Dendritic cell vaccination as post-remission treatment to prevent or delay relapse in acute myeloid leukemia.

Related Articles

Dendritic cell vaccination as post-remission treatment to prevent or delay relapse in acute myeloid leukemia.

Blood. 2017 Aug 22;:

Authors: Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN

Abstract
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%; P<0.0001). In patients ≤65 and >65 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 http://ift.tt/PmpYKN as #NCT00965224.

PMID: 28830889 [PubMed - as supplied by publisher]

http://ift.tt/2wItzhE