DETECTION OF RESIDUAL TUMOR-CELLS IN PATIENTS WITH MALIGNANT-MELANOMARESPONDING TO IMMUNOTHERAPY

Recently, a highly sensitive assay combining reverse transcription and polymerase chain reaction (PCR) to assess for melanoma cells in perip heral blood has been developed. Detection of tyrosinase mRNA, a tissue -specific enzyme in melanocytes and melanoma cells, indicates the pres ence of melanoma cells in peripheral blood. We examined blood samples and bone marrow aspirates from 28 patients with metastatic malignant m elanoma for presence of melanoma cells prior to and after therapy with interferon (IFN)-alpha and interleukin (IL)-2. Ten patients showed an titumor response to immunotherapy, including three complete (CR) and s even partial remissions (PR). Four patients (three PR, one stable dise ase) underwent subsequent resection of residual tumor lesions and had no clinical evidence of disease after surgery. Tyrosinase mRNA was det ected in blood and bone marrow samples from all patients with malignan t melanoma prior to and after immunotherapy, including those with no c linical evidence of disease (median disease-free survival 21 months, r ange 19-28 months). Tyrosinase transcripts were also detected in all p atients with amelanotic melanoma. In contrast, no tyrosinase mRNA was detectable in any of 30 healthy persons or in six patients with other malignancies. The presence of residual melanoma cells may be an import ant indicator of occurrence of delayed relapse.