RESUMEN
Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Amifostina/administración & dosificación , Citarabina/administración & dosificación , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/fisiopatología , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Proyectos Piloto , Pronóstico , Protectores contra Radiación/administración & dosificación , Resultado del TratamientoRESUMEN
CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
Asunto(s)
Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Antígenos Comunes de Leucocito/análisis , Activación de Linfocitos , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Antígenos CD/biosíntesis , Antígenos de Neoplasias/biosíntesis , Complejo CD3/fisiología , Linfocitos T CD4-Positivos/inmunología , Calcio/metabolismo , Ciclo Celular , Humanos , Interleucina-2/farmacología , Antígeno Ki-1 , Proteínas Recombinantes/farmacología , Células Tumorales CultivadasRESUMEN
Patients with Hodgkin's disease, at presentation or in remission, exhibit a persistent defect in cellular immunity. Natural killer cell mediated cytotoxicity is depressed in untreated patients. Humoral immune function is transiently reduced following treatment. The cellular immune defect appears to be the result of enhanced sensitivity to suppressor monocytes and T-suppressor cells, in addition to abnormal interleukin-2 production. Patients with advanced disease have an inherent T-lymphocyte defect. Reed-Sternberg cells function as antigen-presenting cells for mitogen-induced and mixed lymphocyte T-cell proliferation.
Asunto(s)
Enfermedad de Hodgkin/inmunología , Formación de Anticuerpos , Enfermedad de Hodgkin/complicaciones , Humanos , Inmunidad CelularRESUMEN
Patients with Hodgkin's disease, either untreated or in remission, exhibit a persistent defect in cellular immunity. This cellular immune defect appears to be the result of increased sensitivity to suppressor monocytes and T-suppressor cells, in addition to abnormal Interleukin-2 production. T-lymphocyte function is abnormal in patients with advanced disease. The precise origin of Reed-Sternberg and Hodgkin's cells is unknown. Reed-Sternberg cells function as antigen-presenting cells and as accessory cells in mitogen-induced T-cell proliferation. They have properties in common with dendritic cells and activated lymphocytes. L428 cells express a transformation-associated phosphorylated transmembrane protein, with properties of a growth factor receptor, that may play a role in tumorigenic transformation.