6 research outputs found
Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival.
In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs)
electroporated with Wilms’ tumor 1 (WT1) mRNA as post-remission treatment in 30 AML
patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13
patients. Nine patients achieved molecular remission as demonstrated by normalization
of WT1 transcript levels, 5 of which are 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 non-responders (53.8% vs. 25.0%; P=0.01). In patients
receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse
reduction rate of 25% and the 5-year relapse-free survival was higher in responders than in
non-responders (50% vs. 7.7%; P65 years who received DCs
in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared to 51.7% and 18% in
the Swedish Acute Leukemia Registry (SALR). Long-term clinical response was correlated
with increased circulating frequencies of poly-epitope WT1-specific CD8+ T-cells. Long-term
OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed type hypersensitivity-infiltrating CD8+ T-lymphocytes. In conclusion, vaccination of
AML patients 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+ T-cell response. This trial was registered
at www.clinicaltrials.gov as #NCT00965224
Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data
Background Uptake of self-testing and self-management of oral coagulation has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. Methods We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. Findings Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12 800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0.51; 95% CI 0.31-0.85) but not for major haemorrhagic events (0.88, 0.74-1.06) or death (0.82, 0.62-1.09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0.33, 95% CI 0.17-0.66), as did participants with mechanical heart valve (0.52, 0.35-0.77). Analysis of major outcomes in the very elderly (age >= 85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. Interpretation Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-u