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Chromosome studies in mycosis fungoides.

G-banded chromosome analysis was performed on peripheral blood lymphocytes after phytohaemagglutinin stimulation from sixteen patients with mycosis fungoides. A number of chromosome abnormalities were observed in a low proportion of blood lymphocytes in seven patients in later stages of the disease. In four patients similar marker chromosomes in multiple copies were present, some of them without a clearly visible centromere. We conclude that a correlation exists between the presence of chromosome abnormalities in circulating blood lymphocytes and the course of the disease.

Adult↗

Photochemotherapy and topical nitrogen mustard in the treatment of mycosis fungoides.

Eight patients with mycosis fungoides limited to the skin have been treated with either topical nitrogen mustard alone or in combination with photochemotherapy. This regime does not prevent contact sensitization to nitrogen mustard but will clear sanctuary sites of disease which may develop when photochemotherapy is used alone.

Administration, Topical↗

Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies.

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuclear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I125 Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. there was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.

Adult↗

The use of a double-label immunoperoxidase monoclonal antibody technique in the investigation of patients with mycosis fungoides.

Using a double-labelling immunoperoxidase and monoclonal antibodies raised against T helper and T suppressor cells and Langerhans cells, we have found that the clinically involved skin of seventeen mycosis fungoides (MF) patients shows an increase in number of Langerhans cells which are in contact with T helper lymphocytes. T suppressor lymphocytes are also present, but are generally seen singly situated at a distance from the T helper/Langerhans cell clusters.

Adult↗

The cell population in the cutaneous infiltrate of mycosis fungoides: in situ using monoclonal antisera.

T cell antigens were studied in cutaneous sections from five patients with mycosis fungoides (MF). The method allowed cell counting to be undertaken for each monoclonal antiserum. OKT3 (pan T cell) antiserum confirmed the predominantly T lymphocytic nature of the infiltrate, labelling the majority of infiltrating cells. OKT4 (helper/inducer) antiserum positively labelled 90% of the lymphocytes identified as OKT3 +. OKT8 (suppressor) antiserum marked only single or small groups of dermal lymphocytes, which comprised 24% of the cells identified as T lymphocytes. OKT6 (anti-Langerhans) showed positive labelling of dendritic cells in the epidermis and dermis. Fewer positively labelled epidermal dendritic cells were observed in sections from patients receiving PUVA, but no difference was found in the number of OKT6 positive dermal cells. The ratio of helper to suppressor cells in the dermal infiltrate significantly exceeded the normal circulating ratio.

Antibodies, Monoclonal↗

Total skin electron beam irradiation for cutaneous T-cell lymphoma (mycosis fungoides).

Forty patients with the cutaneous T-cell lymphoma (mycosis fungoides) were treated with total skin electron beam irradiation. The total follow-up period was up to 116 months (median 57.5 months). The patients were irradiated with a total dose of 35 Gy over 10 weeks, using the six-field technique. Ten of these patients had lymph node involvement and were subsequently treated with chemotherapy. After the initial electron irradiation complete remission of the skin lesions was obtained in 87.5% of the patients. Relapse of skin lesions occurred in 52% of the patients after 2-72 months (median 4 months). Second line therapy consisted primarily of topical nitrogen mustard. The overall survival rate at 5 years was 70%. Despite the side-effects this treatment was tolerated well by all patients.

Adult↗

A case of mycosis fungoides mimicking actinic reticuloid.

A 61-year-old man presented with erythema and induration of the skin on his face and neck. Initially a photosensitive dermatosis was suspected but this was excluded on further investigation. Mycosis fungoides was diagnosed and the lesions responded to photochemotherapy (PUVA).

Diagnosis, Differential↗

Mycosis fungoides--response to therapy and survival patterns in 85 cases.

