RESUMEN
Recent studies suggest that cells elaborating type 1 cytokines are important mediators of anti-tumor cell-mediated immunity in cutaneous T cell lymphoma. Type 1 cell-mediated immune responsiveness was assessed in 276 patients with cutaneous T cell lymphoma (mycosis fungoides and Sézary syndrome) using 2,4-dinitrochlorobenzene (DNCB) skin testing as part of the initial evaluation. The overall rate of sensitization after one and two DNCB challenges was 32% and 67%, respectively, which is much decreased compared with the expected rate of more than 95% for normal individuals. Moreover, the frequency of DNCB sensitization and allergic contact dermatitis to topically applied mechlorethamine decreased with advancing stage of disease. In addition to the expected strong correlation with stage, we observed that patients who were DNCB test positive were significantly less likely to experience disease progression and had a better overall prognosis compared with DNCB-negative patients. These results support the concept that cell-mediated responses are important in cutaneous T cell lymphoma, and that augmentation of these responses would be therapeutically beneficial.
Asunto(s)
Dinitroclorobenceno/farmacología , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad Tardía/inducido químicamente , Irritantes/farmacología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Mecloretamina/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dinitroclorobenceno/administración & dosificación , Dinitroclorobenceno/inmunología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Hipersensibilidad Tardía/inmunología , Irritantes/administración & dosificación , Linfoma Cutáneo de Células T/inmunología , Masculino , Mecloretamina/administración & dosificación , Mecloretamina/inmunología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/inmunología , Neoplasias Cutáneas/inmunología , Pruebas Cutáneas , Análisis de SupervivenciaAsunto(s)
Dinitroclorobenceno/uso terapéutico , Infecciones por VIH/terapia , Hipersensibilidad Tardía/inmunología , Inmunoterapia , Irritantes/uso terapéutico , Pruebas Cutáneas , Linfocitos T CD8-positivos/inmunología , Catecoles/uso terapéutico , Citocinas/inmunología , Dermatitis Alérgica por Contacto/inmunología , Dinitroclorobenceno/inmunología , Infecciones por VIH/inmunología , Humanos , Activación de Linfocitos , Mecloretamina/inmunología , Mecloretamina/uso terapéutico , Plantas Tóxicas , Células TH1/inmunología , ToxicodendronRESUMEN
Two patients with histologically proven mycosis fungoides, a malignancy of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude possible hypersensitivity reactions to this chemotherapeutic agent. In both patients, allergic contact dermatitis (ACD) developed at the sites of the application and resolved completely after withdrawal of mechlorethamine. The lesions were biopsied and analyzed for the presence of clonal T-cell receptor (TCR)-gamma gene rearrangements using two polymerase chain reaction (PCR)-based assays involving denaturing gradient gel electrophoresis (PCR/DGGE) and ribonuclease protection analysis (PCR/RPA). The former method has a clonal detection threshold of 10(-3)-10(-2), while the latter has a sensitivity of 10(-5). In both cases, the ACD lesions were polyclonal by PCR/DGGE. In contrast, PCR/RPA detected tumor-specific TCR-gamma gene rearrangements in these same lesions. This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range. Analysis of peripheral blood mononuclear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals. The normal skin from one skin patient also lacked detectable TCR-gamma gene rearrangements. These results indicate that mycosis fungoides tumor are present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous presence of detectable levels of these tumor cells in the blood or skin. These findings might be explained by nonspecific recruitment of malignant T cells to sites of local inflammation mediated by non-neoplastic antigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in response to cytokines generated during the ACD reaction. In either case, the present study offers evidence that the malignant cells in myosis fungoides retain at least some capability of responding in vivo to physiologic stimuli.
