title: Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia.
abstract: 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 H2R 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.
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rydström
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hallner
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.|Department of Hematology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Aurelius
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Frida Ewald
authors.initials: FE
authors.lastname: Sander
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Bernson
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Roberta
authors.initials: R
authors.lastname: Kiffin
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Fredrik Bergh
authors.initials: FB
authors.lastname: Thoren
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden; anna.martner@gu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Martner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D006632:Histamine / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011970:Receptors, Histamine H2 / Q000096:biosynthesis; D012074:Remission Induction; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007376:Interleukin-2; D011970:Receptors, Histamine H2; D006632:Histamine