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Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia

Artikel i vetenskaplig tidskrift
Författare Anna Rydström
Alexander Hallner
Johan Aurelius
Frida Ewald Sander
Elin Bernson
Roberta Kiffin
Fredrik Bergh Thorén
Kristoffer Hellstrand
Anna Martner
Publicerad i Journal of Leukocyte Biology
Volym 102
Nummer/häfte 2
Sidor 467-474
ISSN 0741-5400
Publiceringsår 2017
Publicerad vid Sahlgrenska Cancer Center
Institutionen för kliniska vetenskaper
Sidor 467-474
Språk English
Länkar doi.org/10.1189/jlb.5VMA1116-455R
Ämnesord eosinophils, monocytes, dendritic cells, H2R, histamine dihydrochloride, remission maintenance, suppressor-cells, nadph oxidase, group-b, interleukin-2, cancer, monocyte, metaanalysis, expression, Cell Biology, Hematology, Immunology, a r, 1991, british journal of haematology, v77, p491
Ämneskategorier Cancer och onkologi

Sammanfattning

Relapse of leukemia in the postchemotherapy phase contributes to the poor prognosis and survival in patients with acute myeloid leukemia (AML). In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse. The dynamics of myeloid cell counts and expression of activation markers was assessed before and after cycles of immunotherapy and correlated with clinical outcome in terms of relapse risk and survival. During cycles, a pronounced increase in blood eosinophil counts was observed along with a reduction in monocyte and neutrophil counts. A strong reduction of blood monocyte counts during the first HDC/IL-2 treatment cycle predicted leukemia-free survival. The HDC component of the immunotherapy exerts agonist activity at histamine type 2 receptors (H2Rs) that are expressed by myeloid cells. It was observed that the density of H-2 R expression in blood monocytes increased during cycles of immunotherapy and that high monocyte H2R expression implied reduced relapse risk and improved overall survival. Several other activation markers, including HLA-DR, CD86, and CD40, were induced in monocytes and dendritic cells during immunotherapy but did not predict clinical outcome. In addition, expression of HLA-ABC increased in all myeloid populations during therapy. A low expression of HLA-ABC was associated with reduced relapse risk. These results suggest that aspects of myeloid cell biology may impact clinical benefit of relapse-preventive immunotherapy in AML.

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