How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

Despite an increasing desire to use historical cohorts as "synthetic" controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012-2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

Cost-Effectiveness of Extracorporeal Photopheresis in Patients With Chronic Graft-vs-Host Disease.

Background: The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. Methods: A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. Results: Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. Conclusion: This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

Predictors of post traumatic growth in allogeneic hematopoietic stem cell transplantation survivors: a cross-sectional survey.

AIMS: Given the increasing number of Hematopoietic Stem Cell Transplantations (HSCT) performed world-wide, the increasing likelihood of survival following HSCT, and the profound physical, psychosocial, and emotional impact of HSCT on survivors, their carers and families, it is important to identify factors that may contribute to or support post-traumatic growth (PTG) after transplant. In this study, we aimed to investigate the prevalence of PTG in an Australian cohort of long-term allogeneic HSCT survivors and describe associations between PTG and relevant clinical, sociodemographic and psychological variables. METHODS: This was a large, multi-centre, cross sectional survey of Australian HSCT-survivors inviting all those transplanted in New South Wales between 2000 and 2012. Respondents completed the PTG Inventory (PTGI), the Sydney Post-BMT Survey, FACT-BMT, DASS 21, The Chronic Graft versus Host Disease (GVHD) Activity Assessment-Patient Self-Report (Form B), the Lee Chronic GVHD Symptom Scale, and the Fear of Cancer Recurrence Scale. Data was analysed using independent t-tests, one-way analysis of variance, and pearson's correlations, and hierarchical multiple regression adjusted for potential confounders and to ascertain independent associations of explanatory variables with PTG. RESULTS: Of 441 respondents, 99% reported some level of PTG with 67% reporting moderate to high levels of PTG. Female gender, younger age, complementary therapy use, anxiety, psychological distress and psychosocial care, and higher quality of life were associated with higher levels of PTG. Importantly, we also found that PTG was not associated with either chronic GVHD or post-HSCT morbidity. CONCLUSIONS: In this study - the largest study of PTG in long-term allogeneic HSCT survivors - we found that growth appears ubiquitous, with 99% of survivors reporting some degree of PTG and 67% reporting moderate-high levels of PTG. Importantly, we found no association with GVHD or chronic physical post-HSCT morbidity, or adverse financial, occupational or sexual impacts. This suggests that it is the necessity for and experience of, HSCT itself that foments personal growth. Accordingly, healthcare professionals should be alert to the profound and wide-ranging impact of HSCT - and the degree to which survivor's may experience PTG. Identifying interventions that may assist HSCT survivors cope and building their resilience is of utmost importance.

Decisional Regret in Long-Term Australian Allogeneic Hematopoietic Stem Cell Transplantation Survivors: A Cross-Sectional Survey.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an intensive but effective treatment for malignant and non-malignant diseases. However, long-term survival often comes at a cost, with survivors experiencing chronic morbidity and are at risk of relapse and secondary malignancy. This study aimed to describe decisional regret in a large cohort of Australian long-term allo-HSCT survivors. A cross-sectional survey was conducted with 441 adults in New South Wales, assessing quality of life (QoL), psychological, social, demographic, and clinical variables. Less than 10% of survivors expressed regret, with chronic graft-versus-host disease being the most important clinical factor. Psycho-socioeconomic factors such as depression, lower QoL scores, lower household income, higher treatment burden, and not resuming sex post-HSCT were also associated with regret. Findings highlight the need for valid informed consent and ongoing follow-up and support for allo-HSCT survivors dealing with life post-transplant. Nurses and healthcare professionals play a critical role in addressing decisional regret in these patients.

Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, with a median follow-up of 21.5 months and 33.3 months, respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.

Australia and New Zealand Transplant and Cellular Therapies (ANZTCT) position statement: COVID-19 management in patients with haemopoietic stem cell transplant and chimeric antigen receptor T cell.

Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of 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 learned 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 manage our patients optimally.

Challenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.

AIM: To evaluate the accuracy of melphalan test dose pharmacokinetic (PK) predictions of the subsequent high dose (HDM) area under the concentration-versus-time curve (AUC) and to identify sources of prediction error (PE). METHODS: A prospective multicentre PK study was conducted in 40 myeloma patients of median age 60 (range:35-71) years using a 20 mg/m2 test dose administered 1-3 days prior to HDM (predominantly 180 mg/m2). PK data were collected post the test and high doses to compare predicted versus actual AUCs determined using the trapezoidal rule. Test and high dose infusion concentration, volume and duration and the time from preparation to infusion were compared using the paired Wilcoxin rank sign test. The impact of Melphalan administration parameters on PE was evaluated using the Mann-Whitney test. The predictive capacity of a previously published population PK (PopPK) model was also examined. RESULTS: Predicted HDM AUC was within 15% of the observed values in only 63% of patients when analysed using the trapezoidal rule and 70% of patients using PopPK. Test dose infusion concentration, volume, duration and time from preparation to infusion were significantly lower than for HDM (p < 0.005). Test dose administration within 15 min of reconstitution (n = 5) was associated with significantly lower PE than administration times of 16-60 min (n = 22), p < 0.05. Test and HDM infusion concentrations were lower in patients with large PE (> ± 15%), but the differences were not significant (p = 0.078, 0.228, respectively). CONCLUSION: Test dose PK has the potential to predict subsequent HDM exposure to achieve a target AUC once melphalan administration parameters are optimised to account for stability issues in the formulation.

The improvement in overall survival from unrelated donor transplantation in Australia and New Zealand is driven by a reduction in non-relapse mortality: A study from the ABMTRR.

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.

Long-term treatment burden following allogeneic blood and marrow transplantation in NSW, Australia: a cross-sectional survey.

BACKGROUND: Allogenic blood and marrow transplant (allo-BMT) is an arduous treatment used increasingly for many life-threatening conditions. Recognition of the profound impacts of the long term and late effects is ever-growing, as is the healthcare workload (treatment burden) of survivorship. PURPOSE: To quantify the treatment burden of long-term survival following allo-BMT, regarding the range of health services, therapies and investigations accessed by survivors. METHODS: A large, multi-centre cross-sectional survey of adult allo-BMT survivors transplanted between 2000 and 2012 in Sydney, Australia. Participants completed six validated instruments and one purposed designed for the study, the Sydney Post BMT Study (SPBS), answering questions relating to medication use, medical treatments, referrals, assessments and frequency of hospital/clinic attendance. RESULTS: Of the 441 allo-BMT survivors, over a quarter who were more than 2 years post BMT attended the hospital clinic at least monthly, and 26.7% required a number of regular medical procedures (e.g. venesection, extracorpororeal photopheresis). Specialist medical and allied health referral was very common, and compliance with internationally recommended long-term follow-up (LTFU) care was suboptimal and decreased as time from BMT increased. CONCLUSION: Respondents reported a large medication (conventional and complementary), screening, assessment and health care burden. IMPLICATIONS FOR CANCER SURVIVORS: Treatment burden contributes significantly to the 'workload' of survivorship and can have a severe and negative impact on BMT survivors, carers and the healthcare system-making it difficult to comply with optimal care. Clinicians must be primed with skills to identify survivors who are overburdened by the health care required for survival and develop strategies to help ease the burden.

Australia and New Zealand Transplant and Cellular Therapies COVID-19 vaccination consensus position statement.

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.

Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

PURPOSE: Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHODS: Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS: Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CONCLUSION: CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.

Predictors of quality of life in allogeneic hematopoietic stem cell transplantation survivors.

OBJECTIVES: To establish the demographic, medical, transplant, and lifestyle factors that impact Quality of Life (QoL) in long-term survivors of allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). DESIGN: Cross-sectional study utilizing self-report measures. SAMPLE/METHODS: In this cross-sectional study of 441 adult survivors of allo-HSCT, participants completed questionnaires assessing QoL, psychological, social, demographic, and clinical variables. FINDINGS: Factors associated with improved QoL post-allo-HSCT included time since transplant, female gender, attendance at outpatient appointments, health screening uptake, exercise, and resumption of travel. Factors significantly associated with impaired QoL included chronic morbidities (GVHD), taking psychotropic medication, failure to resume sexual activity (in men), male gender, psychological distress, low income or decline in work status, transition to non-physical work, and necessity for post-allo-HSCT care from various health professionals. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Identification of survivors more likely to experience a reduced QoL following allo-HSCT may enable the targeting of health services to the most vulnerable, and the development of interventions and resources. The data from this study led to the development of HSCT Long-Term Follow Up Clinical Guidelines in New South Wales.

SUBA-Itraconazole for Primary Antifungal Prophylaxis After Allogeneic Hematopoietic Cell Transplantation.

Background: Itraconazole (ITZ) is an effective agent when used as primary invasive fungal disease (IFD) prophylaxis, but is limited by drug tolerability and variability in serum concentrations. A new formulation, SUBA-itraconazole (for "super bioavailability"; S-ITZ), addresses the limitations of conventional ITZ formulations. Methods: We conducted a retrospective cohort study at 2 Australian centers to evaluate the safety, tolerability, and effectiveness of S-ITZ as primary antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients without grade II-IV acute graft-vs-host disease, from day 1 until approximately day 100 (cohort A) or day 1 until neutrophil engraftment (cohort B). A total of 204 patients and 1410 trough plasma ITZ concentrations were assessed. Results: The incidence of breakthrough proven/probable IFD at day 180 was 1.0% (95% confidence interval [CI], .2%-3.2%), with 1.6% in cohort A and 0% in cohort B, and overall fungal-free survival of proven/probable IFD was 82.9% (95% CI, 76.8%-87.4%). Preengraftment early permanent S-ITZ discontinuation was 3.4% overall, with no significant difference between cohorts. No patients required cessation due to gastrointestinal intolerance attributed to S-ITZ. The geometric mean trough plasma ITZ concentration was 1130ng/mL (interquartile range, 566-1801ng/mL; coefficient of variation, 56.57%) and the median time to achieve therapeutic levels was 10 days. Conclusions: S-ITZ is a safe and well-tolerated oral formulation and is a novel alternative for primary IFD prophylaxis after HCT.

