic analysis have lead to a new management landscape in myelofibrosis. In view of these recent advances, we aimed to review national practice in transplanting myelofibrosis patients and its outcomes. Methods: A retrospective study was conducted using the Australasian Bone Marrow Transplant Registry (ABMTRR) data on patients who underwent alloSCT for myelofibrosis at Australian/New Zealand transplant centres between 2006 and 2017. Participating centres completed an online questionnaire and responses were reviewed centrally by the ABMTRR. Results: 142 patients underwent alloSCT for myelofibrosis, primary (n=94) or secondary (n=48) (Table 1). 52% had HLA-identical sibling donors and 45% had matched unrelated donors (UD). Median follow-up was 51.8 months (range: 3.1-148). Cytogenetic abnormalities were identified in 29% of 120 patients who were tested pretransplant. JAK2 mutation testing was performed in 74% of patients whilst other mutations (CALR, MPL, EZH2, IDH, SRSF2, ASXL1) were rarely tested (1.4-8.4%). Only 4.2% of patients had next generation sequencing. Before transplant, 16% had splenectomy or splenic irradiation and 54 patients (38%) received JAK 1/2 inhibitors (JAKi), of whom 92.5% had Ruxolitinib. Median time to neutrophil engraftment was 20 (range: 10-43) days whereas median platelet recovery time was 28 (range: 13-230) days. 9 patients (6.3%) had primary graft failure and 11 patients (7.7%) had secondary graft failure. 60% had chimerism studies using cytogenetic or molecular techniques at 3 months post transplant; 63% of those assessed achieved complete (≥95%) donor chimerism. CMV reactivation was detected in 32% and 10% had sinusoidal obstruction syndrome. The cumulative incidence of grade II-IV acute GvHD was 21.4% and grade III-IV acute GvHD was 8.7%. The cumulative incidences of limited and extensive chronic GvHD at 5 years were 11.1% and 18.1% respectively. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GvHD free progression free survival was 54% at 1 year and 42% at 5 years (Figure 1). The cumulative incidence of non-relapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, use of an UD was a significant independent unfavourable risk factor for OS (HR 2.26, 95%CI 1.17- 4.33, p=0.015) and NRM (HR 3.02, 95%CI 1.36-6.71, p=0.007), while splenic irradiation/splenectomy resulted in shortened neutrophil (HR 1.88, 95%CI 1.00-3.54, p=0.05) and platelet recovery time (HR 2.13, 95%CI 1.12-4.05, p=0.02). Use of UD significantly increased the incidence of grade II-IV acute GvHD in multivariate analysis (HR 5.66, 95%CI 1.99-16.11, p=0.001) whereas use of antithymoglobulin or alemtuzumab significantly reduced it (HR 0.27, 95% CI 0.09-0.79, p=0.017). Neither use of JAKi prior to alloSCT nor presence of JAK2 mutation had a significant impact on OS or NRM. 9 patients underwent a second alloSCT for myelofibrosis and median length of time from the first transplant was 22 (range: 1-132) months. 4 patients were transplanted for disease relapse and 3 patients for graft failure. For the second transplant cohort, NRM at day 100 and 1 year were 11.1% (95% CI, 0.4%-40.6%) and 33.3% (95% CI, 6.6%-64%) respectively, while 1-year and 5-year OS were 66.6% (95% CI, 42%-100%) and 44.4% (95% CI, 21.4%-92.2%). Conclusion: Survival rates in alloSCT for myelofibrosis in this Australasian cohort were comparable to international studies. There is a rise in the numbers of patients treated with JAKi pretransplant (Figure 2). Although this does not appear to have any effect on transplant outcomes, reduced symptom burden associated with increasing use of pre-transplant JAKi may increase the numbers of patients considered eligible for alloSCT. Although splenectomy/splenic irradiation had a positive impact on engraftment, it did not improve the survival outcomes. Our results show a negative influence of UD on OS and NRM, possibly related to an increased incidence of acute GVHD in the UD group. In light of the rise in utilization of alloSCT in the management of myelofibrosis, there is a need for further prospective studies incorporating molecular testing and the new comprehensive clinical-molecular myelofibrosis transplant scoring system. Disclosures Spencer: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Specialised Therapeutics Australia: Consultancy, Honoraria. Purtill:MSD: Honoraria; Novartis: Honoraria, Other: Travel for speaking and advisory boards; Gilead: Honoraria, Other: Travel for speaking and advisory