Daratumumab, cyclophosphamide, bortezomib and dexamethasone for non-transplant eligible myeloma (AMaRC 03-16).

In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard of care regimens. In a randomized trial, we tested whether similar improvements would be seen when daratumumab was added to the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen. Non-transplant eligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). 121 patients were randomized, 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the two arms. The median PFS was 16.8m (95%CI 15.3 - 21.7m) and 25.8m (95%CI 19.9 - 33.5) in the VCD and VCDD arms, respectively (HR 0.67, log-rank test p=0.066). In a pre-planned analysis, the estimated PFS at fixed time-points post-randomization demonstrated significantly improved PFS for the daratumumab containing arm from 18 months onwards. The proportions of patients who were progression free at the following time points were: 18 months, 48% vs 68% (p=0.0002); 24 months, 36% vs 52% (p=0.0001); and 30 months, 27% vs 41% (p<0.0001) in the VCD and VCDD arms, respectively. The best overall response and VGPR rate were significantly better in the daratumumab arm (65% vs 86%, p=0.007 and 28% vs 52%, p=0.009) for the VCD and VCDD arms, respectively. Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of non-transplant eligible patients with myeloma. Australian and New Zealand Clinical Trials Registry (ACTRN12617000202369). https://www.anzctr.org.au/.

Meaningful Symptomatic Change in Patients With Myelofibrosis From the SIMPLIFY Studies.

OBJECTIVES: Patients with myelofibrosis develop symptoms due to bone marrow fibrosis, systemic inflammation, and/or organomegaly. Alleviating symptoms improves overall quality of life. Clinical trials have historically defined symptom response as a reduction of at least 50% in Total Symptom Score at week 24 compared with baseline. Whether 50% constitutes a meaningful benefit has not been established. This study determined the meaningful change threshold (MCT) for 2 momelotinib phase III trials, SIMPLIFY-1 and SIMPLIFY-2. METHODS: The absolute and percentage MCT was determined using anchor-based methods applied to the modified Myeloproliferative Neoplasm Symptom Assessment Form v2.0 and Patient Global Impression of Change. MCTs were applied retrospectively to determine responder rates. Generalized estimating equations estimated the treatment-related difference in likelihood of improvement. RESULTS: In SIMPLIFY-1, a Janus kinase inhibitor-naive population, the MCT was 8 points. In SIMPLIFY-2, a previously Janus kinase inhibitor-treated population, the MCT was 6 points. A 32% MCT was determined in both studies, showing that the historic 50% reduction threshold may be a conservative choice. In SIMPLIFY-1, a similar proportion of patients achieved responder status with 24 weeks of momelotinib or ruxolitinib therapy based on the absolute MCT (39% vs 41%, respectively). In SIMPLIFY-2, a significantly greater proportion of patients treated with momelotinib achieved responder states compared with best available therapy based on absolute and percent change MCTs. CONCLUSIONS: This study demonstrates that momelotinib provided clinically meaningful symptom benefit for patients with myelofibrosis and provides insight into the appropriateness of the symptom change threshold used in historical studies.

Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis.

Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical "MF-like" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.

What is the context? We investigated TCF3 (transcription factor 3), a gene that regulates megakaryocyte development, for genomic and proteomic changes in myelofibrosis.Myelofibrosis is the aggressive phase of a group of blood cancers called myeloproliferative neoplasms, and abnormalities in development and maturation of megakaryocytes is thought to drive the development of myelofibrosis.What is new? We report detection of three novel TCF3 mutations in megakaryocytes and decreases in TCF3 protein and gene expression in primary megakaryocytes and platelets from patients with myelofibrosis.This is the first association between loss of TCF3 in megakaryocytes from patients and myelofibrosis.What is the impact? TCF3 dysregulation may be a novel mechanism that is responsible for the development of myelofibrosis and better understanding of this pathway could identify new drug targets.

Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.

PlateletSeq: A novel method for discovery of blood-based biomarkers.

