Prognostic factors in Sézary syndrome: a multivariate analysis of clinical, haematological and immunological features.

BACKGROUND: Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis. PATIENTS AND METHODS: A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. RESULTS: The median survival time was 31 months (range: 1 month-15.7+ years), and the five-year survival 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), Sézary cells (SC) (P < 0.001) and CD4+ cells (P < 0.001), presence of large circulating SC (P < 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P < 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P < 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045). CONCLUSIONS: Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index < or = 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic feature (risk index > 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).

Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma.

BACKGROUND: Response of cutaneous T-cell lymphoma (CTCL) to systemic chemotherapy is unsatisfactory: despite an initially high response rate (RR), duration is always short-lived. OBJECTIVE: To investigate the capability of a third-generation regimen including idarubicin in improving RR and response duration in CTCL patients. METHODS: Twenty-five patients with advanced CTCL (stages IIB and IV) were treated with a 12-week polychemotherapeutic regimen (VICOP-B), which foresees the use of idarubicin in association with etoposide, cyclophosphamide, vincristine, prednisone and bleomycin. RESULTS: The overall objective RR was 80% (36% complete response). The mycosis fungoides (MF) RR was 84%, with a median duration of 8.7 months. The pleomorphic-lymphoma RR was higher (100%), but the corresponding response duration was shorter (median: 3 months). No responses were documented in Sézary syndrome. CONCLUSION: VICOP-B regimen is effective and feasible as first-line chemotherapy in advanced MF, with or without extracutaneous involvement.

[Psychiatry and dermatologic neoplasms: results of an experimental study]. / Psichiatria e neoplasie dermatologiche: risultati di una ricerca sperimentale.

Psycho-oncology has developed during the past decades in the area of medical oncology directly involved in the study of the psychological aspects of cancer. In this study the authors focused in particular on the psychopathological complications of dermatological cancer, the discovery of a possible history of psychiatric disorders prior to the diagnosis of the tumour, the predictive value of the latter concerning further psychiatric complications during cancer, and lastly the possible correlations between stress and the onset of cancer and between religious belief and adaptive strategies. A total of 30 patients suffering from dermatological neoplasia were examined within the setting of a Psychiatric Liaison Service. HDRS and STAI X-1 and 2 were used as psychodiagnostic aids to evaluate the level of depression and anxiety, together with an interview for the clinical evaluation of the patient ad possible life events of particular importance. It was found that 10% of patients conformed to the criteria for the diagnosis of dysthymia and 10% for adaption disorders, and that there was also a high rate of pathological values for status anxiety (66%). These results show that this type of disease is particularly subject to risk for psychiatric complications.

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 recombinant interleukin-2 (rIL-2) i.v. may induce tumour regressions 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 overall 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, eosinophils, CD3+/CD4+, CD25+, CD16/56+ and HLA-DR+ cells was found 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.

Adjuvant therapy of stage IIIb melanoma with interferon alfa-2b: clinical and immunological relevance.

BACKGROUND: The poor prognosis of stage IIIb melanoma (5-year survival: 36%) shows the need for effective adjuvant therapy to prolong disease-free survival. OBJECTIVE: The feasibility and efficacy of interferon alfa-2b (IFN-alpha) therapy in stage IIIb melanoma patients was investigated. METHODS: alpha-IFN was given at a dose of 3 MU i.m. three times a week to 50 patients. Clinical and immunological controls were carried out. RESULTS: The median follow-up was 43 months (range 5-84). Median survival was 43 months and median disease-free survival 39 months. Overall 5-year survival (62%) was higher than that reported in the literature to date. A significant increase of circulating CD56+ and DR+ lymphocytes after therapy was more evident in disease-free patients than in those with progressing disease. CONCLUSIONS: Adjuvant IFN-alpha therapy in stage IIIb melanoma patients is well tolerated and seems to increase survival. However, multicenter randomized trials are needed to confirm these preliminary findings.

Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen.

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.

Thymopentin in Sézary syndrome.

BACKGROUND: Response to the treatment of Sézary syndrome (a cutaneous T-cell lymphoma) is poor. Since patients with this syndrome are elderly, aggressive chemotherapy is poorly tolerated and deep immunodepression may result in fatal opportunistic infections. Immunomodulating therapy seems important in the management of Sézary syndrome. PURPOSE: In a pilot study, we assessed the efficacy of thymopentin (TP-5), a synthetic pentapeptide, correlating clinical responses to the histologic and immunologic effects of the drug. METHODS: Twenty Sézary syndrome patients received 50 mg TP-5 intravenously three times a week for a mean time of 16.3 months. Skin and lymph node histology and immunohistochemistry, circulating lymphoid cell subpopulations, and soluble interleukin-2 receptors were evaluated before treatment and during follow-up. RESULTS: Eight complete remissions and seven partial remissions were obtained (75%). No change was observed in three patients, and disease progression was observed in two patients. The median duration of response was 22 months (complete remission, 25.5 months; partial remission, 14 months). Four-year survival probability was 53.9%. The responses were obtained when circulating Sézary cells were less than 2600/mm3. A significant reduction of CD4+ cells paralleled a CD8+ cell increase. An increase in NK cells (CD16+ and CD56+) was accompanied by significantly longer survival. Serum soluble interleukin-2 receptor values were a useful monitor of the clinical course and treatment. Loss of epidermotropism, reduction of Langherhans' cells, and HLA-DR+ keratinocytes were found. CONCLUSIONS: TP-5 is a potentially useful agent in the treatment of a subgroup of patients with Sézary syndrome; its activity seems to be mediated by an effect on a normal NK cell-like subpopulation. IMPLICATIONS: The biological and clinical role of this therapy in combination with conventional treatments will be the subject of future investigations.

