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Combination chemotherapy for mycosis fungoides: a Southwest Oncology Group study.

Between 1972 and 1977, the Southwest Oncology Group studied the following three chemotherapy programs for the treatment of patients with advanced forms of mycosis fungoides: (a) cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) (seven patients); (b) adriamycin, vincristine, and prednisone (HOP) (five patients); and (c) cyclophosphamide, vincristine, prednisone, and bleomycin (COP plus bleomycin) (12 patients). Among the 24 evaluable patients there was an overall objective response rate of 95% with seven (29%) achieving a complete remission. With the adriamycin-containing chemotherapy, five (42%) of 12 patients achieved a complete remission compared to two (17%) of 12 patients treated with COP plus bleomycin. The median duration of remission (partial plus complete) was longer with the COP plus bleomycin combination (median, 47 weeks) than with the adriamycin-containing combinations (median, 22 weeks; P = 0.03). The median survival for all 24 evaluable patients was 95 weeks and was similar regardless of remission-induction therapy. In summary, combination chemotherapy proved to be effective palliative therapy for advanced mycosis fungoides.

Adult↗

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-gamma and has been in complete remission for more than 6 years.

We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.

Antineoplastic Agents↗

Demodex folliculitis on the trunk of a patient with mycosis fungoides.

A 43-year-old man with tumour stage mycosis fungoides developed multiple follicular pustules on the trunk during total-skin electron beam therapy. A potassium hydroxide preparation of the contents of the pustules revealed the presence of Demodex mites. The patient was treated with 6% sulphur lotion with rapid improvement of the cutaneous lesions. We believe that this case represents a pustular folliculitis caused by Demodex mites. Immunosuppression associated with mycosis fungoides and its treatment may have resulted in the proliferation of this obligate parasite of the pilosebaceous follicle, and the development of the folliculitis.

Adult↗

Photochemotherapy for mycosis fungoides.

Twelve cases of cutaneous mycosis fungoides (MF) with erythroderma, plaques, and tumors were treated with photochemotherapy. Methoxsalen followed two hours later by ultraviolet light (UVA) resulted in clinical clearing of skin lesions in seven patients with plaque stage MF and one patient with erythrodermic MF. Four patients with both plaque and tumor stage MF showed clearing of plaques but not the tumors. Phototherapy units consisted of boxes with 16 to 64 UVA lights. The mean numbers of treatments to clear was 17.4. The mean total dose to clear was 134.8 joules. The mean dose of maintenance UVA was 5.6 joules/sq cm. Histopathologic clearing of mycosis fungoides was demonstrated with the clinical clearing.

Adult↗

Localized mycosis fungoides with prominent epidermotropism: Woringer-Kolopp disease.

A patient had a single, large, sharply demarcated lesion on one leg. Under the mistaken diagnosis of malignant melanoma in situ, the lesion was excised and the area grafted in 1956. There has been no recurrence in the past 20 years. Histologic reevaluation led to a diagnosis of mycosis fungoides with pronounced epidermotropism of the cellular infiltrate. This case has close clinical and histologic resemblance with three cases published in Europe and regarded as a special form of reticulosis as first described by Woringer and Kolopp. Mycosis fungoides with marked epidermotropism is not always a benign localized disease but may be widespread and lead to death.

Adult↗

[Primary cutaneous lymphoma--mycosis fungoides].

Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).

Antigens, CD↗

Scandinavian mycosis fungoides study group.

A multicenter study group on Mycosis Fungoides in Denmark, Norway and Sweden has been active since 1974. Staging procedures based on a 5 stage-system have been established, and treatment protocols have been worked out. Topical nitrogen mustard with and without toleranceinduction has been applied on stage II, and Bleomycin has been randomized against Bleomycin and Methotrexate in stage, III, IV, and V. Protocols containings PUVA are now activated, with PUVA given in combination with Cyclophosphamide for extracutaneous forms of Mycosis Fungoides.

Humans↗

Mucinosis of the mammary areolae and mycosis fungoides.

We present a patient with cutaneous mucinosis of the mammary areolae who developed multiple erythematous macules with clearly defined, geographical edges 1 year after diagnosis. These lesions demonstrated mycosis fungoides on histology. We discuss a possible association between the mucinosis and the mycosis fungoides.