Platelets are small circulating fragments of cells that play important roles in thrombosis, haemostasis, immune response, inflammation and cancer growth. Although anucleate, they contain a rich RNA repertoire which offers an opportunity to characterise changes in platelet gene expression in health and disease. Whilst this can be achieved with conventional RNA sequencing, a large input of high-quality RNA, and hence blood volume, is required (unless a pre-amplification step is added), along with specialist bioinformatic skills for data analysis and interpretation. We have developed a transcriptomics next-generation sequencing-based approach that overcomes these limitations. Termed PlateletSeq, this method requires very low levels of RNA input and does not require specialist bioinformatic analytical skills. Here we describe the methodology, from sample collection to processing and data analysis. Specifically, blood samples can be stored for up to 8 days at 4 °C prior to analysis. Platelets are isolated using multi-step centrifugation and a purity of ≤ 1 leucocyte per 0.26x106 platelets is optimal for gene expression analysis. We have applied PlateletSeq to normal adult blood samples and show there are no age-associated variations and only minor gender-associated differences. In contrast, platelets from patients with myeloproliferative neoplasms show differences in platelet transcript profiles from normal and between disease subtypes. This illustrates the potential applicability of PlateletSeq for biomarker discovery and studying platelet biology in patient samples. It also opens avenues for assessing platelet quality in other fields such as transfusion research.

Symptomatic benefit of momelotinib in patients with myelofibrosis: Results from the SIMPLIFY phase III studies.

BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. RESULTS: Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of <1.5 points between groups for each post-baseline visit in SIMPLIFY-1. In SIMPLIFY-2, the improvement in TSS observed in momelotinib-treated patients was consistent with that observed in SIMPLIFY-1, whereas progressive TSS deterioration was observed with control. Item-level scores were heterogeneous in both studies. A similar and greater proportion of momelotinib-treated patients were categorized as "improved" or "stable" compared with control in SIMPLIFY-1 and SIMPLIFY-2, respectively. Odds ratios for between-group comparison ranged from 0.75 to 1.21 in SIMPLIFY-1, demonstrating similarity in likelihood of symptom improvement. In SIMPLIFY-2, the likelihood of symptom improvement in each item was higher in the momelotinib arm. CONCLUSIONS: These findings suggest that momelotinib provides clinically relevant symptom benefits in the JAK inhibitor-naïve and JAK inhibitor-exposed settings.

Multivariable statistical models to predict red cell transfusion in elective surgery.

BACKGROUND: Predicting red cell transfusion may assist in identifying those most likely to benefit from patient blood management strategies. Our objective was to identify a simple statistical model to predict transfusion in elective surgery from routinely available data. MATERIALS AND METHODS: Our final multicentre cohort consisted of 42,546 patients and contained the following potential predictors of red cell transfusion known prior to admission: patient age, sex, pre-admission hemoglobin, surgical procedure, and comorbidities. Missing data were handled by multiple imputation methods. The outcome measure of interest was administration of a red cell transfusion. We used multivariable logistic regression models to predict transfusion, and evaluated the performance by applying a 10-fold cross-validation. Model accuracy was assessed by comparing the area under the receiver operating characteristics curve. After applying an optimal probability cut-off we measured model accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: 7.0% (n=2,993) of the study population received a red cell transfusion. Our most simple model predicted red cell transfusion based on admission hemoglobin and surgical procedure with a multiply imputed estimated area under the curve of 0.862 (0.856, 0.864). The estimated accuracy, sensitivity, specificity, positive predictive, and negative predictive values at the probability cut-off of 0.4 were 0.934, 0.257, 0.986, 0.573, and 0.946 respectively. DISCUSSION: A small number of variables available prior to admission can predict red cell transfusion with very good accuracy. Our model can be used to flag high-risk patients most likely to benefit from pre-operative patient blood management measures.

Hospital-Acquired Infection, Length of Stay, and Readmission in Elective Surgery Patients Transfused 1 Unit of Red Blood Cells: A Retrospective Cohort Study.