BANS: a discussion of the problem.

The significance of the BANS location (upper Back, posterior Arm, Neck and Scalp) as a prognostic factor in patients with stage I melanoma is controversial. A meta-analysis performed by Weinstock et al. on their own and five comparable studies corroborated the hypothesis that this location is influential in the prognosis of intermediate thickness (0.76-1.69 mm) melanomas. Our study investigated the relationship between BANS subsites, thickness and prognosis in 1,082 stage I melanoma patients from two major Italian centres, Turin and Florence. A BANS primary was observed in 212 (19.5%) patients: recurrences occurred in 85 of them (40.1%) vs 309/870 non-BANS patients (35.5%). Overall survival probabilities were significantly shorter (p less than 0.01) in the BANS group (69.1% vs 76.7% at 5 years; 59% vs 68.5% at 10 years). The prognostic value of the BANS location was confirmed by a multivariate analysis using the Cox proportional hazards model. Stratification of BANS and non-BANS groups by thickness clusters showed a significant difference in both survival (p less than 0.001) and disease-free interval (p less than 0.05) in the 3.01-4.00 mm thickness subset, due to the greater incidence of distant and visceral metastases. In the 0.76-1.69 mm thickness range the significance was p = 0.06.

Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma.

A pilot study was undertaken to evaluate toxicity and activity of recombinant alpha-2b interferon in patients with metastatic malignant melanoma. Interferon was administered at the dosage of 10 x 10(6) IU/m2, 3 times a week i.m. 21 patients entered the study, 17 pretreated with chemotherapy and/or immunotherapy and 6 untreated. We obtained 3 partial responses (14.3%; 95% CL, 3.0-36.3%); 9 patients had stable disease. All patients experienced flue-like symptoms and fever; most fatigue and worsening of performance status. Recombinant interferon alpha-2b at the dosage and schedule used has limited but definite activity in metastatic malignant melanoma; the substantial subjective toxicity must be taken into consideration. Further trials testing recombinant alpha interferon in combination with chemotherapeutic agents, like DTIC, are warranted.

Immunomodulation and Sézary syndrome: experience with thymopentin (TP-5).

The clinical, histological and immunological effects of long-term treatment with thymopentin (TP-5), administered 50 mg i.v. three times a week on alternate days, in four patients with Sézary syndrome is reported. In all four cases reduction of itching, oedema, scaling and thickening, and clearing of erythroderma were noted after 2 months treatment. Peripheral blood Sézary cells decreased in three cases. Reduction or suspension of the drug was followed by a clinical relapse. A loss of epidermotropism and a reduction in cell infiltrates were observed together with a dramatic reduction in epidermal and dermal Langerhans cells. An increase in the proliferative response to mitogens and in IFN-gamma production, and the expression of activation antigens in PHA stimulated cultures occurred after 3 months. HNK-I+ cells increased both in the peripheral blood and in the dermis following a transient increase in IL-2 receptors, suggesting that clinical response in TP-5 treated patients may be mediated by an increased production of IL-2 and consequent generation of cytotoxic cells or release of lymphokines able to augment NK activity.

Changes in T and B lymphocyte subpopulations before, during and after chemotherapy for malignant melanoma.

The behaviour of T and B lymphocyte subpopulations before, during and after chemotherapy with DTIC or CCNU was studied in 87 melanoma patients. The effect on immune status of DTIC administered as adjuvant therapy was also reported. The immunosuppressive effect was found to be higher in patients with normal pretreatment T-cell values than in patients with low pretreatment values, and it was higher in metastatic than in nonmetastatic patients. Where T and B lymphocyte subpopulations were assessed in 10 metastatic patients after each course of chemotherapy, a progressive reduction of T-lymphocytes was observed, indicating a cumulative effect of the drugs with advancing course. The reduction of T lymphocytes was mainly due to the decrease of OKT4+ cells. A normalization of T lymphocyte subpopulations was observed after the suspension of therapy. No significant decrease in the number of B cells was observed in the DTIC treated metastatic patients, whereas a significative reduction in the absolute number was found in those treated with CCNU.