INTERLEUKIN-2 IN NEUROBLASTOMA - CLINICAL PERSPECTIVES BASED ON BIOLOGICAL STUDIES

Stage IV neuroblastoma (NB) is a disease with a poor prognosis. Chemot herapeutical intensification and hematological rescue with autologous bone marrow transplantation (ABMT) achieve some complete remissions (C R), but most patients relapse during the first year. Immunotherapy cou ld be an alternative in this situation of high risk of relapse due to residual disease and ABMT-related immunodepression. Ten stage IV NB pa tients in CR or very good partial remission have been treated with rec urrent 5-day, cycles of high doses of Interleukin-2 (IL2) after ABMT t hroughout one year (usually 5-6 cycles). Natural killer (NK) and lymph okine-activated killer (LAK) cytotoxic activities, as well as phenotyp e and number of circulating NK cells were determined before and after each course of IL2 treatment. The effects promoted by IL2 varied durin g treatment: early cycles IL2 induced a great extent of cell expansion , mainly on CD3(-) /CD16(-)/CD56(+bright) and CD8(+dim) cell phenotype s; conversely late courses of IL2 promoted higher NK cytotoxic activit y bur a lesser increase on circulating NK cells. The indiction of LAK activity did not significantly differ from early and late IL2 treatmen ts. Clinical results are still inconclusive due to the small number of patients. The median follow-up of patients treated with IL2 is 24 mon ths and the disease free survival (DFS) probability is 0.80 +/- 0.12 v s 0.16 +/- 0.15 from a historical control with identical treatment, bu t in the absence of IL2 treatment (p<0.005). IL2 treatment-related tox icity was mild and Mo interruption of the treatment was required. Extr emely accurate hydric control was carried out to avoid, as much as pos sible, the consequences of vascular leak syndrome, one of the most imp ortant toxic effects of IL2 treatment. The results presented here sugg est an evolution of NK activity during IL2 treatment after ABMT, which should be taken into account for the designing of new immunotherapeut ical protocols and opens a promising perspective in treatment of stage IV neuroblastoma.