Lower levels of cyclosporine between days 0 and +21 may reduce later relapses without increasing graft-versus-host disease in children and adolescents with acute lymphoblastic leukemia who undergo myeloablative TBI-based allogeneic hematopoietic cell transplantation.

Abstract

The degree of immunosuppression required for adequate graft-versus-host disease (GVHD) prevention, while keeping an adequate graft-versus-leukemia effect, in children with acute leukemia has not been established. We report the results of a retrospective comparison of cyclosporine levels and relapse rate in children and adolescents with acute lymphoblastic leukemia (ALL). Patients <21 y/o with ALL in remission who underwent TBI-based hematopoietic cell transplantation from related or unrelated donors between 2008 and 2021 were included. Cyclosporine levels were measured twice a week and we calculated the area under the curve (AUC) from D0 to D + 7, D + 14, and D + 21. We included 76 patients. There was a trend towards a lower incidence of relapse in patients with a mean AUC < 200 ng/ml at D + 21 (HR=0.41; p=.08). The 5-year relapse rate was 26.9% for patients with a mean AUC < 200 ng/ml at D + 21 and 43.9% for patients with a mean AUC≥200 ng/ml at D + 21. Relapse protection was restricted to relapses happening after D + 120 (HR=0.21; p=.04). Our results show evidence that pediatric patients with ALL might benefit from lower cyclosporine levels between D0 and D + 21 without a detectable increase in GVHD. Large prospective studies comparing different cyclosporine levels are awaited.