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Exp Hematol ; 44(11): 1024-1033.e1, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27473564

RESUMEN

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment approach for patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Graft versus leukemia (GVL) effects, which are exerted by donor T cells directed against leukemic-associated antigens (LAAs), are considered to play a crucial role in disease eradication. Although the expansion of cytotoxic T lymphocytes (CTLs) specific for cytomegalovirus (CMV) in response to an infection has been shown in multiple studies, data on CTLs mediating GVL effects are limited. To evaluate a potential increase or decrease of T lymphocytes specific for LAAs in the setting of allogeneic HSCT, we monitored leukemia-specific CD8+ T cells throughout the first year after HSCT in 18 patients using streptamer technology. A broad panel of promising LAAs was selected: Wilms tumor protein, proteinase 3, receptor for hyaluronan acid-mediated motility, apoptosis regulator Bcl-2, survivin, nucleophosmin, and fibromodulin. T cells specifically directed against AML- or CLL-associated antigens were found at very low frequencies in peripheral blood. Substantial frequencies of LAA-specific T cells could not be measured at any time point by flow cytometry. In contrast, abundant CMV-pp65-specific T cells were detected in CMV-seropositive patient-recipient pairs and an increase prompted by CMV infection could be demonstrated. In conclusion, T lymphocytes with specificities for the aforementioned LAAs can only be detected in minimal quantities in the early phase after allogeneic HSCT.


Asunto(s)
Antígenos de Neoplasias/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Leucemia Mieloide Aguda/inmunología , Adulto , Anciano , Secuencia de Aminoácidos , Antígenos de Neoplasias/química , Biomarcadores de Tumor , Linfocitos T CD8-positivos/metabolismo , Epítopos de Linfocito T/química , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/terapia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Péptidos/química , Péptidos/inmunología , Fosfoproteínas/inmunología , Trasplante Homólogo , Proteínas de la Matriz Viral/inmunología
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