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Title
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Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
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Author
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Abstract
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| 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(+)T cells. Long-term OS was correlated with interferon-g 1 and tumor necrosis factor-alpha(+) 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 improvedOSrates, which are correlated with the induction of WT1-specific CD8(+) T-cell response. |
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Language
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English
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Source (journal)
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Blood / American Society of Hematology. - New York, N.Y.
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Publication
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New York, N.Y.
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2017
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ISSN
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0006-4971
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DOI
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10.1182/BLOOD-2017-04-780155
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Volume/pages
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130
:15
(2017)
, p. 1713-1721
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ISI
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000412820200009
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Pubmed ID
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28830889
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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