Interleukin-2 therapy after allogeneic bone marrow transplantation for acute myelocytic leukemia: studies in a relevant rat model for AML.
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.
Kloosterman
T C
TC
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
Martens
A C
AC
Osterwalder
B
B
Hagenbeek
A
A
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
D007376:Interleukin-2