Asunto(s)
Dermatitis Alérgica por Contacto/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Femenino , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Mecloretamina/inmunología , Reacción en Cadena de la PolimerasaRESUMEN
A patient with slowly progressive tumor-stage mycosis fungoides (MF), without apparent extracutaneous involvement, received topical immunotherapy with mechlortethamine hydrochloride as the immunogen. A complete remission was achieved after two months of treatment, and the patient has remained free of detectable disease without further treatment for more than seven years. This case is also unusual in that, before treatment, a temporary exacerbation of MF had occurred during three pregnancies. These observations suggest that the natural resistance against the progression of MF in this patient was enhanced by immunotherapy.
Asunto(s)
Mecloretamina/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Adulto , Erupciones por Medicamentos/etiología , Femenino , Humanos , Inmunoterapia/métodos , Mecloretamina/inmunología , Micosis Fungoide/patología , Neoplasias Cutáneas/patologíaRESUMEN
In view of the contradictory results reported in the literature regarding induction of specific immunologic tolerance to mechlorethamine hydrochloride (HN2), the problem was reinvestigated using a "tolerogenic" schedule that had been reported to be effective. Mechlorethamine hydrochloride, 200 microgram, intravenously, was given weekly for five weeks before beginning topical therapy with it. In the test group, five of 13 patients (11 with mycosis fungoides and two with psoriasis) became contact sensitized to mechlorethamine. In another patient, what was probably a contact urticarial reaction developed. In the control group, five of 13 patients (12 with mycosis fungoides, one with parapsoriasis) became contact sensitized to mechlorethamine. Thus, 38% of the patients in both groups became contact sensitized to mechlorethamine. It is concluded that this tolerogenic schedule, just as others previously tried, was not effective in inducing specific tolerance to mechlorethamine.
Asunto(s)
Tolerancia Inmunológica , Mecloretamina/inmunología , Dermatitis por Contacto/inmunología , Dinitroclorobenceno/inmunología , Humanos , Mecloretamina/uso terapéutico , Micosis Fungoide/tratamiento farmacológico , Pruebas del Parche , Psoriasis/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
A group of 220 patients with mycosis fungoides (MF) and other lymphomatous diseases was treated with sustained topical applications of dilute aqueous solutions of mechlorethamine hydrochloride for intervals ranging in excess of seven years. Response to treatment, immunologic responsiveness, and subsequent course and survival were inversely related to magnitude of disease at time of starting treatment. Relapses were common and in most instances were related to failure to maintenance of topical therapy rather than to drug resistance. In selected patients topical therapy with an analog of mechlorethamine (nor-mechlorethamine) and with topical immunogenic agents provided additional improvement.
Asunto(s)
Inmunoterapia , Mecloretamina/administración & dosificación , Micosis Fungoide/terapia , Neoplasias Cutáneas/terapia , Administración Tópica , Anciano , Desensibilización Inmunológica , Dinitroclorobenceno/inmunología , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Hipersensibilidad Tardía/inmunología , Tolerancia Inmunológica , Metástasis Linfática , Masculino , Mecloretamina/análogos & derivados , Mecloretamina/inmunología , Persona de Mediana Edad , Micosis Fungoide/inmunología , Micosis Fungoide/patología , Neoplasias/inducido químicamente , Pronóstico , Neoplasias Cutáneas/patologíaRESUMEN
Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.
Asunto(s)
Dermatitis por Contacto/prevención & control , Desensibilización Inmunológica , Hipersensibilidad a las Drogas/prevención & control , Mecloretamina/efectos adversos , Psoriasis/tratamiento farmacológico , Administración Tópica , Dermatitis por Contacto/etiología , Hipersensibilidad a las Drogas/etiología , Humanos , Masculino , Mecloretamina/inmunología , Mecloretamina/uso terapéutico , Psoriasis/inmunología , Pruebas CutáneasRESUMEN
Further attempts to induce immunological tolerance in 29 psoriatic patients treated topically with mechlorethamine hydrochloride have not been successful using the intravenous route. The rate of sensitization achieved (65%) is not substantially different from the rate for those patients who had no attempt to induce tolerance (55.5%).