BACKGROUND: Most patients transfused red blood cells in elective surgery receive small volumes of blood, which is likely to be discretionary and avoidable. We investigated the outcomes of patients who received a single unit of packed red blood cells during their hospital admission for an elective surgical procedure when compared to those not transfused. METHODS: This retrospective cohort study included elective surgical admissions to 4 hospitals in Western Australia over a 6-year period. Participants were included if they were at least 18 years of age and were admitted for elective surgery between July 2014 and June 2020. We compared outcomes of patients who had received 1 unit of red blood cells to patients who had not been transfused. To balance differences in patient characteristics, we weighted our multivariable regression models using the inverse probability of treatment. In addition to propensity score weighting, our multivariable regression models adjusted for hemoglobin level, surgical procedure, patient age, gender, comorbidities, and the transfusion of fresh-frozen plasma or platelets. Outcomes studied were hospital-acquired infection, hospital length of stay, and all-cause emergency readmissions within 28 days. RESULTS: Overall, 767 (3.2%) patients received a transfusion of 1 unit of red blood cells throughout their admission. In the propensity score weighted analysis, the transfusion of a single unit of red blood cells was associated with higher odds of hospital-acquired infection (odds ratio, 3.94; 95% confidence interval [CI], 2.99-5.20; P < .001). Patients who received 1 unit of red blood cells throughout their admission were more likely to have a longer hospital stay (rate ratio, 1.57; 95% CI, 1.51-1.63; P < .001) and had 1.42 (95% CI, 1.20-1.69; P < .001) times higher odds of 28-day readmission. CONCLUSIONS: These results suggest that avoidance of even small volumes of packed red blood cells may prevent adverse clinical outcomes. This may encourage hospital administrators to implement strategies to avoid the transfusion of even small volumes of red blood cells by applying patient blood management practices.

Jumping translocation involving chromosome 13q in a patient with Crohn's Disease and inv(16)(p13.1q22)/CBFB-MYH11 acute myeloid leukemia.

Jumping translocations (JT) are rare chromosomal rearrangements caused by the translocation of one donor chromosome segment to two or more recipient chromosomes. In the setting of myeloid neoplasms, JT are typically associated with disease transformation to acute myeloid leukemia (AML), and studies to date have found JT to be associated with poor prognosis and short overall survival. However, JT have been only very rarely reported in AML associated with a favorable AML prognostic cytogenetic marker. Additionally, JT have infrequently been described in hematological malignancies associated with autoimmune diseases (AID) such as Crohn's Disease (CD). Here we describe a case of a 40-year-old female with a 24-year history of CD diagnosed with AML harbouring the inv(16)(p13.1q22)/CBFB-MYH11 rearrangement in conjunction with sideline clones containing trisomy 13, tetrasomy 13, and a JT of chromosome 13q12 jumping to 7q32 and 18p11.2. The patient attained molecular remission one month post diagnosis after induction 7 + 3 chemotherapy. Morphologic relapse of disease occurred 27 months post diagnosis. A second molecular remission was attained 3 months later after re-induction chemotherapy. The patient received a sibling bone marrow transplant 32 months post diagnosis and is currently in remission 7 months post allogeneic transplant. To the best of our knowledge, this case represents the first report of JT occurring in inv(16)(p13.1q22)/CBFB-MYH11 AML and the second of JT occurring in an AML patient with prior clinical history of CD. This case provides further insight into the rare occurrence of JT in AML, particularly AML with a favorable cytogenetic marker in conjunction with AID.

Associations of a Preoperative Anemia and Suboptimal Iron Stores Screening and Management Clinic in Colorectal Surgery With Hospital Cost, Reimbursement, and Length of Stay: A Net Cost Analysis.