boards; Janssen: Honoraria. Browett:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Achillion: Research Funding; Beigene: Research Funding. Szer:Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; Prevail Therapeutics: Honoraria, Other: Travel, Research Funding. Ritchie:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria. Greenwood:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gottlieb:Merck: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Novartis: Consultancy; University of Sydney: Employment; Haemalogix P/L: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Diffuse large B cell lymphoma is a heterogenous disease with prognosis known to vary based on histological changes including immunohistochemistry and gene rearrangements by florescence in situ hybridisation (FISH). Both immunohistochemical overexpression as well as gene rearrangements in MYC, BCL2 and BCL6 are thought to contribute to poor prognosis. The benefit of high dose chemotherapy is unclear for those with high grade B cell lymphoma with double hit status (DHL) by FISH , double expressor status (DEL) or gain of MYC/BCL2. The purpose of this study was to retrospectively analyse the effect of escalated chemotherapy in this population over a 5 year period. Methods: All patients with DLBCL treated between 2012-2017 were screened retrospectively for inclusion in the study based on immunohistochemistry and FISH at time of initial diagnosis. Immunohistochemistry was assessed on formalin fixed, paraffin embedded specimens with BCL2 and MYC considered positive at over 40% and 50% respectively. FISH was assessed using dual colour break apart probe. Results: 135 patients were diagnosed with DLBCL of which 53 patients had immunohistochemistry and FISH at diagnosis confirming either, DEL or gain of MYC/BCL2 status. The mean age was 65 years and median follow up 21 months. The overall response rate in DH treated with DA-R-EPOCH was 57%. There were insufficient cases treated with R-CHOP for comparison. Overall response rates in DEL were 94% for DA-R-EPOCH and 93% for R-CHOP. Overall survival (OS) and disease free survival (DFS) in DHL was 6 months and 2 months respectively when treated with DA-R-EPOCH. There was no significant difference in OS or DFS in DEL treated with DA-R-EPOCH compared with R-CHOP (OS: 42 months vs 38 months respectively (p=0.962), DFS 36 months vs 30 months (p=0.931)). Gain of MYC/BCL2 did not affect OS (p= 0.539) or DFS (p=0.439) when comparing treatment regimen. Conclusion: DA-R-EPOCH did not improve treatment response rates OS or DFS in patients with double expresser lymphoma or gain of MYC/BCL2. This study also confirms the previously reported poor outcomes associated with DHL Disclosures No relevant conflicts of interest to declare.

Empirical antifungal therapy is frequently used in hematology patients at high risk of invasive aspergillosis (IA), with substantial cost and toxicity. Biomarkers for IA aim for earlier and more accurate diagnosis and targeted treatment. However, data on the cost-effectiveness of a biomarker-based diagnostic strategy (BDS) are limited. We evaluated the cost effectiveness of BDS using results from a randomized controlled trial (RCT) and individual patient costing data. Data inputs derived from a published RCT were used to construct a decision-analytic model to compare BDS (Aspergillus galactomannan and PCR on blood) with standard diagnostic strategy (SDS) of culture and histology in terms of total costs, length of stay, IA incidence, mortality, and years of life saved. Costs were estimated for each patient using hospital costing data to day 180 and follow-up for survival was modeled to five years using a Gompertz survival model. Treatment costs were determined for 137 adults undergoing allogeneic hematopoietic stem cell transplant or receiving chemotherapy for acute leukemia in four Australian centers (2005-2009). Median total costs at 180 days were similar between groups (US$78,774 for SDS [IQR US$50,808-123,476] and US$81,279 for BDS [IQR US$59,221-123,242], P = .49). All-cause mortality was 14.7% (10/68) for SDS and 10.1% (7/69) for BDS, (P = .573). The costs per life-year saved were US$325,448, US$81,966, and US$3,670 at 180 days, one year and five years, respectively. BDS is not cost-sparing but is cost-effective if a survival benefit is maintained over several years. An individualized institutional approach to diagnostic strategies may maximize utility and cost-effectiveness.

