Key Points• WT1 mRNA-electroporated DCs can prevent or delay relapse in 43% of patients with AML in remission after chemotherapy.• OS compares favorably with the new survival data from the Swedish Acute Leukemia Registry and correlates with molecular and WT1-specific CD8 1 T-cell responses.Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8 1 T cells. Long-term OS was correlated with interferon-g 1 and tumor necrosis factor-a 1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8 1 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8 1 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224. (Blood. 2017;130(15):1713-1721

Background: Infections remain a leading cause of morbidity and mortality in patients with reduced immunity caused by haematological disease and chemotherapy-induced neutropenia. We evaluated the clinical and microbiological impact of discontinuing fluoroquinolone prophylaxis in these patients. Methods: We analysed 154 admissions in three sequential periods of 8 months: long-standing use, discontinuation of prophylaxis and reintroduction of prophylaxis. Clinical endpoints were occurrence of febrile neutropenia, bacteraemia, severe sepsis, septic shock, response to antibiotic therapy, total antibiotic consumption and duration of hospital stay. Microbiological analysis included bacterial isolates from stool and blood cultures and their resistance pattern. Results: No significant increase in serious infectious complications was seen with the discontinuation of prophylaxis. The overall incidence of bacteraemia did not change, but a higher proportion of bacterial isolates were Gram-negative (22.2% vs. 5.9% & 8.6%; P = 0.030), more often multisusceptible (50% vs. 0%) and less fluoroquinolone resistant (10% vs. 100%). Screening of stools showed a higher prevalence of organisms in the discontinuation period (86.7% vs. 37.3% & 55.2%; P ≤ 0.001), but they were more frequently multisusceptible (53.8% vs. 10.5% & 6.3%; P ≤ 0.001). After discontinuation of prophylaxis, fluoroquinolone resistance decreased rapidly from 73.7 to 7.7%, in association with a significant decrease in extended spectrum beta-lactamase (ESBL)-producing isolates from 42.1 to 10.3%. Resistance figures immediately returned to prediscontinuation values after reinstitution of prophylaxis. Conclusions: No clinically relevant short-term drawbacks were observed with the discontinuation of fluoroquinolone prophylaxis in patients with chemotherapy-induced prolonged profound neutropenia, which led to a significant decrease in fluoroquinolone resistance as well as occurrence of ESBL-producing isolates.

INTRODUCTION: Treatment for acute myeloid leukemia (AML) presents a significant economic burden to patients, health care insurers and society, and is expected to remain so in the near future. There are few studies describing the costs of AML in the literature. However, the high cost of treating AML and the demographic evolution of the world population, indicate that such studies are needed to support ongoing efforts to allocate resources efficiently in health care. OBJECTIVE: To describe and compare the costs of AML therapies daily used at the Antwerp University Hospital in adult patients receiving chemotherapy with/without stem cell transplantation and in patients receiving immunotherapy using dendritic cell vaccination. DESIGN AND METHODS: This monocentric study compares direct hospital medical costs of treatment for AML between 2005 and 2010, allocated and charged according to the hospital analytic accounting system. Information on use of medical resources was collected from electronic medical records. Professional and facility charges associated with inpatient and outpatient management were collected using electronic billing information. Drug costs and drug administration costs were based on list prices published by the Belgian reimbursement authority (RIZIV/INAMI). The cost analysis distinguished between group 1, patients treated with induction and consolidation therapy alone; group 2, patients treated with induction and consolidation therapy plus allogeneic hematopoietic stem cell transplantation (HSCT) and group 3, patients treated with induction and consolidation therapy plus immunotherapy using dendritic cells engineered to express the Wilms’ tumor protein (Van Tendeloo et al. Proc Natl Acad Sci USA. 2010;107(31):13824-9). RESULTS AND DISCUSSION: 51 adult patients who were treated for newly diagnosed AML were included. Costs on medical and nursing care at the hematology ward, pharmaceutical prescriptions, transfer episodes to the intensive care ward, laboratory tests and medical imaging were analyzed. The cost of dendritic cell vaccine preparation was € 20 450 per patient. The median cost in group 1 (15 patients) was € 32,648 (range: € 4,759 - € 140,383). Only 1 patient in group 1 went into remission after induction therapy and received consolidation therapy. All patients in group 1 died within 5 year after diagnosis, 13 patients died within 1 year and 5 died within 1 month. The median cost in group 2 (26 patients) was € 184,554 (range: € 87,932 - € 449,155). The median post-consolidation treatment cost in group 2 was € 110,430 (range: € 31,364 - € 255,948). Five-year survival in group 2 was 19%. Seventeen patients in group 2 died within 1 year after HSCT. The median cost in group 3 (10 patients) was € 88,635 (range: € 23,392 - € 215,119). The median post-consolidation treatment cost in group 3 was € 40,748 (range: € 26,907- € 156,870). Five-year survival in group 3 was 30%. Four patients in group 3 died within 1 year after vaccination. CONCLUSION: This study comparing different post-consolidation therapies confirmes the high cost of treating AML and suggests that savings to the healthcare system could be achieved by sustaining complete remission status for longer periods. Dendritic cell vaccination is one of the new therapeutic options to attain a long remission status. Disclosures No relevant conflicts of interest to declare.