Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Research output: Contribution to journalArticle

Abstract

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 CD81 T cells. Long-term OS was correlated with interferon-g1 and tumor necrosis factor-a1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD81 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 CD81 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

Details

Authors
  • Sébastien Anguille
  • Ann L. Van De Velde
  • Evelien L. Smits
  • Viggo F. Van Tendeloo
  • Nathalie Cools
  • Griet Nijs
  • Barbara Stein
  • Eva Lion
  • Ann Van Driessche
  • Irma Vandenbosch
  • Anke Verlinden
  • Alain P. Gadisseur
  • Wilfried A. Schroyens
  • Ludo Muylle
  • Katrien Vermeulen
  • Marie Berthe Maes
  • Kathleen Deiteren
  • Ronald Malfait
  • Emma Gostick
  • Martin Lammens
  • Marie M. Couttenye
  • Philippe Jorens
  • Herman Goossens
  • David A. Price
  • Kristin Ladell
  • Yoshihiro Oka
  • Fumihiro Fujiki
  • Yusuke Oji
  • Haruo Sugiyama
  • Zwi N. Berneman
Organisations
External organisations
  • Antwerp University Hospital
  • University of Antwerp
  • Skåne University Hospital
  • Cardiff University
  • Osaka University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)1713-1721
Number of pages9
JournalBlood
Volume130
Issue number15
Publication statusPublished - 2017 Oct 12
Publication categoryResearch
Peer-reviewedYes