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T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

Adult↗

Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.

Adult↗

Cutaneous malignant melanoma in association with mycosis fungoides.

We retrospectively analyzed the first 461 cases entered into our cutaneous lymphoma database and found 285 cases of mycosis fungoides. We also identified 6 cases of malignant melanoma, all of which were found in patients with mycosis fungoides. The crude rate of melanoma in the general population in England, United Kingdom, in 1998 was 8.8/100,000 in men and 11.4/100,000 in women. The incidence of melanoma found in our cohort of patients with mycosis fungoides was far higher, and in 4 of the 6 patients cannot be explained on the basis of prior therapy. The reason for this association is unclear, but this report emphasizes the risk of second malignancies for patients with cutaneous T-cell lymphoma and melanoma.

Adult↗

Effect of serum of mycosis fungoides patients on lymphocyte transformation.

In vitro transformation of peripheral lymphocytes by PHA was usually impaired in mycosis fungoides patients in the infiltrative plaque and tumor stages, while not being significantly impaired in the premycotic stage. A serum factor, reducing transformation by PHA, was demonstrated in 2 of 5 patients in the premycotic stage as well as in 2 and probably 3 of 4 patients in the infiltrative plaque or tumor stage. This serum factor affected both autologous (mycosis fungoides) and normal lymphocytes. The factor tended to be present in patients whose lymphocytes were impaired rather than in those whose lymphocytes were not significantly impaired. The degree of the reduction by mycosis fungoides serum seemed to correlate with the serum concentration of gamma-globulin rather than that of alpha2-globulin. The possible nature and clinical significance of this factor are discussed.

Humans↗

[Primary cutaneous lymphoma, with the exception of mycosis fungoides].

Cutaneous lymphomas other than mycosis fungoides (MF) form a rare and heterogeneous group. Their clinical behavior remains largely unknown. In this study, the clinical, immunohistological characteristics and follow-up data of 27 well-documented cases of primary cutaneous lymphomas other than MF, limited to the skin (stage IE) were reviewed. The tumors were divided into large-cell lymphomas (LCL) (21/27 = 77 p. 100) and small-cell lymphomas (SML) (6/27 = 23 p. 100). A B-cell phenotype was most often expressed by cutaneous lymphomas (23/27 = 85 p. 100). The clinical course of cutaneous lymphoma was closely dependent upon the histological subtype. Fourteen patients with LCL were treated by radiotherapy alone. Nine patients (64 p. 100) relapsed within two years post-treatment. Seven of them relapsed in the skin outside the initial site, suggesting that radiotherapy alone is not an adequate treatment for these patients. The preliminary results concerning 7 other patients with LCL treated with an initial third generation polychemotherapy regimen are presented.

Adult↗

Cutaneous malignant melanoma appearing during photochemotherapy of mycosis fungoides.

We report a case of malignant melanoma that appeared in a 56-year-old man with mycosis fungoides (stage Ia) during treatment with PUVA. The cumulative UVA dose was 1,177 J/cm2. The pigmented lesion was removed and PUVA therapy discontinued. Histological examination revealed a superficial spreading malignant melanoma (1.77 mm thick, Clark level IV). The delayed-type cutaneous hypersensitivity was studied. The presence of a second malignancy after mycosis fungoides and PUVA therapy may have been coincidental. Nevertheless, this case suggests that the immunosuppression induced by mycosis fungoides and by PUVA therapy might be a pathogenetic factor in the development of malignant melanoma.

Humans↗

Patch tests in Sézary syndrome and mycosis fungoides.

A retrospective series of 34 patients with the diagnoses of Sézary syndrome, pre-Sézary syndrome, or mycosis fungoides had had patch testing. Of these, 27 had at least 1 positive reaction (11 of 12 with pre-Sézary syndrome, 6 of 10 with Sézary syndrome, and 10 of 12 with mycosis fungoides). The highest average number of positive reactions was observed in patients with pre-Sézary syndrome (4.7 per patient). There was no predominance of positive reactions to any one allergen, but 13 of the 27 patients reacted to a metal allergen. Only 1 of 5 patients who had photopatch testing had a positive result. This retrospective study revealed delayed contact hypersensitivity responses in this group of patients and should serve as a basis for prospective consideration of contact dermatitis factors in patients with mycosis fungoides and Sézary states.

