IPH2101 is an anti-killer inhibitory receptor (anti-KIR) mAb that can block KIRmediated inhibition of natural killer (NK)cells

Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment.

BACKGROUND.Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, which is explained by the disease itself and by host‐related factors. The objective of this study was to determine the prognostic role of comorbidities in this population.METHODS.For this single‐center, retrospective study, the authors analyzed the outcome of 133 patients aged ≥70 years who received induction chemotherapy for nonpromyelocytic AML between 1995 and 2004. Comorbidities were evaluated by using an adapted form of the Charlson comorbidity index (CCI).RESULTS.The median patient age was 73 years. The CCI score was 0 for 83 patients (68%), 1 for 16 patients (13%), and >1 for 23 patients (19%). The complete remission (CR) rate was 56%, and the median overall survival was 9 months. In multivariate analysis, 4 adverse prognostic factors for CR were identified: unfavorable karyotype, leukocytosis ≥30 g/L, CD34 expression on leukemic cells, and CCI >1. A score could be generated to allow the stratification of patients into low‐, intermediate‐, and high‐risk groups with CR rates of 87%, 63%, and 37%, respectively. The risk of early mortality and the probability of survival also were different in the 3 risk groups (P = .02 and P = .01, respectively).CONCLUSIONS.The results from this study indicated that associated comorbidities are independent factors that may influence achievement of CR in elderly patients with AML. Such a scoring system may be useful in the prognostic staging systems that are used to identify patients with AML who can benefit from induction chemotherapy. Cancer 2007. © 2007 American Cancer Society.

BackgroundThere is a need for standardization of treatment decisions in older patients with acute myeloid leukemia. The aim of the present study was to analyze the decisional value of poor risk factors in 416 elderly patients treated in the ALFA-9803 trial in order to derive a decisional index.