PMID- 12616107 OWN - NLM STAT- MEDLINE DCOM- 20030926 LR - 20191106 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 26 IP - 2 DP - 2003 Mar-Apr TI - Adjuvant immunotherapy with tumor infiltrating lymphocytes and interleukin-2 in patients with resected stage III and IV melanoma. PG - 156-62 AB - Adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) and interleukin (IL)-2 is reasonably effective in the treatment of patients with advanced melanoma. However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (resected stages III and IV). In a preliminary study, 25 patients (aged 23-72 years) with stage III-IV melanoma who underwent resection of metachronous metastases were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10 IU/m ) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) evaluable patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) rates were 44% and 37%, respectively, at 2 years, and 52% and 45% at 3 years. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10 versus 86 x 10 IU/m, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. Analysis of tumor immunosuppression factors in lymphocytes inside the tumor (TCR zeta and epsilon chains, p56, FAS, and FAS-ligand) confirmed that the immunologic potential of TIL, depressed at the time of metastasectomy, was significantly restored after in vitro culture with IL-2. Adoptive immunotherapy with TIL and IL-2 could improve DFS and OS, although further work is required to determine its role in the treatment of patients with high-risk melanoma. FAU - Ridolfi, Laura AU - Ridolfi L AD - Istituto Oncologico Romagnola, Pierantoni Hospital, Forli, Italy. FAU - Ridolfi, Ruggero AU - Ridolfi R FAU - Riccobon, Angela AU - Riccobon A FAU - De Paola, Franca AU - De Paola F FAU - Petrini, Massimiliano AU - Petrini M FAU - Stefanelli, Monica AU - Stefanelli M FAU - Flamini, Emanuela AU - Flamini E FAU - Ravaioli, Alessandra AU - Ravaioli A FAU - Verdecchia, Giorgio Maria AU - Verdecchia GM FAU - Trevisan, Giusto AU - Trevisan G FAU - Amadori, Dino AU - Amadori D LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Adjuvants, Immunologic) RN - 0 (Interleukin-2) SB - IM MH - Adjuvants, Immunologic/administration & dosage MH - Adult MH - Aged MH - Biopsy, Needle MH - Combined Modality Therapy MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Infusions, Intravenous MH - Interleukin-2/*administration & dosage MH - Lymphocytes, Tumor-Infiltrating/*transplantation MH - Male MH - Melanoma/mortality/*pathology/surgery/*therapy MH - Middle Aged MH - Neoplasm Staging MH - Probability MH - Prognosis MH - Prospective Studies MH - Risk Assessment MH - Skin Neoplasms/mortality/*pathology/surgery/*therapy MH - Statistics, Nonparametric MH - Survival Analysis MH - Treatment Outcome EDAT- 2003/03/05 04:00 MHDA- 2003/09/27 05:00 CRDT- 2003/03/05 04:00 PHST- 2003/03/05 04:00 [pubmed] PHST- 2003/09/27 05:00 [medline] PHST- 2003/03/05 04:00 [entrez] AID - 10.1097/00002371-200303000-00008 [doi] PST - ppublish SO - J Immunother. 2003 Mar-Apr;26(2):156-62. doi: 10.1097/00002371-200303000-00008.