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Socioeconomic deprivation (SED) is a risk factor for reduced survival of hematopoietic stem cell transplant (HSCT) recipients. This study aimed to evaluate access and long-term survival of HSCT recipients.This was a hospital HSCT Registry-based retrospective cohort study. Patients who underwent HSCT from January 2010 to June 2020 were identified. HSCT recipients younger than 16 years of age, patients who reported their residential address as a post office box or the Department of Corrections, and those who left the country after HSCT were excluded from the study. HSCT recipients with the 2018 New Zealand deprivation index (NZDep2018) deciles 8, 9, and 10 were assigned to the higher SED group and those with NZDep2018 deciles from 1 to 7 were allocated to the lower SED group. The total number of New Zealanders in the higher and lower SED strata was obtained from the 2018 Census.Eight hundred fifty-one HSCT recipients met the eligibility criteria. HSCT recipients from the higher and lower SED strata of the New Zealand population had similar access to HSCT (odds ratio = .9; 95% confidence interval (CI): .77-1.04; p = .155). Mortality in the higher and lower SED groups of HSCT recipients was 9.6/100 person-years (95% CI: 7.7-12/100 person-years) and 8.1/100 person-years (95% CI: 6.9-9.4/100 person-years), respectively. The mortality ratio was 1.2 (95% CI: .9-1.6), p = .098. Both groups had similar survival.New Zealand residents from the higher and lower SED strata have similar access to HSCT. SED is not associated with reduced survival in adult HSCT recipients.

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.

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

Staphylococcus haemolyticus is a rare cause of bacterial meningitis and most commonly occurs as a nosocomial infection in patients’ post-neurosurgery. We report a patient post-allogenic stem cell transplant, with no prior history of neurosurgical procedures, who developed S. haemolyticus meningitis and bacteremia following central catheter-related bloodstream infection. The patient failed therapy with vancomycin and daptomycin but was successfully treated with a prolonged course of linezolid. We review the pharmacological management of coagulase negative Staphylococcus (CoNS) meningitis, with a focus on the pharmacokinetic properties of vancomycin, daptomycin and linezolid within the cerebrospinal fluid (CSF).

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are effective induction therapy for acute promyelocytic leukaemia (APL). However, early thrombo-haemorrhagic complications and mortality remain high. We aimed to investigate how the timing of ATRA initiation and the inclusion of ATO influence patient outcomes. Clinical records were retrospectively reviewed for all patients treated for APL in a single, tertiary centre during 2000-2017. Among 70 patients with APL, 36 (51.4%) presented with thrombo-haemorrhagic complications, and four (5.8%) died within 30 days. The median time to ATRA initiation was 11.2 (range 0-104) h from the time of admission. Patients requiring more transfusions started on ATRA sooner (P = 0.04). Patients with adverse early events did not start ATRA later (P = 0.99). Nevertheless, patients that required additional tests for diagnosis (PML immunofluorescence or molecular) started on ATRA later (28.5 versus 5.3 h; P 0.0001), and had more thrombo-haemorrhagic complications (P = 0.04). Long-term survival was actually better in patients who started ATRA later (P = 0.03), which is likely explained by higher proportion of low risk patients in this group. Patients treated with ATO (n = 23) maintained higher fibrinogen levels and required less transfusions during induction (P 0.05), with no disease-related deaths in this group over a median follow-up time of 37.8 months (interquartile range 44.9 months). In summary, fast ATRA initiation reduces early but not late adverse events in APL patients, and the inclusion of ATO helps further improve both early and late outcomes in APL.

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

Background: Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HCT) is an established therapy using alternative donors for patients with Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS). There is a limited body of evidence for older patients undergoing Haplo-HCT in AML and MDS. Studies describing Haplo-HCT in older patients have used a high proportion of bone marrow (BM) derived grafts and a variety of conditioning regimens. In this setting, Haplo-HCT demonstrates acceptable Non-Relapse Mortality (NRM) and chronic Graft Versus Host Disease (cGVHD) rates of less than 10% (Ciurea. Biology of Blood and Marrow Transplantation. 2018 Jun 1;24(6):1232-6.). In Australia and New Zealand, Haplo-HCT is predominantly performed using peripheral blood (PB). We performed a retrospective national registry study to examine the outcomes of Haplo-HCT using PB in older patients. Methods: Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB Haplo-HCT for AML/MDS between January 2010 and July 2020. Cumulative incidence functions were used for engraftment, CMV reactivation, acute GVHD, chronic GVHD, relapse, and NRM. The competing risk for engraftment, CMV reactivation and GVHD was death. Relapse and NRM were competing risks for each other. Overall survival (OS), relapse-free survival (RFS), and composite GVHD and RFS (GRFS) were calculated using Kaplan-Meier analyses. The impact of pre-transplant factors on these endpoints was analyzed using Cox regression. Results: A total of 44 patients were included in the analysis. The median follow-up time was 734 days. The median age was 68 (range 65-74) with a median Karnofsky Performance Status of 90. Thirty patients (68.2%) had AML while 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was non-myeloablative fludarabine, cyclophosphamide and TBI (73.8%), the remainder of the patients received either melphalan or busulfan based regimens, the majority were reduced intensity with only 2 patients undergoing myeloablative conditioning. All patients received post-transplant cyclophosphamide and mycophenolate mofetil with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporin (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients, at a median of 18 days while platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of CMV reactivation and CMV disease were 52.5% and 5.1% at 1 year The incidence of Grade 2-4 aGVHD was 18.2%. The incidence of cGVHD at 2 years was 40.7%, with extensive cGVHD occurring in 17.7% of patients. The incidences of relapse and NRM at 2 years were 8.8%. and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year OS was 74%. RFS and GRFS at 2 years was 70% and 48% (Figure 1). Recipient age, donor age or disease type (AML vs MDS) had no significant impact on OS or GRFS. Conclusion: These results confirm the safety and effectiveness of Haplo-HCT for AML/MDS in older patients. The rates of cGVHD were higher than expected given the lower rates reported in other studies using PTCy GVHD prophylaxis. Haplo-HCT using a PB graft demonstrates good long-term disease control with reasonable rates of NRM and cGVHD for older patients with AML/MDS. Figure 1 Figure 1. Disclosures Bajel: Abbvie, Amgen, Novartis, Pfizer: Honoraria; Amgen: Speakers Bureau. Perera: Abbvie: Speakers Bureau; BMS: 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. 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 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.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.

