title: Low-dose subcutaneous interleukin-2 in patients with minimal residual lymphoid neoplasm disease.
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 6x10(-3) Lytic Units (LU)/ml to 80x10(-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<0.0001). Disease-free survival was determined in 14 patients who completed the treatment and compared with historical controls. Patients treated with IL-2 had the same relapse risk (median time to relapse 11.1 months, 95% confidence interval 5.5-16.6) as did controls (median time to relapse 9.7 months, 95% confidence interval 1-27.7) (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.
authors.affiliation: Department of Hematology, Institut Catalá d'Oncología, Hospital Duran i Reynals, Ciutat Sanitaria i Universitària de Bellvitge, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: González-Barca
authors.forename: A
authors.initials: A
authors.lastname: Grañena
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Sevilla
authors.forename: V
authors.initials: V
authors.lastname: Moreno
authors.forename: A
authors.initials: A
authors.lastname: Salar
authors.forename: F
authors.initials: F
authors.lastname: Rueda
authors.forename: J
authors.initials: J
authors.lastname: García
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000097:blood; D013997:Time Factors
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2