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

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 400 000/IU/m(2)/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 (800 000-1 000 000 IU/m(2)/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.