The clinical course and management of 85 cases of mycosis fungoides presenting over a 20-year period are described. The extent of skin involvement and presence of lymphadenopathy were seen to be important prognostic factors. The following survival patterns were observed. In eight cases with limited plaque disease there was prolonged disease-free survival after treatment with kilovoltage X-rays; after a median follow-up of 64 months there was only one case of progression to generalized disease. In 49 cases of generalized skin disease (plaque disease +/- tumours; erythroderma) treated with total skin electron beam therapy there was a 24% 5-year disease-free survival; this potential for long-term survival was seen in cases with generalized plaque disease without lymphadenopathy. The remainder of the cases showed a continuously relapsing course. The extent of skin involvement and presence of lymphadenopathy can both be used as known prognostic factors to adopt a logical plan of treatment.

Adult↗

Treatment of mycosis fungoides with recombinant interferon-alpha 2a2 alone and in combination with etretinate.

Eleven patients with mycosis fungoides (MF) were treated with recombinant alpha-interferon (rIFN-alpha 2a2) in combination with etretinate (seven patients) or alone. One patient, who also received etretinate, went into complete remission and remained without signs of MF after 18 months. Six patients experienced partial remission; one of these was treated with rIFN-alpha 2a alone and was clinically in complete remission, but had still a pleomorphic skin infiltrate. Two patients were non-evaluable, and two stopped therapy due to progressive disease. Five patients discontinued therapy due to side-effects although three had partial remission of their disease. Only four patients received 12 months therapy. The study shows that rIFN-alpha 2a in combination with etretinate or alone can induce remission of MF.

Aged↗

Concentrations of nitrogen mustard in the air during topical treatment of patients with mycosis fungoides.

Acute and chronic side-effects have been reported during topical treatment of mycosis fungoides with nitrogen mustard (HN2). In order to estimate the risk for the nurse applying topical HN2, the concentration of HN2 in the air during treatment was measured. Air samples were obtained before, and during the 20-min treatment period close to the nurse and patient, and continuously at a distance of 1 m from the patient. The mean concentration of HN2 in the air during treatment was 0.036 mg/m3. Immediately after treatment the concentration dropped to 0.004 mg/m3. The mean cumulative concentration in the room during the 3 1/2 h of the experiment was 0.012 mg/m3. If the MAC (maximal allowable concentration) value of 0.05 mg/m3 for the comparable sulphur mustard is used as a guideline, then with a treatment procedure of 20 min this level is not exceeded. Nevertheless, it is important to minimize the exposure of nursing staff to HN2.

Administration, Topical↗

Immunophenotyping on simultaneously occurring plaques and tumours in mycosis fungoides and Sézary syndrome.

Skin biopsy specimens from 15 patients with mycosis fungoides and Sézary syndrome, with simultaneously occurring plaques and tumours, were examined to assess phenotypic deviation. We focused on immunophenotypic differences between the two types of lesions with respect to the T-cell markers CD2, CD3, CD4, CD5 and CD8. In six patients (40%) loss of one or more T-cell markers occurred in at least one of the lesions. Three of the patients studied (20%) showed a difference in immunophenotype between plaques and tumours, with an additional loss of one of the T-cell markers in the tumours (respectively, CD5, CD2 and CD4). All three of these patients showed a larger number of blast cells in the tumour compared with the plaque. No correlation between this loss of antigenicity and the prognosis was observed. The results of this study show that different immunophenotypes can occur simultaneously in an individual patient. Furthermore, we were able to confirm a relationship between the number of intraepidermal CD1+ cells in plaque lesions and the prognosis.

Antigens, CD↗

Extracorporeal photochemotherapy induces apoptosis of infiltrating lymphoid cells in patients with mycosis fungoides in early stages. A quantitative histological study.