BACKGROUND: In 2016, a preoperative clinic was implemented to screen, evaluate, and manage anemia and suboptimal iron stores at a major tertiary care medical center in Western Australia. Few studies compare the costs and reimbursements associated with preoperative anemia and suboptimal iron stores management. The objective of our study was to conduct a net cost analysis associated with the implementation of this clinic. METHODS: We designed a retrospective cohort study involving elective colorectal surgical admissions over a 3-year period. The baseline year selected was the 2015-2016 financial year, with outcomes in the 2016-2017 and 2017-2018 year compared to baseline. The study perspective was the Western Australian Health System. Hospital costs were extracted from the health service clinical costing system, which captures costs at the admission level. The primary outcome was net cost, defined as gross cost minus reimbursement (or funding) received. RESULTS: Our 3-year study included 544 admissions for elective colorectal surgery. After the implementation of the preoperative clinic, 73.4% (n = 257) of admissions were screened for anemia and suboptimal iron stores, and 31.4% (n = 110) received intravenous iron. In our adjusted analysis, when comparing the final year (2017-2018) with baseline (2015-2016), the units of red blood cells transfused per admission decreased 53% (142 vs 303 units per 1000 discharges; P = .006), and mean hospital length of stay decreased 15% (7.7 vs 9.1 days; P = .008). When comparing the final year with baseline, rectal resection admissions were associated with a mean decrease in the net cost of Australian dollar (A$) 7619 (95% confidence interval, 4230-11,008; P < .001) between 2015-2016 and 2017-2018. For small and large bowel procedures, there was a mean decrease of A$6744 (95% confidence interval, 2430-11,057; P = .002). CONCLUSIONS: The implementation of a preoperative anemia and suboptimal iron stores screening and management clinic in elective colorectal surgery was associated with reductions in red cell transfusions, length of stay, and net costs.

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma.

Zanubrutinib (BGB-3111) is a next-generation Bruton tyrosine kinase inhibitor designed to be more selective with fewer off-target effects. We conducted a phase 1 study to assess the safety of its combination with obinutuzumab and evaluate early efficacy in 81 patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or relapsed/refractory (R/R) follicular lymphoma (FL). In this phase 1b study, zanubrutinib was tolerable at 160 mg twice daily or 320 mg once daily combined with IV obinutuzumab in patients with CLL/SLL (n = 45) and FL (n = 36). Common adverse events (AEs) included upper respiratory tract infection (51%; n = 23), neutropenia (44%; n = 20), contusion (33%; n = 15), cough, diarrhea, or fatigue (27%; n = 12 each), and pyrexia (22%; n = 10) in CLL/SLL patients and upper respiratory tract infection (39%; n = 14), contusion (28%; n = 10), fatigue (25%; n = 9), and cough (22%; n = 8) in FL patients. Neutropenia was the most common grade 3/4 AE (CLL/SLL, 31% [n = 14]; FL, 14% [n = 5]). Five patients required temporary dose reductions, and 5 discontinued the study drug because of AEs. Overall response rate (ORR) was 100% (n = 20) in treatment-naïve CLL patients and 92% (n = 23) in R/R CLL patients. ORR in 36 R/R FL patients was 72% (n = 26), with 14 complete and 12 partial responses. Median follow-up was 29 months (range, 8-37) for CLL patients and 20 months (range, 2-37) for FL patients. Zanubrutinib and obinutuzumab combination therapy was generally well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02569476.

The Occurrence of Richter's Syndrome during Treatment with Obinutuzumab and Chlorambucil.

Chronic lymphocytic leukaemia is a slow-growing leukaemia of developing B-lymphocytes, which may transform to an aggressive lymphoma known as Richter's syndrome. While Richter's syndrome can present in untreated or relapsed-refractory cases, it may occur upon the commencement of less intensity treatment regimens. We present a case of Richter's syndrome following treatment with chlorambucil and obinutuzumab and review of available literature on the topic.

An unusual case of plasmablastic lymphoma presenting as dermatomyositis.

We report a rare case of aggressive plasmablastic lymphoma with an initial presentation of dermatomyositis. The challenges associated with the diagnosis and treatment approach are also highlighted in this case report.

Platelets in myeloproliferative neoplasms have a distinct transcript signature in the presence of marrow fibrosis.

