Low‐dose subcutaneous interleukin‐2 in patients with minimal residual lymphoid neoplasm disease

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Abstract
Interleukin‐2 (IL‐2) is a cytokine that became available for clinical use with the development of recombinant DNA technology. Patients with resistant or relapsed lymphoid neoplasm have been treated with high‐dose IL‐2 with some responses. The aim of the present study is to determine whether there may be a biological justification for the use of low dose subcutaneous (s.c.) IL‐2 as maintenance therapy in patients with lymphoid neoplasm in complete remission with high risk of relapse. We treated 15 patients with sc IL‐2, 4.5 Million International Units (MIU) daily, 5 days per week for 12 consecutive weeks, in the outpatient clinic. This therapy was well tolerated and could be administered in an outpatient regimen. It increased the eosinophil count (p = 0.009), but the number of granulocytes, monocytes, T‐lymphocytes and B‐lymphocytes did not change. The number of natural killer (NK) cells increased from 11% to 35% of all lymphocytes during IL‐2 therapy (p = 0.0006). Effector lymphokine‐activated killer activity (eLAK) also increased from 6 × 10‐3 Lytic Units (LU)/ml to 80 × 10‐3 LU/ml (p = 0.02). All these changes reached a “plateau” after the 4th week of therapy. The increase in the number of NK cells correlated strongly with the increase in eLAK activity (r = 0.96, p p = 0.9). Low dose s.c. IL‐2 stimulated NK proliferation, which generated cytotoxic activity in vivo in patients with lymphoid neoplasms. However, these patients did not have a lower risk of disease relapse compared to historical controls.

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