Extracorporeal photochemotherapy (ExP) is a well-tolerated new form of chemoimmunotherapy, which is considered to be effective for cutaneous T-cell lymphoma (CTCL) and the treatment of choice for Sézary syndrome. Improvements have also been seen in patients with non-erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells are not detectable in the peripheral blood. In this study, we used ExP as a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other therapies. We observed a clinical improvement in the disease after 12 months of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin biopsies of large plaque lesions before and after the treatment. We undertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following parameters; lymphoid cell density (LCD), Ki67 + lymphoid cell nuclei percentage (Ki67 + Lcn percentage), and apoptotic index (AI). Significant decreases in the lymphoid cell infiltrate and in cell proliferation, and a significant increase in AI were observed after therapy. The mean LCD decreased from 187 +/- 33 to 34 +/- 17.7, Ki67 + Lcn mean percentage decreased from 16.9 +/- 3.9 to 4.9 +/- 2.4, and the AI mean value increased from 0.05 +/- 0.03 to 2.41 +/- 1.54. Our results suggest a role for apoptosis in the improvement of the skin lesions and are in line with some reports on the mode of action of ExP. Although the way in which ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell-mediated anticlonotypic activity against circulating pathogenic clones. Furthermore, a release of tumour necrosis factor alpha (TNF-alpha) by circulating monocytes has been demonstrated after ExP. Both are known to induce cell death by apoptosis.

Aged↗

Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy.

BACKGROUND: 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. OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Efficacy of monochromatic excimer laser radiation (308 nm) in the treatment of early stage mycosis fungoides.

BACKGROUND: Various reports have recently shown the efficacy of narrowband ultraviolet (UV) B phototherapy at 311 nm in the treatment of early stage mycosis fungoides (MF). OBJECTIVES: To examine the effectiveness and tolerability of monochromatic excimer light (MEL) at 308 nm as a first treatment for early stage MF (stage IA). METHODS: Ten lesions from five patients with a clinical and histological diagnosis of MF were treated with repeated applications of MEL until complete remission was achieved or up to a maximum of 10 applications, with a cumulative dose of 308 nm UVB of between 6 and 12 J cm(-2). All patients were observed every 2 weeks for 2 months, with a 1-year follow-up. Results At present, all patients are in complete remission, with no side-effects. CONCLUSIONS: Based on these results, MEL can be considered a useful tool in the treatment of early stage MF.

Adult↗

T-cell receptor gamma gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings.

BACKGROUND: 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). MATERIALS AND METHODS: 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)-gamma 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. OBJECTIVE: 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. RESULTS: 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 > or = 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score > or = 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. CONCLUSIONS: 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.

CD8-Positive T-Lymphocytes↗

Prognostic factors and prediction of prognosis by the CTCL Severity Index in mycosis fungoides and Sézary syndrome.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. OBJECTIVES: To improve prediction of survival in patients with CTCL. METHODS: Prognostic factors including tumour-node-metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sézary syndrome). The Brier score was used to quantify the quality of individual prediction. RESULTS: Estimated 5-year survival rate (SR5) differed according to TNM stage: stage IA, 100% (95% confidence interval 70-100%); IB-III, 86% (73-100%); IVA, 54% (32-91%); IVB, 0% (0-52%). In a multivariate analysis, two independent prognostic factors were identified: lymph node (P = 0.036) and blood involvement (P = 0.015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula: SR5 = 124-2 x (CTCL-SI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sézary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30% regarding individual predictive power. CONCLUSIONS: Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.

Adult↗

Pegylated liposomal doxorubicin in stage IVB mycosis fungoides.

BACKGROUND: Previous studies have shown that pegylated liposomal doxorubicin (LD) is effective in the treatment of relapsing or recalcitrant cutaneous T-cell lymphoma. OBJECTIVES: To evaluate the activity and toxicity of LD in patients with stage IVB mycosis fungoides (MF). METHODS: In this retrospective study, we evaluated outcomes and recorded adverse effects in 10 patients with MF (seven men and three women) with extracutaneous involvement. Patients were treated with LD 20 mg m(-2) administered intravenously every 4 weeks. RESULTS: All patients received at least two cycles of LD, three patients received four cycles and one patient received six cycles. Three patients (30%) had a partial response and two patients had stable disease. Grade 1-2 leucopenia occurred in three of the 10 patients, and grade 4 leucopenia in one. Three patients had grade 2 palmoplantar erythrodysaesthesia. CONCLUSIONS: This study demonstrates that LD is beneficial in terms of activity and toxicity in stage IVB MF. These observations should be verified in larger studies.

Aged↗