Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma

Maurizio Vaglini, Filiberto Belli, Mario Santinami, Flavio Arienti, Giorgio Parmiani, Laura Persiani, Nicola Santoro, Maria Grazia Inglese, Fortunato D'Elia, Natale Cascinelli

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Abstract

Background: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. Methods: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9-12 × 106 IU/M2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8-28 × 109) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9-12×106 IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. Results: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Conclusions: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalAnnals of Surgical Oncology
Volume2
Issue number1
DOIs
Publication statusPublished - Jan 1995

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Keywords

  • Immunotherapy
  • Interleukin-2
  • Isolation perfusion
  • Lymphokine-activated killer cells
  • Melanoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

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