Natural Killer Cell-Enriched Donor Lymphocyte Infusions from A 3-6/6 HLA Matched Family Member following Nonmyeloablative Allogeneic Stem Cell Transplantation

NK cell function was measured by their capacity to lyse K562 target cells, which is dependent upon the content of CD56⁺ effector cells within a sample. Improved NK cell ability to lyse the target cells is denoted by a steeper line as effector-to-target cell ratios increase. Typical results following T cell-depleted nonmyeloablative therapy are noted here. At 2 months following transplant in this patient there were still not enough lymphocytes to quantify a meaningful response (indicated with a stippled line). There was marginal recovery at approximately 4 months (black squares) and still only modest recovery at 6 months (shown with black triangles). Error bars represent the standard deviation derived from triplicate samples.

Impact of NK cell-enriched DLI. (A) NK cell function was measured at 6 to 8 weeks posttransplant, immediately prior to receiving NK infusions. At that time, NK cell function had returned fully in only a few patients (Full), whereas 2 additional patients demonstrated at least some NK cell function (Mid). However, the majority of patients demonstrated low NK cell function (Low) or did not recover sufficient lymphocytes to assay NK function (No, indicated with a stippled line). (B) The total recovery of lymphocytes to the peripheral blood was examined within each patient group. At 6 to 8 weeks posttransplant, lymphocyte recovery was only consistently strong among patients that recovered full NK cell function (Full). (C) The impact of NK cell donor lymphocyte infusion (DLI) was monitored in patients that had not previously responded (“Low” or “No” NK cell function patients in panel A). Of those patients, 4 responded within 6 to 8 weeks after a single NK cell DLI. (D) In 1 patient, NK cell function returned gradually following a second and third DLI. In all panels, the error bars represent the standard deviation derived from triplicate samples. ^∗The “0” measure for percent lysis refers to patients with functional ability below the level of detection in this assay because of either poor function and/or too few cells recovered to have been measured with this assay.