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Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.


ABSTRACT: Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8+ (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distribution of cytotoxic T cells was observed comprising a reduction of T effector memory cells and a concomitant increase of T effector cells. The dynamics of T cell subtypes during immunotherapy prognosticated relapse and survival, in particular among older patients and remained significantly predictive of clinical outcome after correction for potential confounders. Presence of CD8+ T cells with specificity for leukemia-associated antigens identified patients with low relapse risk. Our results point to novel aspects of T cell-mediated immunosurveillance in AML and provide conceivable biomarkers in relapse-preventive immunotherapy.

SUBMITTER: Sander FE 

PROVIDER: S-EPMC4884940 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.

Sander Frida Ewald FE   Rydström Anna A   Bernson Elin E   Kiffin Roberta R   Riise Rebecca R   Aurelius Johan J   Anderson Harald H   Brune Mats M   Foà Robin R   Hellstrand Kristoffer K   Thorén Fredrik B FB   Martner Anna A  

Oncotarget 20160201 7


Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8+ (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distributio  ...[more]

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