title: Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia.
abstract: We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38% (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8(+) T cells (59%). Irradiation of CTL limited proliferation by 96% but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Jurickova
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.forename: A M
authors.initials: AM
authors.lastname: Yeager
authors.forename: M W
authors.initials: MW
authors.lastname: Boyer
mesh_terms: D000293:Adolescent; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006239:Haplotypes / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007223:Infant; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D010290:Parents; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D016896:Treatment Outcome