Transfer factor therapy in mycosis fungoides: a double-blind study

Sixteen patients with mycosis fungoides (MF) were given either active transfer factor (TF) or heat-inactivated TF as additional therapy to topical nitrogen mustard or PUVA. The TF was prepared from non-selected healthy blood donors. The clinical evaluation after 2 years of therapy showed that among 8 patients treated with active TF, none went into complete remission of their disease 4 patients had partial remission, one was unchanged, 2 progressed, and one died of active MF. In the placebo-treated group, 5 patients achieved complete remission and 2 partial remission. One patient died early in the trial due to cardiac disease. Immunological studies during the first year of therapy revealed cutaneous anergy towards tuberculin in most patients. This anergy did not change during TF therapy and differed from normal lymphocyte reactivity in vitro after tuberculin stimulation. At the start of treatment the patients had diminished levels of T lymphocytes in peripheral blood. A temporary increase was observed in the total number of T lymphocytes in patients after one month of treatment with active TF. After one year the T lymphopenia had disappeared in both groups. The mitogen reactivity of lymphocytes was found to be normal (PHA, PWM) or somewhat reduced (Con A). It is concluded that under the conditions employed in this trial, TF was not able to prevent progression of early mycosis fungoides, when viewed over a period of 2 years.     

Narrowband UVB and PUVA in the treatment of mycosis fungoides: a retrospective study

Psoralen plus ultraviolet A (PUVA) is widely used as first-line therapy for treatment of mycosis fungoides. Narrowband ultraviolet B (NB-UVB) has also been shown to be effective for treatment of early mycosis fungoides. The aim of this retrospective study was to analyse the response to treatment and relapse-free interval for PUVA and NB-UVB therapies in mycosis fungoides. Forty patients were treated with PUVA or NB-UVB between 1980 and 2003. All patients had failed to respond to topical therapy or were unwilling to use it. PUVA therapy was used between 1980 and 1997. Thereafter, the choice between PUVA (twice a week) and NB-UVB therapy (three times a week) depended on stage and extent of the disease as well as on how far patients had to travel). Twelve patients (stage IA-IIB) were treated with NB-UVB and 28 patients (stage IA-IVA) with PUVA. No maintenance therapy was given. Six patients (50%) had a complete response, 4 (33%) had a partial response and 2 (16%) had a failed response to NB-UVB but had stable disease. PUVA led to a complete response in 18 (64%), a partial response in 6 (21%) and a failed response in 4 (14%) patients. The median relapse-free interval was 11.5 months in the NB-UVB treated group and 10 months in the PUVA group. The majority of the patients (79%) had stage IA and IB disease. Of these, 6 of 10 (60%) in the NB-UVB group and 13/21 (62%) in the PUVA group had a complete response to treatment. These results show that PUVA and NB-UVB are effective treatments for early mycosis fungoides.     

Pagetoid reticulosis, epidermotropic mycosis fungoides and mycosis fungoides: a disease spectrum

Using a standard technique involving monoclonal antibodies against T-cell subsets, we have shown that almost all the infiltrating T-cells in the epidermis of a patient with Pagetoid reticulosis (PR), one with epidermotropic mycosis fungoides (EMF) and one with poikiloderma atrophicans vasculare (PAV), were OKT8 positive (presumed cytotoxic/suppressor) T-cells. The infiltrating T-cells in the epidermis of a patient with limited plaque stage mycosis fungoides (MF), however, were almost exclusively Leu 3a-positive (presumed helper/inducer) T-cells as is usually found in this condition. The keratinocytes in the patients with PR, EMF and PAV were HLA-DR-positive whilst those in the patient with MF were HLA-DR-negative. We consider these four diseases to be part of the spectrum of mycosis fungoides, the first three conditions representing the early or benign end of the spectrum.     

Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients

BACKGROUND: Although low-dose methotrexate has been used to treat mycosis fungoides for many years, documentation is very limited. OBJECTIVE: Our purpose was to review our experience with methotrexate in the treatment of 69 patients with patch/plaque and tumor stage mycosis fungoides observed for up to 201 months. METHODS: This was a retrospective study. Data are presented in terms of response rates and time to treatment failure. RESULTS: The greatest number of patients (60) had patch/plaque stage T2 disease (>/=10% skin involved). Of these, 7 (12%) achieved complete remission and 13 (22%) achieved partial remission for a total response rate of 20 of 60 (33%). The median time to treatment failure was 15 months. Only 1 of 7 patients with tumor stage disease responded. Side effects caused treatment failure in 6 (9%) of the total cohort of 69 patients. CONCLUSION: Low-dose methotrexate may be of value in the treatment of a subset of patients with patch/plaque mycosis fungoides resistant to other therapies.     

Photodynamic therapy with methyl-aminolaevulinic acid for mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. There are a wide range of treatments for early-stage and advanced-stage mycosis fungoides. Photodynamic therapy (PDT) has emerged as a new treatment modality due to its safety and efficacy. The aim of this study was to investigate the safety and efficacy of PDT with methyl-aminolaevulinic acid (MAL) for the treatment of mycosis fungoides. Ten patients with mycosis fungoides were enrolled in this study. A 16.8% MAL cream was applied under occlusive dressing for 3 h. The lesion was irradiated at 37.5 J/cm2 with red light. The patients underwent two sessions of PDT at one-week intervals. Follow-up biopsy was performed 3 months after the last treatment. In case of partial response, treatment was repeated once a week until complete response. Seven patients had a good therapeutic response. Complete and partial responses were seen in 5 and 2 patients, respectively. During the follow-up period (8-31 months), 6 of the 7 patients remained in stable remission. The treatment was well-tolerated overall, and no patients discontinued the PDT due to pain. In conclusion, PDT with MAL is a fast, effective and well-tolerated treatment for unilesional mycosis fungoides.     

Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study

BACKGROUND: Treatment of early-stage mycosis fungoides (MF) consists of topical steroids, phototherapy (UVB), photochemotherapy (psoralen plus UVA [PUVA]), topical nitrogen mustard, or total skin electron-beam irradiation. It has been reported that the same effective UVB dose is safer than PUVA regarding carcinogenicity and produces fewer side effects. Narrowband UVB (311 nm) results in less irritation and erythema and is more effective compared with broadband UVB. OBJECTIVE: Our purpose in this retrospective study was to analyze the response to treatment, relapse-free interval, and irradiation dose in 56 patients with early-stage MF (stage Ia and Ib). A total of 21 patients were treated with narrowband UVB (311 nm); 35 patients were treated with PUVA. RESULTS: Narrowband UVB treatment led to complete remission in 17 of 21 patients (81%), partial remission in 4 of 21 (19%), and none showed progressive disease. PUVA treatment led to complete remission in 25 of 35 patients (71%), partial remission in 10 of 35 (29%), and none showed progressive disease. The mean relapse-free interval for patients treated with UVB was 24.5 months (range, 2-66 months) and for patients treated with PUVA, 22.8 months (range, 1-43 months). CONCLUSION: Narrowband UVB therapy for patients with early-stage MF is an effective treatment modality. It has several advantages over treatment with broadband UVB and PUVA. When treating patients with early-stage MF it may be beneficial to start with narrowband UVB therapy and, if there is progression or no response, switch to PUVA therapy.     

Hypopigmented mycosis fungoides in childhood and adolescence: a long‐term retrospective study

Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long‐term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty‐five patients had clinical follow‐up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T‐lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1–12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow‐up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing‐and‐waning course and relapse after discontinuation of therapy, requiring repetitive treatment.     

Prednimustine in mycosis fungoides: a report from the Scandinavian mycosis fungoides study group.

Prednimustine, a chlorambucil ester of prednisolone, was administered orally to 5 patients with mycosis fungoides in advanced tumour stage. Partial remission was obtained in 2 of the patients. However, we do not consider the agent to be particularly advantageous for the treatment of mycosis fungoides.     

Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides

Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma. Several rare clinicopathological variants of mycosis fungoides have been described. Patients with these variants often also have classic mycosis fungoides at other sites of the body. Anetoderma is a cutaneous disorder in which multiple, oval lesions or atrophic plaques with wrinkled surface develop progressively due to loss of the dermal elastic tissue. Primary anetoderma occurs when there is no underlying associated disease and it arises on clinically normal skin, whereas secondary anetoderma appears in the same site as a previous specific skin lesion. There is a large list of heterogeneous dermatoses associated with secondary anetoderma. Two patients developed areas of secondary anetoderma on plaque stage lesions of mycosis fungoides. The lesions consisted of exophytic nodular lesions, with very soft consistency on palpation, scattered over the hyperpigmented plaques in one patient and violaceous indurated plaques with overlying epidermal atrophy and mild scale in the other. Histopathological study demonstrated that the cells involving the dermis were mainly T-helper lymphocytes, with few histiocytes and some multinucleate giant cells engulfing distorted elastic fibres. Elastic tissue stain demonstrated that elastic fibres were almost completely absent in the dermis of the anetodermic lesions. Anetodermic mycosis fungoides should be added to the list of clinicopathological variants of mycosis fungoides and mycosis fungoides should also be considered as a possible disease causing secondary anetoderma. Anetodermic mycosis fungoides shows clinical and histopathological features different from those of granulomatous slack skin.     

Familial cutaneous mycosis fungoides: successful treatment with a combination of gemcitabine and alemtuzumab

We report a familial cutaneous T-cell lymphoma in father and son. After different treatment modalities without lasting responses, the son was treated with gemcitabine as single agent and due to insufficient effect with alemtuzumab monotherapy. Only after the two drugs had been combined did we observe a remarkable response of the skin lesions and disappearance of enlarged lymph nodes. The combined treatment with gemcitabine and alemtuzumab was well tolerated, and no increased toxicity was noted. The combination of these two active agents may provide an additional option in the treatment of cutaneous T-cell lymphoma.     

The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy

Background: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. Aim: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. Methods: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4–52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. Results: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. Discussion: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.     

Mycosis fungoides: a retrospective study

The clinical course of ninety patients with the histopathologic diagnosis of mycosis fungoides is reviewed. An attempt is made to correlate sex, age, of onset, lesion type, and form of therapy with outcome of the disease. The data indicate that mycosis fungoides affects predominantly middle-aged males. Patients developing tumors or erythroderma in middle age or later tend to have a shorter survival. More aggressive therapy is associated with shortened survival. Most deaths were due to unknown or unrelated processes and therapeutic complications. The data support the theory that mycosis fungoides can be a relatively nonaggressive cutaneous lymphoma. In an attempt to treat aggressively, we may be exposing patients to increased mortality.