Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study

Abstract

Use of IL-2 therapy after autologous transplantation is currently being explored to reduce relapse rate. Low doses of the cytokine induce significant immunomodulation avoiding the severe side-effects associated with high-dose IL-2 therapy. However, low-dose IL-2 is usually given by continuous infusion through central venous lines with the consequent risks of thrombosis and infections. Twenty-six consecutive patients who received autologous transplants received low-dose IL-2 after stable engraftment had been achieved. The first 13 patients (group A) were scheduled to receive 400000/IU/m²/day for 3 months by continuous intravenous infusion. Ten of these patients suffered infectious episodes, mainly bacteriemias that often necessitated delaying IL-2 therapy (median delivered dose: 32% of planned). The next 13 patients were then assigned to receive IL-2 (800000–1000000 IU/m²/day for 3 months) subcutaneously (group B). For group B patients, median dose intensity was 84% (P = 0.01 when compared with group A patients). Only one severe infectious episode was observed in these patients. Clinical toxicity in group B patients consisted mainly of s.c. nodules. Immunomodulation, measured as an increase in the absolute number of CD56⁺ cells and CD56^+bright cells, was higher in patients who received the cytokine by the subcutaneous route (median peak increase of CD56⁺ cells: 160 and 220% for group A and B patients respectively; median peak increase of CD56^+bright cells: 210% and 310% for group A and B respectively, P < 0.05 between groups a and b). no statistically significant increment of t lymphocytes was observed in any group. no hematologic toxicity was observed apart from eosinophilia, which was very marked in group b (P < 0.01). our results show that low-dose s.c. il-2 therapy is associated with low clinical and hematologic toxicity after autologous transplantation. the immunomodulation achieved is no less than that achieved with the i.v. approach.