Adult↗

Mycosis fungoides palmaris et plantaris: successful treatment with the carbon dioxide laser.

Mycosis fungoides palmaris et plantaris (MFPP) is an uncommon form of mycosis fungoides with main involvement on palms and soles. The lesions may be quite hyperkeratotic. A 56-year-old patient with MFPP was successfully treated with the carbon dioxide (CO2) laser. There was no recurrence of disease at treated sites and excellent cosmetic results were obtained. Treatment with the CO2 laser may be considered a therapeutic option.

Foot↗

Transfer factor in mycosis fungoides: a case report on a patient "cured".

A report is given of the successful treatment with transfer factor as an additional therapeutic agent of a patient in the tumour stage of mycosis fungoides who had not responded to conventional treatment with nitrogen mustard, methotrexate, or grenz rays alone. Besides twelve injections of transfer factor, the patient received X-irradiation, 1 400 r (50 kV 1 mm Al) in all, to three tumours. The combined treatment induced sustained remissions. When that patient died from a coronary infarct 5 years after treatment began, autopsy showed no evidence of mycosis fungoides at all.

Humans↗

[Mycosis fungoides. Early diagnosis and evaluation of treatment by polymerase chain reaction].

We describe the case of a 60-year-old man who, after seven years with eczematous changes, developed erythrodermia, clinically suspect of mycosis fungoides. T-cell receptor gamma (TCR-gamma) gene rearrangements were retrospectively investigated by polymerase chain reaction (PCR). DNA from a formalin-fixed, paraffin-embedded punch biopsy showed a monoclonal pattern compatible with mycosis fungoides two years before the diagnosis was confirmed histopathologically. PCR was also used to evaluate the effect of different treatments. This case demonstrates the value of PCR for early diagnosis and evaluation of treatment of cutaneous T-cell lymphoma.

Humans↗

Mycosis fungoides with involvement of the oral cavity.

Mycosis fungoides rarely involves the oral cavity. To our knowledge only 29 cases of oral cutaneous T-cell lymphoma have been described up to 1994. This report presents a case of mycosis fungoides with involvement of the oral cavity in a 57-year-old man who died from septicemia 7 months after the onset of oral involvement.

Diagnosis, Differential↗

Granulomatous mycosis fungoides.

We report a new observation of granulomatous mycosis fungoides. The diagnosis was able to be made only after performing multiple biopsies during the course of the disease. Initial evolution was rapidly favourable with electrontherapy. A granulomatous reaction is, except in Hodgkin's disease, a rare phenomenon in lymphoproliferative disorders, particularly in cutaneous T cell lymphoma. This variant of mycosis fungoides raises the problem of the histological differentiation from other granulomatous dermatoses, mainly sarcoidosis. Its prognostic significance is disputed and its pathogenesis remains unknown.

Biopsy, Needle↗

Can proctological procedures resolve perianal pruritus and mycosis? A prospective study of 23 cases.

Twenty-three patients with pruritus ani associated with anal mycosis underwent primary treatment of a concurrent anal disorder. The anal disorders included haemorrhoids (n = 9), fissure (n = 8), anal spasm without fissure (n = 5), and occult mucosal prolapse (n = 1). Pretreatment investigation of faeces for parasites was negative. The glucosal tolerance test and white blood cell count were normal in all cases. Culture of skin smears from the perianal region was positive for Candida only in 16 patients, Dermatophytes only in 6 and a combination of both in 1 patient. Following the appropriate proctological procedure, pruritus resolved or markedly improved in 20 patients. The remaining three patients required antifungal treatment with econazole. Two of these, however, continued to complain of pruritus. It is suggested that in patients with pruritus ani associated with perianal mycosis, antimycotic therapy should be used only if fungal infection persists after treatment of the underlying proctological disease.

Adolescent↗

Pharmacokinetics-pharmacodynamics of micafungin in Japanese patients with deep-seated mycosis.

The objective of this study was to describe the pharmacokinetic profile and investigate the effective concentration of micafungin in Japanese male patients with deep-seated mycosis. 66 patients were treated with i.v. micafungin 12.5-150 mg intravenously for up to 56 days. At this dose range, micafungin showed linear pharmacokinetics, and the mean values of Cmax and Cmin amounted to 3.16-12.9 microg/mL and 0.70-3.68 microg/mL, respectively. The mean value for the elimination half-life was 13.5 h (95 samples from 65 patients), and it remained almost constant over the dose range. In addition, the elimination half-life was not influenced by age, gender or weight, and was similar to that found in healthy subjects. The active metabolites M1 and M2 were detectable, but their exposure was lower than that of the unchanged drug. The pharmacokinetic-pharmacodynamics ob micafungin were then investigated. The overall clinical response rate against aspergillosis and candidiasis showed good results at a dose of 50 mg and over. The Cmax and Cmin at the latter dose amounted to 5.16 and 1.41 microg/mL, respectively. In conclusion, micafungin showed linear pharmacokinetics at doses ranging from 12.5 to 150 mg, and the effective concentration was considered to be over 5 microg/mL as maximum level in Japanese patients with deep-seated mycosis such as candidiasis and aspergillosis.

Adult↗

Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).

BACKGROUND: Total skin irradiation for early-stage mycosis fungoides produces clinical remission in 90% of patients, but the median duration of remission is only 2 to 4 years. Etretinate has proven efficacy in advanced mycosis fungoides. Its potential as adjuvant therapy to radiation could be limited by toxicity from the combination. OBJECTIVE: Our purpose was to determine whether oral etretinate at 1 mg/kg can be combined with 35 Gy of radiation without intensifying or prolonging the radiation reaction and to determine the relapse-free survival rate. METHODS: Twenty-three patients began etretinate on day one of radiation and the dose was reduced for nose bleeds, dry skin, or hyperlipidemia. During the reaction skin toxicity questionnaires were completed weekly. Nine concurrent patients receiving only radiation completed identical forms. RESULTS: Etretinate did not intensify the skin reaction but did prolong it by 2 weeks. At a median follow-up of 2 years the relapse-free survival rate in complete responders was similar to stage-matched concurrent and historic control subjects. CONCLUSIONS: Both radiation and etretinate can be given together with acceptable toxicity and without compromising either therapy.

Administration, Oral↗

Sitobion avenae alatae infected by Pandora neoaphidis: their flight ability, post-flight colonization, and mycosis transmission to progeny colonies.

Epizootics caused by the obligate Entomophthorales pathogen Pandora neoaphidis may result from more than one possible means of fungal dissemination among host aphids, but we hypothesize that wide dispersal of the fungus is most likely to be associated with the flight behavior of migratory alates. We tested this hypothesis in a simulation experiment by assessing the flight capability of Sitobion avenae alates infected with P. neoaphidis and the potential of their post-flight survival, colonization, and mycosis transmission to progeny. A total of 281 alates were inoculated with P. neoaphidis, individually flown for up to 5h and 9km in a computer-monitored flight mill system and then reared for 10 days on wheat seedlings. The infected alates were capable of surviving on average for 2.9 days (range 1-7 days) and leaving 4.6 nymphs prior to deaths. Transmission of fungal infection within progeny colonies occurred after the mother alates died from P. neoaphidis mycosis. The level of contagious infection among the nymphs reached up to 16.8% within 7 days but varied with the survival time of the infected mother alates after flight. Based on stepwise polynomial regression analysis, progeny colony size was highly correlated with the interactions of flight time with both post-flight survival time and the number of nymphs left per alate before death (r2 = 0.997). Progeny mortality on day 5 after colonization was inversely correlated with post-flight survival time (r2 = 0.949) whereas infection on day 7 was correlated with flight distance and an interaction of post-flight survival time with fecundity of the infected alates (r2 = 0.970). Progeny mortality observed on day 10 was merely correlated to mortality observed on day 5 (r2 = 0.946). These results indicate a successful transmission of alate-borne P. neoaphidis to progeny colonies and further support our hypothesis on the means of primary dispersal of aphid epizootics by migratory alates in a geographically wide range.

Animals↗