title: Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia.
abstract: T-cell-targeting immunotherapy is now considered in acute myelogenous leukemia (AML). Immunotherapy seems most effective for patients with a low AML cell burden, and a possible strategy is therefore to administer immunotherapy early after intensive chemotherapy when patients have a low leukemia cell burden and severe treatment-induced cytopenia. To further investigate this possible therapeutic approach we used a whole blood assay to characterize the proliferative responsiveness (3H-thymidine incorporation) of circulating T cells from AML patients with severe treatment-induced leukopenia, i.e., peripheral blood leukocyte counts < 0.5x10(9)/l. This assay will reflect both quantitative and qualitative differences. Responses were compared for 17 AML patients, 6 patients with acute lymphoblastic leukemia (ALL), and a group of 21 healthy controls. Most circulating leukocytes in the AML patients were T lymphocytes, whereas B lymphocytes and monocytes usually constituted < 10%. Anti-CD3-stimulated proliferation was significantly lower for AML patients compared with healthy controls. However, proliferation in response to anti-CD3 + anti-CD28 did not differ for AML patients and healthy controls, an observation suggesting that T cells from AML patients have an increased responsiveness in the presence of optimal costimulation that compensates for the quantitative T-cell defect. In contrast, the responses were significantly lower for ALL than for AML patients. We conclude that the remaining T-cell population in AML patients with severe chemotherapy-induced cytopenia show an increased proliferative responsiveness and may represent a therapeutic target when antileukemic immunotherapy is tried in combination with intensive chemotherapy.
authors.affiliation: Division for Infectious Diseases, Department of Medicine, Haukeland University Hospital, University of Bergen, Norway. oystein.wendelbo@helse-bergen.no
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Wendelbo
authors.forename: Ingerid
authors.initials: I
authors.lastname: Nesthus
authors.forename: Malvin
authors.initials: M
authors.lastname: Sjo
authors.forename: Kristin
authors.initials: K
authors.lastname: Paulsen
authors.forename: Peter
authors.initials: P
authors.lastname: Ernst
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology*; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D013936:Thymidine