DECREASING CD4 CD8 RATIO DURING PROLONGED 4-DRUG CHEMOTHERAPY PLUS INTERFERON TREATMENT FOR METASTATIC MELANOMA/

A chemotherapy regimen consisting of dacarbazine, vincristine, bleomyc in and lomustine in combination with natural leukocyte interferon (IFN )-alpha was administered to 48 metastatic melanoma patients with very favorable results. The frequencies of peripheral blood lymphocyte subs ets during this treatment were monitored by flow cytometry in order to elucidate the underlying antitumor mechanism. Analysis of 467 periphe ral blood samples revealed a significant decrease during treatment in absolute values of all lymphocyte subsets (CD4, CD8, CD56) as well as in total lymphocyte count. All the values returned to normal after dis continuation of treatment. Significant alterations in proportions of l ymphocyte subsets were detected. Notably, the CD4(+)/CD8(+) ratio show ed changes related to response, treatment duration, and disease progre ssion. Exceptionally high CD4(+)/CD8(+) ratios (up to 14) were observe d soon after the start of treatment in some of the patients later achi eving a complete response. During the course of treatment, in 76% of t he patients receiving at least a 2-month treatment, the CD4(+)/CD8(+) ratio decreased to less than 1.0. Peculiarly, the nadir CD4(+)/CD8(+) ratio was consistently observed 1-6 months before clinically detectabl e disease progression, suggesting a relation between CD4(+)/CD8(+) rat io and tumor control.