Allergens↗

T- and B-cells and IgE in mycosis fungoides.

The role of T- and B-lymphocytes and serum IgE was studied in 22 patients with mycosis fungoides. The distribution of B-cells in peripheral blood was normal, while the mean percentage of T-cells was significantly lower than in 14 healthy controls. Four patients with mycosis fungoides in stages I to IV had a highly elevated serum IgE, while serum IgE in remaining patients was slightly elevated, normal, or subnormal. The mean serum IgE level was not significantly elevated. Our results tend to show that a reduced ability to react with cellular immunity may be an important factor in mycosis fungoides. This may have therapeutic aspects.

Adolescent↗

Mycosis fungoides and cutaneous Hodgkin's disease in the same patient: a case report.

We describe a case of a 34-year-old man who presented with a 10-year history of mycosis fungoides and recent onset of inguinal lymphadenopathy, fever, and cutaneous nodules on the right hip. Biopsy of the inguinal lymph node showed mixed cellularity Hodgkin's lymphoma. Biopsy of the pre-existing skin lesions showed mycosis fungoides, while that of the nodules on the hip revealed cutaneous Hodgkin's lymphoma. Immunohistochemical and molecular analysis demonstrated a null phenotype in the Reed-Sternberg cells of the Hodgkin's disease lesions, and a T-cell phenotype in the lymphoid cells of the mycosis fungoides lesions. He was treated with chemotherapy for Hodgkin's disease, which is in remission 11 years later. Topical nitrogen mustard and maintenance PUVA therapy have been used for the mycosis fungoides, which is also in remission.

Adult↗

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.

Adult↗

The Sézary cell in the blood of patients with mycosis fungoides.

A study of 96 patients with an original diagnosis of mycosis fungoides revealed that 84 did not have circulating Sézary cells. Of the 12 patients with Sézary cells, only 3 had more than 15%. The 12 patients had benign and malignant skin diseases. The Sézary cell does not seem to have any importance in the pathogenesis of mycosis fungoides.

Adolescent↗

T-cell subsets with a naive phenotype are selectively decreased in the peripheral blood of patients with mycosis fungoides.

Peripheral blood lymphocytes of 33 patients with histopathologic confirmation of mycosis fungoides and 27 healthy controls matched for age and sex were analyzed with a panel of monoclonal antibodies using both single and dual color immunofluorescence. Patients with mycosis fungoides had a significant reduction in the percentage of circulating T cells with a naive phenotype (i.e., CD4+2H4+ and CD4+Leu8+), as well as a significant reduction in the absolute numbers of circulating lymphocytes with the phenotype CD8+Leu8+ compared to the control cohort. The reduction in circulating naive T cells was found to occur irrespective of stage of disease, duration of disease, or mode of treatment. The depletion of circulating naive T cells may reflect increased conversion to memory T cells in the peripheral blood or skin.

Antibodies, Monoclonal↗

Coincidental occurrence of pernicious anemia and mycosis fungoides in two elderly males.

We experienced two rare cases of pernicious anemia that presented in the course of mycosis fungoides in elderly males. Pernicious anemia has recently been reported to be caused by autoimmune gastritis that produces autoantibodies to gastric parietal cells and intrinsic factor. Immunological abnormalities in mycosis fungoides are reported to induce autoimmune diseases (i.e., autoimmune hemolytic anemia, anti-phospholipid antibody syndrome, arthritis, myasthenia gravis, necrotizing vasculitis, and vitiligo); the pernicious anemia in our two patients may have been closely related to the mycosis fungoides.

Aged↗

The ultrastructure of mycosis fungoides, of Sezary's syndrome, and of Woringer-Kolopp's disease (pagetoid reticulosis).