This study reports on the outcome of 95 allogeneic hematopoietic cell transplants (HCTs) using reduced intensity conditioning (RIC) performed for patients with multiple myeloma (MM) in Australia and New Zealand between 1998 and 2006. The median age at HCT was 52 years. Of the 32 patients for whom the allograft was performed as a first transplant, 15 (47%) had their allograft less than 1 year from diagnosis, while for the 63 patients who had an allograft following an autograft, nine (14%) were allografted within 1 year post-diagnosis (p < 0.001). The cumulative incidence of transplant-related mortality (TRM) was 19% at 1 year post-transplant. At 5 years post-transplant the overall survival (OS) was 40% and progression-free survival (PFS) was 23%, with no apparent survival plateau. Three factors were independently favorable predictors of OS in a Cox regression model: immunoglobulin G (IgG) myeloma (hazard ratio [HR] = 0.42, 95% confidence interval [CI] 0.24-0.75, p = 0.004), a human leukocyte antigen (HLA)-identical sibling donor (HR = 0.37, 95% CI 0.18-0.74, p = 0.005), and less than 1 year between MM diagnosis and RIC HCT (HR = 0.27, 95% CI 0.12-0.59, p = 0.001). Patterns of outcome indicate that RIC HCT may offer the potential for cure for only a small group of patients with MM.

Summary Although β-thalassaemia is common throughout the world, it has not been previously described in Polynesia. We report a novel sequence insertion where homozygosity for the defect results in transfusion-dependent anaemia. The repeated 45 base pair (bp) insertion causes duplication of the start codon and consequent transcription from the original initiation code would be predicted to lead to the production of an irrelevant seven-residue peptide, while residual translation from the novel initiation site would result in diminished yields of β-globin and consequent clinical β+-thalassaemia.

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

Failure of cisplatin-based chemotherapy in advanced germ cell tumour (GCT) is associated with a poor outcome. High-dose chemotherapy and auto-SCT is one therapeutic option, although the long-term outcome after this procedure is unclear. We conducted a multicentre cohort study of consecutive patients undergoing a single auto-SCT for GCT between January 1986 and December 2004. Of 71 subjects, median follow-up is 10.1 years. OS at 5 years is 44.7% (95% confidence interval (CI) 32.9-56.5%) and EFS is 43.5% (95% CI 31.4-55.1%). There were seven (10%) treatment-related deaths within 100 days of auto-SCT. Three (4.2%) patients developed secondary malignancies. Of 33 relapses, 31 occurred within 2 years of auto-SCT. Two very late relapses were noted 13 and 11 years after auto-SCT. In multivariate analysis, favourable outcome was associated with IGCCC (International Germ Cell Consensus Classification) good prognosis disease at diagnosis, primary gonadal disease and response to salvage chemotherapy. We conclude that auto-SCT results in successful outcome for a relatively large subgroup of patients with high-risk GCT. Late relapses may occur, a finding not previously reported.

Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19-56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27-58%] and 48% (95% CI: 32-63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III-IV acute graft-versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse

G-CSF mobilized peripheral blood (G-PB) allografts lead to faster hematologic recovery than marrow grafts, but with more chronic GvHD(cGvHD). We hypothesized that G-CSF stimulated marrow (G-BM) may result in faster hematological recovery with less cGvHD. Methods We conducted a Phase III randomised multicenter trial of matched sibling G-PB vs G-BM allografts in adults with hematologic malignancies. The primary endpoint was time to treatment failure defined as the first occurrence of extensive cGvHD, relapse or death from any cause. Thirteen centers in Canada, Saudi Arabia, U.S., Australia and New Zealand enrolled patients. Adaptive stratification (minimization) balanced treatment groups by center, disease, disease risk and conditioning. Donors received G-CSF 5 mg/kg/d sc for 4 or 5 days and underwent apheresis on Day 5 and, if necessary, on Day 6 or marrow harvest on Day 5. Eligible recipients between 16 and 65 years received myeloablative conditioning and cyclosporine/methotrexate as GvHD prophylaxis. The study began before widespread adoption of the NIH GvHD consensus guidelines so cGvHD was characterized as limited or extensive. Immunophenotyping and functional assays performed on donor cells were correlated with incidence of cGvHD. Results Between 2007 and 2012, 230 sibling donor-recipients were randomized to receive either a G-PB or G-BM allograft; 3 randomized to G-PB and 4 to G-BM were inevaluable (4 relapsed before transplant, 1 donor withdrew before collection, 1 recipient withdrew consent and 1 was ineligible (non-myeloablative conditioning)). Indication for allograft was AML (109; 49%), ALL (57; 25%); MDS/MPD(31; 14%), CML(13; 6%), lymphoproliferative disorder(NHL/MCL/CLL)(12; 5%) and biphenotypic leukemia(1). 77(70%)(G-PB) and 71(63%)(G-BM) recipients had low-risk disease (AML or ALL in CR1, RA, RARS, CML in 1st CP). Donor and recipient ages, sex and CMV immune status were balanced between groups. Donors tolerated mobilization well although one donor (G-PB) died of a cardiac event while receiving G-CSF. Median nucleated cells per kg were 7.59x108 (2.73-18.64) and 5.92x108 (0.94-13.23) in the G-PB and G-BM arms respectively (P With a median follow-up of 36 months (range 9.6-48), using Cox proportional hazards multivariable modelling adjusted for the 4 minimization factors, time to treatment failure did not differ significantly between arms (HR 0.91; 95% CI 0.68-1.22; P= 0.52). There was a significantly delayed time to onset of overall cGvHD in the G-BM arm (HR=0.66; 95% CI 0.46-0.95; P=0.03) but time to onset of extensive cGvHD did not differ significantly between arms (HR=0.76; 95% CI 0.52-1.10; P=0.15). Other results are shown below: Evaluation of donor immune populations showed that IFNg+ CD4 T cells and CD56bright NK cells were protective against cGvHD in G-PB and G-BM recipients. In contrast, specific B cell populations consistent with memory or exhausted B cells were associated with cGvHD in G-PB recipients (CD19+CD27+, p=0.05, CD19+ CD21lo, p=0.009) but not in G-BM. Conclusions In this large prospective randomized trial, the primary endpoint of time to treatment failure did not differ between G-PB and G-BM. OS and RFS were also not significantly different between arms. Neutrophil and platelet recovery were slower by a median of 3 days with G-BM. However, time to overall cGvHD was significantly delayed in G-BM recipients with non-significant trends of less acute and less extensive cGvHD with G-BM. cGvHD correlated with different cell populations in G-PB and G-BM suggesting that donor source can influence the mechanism of cGvHD. Further analyses are underway to determine the clinical impact of these differences. Disclosures: No relevant conflicts of interest to declare.

Abstract 4143 AIM: Fludarabine Melphalan (FluMel) is the commonest Reduced Intensity Conditioning (RIC) regimen used in Australia and New Zealand. This study aims to assess the relative benefit of this regimen in both lymphoid and myeloid malignancies and to further delineate risk factors associated with an improved survival using RIC conditioning. METHOD: This was an ABMTRR based retrospective study assessing the outcome of FluMel RIC allografting in 9 Australian and New Zealand Centres between 1998 and 2008. Data was collected from centres using an excel based eCRF emailed to centres. Analysis was performed using Stata software and a p value less than 0.05 was considered significant. RESULTS: Median follow up was 3.4 years. There were 342 patients with a median age of 54 years (18–68) and 61% were male. 234 patients had myeloid malignancies with AML (n=166) being the commonest indication whereas there were 110 lymphoid patients with NHL (n=64) the main indication. TRM at D100 was 14% with no significant difference between the groups. OS and DFS were similar between myeloid and lymphoid patients (50% and 43% at 5 years respectively). There was no difference in the cumulative incidence of relapse and GVHD between the groups. Multivariate analysis revealed 4 adverse risk factors for DFS: non-HLA identical sibling donor, not in remission at transplant, previous autologous transplant, and recipient CMV +ve. The presence of Chronic GVHD was associated with a better DFS predominantly due to a marked reduction in relapse (HR 0.44, p=0.003). CONCLUSION: This is one of the largest analyses of Fludarabine Melphalan RIC transpants performed. This dataset confirms that FluMel provides durable remissions in both myeloid and lymphoid malignancies with 50% overall survival at 5 years. The multivariate analysis provides important clues for improving outcomes when planning FluMel conditioning in patients with haematological malignancies. Disclosures: No relevant conflicts of interest to declare.