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

The benefits of non-myeloablative stem cell transplant in older patients with acute myeloid leukaemia are unclear. We compare the long-term outcomes of this regimen in those aged 55-65 years in first remission with a chemotherapy only cohort that achieved durable morphologic remission. Five-year overall survival was similar (32% vs 33%, P = 0.90), as was relapse-free survival (23% vs 20%, P = 0.37). There was a trend for decreased relapse that was balanced against increased non-relapse mortality with transplantation.

Prognostic factors for multiple myeloma (MM) after allogeneic haemopoietic stem cell transplantation (alloHSCT) are poorly characterised. Two potential factors include minimal residual disease (MRD) and CD3+ donor-specific chimerism. We retrospectively examined 93 consecutive patients who received upfront or deferred tandem auto-alloHSCT. Bone marrow (Euroflow) MRD was assessed pre-alloHSCT and 3-monthly post-alloHSCT. CD3+ donor chimerism was assessed at D30, D60, D90, 6 m and 12 m post-alloHSCT. There was no statistical difference between upfront and deferred transplants in progression free survival (PFS) (34 m vs. 15 m respectively, p = 0.20) and overall survival (OS) (75.5 m vs. 62.7 m respectively, p = 0.56). Patients who were MRD-positive post-alloHSCT had inferior PFS to MRD-negative patients from 6 m (6 m HR 3.32, p = 0.02; 9 m HR 4.08, p = 0.003; 12 m HR 4.47, p = 0.008). Attainment or maintenance of MRD-negativity predicted reduced relapse risk (23.5% vs. 62.5%, p = 0.04). However, there was no significant difference in OS between the MRD-negative and positive groups. Full CD3+ donor chimerism at early time points (D30 and D90) was associated with increased risk of acute GVHD (D30 p

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

Objectives Adoptive immunotherapy using donor‐derived antigen‐specific T‐cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT). Methods We treated 11 patients with a prophylactic infusion of 2 × 107 cells per square metre donor‐derived T‐cells targeting seven infections (six viral and one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein–Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK virus (BKV) and Aspergillus fumigatus. Results T‐cell products were successfully generated in all patients with 10 products responsive to 6 or 7 infections. T‐cell infusions were associated with increases in antigen‐experienced activated CD8+ T‐cells by day 30. CMV, EBV and BKV reactivation occurred in the majority of patients and was well controlled except where glucocorticoids were administered soon after T‐cell infusion. Three patients in that circumstance developed CMV tissue infection. No patient required treatment for invasive fungal infection. The most common CMV and EBV TCR clonotypes in the infusion product became the most common clonotypes seen at day 30 post‐T‐cell infusion. Donors and their recipients were recruited to the study prior to transplant. Grade III/IV graft‐versus‐host disease developed in four patients. At a median follow‐up of 390 days post‐transplant, six patients had died, 5 of relapse, and 1 of multi‐organ failure. Infection did not contribute to death in any patient. Conclusion Rapid reconstitution of immunity to a broad range of viral and fungal infections can be achieved using a multi‐pathogen‐specific T‐cell product. The development of GVHD after T‐cell infusion suggests that infection‐specific T‐cell therapy after allogeneic stem cell transplant should be combined with other strategies to reduce graft‐versus‐host disease., In this study, 12 patients were treated with ex vivo expanded donor‐derived T‐cells specific for seven virus and fungal pathogens. There was no acute infusion‐related toxicity. CD8 T‐cell numbers in the peripheral blood rose within 30 days of infusion. Graft‐versus‐host disease and corticosteroid use were associated with viral reactivation; no patient developed fungal disease. Relapse (n = 5) and multi‐organ failure (n = 1) were the causes of death. Infection did not contribute to death in any patient.

Prognostic factors for multiple myeloma (MM) after allogeneic haemopoietic stem cell transplantation (alloHSCT) are poorly characterised. Two potential factors include minimal residual disease (MRD) and CD3

Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant-related mortality from infection and graft-versus-host disease. We report on five adult patients receiving rescue alloSCT2 using haploidentical peripheral blood stem cells. All patients achieved neutrophil engraftment, two subsequently died from sepsis and disease relapse, respectively. Three patients remain alive up to 2 years post-transplant. We suggest consideration of haploidentical alloSCT2 for patients with graft failure.

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

Background: Disease relapse remains the main cause of mortality after allogeneic stem cell transplantation (allo-SCT) for patients with myeloid malignancies. Loss of donor chimerism (DC) is commonly used as a biomarker of impending relapse, which allows the initiation of pre-emptive therapies such as withdrawal of immunosuppression or donor lymphocyte infusion (DLI). Surprisingly, there are few if any direct comparisons of peripheral blood CD34+ and CD3+ DC as biomarkers to predict relapse. We hypothesized that loss of CD34+ DC may be a more direct measure of impending relapse given most myeloid malignancies express CD34. Methods: We prospectively measured peripheral blood CD34+ and CD3+ DC on days 30, 60, 90, 120 and 180 following allo-SCT for patients with AML (n=113) or MDS (n=23) transplanted at a single centre between July 2011 and November 2019. Chimerism analysis was performed using purified cell subsets isolated from 60 mL peripheral blood using PCR-based amplification of short tandem repeats (STRs). The goal of this retrospective analysis was to compare the value of CD3+ and CD34+ DC for predicting relapse. Institutional practice for CD34+ DC below 80% included a bone marrow biopsy to identify morphologic relapse and donor lymphocyte infusion. Statistical analysis was performed with R 3.5.2 (The R project for Statistical computing) or GraphPad (v8.2.0). Results: Overall, 41 of 136 (30%) patients had morphologic relapse at a median time of 153 days after allo-SCT (range 50-1742). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CD3+ and CD34+ donor chimerism for morphologic relapse is shown in Figure 1A. CD34+ DC outperformed CD3+ DC in all criteria, irrespective of the percentage chosen. Furthermore, a concurrent reduction in CD34+ DC was seen in almost all patients (14/16 at the 80% level) that had a fall in CD3+ DC. A fall in CD34+ DC below 80% was highly predictive for relapse, with a 5 year relapse free survival of only 17% compared with 80% for those that maintained DC > 80% for the first 180 days (Figure 1B). To determine the clinical utility of CD34+ DC, we measured the time to relapse in those patients that had a fall in DC without morphologic relapse at the time of DC measurement (Figure 1A). Based upon our institutional trigger of CD34+ DC < 80%, the median time to relapse was 49 days in 22 patients. In contrast, a CD34+ DC < 90% had a much longer time to relapse (71 days). However, this longer lead time would come at the price of unnecessary intervention in almost half of all patients as the PPV for CD34+ DC < 90% was only 55%. Loss of CD3+ DC had the longest lead time (> 70 days), however it was only useful up to 10 (24%) of all relapses. Finally, DLI administered for CD34+ DC < 80% maintained durable remission (> 12 months) in only 2 of 19 patients. Conclusion: This is the largest comparison of peripheral blood CD34+ and CD3+ DC following allo-SCT. Our results show that monthly monitoring of CD34+ DC in the first 6 months after allo-SCT is a more useful biomarker than CD3+ DC for predicting relapse in patients allografted for AML or MDS. The level of CD34+ DC chosen to trigger intervention should be guided by characteristics of the intervention such as toxicity and expected response time. Given the relative ineffectiveness of DLI for CD34+ < 80%, we suggest that 90% may provide greater time for immunologic responses. Figure Legend (A) Characteristics of different levels of CD3 and CD34 DC at any time in the first 180 days post-allo-SCT. Number of patients that fulfil the level in the total cohort of 136 patients. Number of patients before relapse indicates the number that do not have morphologic relapse at the time of DC measurement. Median days before relapse is shown for those patients. (B) Relapse free survival of patients according to CD34+ DC > 80% (blue line) or < 80% (yellow line) in the first 180 days. Disclosures Spencer: AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Celgene, Janssen and Takeda: Speakers Bureau; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria. Wei:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; MacroGenics: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Research Funding; Walter and Eliza Hall Institute: Other: former employee and receives a fraction of its royalty stream related to venetoclax; Pfizer: Honoraria; Genentech: Honoraria; Astra Zeneca: Honoraria, Research Funding; AbbVie Inc.: Consultancy, Honoraria, Research Funding.