Skin lesions of 13 cases of mycosis fungoides, 2 cases of Sézary's syndrome and one case of Woringer-Kolopp's disease were studied. In mycosis fungoides two main cell types were observed: small atypical lymphoid cells, and large atypical lymphoid cells. The small atypical lymphoid cells were characterized by dense nuclei with varying degrees of nuclear lobulation. Normal-appearing lymphocytes and typical mycosis cells were in this cell group. The large atypical lymphoid cells were characterized by large nuclei with little lobulation and by less chromatin condensation, as well as by a more abundant cytoplasm. Their identification is discussed and indications of their possibly being neoplastic or proliferating lymphoblasts are given. In Sézary's syndrome Sézary cells with more lobulated nuclei than in mycosis cells and lymphoblast-like cells as in mycosis fungoides could be found. In Woringer-Kolopp's disease cells similar to Sézary cells aggregated mainly in the epidermis. No interdigitating reticulum cells and no other morphological signs of a specific lymphocyte microenvironment were found in any of the cases.

Dermatitis, Exfoliative↗

Hypopigmented mycosis fungoides: treatment and a 6(1/2)-year follow-up of 9 patients.

BACKGROUND: The clinical course of hypopigmented mycosis fungoides has not been well described. OBJECTIVE AND METHODS: We sought to review the management and follow-up of patients with hypopigmented mycosis fungoides evaluated between January 1990 and August 1998. RESULTS: There were 7 African American and 2 Asian patients (5 male and 4 female patients); 8 had stage Ia and 1 had stage Ib disease. The mean age at diagnosis was 34.4 years, the mean latent period was 9.2 years, and the mean follow-up period after diagnosis was 6.5 years. Treatment modalities used included psoralen UVA, UVB, and topical mechlorethamine. Eight had complete clinical responses, and another had a partial response. The remission period ranged from 2 months to 3 years. In all but one patient, lesions recurred; all responded rapidly to another course of therapy. CONCLUSION: Hypopigmented mycosis fungoides is characterized by early onset, occurrence in dark-skinned individuals, and good response to therapy. Recurrences are common. In most, it has a biologically benign course.

Adolescent↗

Variably acid-fast pleomorphic bacteria as a possible cause of mycosis fungoides. A report of a necropsied case and two living patients.

Variably acid-fast coccoid forms, suggestive of acid-fast, cell-wall-deficient forms of mycobacteria, were observed in microscopy of sections of skin from three patients with mycosis fungoides. Similar coccoid forms were also seen in sections of the heart, lung, liver, lymph nodes, connective tissue, and other organs of one of them who died, and in biopsy material from lymph nodes obtained one year antemortem in that patient. The present findings of microbes in mycosis fungoides may be related to the previous findings of acid-fast bacteria in mycosis fungoides and other malignancies as reported by other investigators. The present histopathologic findings also suggest that mycosis fungoides may be an infectious disease of mycobacterial origin.

Adult↗

[Topical, intratumor and intravenous nitrogen mustard in the treatment of mycosis fungoides (author's transl)].

Topical nitrogen mustard (NH2) is recommended in mycosis fungoides stages 1 or 2 (eczematous premycotic phase and plaque stage), intratumor infiltration in stage 3 (tumor stage) and intravenous administration in stages 4 and 5 (widespread disease). Following these criteria ten patients with mycosis fungoides have been treated with NH2. Six cases were included in stages 1 or 2 and complete remission was achieved in four of them. Therapy had to discontinued in one case due to allergic hypersensitivity. The remaining patient experienced clinical improvement after 27 months of continued treatment. There were three patients in stages 4 and 5 and all their plaques disappeared after topical NH2, but tumor regression was completely achieved in one case adn partially in the remaining two. A case with Sezary's syndrome was treated in addition with chlorambucil. Association of newer palliative measures (topical NH2, high energy electron beam therapy, nitrosourea derivatives) offer a hope of cure for patients in stages 1 or 2. Tumor stage requires systemic chemotherapeutic agents (chlorambucil tablets and intravenous nitrogen mustard).

Administration, Topical↗

Rapid pulmonary dissemination in mycosis fungoides simulating pneumonia. A case report and review of the literature.

Mycosis fungoides is a neoplastic disease with extranodal dissemination most frequently to the lung. The roentgenographic and clinical manifestations in these patients may simulate pneumonia and delay appropriate treatment. Disseminated disease is thought to occur in the setting of involvement of the peripheral blood with the neoplastic cells. A case of rapid pulmonary involvement with mycosis fungoides which simulated pneumonia is presented in which there was no peripheral blood manifestation of the disease.

Adult↗