Outcomes of adults with refractory or relapsed acute myeloid leukemia treated with azacitidine and venetoclax compared to other therapies: a multicenter retrospective study.

This study reports characteristics and outcomes of adults who received Azacitidine-Venetoclax (AZA-VEN) compared to other salvage therapies (NO-AZA-VEN) as first salvage therapy for acute myeloid leukemia (AML). The clinical data of 81 patients with a diagnosis of relapsed or refractory AML were analyzed. The ORR was comparable for both groups (55% vs 57%, p = 0.852). Median OS (6.8 vs 11.2 months, p = 0.053) and median RFS (6.9 vs 11.2 months, p = 0.488) showed a trend in favor of the NO-AZA-VEN group. OS was significantly longer with NO-AZA-VEN for ELN 2022 risk category sub-group, patients under 60 years old, primary AML and for patients who underwent allo-hematopoietic stem cell transplant after salvage therapy. There was no statistical difference in complications of treatment such as febrile neutropenia, intensive care unit stay, septic shock and total parenteral nutrition. Those results do not support the preferential use of AZA-VEN over other regimens in R/R acute myeloid leukemia.

Combined erythropoietin and iron therapy for anaemic patients undergoing transcatheter aortic valve implantation: the EPICURE randomised clinical trial.

AIMS: The aim of this study was to evaluate, in anaemic patients, the efficacy of erythropoietin (EPO) in reducing red cell (RC) transfusion rates post TAVI. METHODS AND RESULTS: This was a randomised double-blind trial. Patients with severe symptomatic aortic stenosis and concomitant anaemia with an indication for TAVI were randomised (1:1) to receive two weight-based doses of EPO (darbepoetin alfa)+iron or placebo at days 10 (±4 days) and 1 (±1 day) pre TAVI. The primary outcome was the rate of RC transfusions at 30 days. A total of 100 patients (mean age 81±7 years, male 49%) were included: 48 patients received EPO (+iron) and 52 patients received placebo. Baseline characteristics and procedural findings were well balanced between groups except for baseline haemoglobin levels, which were lower in those patients receiving EPO (10.7±1.2 vs. 11.3±1.1 g/dl, p=0.01). The rate of 30-day RC transfusion was similar in both groups (27.1 vs. 25.0% in the EPO and placebo groups, respectively; adjusted odds ratio 1.05, 95% CI: 0.42-2.64, p=0.92), and no differences were observed in the number of RC units per transfused patient (1 [1-3] vs. 2 [1-2] in the EPO and placebo groups, respectively, adjusted p=0.99). Rates of 30-day mortality, stroke, new-onset atrial fibrillation, acute kidney injury, and troponin peak were also similar between groups (p>0.20 for all). CONCLUSIONS: EPO (+iron) administration failed to reduce RC transfusion rates or the per-patient number of transfusion units in anaemic patients undergoing TAVI.

Comparative net cost impact of the utilization of romiplostim and intravenous immunoglobulin for the treatment of patients with immune thrombocytopenia in Québec, Canada.

OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction, sub-optimal platelet production, and mild-to-severe bleeding. Nplate® (romiplostim), a thrombopoietin receptor agonist, and intravenous immunoglobulin (IVIg), an expensive and occasionally scarce blood product, are used in the treatment of ITP. The objective of this study was to compare the total cost of treating patients with romiplostim vs IVIg in Québec, Canada. METHODS: A net cost impact model was developed to calculate the annual cost of romiplostim compared with IVIg based on actual practice observations in all patients (n = 95) treated for chronic ITP with IVIg from April 2010 to March 2011 in two participating hospitals. The model included costs of: drug acquisition, drug preparation and administration, patient monitoring, and indirect costs. Healthcare practitioners were consulted regarding romiplostim and IVIg treatment algorithms and the resources involved in patient monitoring. RESULTS: The average annual drug acquisition costs of romiplostim and IVIg were $48,024 and $98,868, respectively. Lower costs for drug preparation and administration ($309 vs $1245) and less time lost from work ($256 vs $2086) were attributed to romiplostim. The cost of follow-up monitoring was the same for both romiplostim and IVIg ($121). The total average annual per patient costs for romiplostim vs IVIg were, respectively, $48,710 and $102,320. The use of romiplostim was projected to save, on average, almost $54,000 per patient per year. LIMITATIONS: The study was conducted in two hospitals in Québec. Romiplostim may show different cost savings in other hospitals and other provincial and national jurisdictions. CONCLUSIONS: Scarce blood products must be used wisely. Romiplostim can allow for improved healthcare resource allocation by reserving IVIg for use in other areas of greater need while also providing cost savings for the overall provincial healthcare budget.