Marrow fibrosis is a significant complication of myeloproliferative neoplasms (MPN) that affects up to 20% of patients and is associated with a poor prognosis. The pathological processes that lead to fibrotic progression are not well understood, but megakaryocytes have been implicated in the process. The aim of this study was to determine whether platelets, derived from megakaryocytes, have transcriptomic alterations associated with fibrosis. Platelets from MPN patients with and without fibrosis and non-malignant control individuals were assessed using next generation sequencing. Results from the initial training cohort showed discrete changes in platelet transcripts in the presence of marrow fibrosis. We identified more than 1000 differentially expressed transcripts from which a putative 3-gene fibrotic platelet signature (CCND1, H2AX [previously termed H2AFX] and CEP55) could be identified. This fibrosis-associated signature was assessed blinded on platelets from an independent test MPN patient cohort. The 3-gene signature was able to discriminate between patients with and without marrow fibrosis with a positive predictive value of 71% (93% specificity, 71% sensitivity). This demonstrates that assessment of dysregulated transcripts in platelets may be a useful monitoring tool in MPN to identify progression to marrow fibrosis. Further, sequential monitoring could have clinical applications for early prediction of progression to fibrosis.

Prognostic factors and the impact of frontline therapy in peripheral T-cell lymphoma: 10 years of 'real-world' experience from Western Australia.

We present an analysis of 98 consecutive patients with peripheral T-cell lymphoma (PTCL) treated over a 10-year period within Western Australia. The most common frontline therapies were CHO(E)P (47%), HyperCVAD (21%), and reduced intensity therapy or supportive care alone (19%). Median and 4-year overall survival (OS) for the whole cohort were 1.59 years and 34%. Amongst CHO(E)P and HyperCVAD-treated patients, elevated LDH, advanced stage, IPI >1, and non-ALK + ALCL histology predicted inferior progression-free survival (PFS). Inferior OS was predicted by elevated LDH, age >60, IPI >1, and non-ALK + ALCL histology. Response rates and PFS were not significantly different between patients treated with CHO(E)P or HyperCVAD. OS was longer in the HyperCVAD group, however this was not significant on multivariable analysis and appears to relate to the younger age and more aggressive therapy at relapse in this group. Our data confirmed the prognostic utility of the IPI in patients with PTCL and do not demonstrate a clear benefit of HyperCVAD.

Multimodal Patient Blood Management Program Based on a Three-pillar Strategy: A Systematic Review and Meta-analysis.

OBJECTIVES: To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome. BACKGROUND: PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia. METHODS: A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217). RESULTS: Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55-0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference -0.43, 95% CI -0.54 to -0.31, P < 0.00001), hospital length of stay (mean difference -0.45, 95% CI -0.65 to -0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74-0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80-0.98, P = 0.02). CONCLUSIONS: Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.

Blood use in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation: the impact of a health system-wide patient blood management program.

BACKGROUND: Little is published on patient blood management (PBM) programs in hematology. In 2008 Western Australia announced a health system-wide PBM program with PBM staff appointments commencing in November 2009. Our aim was to assess the impact this program had on blood utilization and patient outcomes in intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. STUDY DESIGN AND METHODS: A retrospective study of 695 admissions at two tertiary hospitals receiving intensive chemotherapy for acute leukemia or undergoing hematopoietic stem cell transplantation between July 2010 and December 2014 was conducted. Main outcomes included pre-red blood cell (RBC) transfusion hemoglobin (Hb) levels, single-unit RBC transfusions, number of RBC and platelet (PLT) units transfused per admission, subsequent day case transfusions, length of stay, serious bleeding, and in-hospital mortality. RESULTS: Over the study period, the mean RBC units transfused per admission decreased 39% from 6.1 to 3.7 (p < 0.001), and the mean PLT units transfused decreased 35% from 6.3 to 4.1 (p < 0.001), with mean RBC and PLT units transfused for follow-up day cases decreasing from 0.6 to 0.4 units (p < 0.001). Mean pre-RBC transfusion Hb level decreased from 8.0 to 6.8 g/dL (p < 0.001), and single-unit RBC transfusions increased 39% to 67% (p < 0.001). This reduction represents blood product cost savings of AU$694,886 (US$654,007). There were no significant changes in unadjusted or adjusted length of stay, serious bleeding events, or in-hospital mortality over the study. CONCLUSION: The health system-wide PBM program had a significant impact, reducing blood product use and costs without increased morbidity or mortality in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation.