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

Journal article
Authors Johan Aurelius
Lars Möllgård
Roberta Kiffin
Frida Ewald Sander
Staffan Nilsson
Fredrik Bergh Thorén
Kristoffer Hellstrand
Anna Martner
Published in Leukemia & Lymphoma
ISSN 1042-8194
Publication year 2019
Published at Department of Mathematical Sciences
Sahlgrenska Cancer Center
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Biomedicine, Department of Infectious Medicine
Language en
Links dx.doi.org/10.1080/10428194.2019.15...
Keywords Acute myeloid leukemia, consolidation chemotherapy, anthracycline, cytarabine, immunotherapy, acute myeloid-leukemia, high-dose cytarabine, calreticulin exposure, remission maintenance, cell transplantation, adult patients, chemotherapy, therapy, histamine, relapse, Oncology, Hematology
Subject categories Infectious Medicine

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(+) T-EM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.

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Utskriftsdatum: 2019-11-12