The influence of bleeding on trigger changes for platelet transfusion in patients with chemotherapy-induced thrombocytopenia.

BACKGROUND: For patients with thrombocytopenia without bleeding risk factors, a platelet transfusion trigger of 10 × 10(9) /L is recommended. No studies have evaluated the clinicians' decision-making process leading to trigger changes. STUDY DESIGN AND METHODS: We report on the evaluation of trigger changes and the relation with bleeding. Eighty patients previously enrolled in the SPRINT trial represent the patient population for the current analysis. RESULTS: Seventy-four patients had a starting trigger of 10 × 10(9) /L. Only a minority of patients treated with chemotherapy alone (3/12, 25%) and autologous transplant (6/15, 40%) had a change in their trigger in contrast to the majority of allogeneic transplant (37/47, 79%; p = 0.001 and p = 0.009, respectively, when compared to allogeneic transplant group). Bleeding was the main reason reported by clinicians for a trigger change, but the occurrence of significant bleeding (Grade 2-4) was similar in patients with or without a trigger change (51 and 54%, p = 1.00). Clinicians were influenced by the bleeding system: grade 1 mucocutaneous bleeding leading to a trigger change was overrepresented (71% of cases), as was grade 2 genitourinary bleeding not leading to a trigger change (57% of cases). CONCLUSION: A universal trigger of 10 × 10(9) /L may not be maintained in a diverse population of patients with their respective bleeding risk factors. Because the trigger is changed often, it may not be as effective as previously believed.

Cell loss and recovery in umbilical cord blood processing: a comparison of postthaw and postwash samples.

BACKGROUND: Engraftment after umbilical cord blood (UCB) transplantation is highly dependent on nucleated cell (NC) and CD34+ cell content. Current standard postthaw (PT) processing includes a wash step to remove dimethyl sulfoxide (DMSO), lysed red cells, and stroma. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant have yet to be systematically reported. This study examines the effect of the wash step as well as that of PT storage on various quality control variables of UCB units. STUDY DESIGN AND METHODS: Ten units were thawed and washed based on the New York Blood Center method. Samples were removed from each unit at six time points: prefreeze (PF), immediately PT, immediately postwash (PW), and 1, 2, and 5 hours PW. On each sample, total nucleated cell (TNC) count, CD34+ cell enumeration, colony-forming unit (CFU)-granulocyte-macrophage, and viability assays (fluorescence microscopy [acridine orange/propidium iodide, or AO/PI] and flow cytometry [7-aminoactinomycin]) were obtained. RESULTS: TNC counts decreased PT and at subsequent time points; the PT TNC recovery was 89 percent compared to 82 percent PW (p < 0.01). TNC recovery decreased to 90 percent of PW (82% of PT) values (p < 0.01) and 83 percent of PW (76% of PT) values (p < 0.001), at 2 and 5 hours PW, respectively. CD34+ cell loss PT was not significant. Viability by AO/PI decreased PT and plateaued over time. In contrast, viability by flow cytometry remained higher and increased slightly over time. CFUs were significantly lower PT, recovering PW. CONCLUSIONS: Our data indicate that the thawing and washing results in a substantial loss of cells, with TNC loss approaching 20 percent when compared with PF counts; the wash step was responsible for nearly half of the cell loss. The reduced PT viability was expected. Elapse of time PW resulted in further loss of NCs but no detectable significant changes in CD34+ cell content and viability and/or CFU.