Background Severe pulmonary chronic graft versus host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation. Few treatments influence outcome, with 5-year overall survival as low as 13%. Lung transplantation (LTx) has been reported in small numbers of patients worldwide. Methods We investigated the outcomes of LTx performed for this indication at 2 large Australian LTx centers. Results Eighteen patients (aged 10-64 y; median, 29.6 y) received bilateral deceased lung transplants for pulmonary chronic GVHD between 2002 and 2017. LTx was performed at a median of 8.6 years after allogeneic stem cell transplantation (range, 2-23 y) with a median interval of 16 months from the time of transplant unit review to LTx. There were 2 early infective deaths and 3 further deaths from pulmonary infection and lung allograft rejection. There were no primary disease relapses. At a median follow-up of 5 years, the 5-year overall survival post-LTx is 80% and comparable to the Australia and New Zealand registry data of 64% for LTx performed for all indications. Conclusions From one of the largest series of deceased LTx for this indication, we conclude that it is a feasible option for selected patients with severe pulmonary GVHD. The outcomes appear superior to that of non-LTx-based therapies and similar to the survival of the general LTx population. Establishing guidance on referral triggers, patient eligibility, organ selection, prophylaxis of allograft rejection, and supportive care would assist hematopoietic and lung transplant units in optimizing resource allocation and patient outcomes.

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.

Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant-related mortality from infection and graft-versus-host disease. We report on five adult patients receiving rescue alloSCT2 using haploidentical peripheral blood stem cells. All patients achieved neutrophil engraftment, two subsequently died from sepsis and disease relapse, respectively. Three patients remain alive up to 2 years post-transplant. We suggest consideration of haploidentical alloSCT2 for patients with graft failure.

Chronic lymphocytic leukaemia (CLL) occurs rarely with pregnancy and monoclonal B-Lymphocytosis (MBL) has not previously been described in this setting. CLL is predominantly a disease of the elderly and affects men twice as often as women and hence only an estimated 2% of patients are females of childbearing age. We identified only five reported cases of CLL in pregnancy in the literature. We describe two additional cases, plus three other women with CLL dealing with pregnancy-related decisions. We review the literature and discuss proposals for management and issues that arise in this relatively uncommon occurrence. In contrast to many other haematological malignancies where longer remissions are typically associated with a lower risk of relapse, most patients with CLL who require treatment will ultimately relapse with current therapy. This complex setting requires careful consideration and well informed patients to assist with decisions related to pregnancy.

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 Relapse remains the leading cause of death for patients with acute myeloid leukemia (AML). Some patients at high risk of relapse are ineligible for allogeneic stem cell transplantation due to age, comorbidities or the absence of a suitable donor. Infusion of fresh haploidentical cells from family donors (microtransplantation) has resulted in improvement in disease-free survival without the development of graft-versus-host disease (GVHD). However, obtaining family donor haploidentical G-CSF primed cells at short notice places a strain on transplant centres because of the requirement for rapid donor evaluation, testing and apheresis. In a Phase I study, we investigated the use of cryopreserved partially HLA-matched cells from unrelated donors as an immediately available alternative to family donors in AML patients ineligible for transplant. Method A bank of G-CSF primed and steady state apheresis products from 31 normal stem cell transplant donors that were no longer required for their originally intended recipients was established at two transplant centres. Patients in first complete remission (CR) of AML following induction therapy who were not candidates for allogeneic transplant were infused with partially HLA-matched (2/8 HLA-A, -B, -C or DR antigens) unrelated donor apheresis products at a dose of 0.5 x108 CD3 cells/kg following 3 days of cytarabine 2g/m2 BD. No GVHD prophylaxis was given. Up to three cycles were given at 2-month intervals. The presence of microchimerism was assessed via droplet digital PCR using primers/probes targeting 29 bi-allelic insertion/deletion loci. Results A total of eight cell infusions have been administered to three patients (Table 1). Non-neutropenic fever occurred within 24 hours of 5 of 8 infusions. Two febrile reactions were associated with transient rashes that were not consistent with GVHD on biopsy. These resolved spontaneously. There were no cases of GVHD following infusion. Median time to neutrophil recovery was 21.5 days (range 13-34) and platelets 17 days (9-39) post commencement of chemotherapy. One patient relapsed 256 days after his 3rd infusion and subsequently died, the other two remain in CR on trial. Of six infusions analysed, microchimerism has been detected in all cases up to 57 days post infusion (Figure 1). Conclusion Infusion of partially HLA-matched cells from unrelated donors results in minimal toxicity and engraftment of donor cells lasting up to 2 months post-infusion. Early non-neutropenic fevers and rashes are common. The effect of donor cells on disease recurrence will be determined through recruitment of additional patients and longer follow up. Table 1 Patient details Table 1. Patient details Figure 1 Donor DNA detected following partially HLA matched unrelated donor cell infusions Figure 1. Donor DNA detected following partially HLA matched unrelated donor cell infusions Disclosures Gottlieb: Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Indee: Membership on an entity's Board of Directors or advisory committees.