Abstract 1627: Phenotypic and functional evaluation of peripheral blood cell subsets in children at the completion of induction therapy for acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounting for more than one quarter of the new cases of pediatric cancer each year. Despite significant improvements in cure rates, recurrent ALL causes 10% of childhood cancer deaths and the need for new treatment strategies has not diminished. Although ALL has long been viewed as a poor target for immune therapy, it has recently been reported that the peripheral blood absolute lymphocyte count (ALC) at completion of induction chemotherapy is prognostic for outcome. This finding suggests that the immune environment during therapy may play a role in protecting against disease progression. It is currently unknown, however, whether ALC is simply a marker of bone marrow recovery or whether particular immune cell subsets at this early time-point confer a beneficial effect. To address this question, we have initiated a flow-cytometric study of 20 peripheral blood leukocyte populations, obtained at Day 29 from children undergoing therapy for precursor B cell ALL. The goal of this study is to correlate the size and responsiveness of the cell subsets with ALC in order to identify potential immune-mediators of the high ALC-associated favorable outcome. To date we have evaluated 8 patients for T cells (5 subsets), B cells (6 subsets), NK cells (3 subsets), NKT cells (2 subsets), dendritic cells (2 subsets), monocytes, and granulocytes. In addition to this extensive phenotypic characterization, all Day 29 blood samples have been stimulated with a panel of Toll-like receptor (TLR) ligands to evaluate functional responsiveness. Although we have not yet identified a single lymphocyte population that significantly correlates with ALC, clear trends, most notably with myeloid dendritic cells, have emerged that suggest that ALC may be indicative of specific immune activity. TLR-induced cytokine production is currently being quantified to determine whether higher ALC correlates with a specific pattern of response. While a large-scale prospective study to validate prognostic significance of ALC in children with high-risk ALL is underway, to our knowledge our ongoing study is the first to investigate the specific leukocyte composition of Day 29 peripheral blood for significant links with ALC. The identification of the mechanism(s) underlying ALC-associated outcomes may reveal novel strategies for enhanced immune-mediated control of ALL after chemotherapy.

Citation Format: Nina Rolf, Amina Kariminia, Kinga K. Smolen, Caron Strahlendorf, Gregor S. Reid. Phenotypic and functional evaluation of peripheral blood cell subsets in children at the completion of induction therapy for acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1627. doi:10.1158/1538-7445.AM2015-1627