3 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