title: Interleukin-2 therapy after allogeneic bone marrow transplantation for acute myelocytic leukemia: studies in a relevant rat model for AML.
abstract: One of the major problems in the treatment of leukemia with BMT remains leukemia relapse. It has generally been established that allogeneic BMT, compared with autologous BMT, gives rise to a graft-versus-leukemia reaction (GVLR), usually associated with GVHD. To explore a possible role for post-BMT immunotherapy, recombinant human IL-2 therapy has been studied in the Brown Norway acute myelocytic leukemia (BNML), a rat leukemia model relevant for human AML. The antileukemic efficacy of rhIL-2 therapy is studied applying different doses of rhIL-2 after syngeneic or allogeneic BMT. rhIL-2 treatment post-syngeneic BMT showed a small, borderline significant GVLR. Repeated rhIL-2 treatment after allogeneic BMT resulted either in no significant antileukemic effect or in lethal GVHD when 'low' or 'high' doses were administered, respectively. An intermediate dose, however, induced a significant GVLR without the induction of (lethal) GVHD. Transplantation of allogeneic rat BM, which contains only a few lymphocytes, does not result in a significant GVLR or GVHD and thus resembles human HLA-matched allogeneic T cell-depleted (TCD) BMT. In conclusion, from the rat studies presented it appears that the GVLR lost by TCD of the allogeneic graft, may be more than fully compensated by IL-2 treatment post-allogeneic TCD BMT.
authors.affiliation: Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: Kloosterman
authors.forename: A C
authors.initials: AC
authors.lastname: Martens
authors.forename: B
authors.initials: B
authors.lastname: Osterwalder
authors.forename: A
authors.initials: A
authors.lastname: Hagenbeek
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D018365:Neoplasm, Residual / Q000628:therapy; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D007376:Interleukin-2