Fear of cancer recurrence following allogeneic haematopoietic stem cell transplantation (HSCT) for haematological malignancy: A cross-sectional study.

PURPOSE: The aim of this study was to quantify the prevalence of Fear of Cancer Recurrence (FCR) in patients with a prior haematology malignancy surviving more than one year post allogeneic haematopoietic stem cell transplantation (HSCT), and to identify the demographic, medical and psychological factors associated with FCR occurrence. METHOD: Participants were adult allogeneic HSCT recipients who had undergone the procedure for acute leukaemia or other haematological malignancy between the years 2000-2012 in Sydney, Australia. They completed a purpose designed survey and six other validated instruments which assessed FCR, psychological functioning, quality of life, demographic, social and clinical variables. RESULTS: Of the 364 respondents, approximately 11% of the sample lived with severe FCR while only 5% of subjects reported having no FCR. Variables significantly associated with higher FCR included unemployment, a shorter time (years) post-transplant, not attending to health screening (PAP smear), a secondary diagnosis of skin cancer, younger age, referral to a psychiatrist and taking psychotropic medication. Higher psychological distress (depression, anxiety, stress) and lower quality of life made a significant contribution to the prediction of FCR. CONCLUSIONS: Post HSCT follow-up care should include an assessment and discussion regarding FCR to balance both realistic and unrealistic cancer recurrence risks. Managing FCR is one of the most ubiquitous unmet needs of survivors of haematological disease and it is important that HSCT nurses are both aware of the fear, and are equipped with knowledge on how to help patients navigate it with realistic expectations.

Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.

CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69- and CD69+ subsets, while only CD69- cells are found in PB. Within the BM-TTE compartment, CD69- and CD69+ cells are found in comparable proportions in controls, while CD69- cells are dominant in MGUS and SMM and predominantly either CD69- or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69-TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69-TTE cells include multiple oligoclonal expansions of T-cell receptor/Vß families shared between BM and PB of NDMM. Oligoclonal expanded CD69-TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69-TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69-TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69- and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease.

Variable CD34+ recovery of cryopreserved allogeneic HPC products: transplant implications during the COVID-19 pandemic.

Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.

Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era: A Retrospective Analysis from the Australasian Bone Marrow Transplant Recipient Registry.

To review the updated trends of national practice and outcomes in transplantation to treat myelofibrosis (MF), we retrospectively evaluated 142 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) for primary (n = 94) or secondary (n = 48) MF at an Australian/New Zealand transplantation center between 2006 and 2017. The median duration of follow-up was 51.8 months (range, 3.1 to 148 months). The median age at allo-HSCT was 56 years (range, 26 to 69 years). Fifty-two percent of the patients had HLA-identical sibling donors, and 45% had matched unrelated donors (UD). Conditioning regimens were predominantly reduced intensity (83%). Before transplantation, 16% of the patients had undergone splenectomy or splenic irradiation, and 38% (n = 54) received JAK inhibitor therapy. JAK2 mutation testing was performed in 66.9% of the patients, whereas other mutations (CALR, MPL, ASXL1, SRSF2, U2AF1Q57, EZH2, and IDH1/2) were rarely tested (1.4% to 8.4%). Only 4.2% of patients had next-generation sequencing mutation analysis. The median time to neutrophil engraftment was 19 days (range, 10 to 43 days), and the median time to platelet engraftment was 27 days (range, 13 to 230 days). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 21.4% at 100 days, and that of extensive chronic GVHD (cGVHD) at 5 years was 18.1%. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GVHD-free, relapse-free survival was 54% at 1 year and 42% at 5 years. The cumulative incidence of nonrelapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, age ≥65 years and use of an UD were identified as significant unfavorable risk factors for OS and NRM. Use of an UD increased the incidence of aGVHD, whereas administration of antithymocyte globulin/alemtuzumab lowered the risk of both aGVHD and cGVHD. Pretransplantation splenectomy/splenic irradiation had a positive influence on time to engraftment. There have been no improvements in the outcomes of allo-HSCT for MF in Australasia over the last decade, with a low uptake of molecular genomic technology due to limited access to funding.

Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG.

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.