Background Herpes zoster (HZ) and its complications can have a substantial impact on patients’ quality of life (QoL), particularly in immunocompromised patients. The vaccine efficacy (VE) of an adjuvanted recombinant zoster vaccine (RZV) was studied in a randomized, placebo-controlled, phase 3 study in adult hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). The VE in preventing HZ cases was 68.2% (95% CI: 55.6%–77.5%). Herein we report the impact of the vaccine on patients’ quality of life (QoL) associated with HZ episodes. Methods HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1–2 months apart and followed for the occurrence of HZ. QoL parameters were measured by the Short-Form health survey (SF-36) and Euro-Quality of Life-5 Dimension (EQ-5D) at baseline, 1 month and 1 year post-dose 2, as well as during suspected HZ episodes in conjunction with the Zoster Brief Pain Inventory (ZBPI). For confirmed HZ cases, QoL scores were compared between the vaccine and placebo groups. The RZV impact in reducing the ZBPI Burden of Illness and Burden of Interference scores was estimated in patients in the modified total vaccinated cohort (mTVC). The 2 scores were calculated from the area under the curve (Days 0 to 182) of the ZBPI Worst Pain and ZBPI Activities of Daily Living scores, respectively, assuming a score of 0 for patients who did not have a confirmed HZ episode. Results Both the ZBPI maximum Worst Pain and Average Pain scores were significantly lower in the vaccine than placebo group (Table 1), suggesting less burden in breakthrough HZ cases following RZV. Consequently, the HZ Burden of Illness and Burden of Interference VE estimates were higher than the HZ VE estimate. RZV showed statistically significantly better QoL scores than placebo one week following rash-onset among patients with confirmed HZ, i.e., SF-36 bodily pain, social functioning, role emotional, mental health and mental component scores, and the EQ-5D Utility Score. Conclusion In addition to reducing the risk of HZ and HZ complications, RZV significantly reduces the impact of HZ on patient’s QoL in those who develop breakthrough disease. Funding: GlaxoSmithKline Biologicals SA. Disclosures D. Curran, GlaxoSmithKline: Employee, GSK Shares and Salary. A. Bastidas, GSK: Employee, Salary. M. El Idrissi, GSK: Employee and Shareholder, Salary. S. Matthews, GSK group of companies: Consultant, Consulting fee. L. Oostvogels, GSK group of companies: Employee, Salary and stock and stock option. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit.

Background Preclinical studies suggest granulocyte-colony stimulating factor (G-CSF) holds promise for treating ischemic heart disease; however; its clinical safety and efficacy in this setting remain unclear. We elected to evaluate the safety and efficacy of G-CSF administration in patients with refractory "no-option" ischemic heart disease. Methods Twenty patients (18 males, 2 females, mean age 62.4 years) were enrolled and underwent baseline cardiac ischemia assessment (CA) (angina questionnaire, exercise stress test [EST], technetium Tc 99m sestamibi and dobutamine-stress echocardiographic imaging). Patients then received open-label G-CSF commencing at 10 μg/kg SC for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF + ESTs were repeated but, in addition, leukapheresis and a randomized double-blinded intracoronary infusion of CD133 + or unselected cells were performed. Final CA occurred 3 months thereafter. Results There were no deaths, but only 16 patients were permitted to complete the study. Eight events fulfilled prespecified "adverse event" criteria, including 4 troponin I–positive events and 2 episodes of thrombocytopenia. Also, frequent minor troponin I–positive events (troponin I P Conclusions Granulocyte-colony stimulating factor administration was associated with improvement in a range of subjective outcomes. However, adverse events were common, and objective measures of cardiac perfusion/ischemia were unchanged.

Objective The transforming growth factor β superfamily member macrophage inhibitory cytokine 1 (MIC-1) is expressed upon macrophage activation, regulated by the p53 pathway, and linked to clinical events in atherosclerosis and cancer. Since rheumatoid arthritis (RA) shares similar etiopathologic mechanisms with the above diseases, we sought to determine the clinical utility of determining MIC-1 serum levels and MIC-1 genotype in the management of RA. Methods Ninety-one RA patients were recruited. Serum was collected from 83 of these patients and synovial biopsy samples were collected from the remaining 8 patients. Of the 83 patients from whom serum was collected, 61 were treated on an outpatient basis (defined as having nonsevere disease), and 22 patients went on to undergo hemopoietic stem cell transplantation (HSCT) (defined as having severe disease). Results Serum levels of MIC-1 were higher in RA patients and reflected disease severity independently of classic disease markers. MIC-1 was detected in rheumatoid synovial specimens, and allelic variation of MIC-1 was associated with earlier erosive disease and severe treatment-resistant chronic RA. Additionally, algorithms including serum and/or allelic variation in MIC-1 predicted response to HSCT, the presence of severe disease, and joint erosions. Conclusion Determination of serum levels of MIC-1 and MIC-1 genotype may be clinically useful in the management of RA as well as in selection of patients for HSCT, since they predict disease course and response to therapy. The data indicate a potential role for MIC-1 in RA pathogenesis. These results warrant larger prospective studies to fully delineate and confirm a role for MIC-1 genotyping and serum estimation in patient selection for HSCT and in the management of RA.