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The in vitro effect of a calf thymus extract (TP-1) on peripheral blood lymphocytes was evaluated in sixty-six melanoma patients. Twenty out of forty-five statue I and seventeen out of twenty-one stage IIb patients presented depressed T lymphocyte values. A statistically significant increase in E-rosette-forming cells (E-RFC) was observed in seventeen (85%) stage I and twelve (70.5%) stage II patients. In thirteen (65%) stage I and eight (47%) stage II patients E-RFC reached normal values. Our results indicate that the fall of T lymphocytes in the peripheral blood of melanoma patients is often related to an increase in TP-1 sensitive cells which suggests the possibility of a thymic hormone deficiency in these patients. [ABSTRACT FROM AUTHOR]

A dominant T-cell clone can be detected by polymerase chain reaction (PCR) in 40–90% of cutaneous samples from patients with cutaneous T-cell lymphoma (CTCL). From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sézary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64·5%) and CTCL in 194 (35·5%). T-cell receptor (TCR)-γ gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T-cell lineage antigen loss, using univariate and multivariate logistic regression analyses. To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T-cell clonality. A clonality was demonstrated in 83·5% of CTCL and in 2·3% of BID ( P < 0·001). A significantly higher percentage of clonal cases was associated with the cutaneous T-score (71·4% in T1, 76·1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T-cell lineage antigen loss (93·9% vs. 77·4%). Moreover, clonality was closely related to an increase in the histopathological score (51·3% in the samples with a score < 5, compared with 92% in the lesions with ≥ 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score ≥ 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3·6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR-negative patients showed a long-standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13·8%) positive patients. The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92·7%) in CTCL patients. The finding of a clonal T-cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T-score or immunophenotype. [ABSTRACT FROM AUTHOR]

Purine analogues [fludarabine monophosphate (FAMP); deoxycoformycin and 2-chlorodeoxyadenosine) and extracorporeal photochemotherapy (ECP) have been suggested to be active agents in advanced cutaneous T-cell lymphoma (CTCL) patients. To explore further the clinical efficacy and safety of FAMP monochemotherapy in advanced CTCL and to evaluate if the sequential association of ECP to FAMP in selected patients may improve the response rate (RR) and/or lengthen the remission duration. Forty-four CTCL patients [17 Sézary syndrome (SS); 26 mycosis fungoides (MF), stage IIB–IV or with peripheral blood involvement; one MF associated with lymphomatoid papulosis (LyP)] were enrolled in this pilot cohort study. All the patients received FAMP 25 mg m−2 5 days monthly; 19 patients (43·2%) underwent ECP after FAMP was discontinued. The majority of patients with erythrodermic CTCL or peripheral blood involvement underwent the combined FAMP–ECP schedule. After a median follow-up of 4·2 years, the overall FAMP RR was 29·5% (13/44); a higher RR was obtained in SS (35·3%) than in MF patients (25·9%). According to the treatment group, the RR of the FAMP–ECP group (63·2%) was significantly higher than that of the FAMP monotherapy group (24%; P = 0·021). No statistically significant difference was found in time-to-progression (TTP) or survival by therapy group, even if the TTP of the patients treated with the FAMP–ECP combination therapy was higher (median 13 vs. 7 months). A decrease or a normalization in the CD4+CD26– circulating subset was observed in responding patients, paralleling the reduction in the circulating Sézary cells. FAMP confirms its clinical activity as a single agent in SS; conversely, FAMP results do not compare favourably with other therapeutic approaches for advanced stage MF patients. The sequential association of ECP after FAMP seems to increase the RR, even if future randomized studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Various enzymatic or mechanical methods have been proposed in the past to dissociate cells from different solid tissues. An automated mechanical disaggregation device (Medimachine™) has recently been proposed. Unfortunately, most of these techniques are associated with a high cellular damage and a low cell recovery and are difficult to apply to skin biopsies. In this paper, we propose a combined enzymatic and mechanical method based on Medimachine™, useful for the isolation of skin infiltrating T-lymphocytes from small cutaneous biopsies. As this method is easy and allows for a more correct qualitative and quantitative cytofluorimetric analysis of the lymphocyte subsets, it may be useful in the immunophenotyping of cutaneous T-cell lymphomas. [ABSTRACT FROM AUTHOR]