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Leuk Lymphoma. 2019 Nov;60(11):2771-2778. doi: 10.1080/10428194.2019.1599110. Epub 2019 Apr 17.

Anthracycline-based consolidation may determine outcome of post-consolidation immunotherapy in AML.

Author information

1
TIMM Laboratory, Sahlgrenska Cancer Center, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
3
Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.

Abstract

Consolidation chemotherapy in acute myeloid leukemia (AML) aims at eradicating residual leukemic cells and mostly comprises high-dose cytarabine with or without the addition of anthracyclines, including daunorubicin. Immunogenic cell death (ICD) may contribute to the efficacy of anthracyclines in solid cancer, but the impact of ICD in AML is only partly explored. We assessed aspects of ICD, as reflected by calreticulin expression, in primary human AML blasts and observed induction of surface calreticulin upon exposure to daunorubicin but not to cytarabine. We next assessed immune phenotypes in AML patients in complete remission (CR), following consolidation chemotherapy with or without anthracyclines. These patients subsequently received immunotherapy with histamine dihydrochloride (HDC) and IL-2. Patients who had received anthracyclines for consolidation showed enhanced frequencies of CD8+ TEM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.

KEYWORDS:

Acute myeloid leukemia; anthracycline; consolidation chemotherapy; cytarabine; cytotoxic T cells ; immunotherapy

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