title: Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study.
abstract: 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/m2/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/m2/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.
authors.affiliation: Department of Haematology, Universidad de Alcala de Henares, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: López-Jiménez
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Oteyza
authors.forename: A
authors.initials: A
authors.lastname: Munoz
authors.forename: C
authors.initials: C
authors.lastname: Parra
authors.forename: L
authors.initials: L
authors.lastname: Villalón
authors.forename: P
authors.initials: P
authors.lastname: Ramos
authors.forename: M
authors.initials: M
authors.lastname: Maldonado
authors.forename: J
authors.initials: J
authors.lastname: García-Laraña
authors.forename: E
authors.initials: E
authors.lastname: Otheo
authors.forename: E
authors.initials: E
authors.lastname: Roldán
authors.forename: A
authors.initials: A
authors.lastname: García-Avello
authors.forename: J
authors.initials: J
authors.lastname: Odriozola
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D002405:Catheterization, Central Venous; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007239:Infections / Q000209:etiology; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D009369:Neoplasms / Q000628:therapy; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha