Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients

The biological mechanisms of chemoimmunotherapy efficacy in vivo have not been fully clarified; furthermore, few data are available to predict its efficacy on the basis of clinical and immunological pretreatment factors. In this paper, pre- and post-treatment serum levels of cytokines (interleukin [IL]-6, IL-10, IL-12 and neopterin) and soluble IL-2 receptors (sIL-2R), as well as circulating levels of T-cell and NK subpopulations, were analysed according to clinical outcome in 66 advanced metastatic melanona (MM) patients treated with subcutaneous IL-2 in association with interferon-alpha, cisplatin and tomoxifen. Our purpose was to correlate the immune modifications during treatment with the clinical response and to define pretreatment factors with predictive value for clinical outcome. The overall response rate was 35%, with a median overall survival of 11.3 months. During treatment, responding patients showed a commom marked increase in IL-12 (mainly released by activated macrophages), sIL-2R and enopterin serum levels, associated with high levels of total lymphocytes and circulating natural killer lymphocytes; progressing patients were characterized by an increase in tumor burden). Multivariate analysis showed that high pretreatment IL-12 levels (P=0.05) and, to a lesser extent, lactate dehydrogenase levels in the normal range (<450U/I; P=0.061) are independent favourable prognostic factors for survival. Our results show that macrophage activation in an immunostimulating way either before or during treatment is associated with a better clinical response and improved survival in advanced MM patients treated with IL-2-based chemoimmunotherapy

Mycosis fungoides in patients under 20 years of age: report of 7 cases, review of the literature and study of the clinical course

Background: Mycosis fungoides (MF) is rare in young patients. Its clinical behavior is stil uncertain, as some reports have suggested that is has a more aggressive course than does the adult-onset type. Aim: To ascertain if early-onset MF represents a heterogeneous group of cutaneous T cell lymphomas. Materials and Methods: Clinical, immunohistopathological and follow-up data of early-onset (<20 years of age) MF cases reported in the literature (n = 42) plus 7 described herein were compared with those of a cohort of adult-onset MF patients (n = 252) diagnosed at our institution since 1975. Results: The majority of the 49 early-onset MF patients had patch-plaque stage disease at diagnosis. Ten had hypopigmented lesions. The predominant phenotype was CD3+CD4+CD7-CD8-. Seven patients had a stage progression, 6 with extracutaneous involvement. Five- and 10-year survical rates 93 and 74% respectively. Conclusions: No statistically significant differences were found in the disease course between early-and adult-onset MF

Multiple primary melanomas: analysis of 49 cases

Development of multiple primary melanomas is a rare but well recognized disease, with an estimated incidence ranging from, 1.75% to 8.5% in several series. The clinical, histological and epidemiological charactristics of 49 patients, identified from 2470 with histologically confirmed melanoma, are described in this study. Thirty-five of these patients had two primary melanomas, 11 had three melanomas and three had four, five and six melanomas, respectivelly. Diagnosis was concurrent in 22 patients (45%(; in the remaining ceses the median time interval between the first ans second melanoma was 22.6 months and the longest interval was 21.5 years. The mean Breslow's thickness decreased significantly (P<0.001) from the first melanoma to the second and third lesion. The mulpiple melanoma patients had a higher percentage of subjects over 70 years of age or with lentigo maligna melanoma than single melanona patients. The mean follow-up time was 12 years (range 4-23 years) The 5-year survival rate from first melanoma excison (83%) does not differ from that of patients with a single melanoma. In conclusion, the presence of multiple primary melanomas does not appear to be a negative prognostic factor; our data show the importance of close follow-up in melanoma patients in order to detect not only metastases, but also subsequent primaries in their earliest phases

Prognostic factors in Sezari syndrome: a multivariate analysis of clinical haematological and immunological features

Background: Sezary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to asses by multivariate analysis the predictive value with respect to survical of series of clinical, haematological ans immunological parameters taken at SS diagnosis. Patients and methods: A cohort of 62 SS patientsdiagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. Results: The median survical time was 31 months (range: 1 month-15.7+ years), and the five-year survical rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sezary cells (SC) (P 1; n = 20) are characterized by an aggressive disase course not modifiable by traditional therapies (five-year survical: 5%

Low-dose integrated chemoimmuno-hormonotherapy with cisplatin, subcutaneous interleukin-2, alpha-interferon and tamoxifen for advanced metastatic melanoma - a pilot study

Recently, Khayat et al. reported that high-dose recombinent interleukin-2 (rIL-2) i.v. may induce tumour regression in metastatic melanoma patients through an association with cisplatin (CDDP) and alpha-interferon (alpha-IFN). Treatment-related toxicities are, however, important. Previous studies have demonstrated that rIL-2 toxicity may be reduced through a subcutaneous injection. In order to evaluate the effectiveness of low subcutaneous rIL-2 doses in a chemoimmuno-hormonotherapeutic combination, 36 metastatic melanoma patients were treated with CDDP, rIL-2, alpha-IFN and tamoxifen (TAM). The overall response rate was 47.2% five patients had complete response (14%), 12 partial response (33%) and 13 stable disease (36%). Median response duration was 6.4 months (range: 2-29+). Median overal survival was 10 months (range: 3-36+). The CDDP/rIL-2/alpha-IFN/TAM regimen was effective both on soft tissue and visceral metastases. Toxicity was low and patient management did not require an intensive care unit. A statistically significant increase in both percentage and absolute values of lymphocytes, eosinophilis, CD3+/CD4+, CD5+, CD16/56 + and HLA-DR+ cells wasfound in all patients after two treatment courses. This study shows that lower doses of subcutaneous rIL-2, as well as CDDP and alpha-IFN, associated with TAM, may have similar anticancer efficacy with respect to Khayat's schedule but lower toxicity

Adhesion molecules in lymphomatoid granulomatosis

The expression of some adhesion molecules of the integrin family and their ligands was investigated in skin biopsies from a patient with lymphomatoid granulomatosis (GL), who at onset presented cutaneous lesions followed by lung and brain involvement. The angiocentric and angioestructive skin infiltrate consisted mainly of T helper 'memory' cells (CD2+, CD3+, CD4+, CD5+, Cd7+, CD45RO+) with a variable expression of activation antigens (CD25-, CD38+, CD71+, HLA-DR+) and 20% Ki67 + (nearly all atypical cells). T cells highly expressed alpha3beta1 and alpha5B1 integrins, along with integrins of the beta2 family. A modification of the expression pattern in laminin and collagen IV and an increased expression of tenascin and fibronectin were also observed