A phase I/II trial of interleukin-15-stimulated natural killer cell infusion after haplo-identical stem cell transplantation for pediatric refractory solid tumors

Background aims. Preliminary data suggest that T-cell depleted haplo-identical stem cell transplantation (haplo-SCT) has a clinically beneficial allograft-versus-tumor effect associated with natural killer (NK) cell immune reconstitution. Methods. This phase I/II trial descriptively evaluates the feasibility of interleukin (IL)-15-stimulated NK cell infusion after haplo-SCT in pediatric patients with refractory solid tumors. Results. Six patients received an IL-15-stimulated NK cell infusion at 30 days after haplo-SCT. The mean number of infused NK cells per product was 11.3 x 10(6)/kg (range, 3-27 x 10(6)/kg). The T-cell count was <1 x 10(3)/kg in all patients (range, 0-0.75 x 10(3)/kg). No toxic effects related to IL-15-stimulated NK cell infusion were observed. Four of the six patients showed a clinical response (one achieved very good partial remission, two achieved partial remission and one had stable disease). One patient had progressive disease, and the response was not evaluated in the remaining patient. After a median follow-up period of 310 days, all patients had died: four of cancer relapse, one of cancer-associated thrombotic micro-angiopathy and one of acute graft-versus-host disease. Conclusions. The adoptive transfer of allogeneic IL-15-stimulated NK cells might be feasible and safe in heavily pretreated pediatric patients with refractory solid tumors, though the advanced stage of disease and toxic effects of haplo-SCT may limit the efficacy of NK cell infusion in this population.