After Treatment Decrease of Bone Marrow Tregs and Outcome in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia

Abstract

An emerging body of evidence demonstrates that defects in antileukemic effector cells in patients with acute myeloid leukemia (AML) can contribute to the development and/or persistence of the disease. In particular, immune suppressive regulatory T cells (Tregs) may contribute to this defective antileukemic immune response, being recruited by bone marrow leukemic cells to evade immune surveillance. We evaluated Tregs (CD4+/CD45RA-/CD25high/CD127low), performing multiparametric flow cytometry on freshly collected bone marrow aspirate (BMA), in addition to the usual molecular and cytogenetic work-up in newly diagnosed AML patients to look for any correlation between Tregs and the overall response rate (ORR). We studied 39 AML younger patients (<65 years), all treated with standard induction chemotherapy. ORR (complete remission (CR)+CR with incomplete hematologic recovery (CRi)) was documented in 21 out of 39 patients (54%); two partial responder patients were also recorded. Apart from the expected impact of the molecular-cytogenetic group (p=0.03) and the NPM mutation (p=0.05), diagnostic BMA Tregs did not show any correlation with ORR. However, although BMA Tregs did not differ in the study population after treatment, their counts significantly decreased in responder patients (p=0.039), while no difference was documented in nonresponder ones. This suggested that the removal of Treg cells is able to evoke and enhance anti-AML immune response. However, the role of BMA Tregs in mediating immune system-AML interactions in the diagnostic and posttreatment phase should be confirmed in a greater number of patients.