IMMUNOLOGICAL AND CLINICAL MODIFICATIONS FOLLOWING LOW-DOSE SUBCUTANEOUS ADMINISTRATION OF RIL-2 IN NON-HODGKINS-LYMPHOMA PATIENTS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION

In order to induce a therapeutic immunomodulatory activity, 11 patient s with high-grade non-Hodgkin's lymphoma (HG-NHL) at a median of 42 da ys after autologous bone marrow transplantation (ABMT) received recomb inant interleukin-2 (rIL-2) subcutaneously at a dose of 2 internationa l megaunits (IMU)/m(2) every other day for 2 weeks and then 3 IMU/m(2) twice a week for 1 year. Immunological studies, including T and natur al killer (NK) cell subset assessment, together with functional assay, such as NK and CD16-mediated cytotoxic activities, were performed bef ore therapy, after 2 weeks and then monthly. Phenotypic analyses showe d a significant and persistant (P = 0.001) increase in the proportion and absolute number of total lymphocytes and, particularly of both CD1 6 and CD56 NK cells, from pre-treatment values of 14 and 18% to 30 and 38% respectively, recorded after 6 months of therapy. No changes were observed in CD25 (p55)-positive cells, while a significant increase f rom 13 to 33% (after 6 months) was observed in CD122-positive cells. F urthermore, rIL-2 administration led to an enhancement of NK activity even at the lowest effector:target ratio and of CD16-mediated cytotoxi c activity. Clinical tolerance was acceptable with moderate fever and fluid retention observed only at the onset of rIL-2 treatment. None of the patients have progressed with a median follow-up of 22 months (ra nge 10-42 months) after starting therapy. In addition, two patients wi th a residual disease after ABMT, one in the liver and the second in t he lymph nodes, obtained a complete response after 10 and 7 months of rIL-2 therapy, respectively. These preliminary data suggest that the i nfusion of low-dose rIL-2 s.c. after ABMT is safe and well tolerated a nd can selectively increase the NK cell number and function. Additiona l patients are needed in order to assess the impact of these immunolog ical changes on relapse-free survival after ABMT for HG-NHL.